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Prince Last Mudenda Zilundu
- Assistant Professor
- Ext: --
Assistant Professor of Anatomy in the College of Dentistry, Ajman University. He graduated from the College of Health Sciences, University of Zimbabwe (Human Anatomy and Occupational Therapy). Pursued his MSc and PhD in the field of Human Anatomy with specialization in Neuroscience Research. He has over 15 years of exposure to Anatomy Education as well significant experience teaching Anatomy to medical, dental, radiography, nursing science, occupational and physiotherapy students. He is a certified Occupational Therapist, editorial board member of Frontiers in Neuroanatomy and reviews for several anatomical sciences and Neuroscience journals. He has published over 20 articles in international journals in the field of Anatomy and Neurosciences.
Education
- PhD in Human Anatomy, Embryology and Histology, Sun Yat-sen University, China, 2021
- MSc Anatomy, University of Zimbabwe, Zimbabwe, 2012
- BSc (Hons) Occupational Therapy, University of Zimbabwe, Zimbabwe, 2008
- BSc (Hons) Intercalated Human Anatomy, University of Zimbabwe, Zimbabwe, 2006
PhD in Human Anatomy, Embryology and Histology, Sun Yat-sen University, China, 2021
MSc Anatomy, University of Zimbabwe, Zimbabwe, 2012
BSc (Hons) Occupational Therapy, University of Zimbabwe, Zimbabwe, 2008
BSc (Hons) Intercalated Human Anatomy, University of Zimbabwe, Zimbabwe, 2006
Experience
- Assistant Professor, Basic and Medical Sciences Department, Ajman University, United Arab Emirates, January 2022-
- Anatomy technician (3D/prossected models), Guoxiwang Teaching Aids Company limited, China, August 2021-December 2021
- Graduate teaching Assistant, Anatomy Department, Sun Yat-sen University, China, August 2017-December 2020
- Lecturer, Anatomy and Physiology, National University of Science and Technology, Zimbabwe, August 2018-December 2021
- Lecturer (Anatomy) with courses in Occupational Therapy, Departments of Anatomy and Rehabilitation, University of Zimbabwe, Zimbabwe, October 2012 to 2017
- Assistant Lecturer (Anatomy) with courses in Occupational Therapy, Departments of Anatomy and Rehabilitation, University of Zimbabwe, Zimbabwe, September 2008 to September 2012
- Demonstrator of Gross Anatomy, Anatomy Department, University of Zimbabwe, Zimbabwe, August 2005-Sptember 2008
Assistant Professor, Basic and Medical Sciences Department, Ajman University, United Arab Emirates, January 2022-
Anatomy technician (3D/prossected models), Guoxiwang Teaching Aids Company limited, China, August 2021-December 2021
Graduate teaching Assistant, Anatomy Department, Sun Yat-sen University, China, August 2017-December 2020
Lecturer, Anatomy and Physiology, National University of Science and Technology, Zimbabwe, August 2018-December 2021
Lecturer (Anatomy) with courses in Occupational Therapy, Departments of Anatomy and Rehabilitation, University of Zimbabwe, Zimbabwe, October 2012 to 2017
Assistant Lecturer (Anatomy) with courses in Occupational Therapy, Departments of Anatomy and Rehabilitation, University of Zimbabwe, Zimbabwe, September 2008 to September 2012
Demonstrator of Gross Anatomy, Anatomy Department, University of Zimbabwe, Zimbabwe, August 2005-Sptember 2008
Teaching Area
- Gross Anatomy (Head and Neck)
- Integrated Biological Sciences
- Histology
- Embryology
- Neuroanatomy
- Kinesiology and Applied Biomechanics
- Occupational Therapy techniques
- Gross Anatomy (whole body and Dissection based)
Gross Anatomy (Head and Neck)
Integrated Biological Sciences
Histology
Embryology
Neuroanatomy
Kinesiology and Applied Biomechanics
Occupational Therapy techniques
Gross Anatomy (whole body and Dissection based)
Research
- Neurosciences
- Medical Education: Anatomy
Neurosciences
Medical Education: Anatomy
Publications
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JournalKe Zhong, Yu Huang, Prince Last Mudenda Zilundu, Yaqiong Wang, Yingying Zhou, Guangyin Yu, Rao Fu, Sookja Kim Chung, Yamei Tang, Xiao Cheng, Lihua Zhou, Motor neuron survival is associated with reduced neuroinflammation and increased autophagy after brachial plexus avulsion injury in aldose reductase-deficient mice, Journal of Neuroinflammation, Nov 2022, doi: 10.1186/s12974-022-02632-6
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JournalJifeng Zhang, Prince Last Mudenda Zilundu, Wenbin Zhang, Guangyin Yu, Sumei Li, Lihua Zhou, Guoqing Guo, The use of a surgical boot camp combining anatomical education and surgical simulation for internship preparedness among senior medical students, BMC Medical Education, Jun 2022, doi: 10.1186/s12909-022-03536-y
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JournalPrince L M Zilundu, Fidelis Chibhabha, Guangyin Yu, Rao Fu, Li-Hua Zhou, Pre-Clinical Medical Students' Use of Motivational and Cognitive Study Strategies During Anatomy Learning: A Three-Year Cross-Sectional Survey, Anatomical Sciences Education, Mar 2021, doi: 10.1002/ase.2070
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JournalPrince L M Zilundu, Fidelis Chibhabha, Samson Chengetanai, Rao Fu, Li-Hua Zhou , Zimbabwean PreClinical Medical Students Use of Deep and Strategic Study Approaches to Learn Anatomy at Two New Medical Schools, Anatomical Sciences Education, Jun 2021, doi: https://doi.org/10.1002/ase.2064
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JournalJi-Feng Zhang, Prince Last Mudenda Zilundu, Rao Fu, Xue-Feng Zheng, Li-Hua Zhou, Guo-Qing Guo, Medical students' perceptions and performance in an online regional anatomy course during the Covid-19 pandemic, Anatomical Sciences Education, Jun 2022
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JournalLong-Term Suppression of c-Jun and nNOS Preserves Ultrastructural Features of Lower Motor Neurons and Forelimb Function after Brachial Plexus Roots Avulsion, Cells, Jun 2021
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JournalZaara Liaquat, Xiaoying Xu, Prince Last Mudenda Zilundu, Rao Fu, Lihua Zhou, The Current Role of Dexmedetomidine as Neuroprotective Agent: An Updated Review, Brain Sciences, Jun 2021
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JournalKe Zhong, Yingqin Li, Ying Tang, Guangyin Yu, Prince Last Mudenda Zilundu, Yaqiong Wang, Yingying Zhou, Xiaoying Xu, Rao Fu, Lihua Zhou, Cytokine profile and glial activation following brachial plexus roots avulsion injury in mice, Journal of Neuroimmunology, Apr 2021
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JournalYing Tang, Yingqin Li, Guangyin Yu, Zemin Ling, Ke Zhong, Prince L M Zilundu, Wenfu Li, Rao Fu, Li-Hua Zhou, MicroRNA-137-3p Protects PC12 Cells Against Oxidative Stress by Downregulation of Calpain-2 and nNOS, Cellular and Molecular Neurobiology, Jun 2020
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JournalJi-Feng Zhang, Prince Last Mudenda Zilundu, Lihua Zhou, Guo-Qing Guo, Supplementary Regional Anatomy Teaching by Surgeons Enhances Medical Students Mastery of Anatomical Knowledge and Positively Impacts Their Choice of Future Career, Journal of Surgical Education, May 2020
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JournalZhou LN, Wang JC, Zilundu PLM, Wang YQ, Guo WP, Zhang SX, Luo H, Zhou JH, Deng RD, Chen DF, A comparison of the use of adipose-derived and bone marrow-derived stem cells for peripheral nerve regeneration in vitro and in vivo, Stem Cell Research And Therapy, Apr 2020
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JournalGuangyin Yu, Prince Last Mudenda Zilundu, Linlin Liu, Ke Zhong, Ying Tang, Zemin Ling, Li-Hua Zhou, ERRγ is downregulated in injured motor neuron subpopulations following brachial plexus root avulsion, Experimental and Therapeutic Medicine, Nov 2019
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JournalGuangyin Yu, Prince Last Mudenda Zilundu, Xiaoying Xu, Yingqin Li, Yingying Zhou, Ke Zhong, Rao Fu, Li-Hua Zhou, The temporal pattern of brachial plexus root avulsion-induced lncRNA and mRNA expression prior to the motoneuron loss in the injured spinal cord segments, Neurochemistry International, Nov 2019
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JournalXiao Cheng, Patrick K K Yeung, Ke Zhong, Prince L M Zilundu, Lihua Zhou, Sookja K Chung, Astrocytic endothelin-1 overexpression promotes neural progenitor cells proliferation and differentiation into astrocytes via the Jak2/Stat3 pathway after stroke, Journal of Neuroinflammation, Nov 2019
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JournalThe applied anatomy and clinical significance of the proximal, V1 segment of vertebral artery, Folia Morphologica (Warsz), Apr 2019
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JournalQiu Y, Wu X, Zhuang Z, Li X, Zhu L, Huang C, Zhuang H, Ma M, Ye F, Chen J, Wu Z, Yu X, An M, Chen R, Chen J, Guan L, Sang H, Ye Y, Han Y, Chen Z, Qin H, Zhu H, Zhou Y, Zilundu PLM, Xu D, Zhou L., Anatomical variations of the aortic arch branches in a sample of Chinese cadavers: embryological basis and literature review, Interactive CardioVascular and Thoracic Surgery, Nov 2018
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JournalSun JB, Li Y, Cai YF, Huang Y, Liu S, Yeung PK, Deng MZ, Sun GS, Zilundu PLM, Hu QS, An RX, Zhou LH, Wang LX, Cheng X., Scutellarin protects oxygen/glucose-deprived astrocytes and reduces focal cerebral ischemic injury, Neural Regeneration Research, Aug 2018
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JournalLi YQ, Song FH, Zhong K, Yu GY, Zilundu PLM, Zhou YY, Fu R, Tang Y, Ling ZM, Xu X, Zhou LH, Pre-Injection of Small Interfering RNA (siRNA) Promotes c-Jun Gene Silencing and Decreases the Survival Rate of Axotomy-Injured Spinal Motoneurons in Adult Mice, Journal of Molecular Neuroscience, Jul 2018
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JournalLi XZ, Chen J, Zhuang ZK, Ma MJ, Zhuang HJ, Qiu YM, Ye F, Wu XX, Prince LM Zilundu, Zhou LH, XuDZ., A rare case of the dual origin of the right vertebral artery with an aortic arch origin of the left vertebral artery, The European Journal of Anatomy, Jun 2018
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JournalZilundu PLM, Zhou LH, Gene Therapy for Brachial Plexus Root Avulsion and Spinal Cord Injuries: A Review, Journal of Jinan University (Natural Science & Medicine Edition), Mar 2017, doi: DOI: 10.11778/j.jdxb.2017.01.001
Ke Zhong, Yu Huang, Prince Last Mudenda Zilundu, Yaqiong Wang, Yingying Zhou, Guangyin Yu, Rao Fu, Sookja Kim Chung, Yamei Tang, Xiao Cheng, Lihua Zhou, Motor neuron survival is associated with reduced neuroinflammation and increased autophagy after brachial plexus avulsion injury in aldose reductase-deficient mice, Journal of Neuroinflammation, Nov 2022, doi: 10.1186/s12974-022-02632-6
Brachial plexus root avulsion (BPRA) is frequently caused by high-energy trauma including traffic accident and birth trauma, which will induces massive motoneurons (MNs) death as well as loss of motor and sensory function in the upper limb. The death of MNs is attributed to energy deficiency, neuroinflammation and oxidative stress at the injured ventral horn of spinal cord triggered by BPRA injury. It has been reported which aldose reductase (AR), an endogenous enzyme that catalyzes fructose synthesis, positively correlates with the poor prognosis following cerebral ischemic injury, diabetic retinopathy and diabetic peripheral neuropathy. However, the role of AR in BPRA remains unknown. Herein, we used a mouse model and found that in the spinal cord of BPRA mice, the upregulation of AR correlated significantly with (1) an inactivated SIRT1-AMPK-mTOR pathway and disrupted autophagy; (2) increased byproducts accumulation of lipid peroxidation metabolism and neuroinflammation; and (3) increased MNs death. Furthermore, our results demonstrated the role of AR in BPRA injury whereby the absence of AR (AR knockout mice, AR-/-) prevented the hyper-neuroinflammation and disrupted autophagy as well as motor neuron death caused by BPRA injury. Finally, we further demonstrate that AR inhibitor epalrestat is neuroprotective against BPRA injury by increasing autophagy level, alleviating neuroinflammation and rescuing MNs death in mice. Collectively, our data demonstrate that the AR upregulation in the spinal cord is an important factor contributing to autophagy disruption, neuroinflammation and MNs death following brachial plexus roots avulsion in mice. Our study also provides a promising therapy drug to assist re-implantation surgery for the treatment of BPRA.
About the journal
Jifeng Zhang, Prince Last Mudenda Zilundu, Wenbin Zhang, Guangyin Yu, Sumei Li, Lihua Zhou, Guoqing Guo, The use of a surgical boot camp combining anatomical education and surgical simulation for internship preparedness among senior medical students, BMC Medical Education, Jun 2022, doi: 10.1186/s12909-022-03536-y
Abstract Background: Senior medical students feel unprepared for surgical procedures and care for surgery patients when they begin their internship. This study sought to introduce and evaluate a surgical boot camp training for senior medical students. Methods: A 44-h surgical boot camp program of lectures on clinical practice simulation, anatomical dissections, and simulated operation on cadavers was designed, implemented, and evaluated during the 2018 to 2019 academic year. A self-administered questionnaire was used to assess students' perceptions of the content, delivery, and self-confidence. The mini-Clinical Evaluation Exercise (mini-CEX) and the Operative Performance Rating System were used to assess skills essential to good clinical care and to facilitate feedback. Results: Over 93% of the students were satisfied with the surgical boot camp, training equipment, and learning materials provided. After six sessions of training, 85.3% reported gaining self-confidence and performed better in some surgical procedures such as major gastrectomy. The mini-CEX scores suggested significant improvement in the students' clinical skills, attitudes, and behaviors (P < 0.01). Ninety-eight percent of students felt that the anatomical knowledge taught met their needs. The scores of the Operative Performance Rating System suggested that the students' surgical skills such as instruments handling, incising, treatment of surrounding tissues (blood vessels, nerves), and smoothness of the whole operation had increased significantly following the surgical boot camp (All P < 0.01). Conclusion: The surgical boot camp curriculum improved students' satisfaction and confidence in core clinical practice competencies. Therefore, medical schools the world over should continue to seek ways to bridge the gaps between pre-clinical, clinical, and internship training.
About the journal
Prince L M Zilundu, Fidelis Chibhabha, Guangyin Yu, Rao Fu, Li-Hua Zhou, Pre-Clinical Medical Students' Use of Motivational and Cognitive Study Strategies During Anatomy Learning: A Three-Year Cross-Sectional Survey, Anatomical Sciences Education, Mar 2021, doi: 10.1002/ase.2070
Medical students' motivation and study strategies are crucial in determining academic performance. This study aimed to assess the motivation and learning strategies of medical students as well as their association with performance in anatomy examinations. The Motivated Strategies for Learning Questionnaire, two focus group discussions, and students' current anatomy cumulative grade point average (cGPA) were used. Generally, the medical students strongly felt that anatomy is fundamental to the practice of medicine and surgery. This result was consistent with high task value scores of 5.99 ± 1.25. They were also driven by extrinsic goal orientation (5.59 ± 1.42) and intrinsic goal orientation (5.08 ± 1.26). Most medical students typically relied on elaboration (5.35 ± 1.25) ahead of other cognitive strategies namely rehearsal (5.30 ± 1.11), organization (5.15 ± 1.34), and lowest-rated critical thinking (4.77 ± 1.19). The students also relied on resource management strategies, effort regulation (5.15 ± 1.20) and time and study environment regulation (5.03 ± 1.03) more than the moderately scored peer learning (4.95 ± 1.50) and help-seeking (4.95 ± 1.09). In the focus group discussions, students reported that they often narrate or explain to each other what they would have read and understood from anatomy lectures, tutorials, and textbooks. They also bemoaned the lack of institutional support for stress burdens. The motivation and learning strategies subscales were not correlated with anatomy cGPA. Males were driven by extrinsic goals and experienced significantly higher levels of test anxiety than females (P < 0.05). Knowing the motivation and learning strategies students employ early in the medical curriculum can be leveraged to promote self-directed learning and academic achievement.
About the journal
Prince L M Zilundu, Fidelis Chibhabha, Samson Chengetanai, Rao Fu, Li-Hua Zhou , Zimbabwean PreClinical Medical Students Use of Deep and Strategic Study Approaches to Learn Anatomy at Two New Medical Schools, Anatomical Sciences Education, Jun 2021, doi: https://doi.org/10.1002/ase.2064
Anatomy is a challenging preclinical subject owing to the vast amount of information that students need to master. The adoption of relevant study approaches is key to the development of a long-lasting understanding of anatomical subject matter. Phenomenographic educational research describes the medical students as using a variable mix of deep, strategic, and surface approaches to study. Continually assessing students' learning preferences and approaches is crucial for achieving the desired learning outcomes. The approaches to studying anatomy in two groups of first-year Zimbabwean medical students from two newly established medical schools were collected using the Approaches and Study Skills Inventory for Students (ASSIST) instrument and than analyzed. At least 90% of the students believed that anatomy involved reproducing knowledge or personal understanding and development. Overall, the majority of the students adopted deep and strategic approaches, while a distant minority used the surface approach. There was no significant correlation between either the students' sex or age and their preference for a specific approach to studying. The mean anatomy grades for students using a strategic approach were significantly higher than those using deep or surface approaches. The number of strategic learners was double that of deep learners among the high achievers subgroup. The strategic approach positively correlated with performance in examinations. Generally, the students shared a common understanding of the concept of anatomy learning. Studies such as this can assist with the identification of students at risk of failure and empower lecturers to recommend the adoption of more beneficial strategic and deep learner traits.
About the journal
Ji-Feng Zhang, Prince Last Mudenda Zilundu, Rao Fu, Xue-Feng Zheng, Li-Hua Zhou, Guo-Qing Guo, Medical students' perceptions and performance in an online regional anatomy course during the Covid-19 pandemic, Anatomical Sciences Education, Jun 2022
The present study evaluated the students' psychological well-being, experiences, performance, and perception of learning regional anatomy remotely. A regional anatomy remote learning curriculum was designed and learning materials were delivered virtually to 120 undergraduate medical students at Jinan University, China. All the students consented and voluntarily participated in this study by completing self-administered online questionnaires including the Zung's Self-Rating Anxiety and Depression Scales at the beginning and end of the learning session. A subset participated in focus group discussions. Most of the students (90.0%) positively evaluated the current distance learning model. More than 80% were satisfied with the content arrangement and coverage. Many students preferred virtual lectures (68.2%) and videos showing dissections (70.6%) during the distance learning sessions. However, writing laboratory reports and case-based learning were the least preferred modes of learning as they were only preferred by 23.2% and 14.1% of the students, respectively. There was no significant lockdown-related anxiety or depression reported by students using depression and anxiety scales as well as feedback from focus group discussions. The surveyed students' confidence scores in distance learning were significantly higher after 5 weeks than at the beginning of the session (3.05 ± 0.83 vs. 3.70 ± 0.71, P < 0.05). Furthermore, the present results showed no significant differences between the current group's academic performance in the unit tests as well as the final overall evaluation for different parts of the course compared to that of the previous year's cohort. The findings above were congruent with focus group discussion data that the use of the online teaching platform for regional anatomy significantly improved the students' confidence in virtual and self-directed learning and did not negatively affect their academic performance.
About the journal
Long-Term Suppression of c-Jun and nNOS Preserves Ultrastructural Features of Lower Motor Neurons and Forelimb Function after Brachial Plexus Roots Avulsion, Cells, Jun 2021
Brachial plexus root avulsions cause debilitating upper limb paralysis. Short-term neuroprotective treatments have reported preservation of motor neurons and function in model animals while reports of long-term benefits of such treatments are scarce, especially the morphological sequelae. This morphological study investigated the long-term suppression of c-Jun- and neuronal nitric oxide synthase (nNOS) (neuroprotective treatments for one month) on the motor neuron survival, ultrastructural features of lower motor neurons, and forelimb function at six months after brachial plexus roots avulsion. Neuroprotective treatments reduced oxidative stress and preserved ventral horn motor neurons at the end of the 28-day treatment period relative to vehicle treated ones. Motor neuron sparing was associated with suppression of c-Jun, nNOS, and pro-apoptotic proteins Bim and caspases at this time point. Following 6 months of survival, neutral red staining revealed a significant loss of most of the motor neurons and ventral horn atrophy in the avulsed C6, 7, and 8 cervical segments among the vehicle-treated rats (n = 4). However, rats that received neuroprotective treatments c-Jun JNK inhibitor, SP600125 (n = 4) and a selective inhibitor of nNOS, 7-nitroindazole (n = 4), retained over half of their motor neurons in the ipsilateral avulsed side compared. Myelinated axons in the avulsed ventral horns of vehicle-treated rats were smaller but numerous compared to the intact contralateral ventral horns or neuroprotective-treated groups. In the neuroprotective treatment groups, there was the preservation of myelin thickness around large-caliber axons. Ultrastructural evaluation also confirmed the preservation of organelles including mitochondria and synapses in the two groups that received neuroprotective treatments compared with vehicle controls. Also, forelimb functional evaluation demonstrated that neuroprotective treatments improved functional abilities in the rats. In conclusion, neuroprotective treatments aimed at suppressing degenerative c-Jun and nNOS attenuated apoptosis, provided long-term preservation of motor neurons, their organelles, ventral horn size, and forelimb function.
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Zaara Liaquat, Xiaoying Xu, Prince Last Mudenda Zilundu, Rao Fu, Lihua Zhou, The Current Role of Dexmedetomidine as Neuroprotective Agent: An Updated Review, Brain Sciences, Jun 2021
Dexmedetomidine, selective α2-adrenergic agonist dexmedetomidine, has been widely used clinically for sedation and anesthesia. The role of dexmedetomidine has been an interesting topic of neonatological and anesthetic research since a series of advantages of dexmedetomidine, such as enhancing recovery from surgery, reducing opioid prescription, decreasing sympathetic tone, inhibiting inflammatory reactions, and protecting organs, were reported. Particularly, an increasing number of animal studies have demonstrated that dexmedetomidine ameliorates the neurological outcomes associated with various brain and spinal cord injuries. In addition, a growing number of clinical trials have reported the efficacy of dexmedetomidine for decreasing the rates of postoperative neurological dysfunction, such as delirium and stroke, which strongly highlights the possibility of dexmedetomidine functioning as a neuroprotective agent for future clinical use. Mechanism studies have linked dexmedetomidine's neuroprotective properties with its modulation of neuroinflammation, apoptosis, oxidative stress, and synaptic plasticity via the α2-adrenergic receptor, dependently or independently. By reviewing recent advances and preclinical and clinical evidence on the neuroprotective effects of dexmedetomidine, we hope to provide a complete understanding of the above mechanism and provide insights into the potential efficacy of this agent in clinical use for patients.
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Ke Zhong, Yingqin Li, Ying Tang, Guangyin Yu, Prince Last Mudenda Zilundu, Yaqiong Wang, Yingying Zhou, Xiaoying Xu, Rao Fu, Lihua Zhou, Cytokine profile and glial activation following brachial plexus roots avulsion injury in mice, Journal of Neuroimmunology, Apr 2021
Inflammation and tissue infiltration by various immune cells play a significant role in the pathogenesis of neurons suffering the central nervous systems diseases. Although brachial plexus root avulsion (BPRA) leads to dramatic motoneurons (MNs) death and permanent loss of function, however, the knowledge gap on cytokines and glial reaction in the spinal cord injury is still existing. The current study is sought to investigate the alteration of specific cytokine expression patterns of the BPRA injured spinal cord during an acute and subacute period. The cytokine assay, transmission electron microscopy, and histological staining were utilized to assess cytokine network alteration, ultrastructure morphology, and glial activation and MNs loss within two weeks post-injury on a mouse unilateral BPRA model. The BPRA injury caused a progressively spinal MNs loss, reduced the alpha-(α) MNs synaptic inputs, whereas enhanced glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor molecule-1 (IBA-1), F4/80 expression in ipsilateral but not the contralateral spinal segments. Additionally, cytokine assays revealed BPRA significantly altered the level of CXCL1, ICAM1, IP10, MCP-5, MIP1-α, and CD93. Notably, the elevated MIP1-α was mainly expressed in the injured spinal MNs. While the re-distribution of CD93 expression, from the cytoplasm to the nucleus, occasionally occurred at neurons of the ipsilateral spinal segment after injury. Overall, these findings suggest that the inflammatory cytokines associated with glial cell activation might contribute to the pathophysiology of the MNs death caused by nerve roots injury.
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Ying Tang, Yingqin Li, Guangyin Yu, Zemin Ling, Ke Zhong, Prince L M Zilundu, Wenfu Li, Rao Fu, Li-Hua Zhou, MicroRNA-137-3p Protects PC12 Cells Against Oxidative Stress by Downregulation of Calpain-2 and nNOS, Cellular and Molecular Neurobiology, Jun 2020
The imbalance between excess reactive oxygen species (ROS) generation and insufficient antioxidant defenses contribute to a range of neurodegenerative diseases. High ROS levels damage cellular macromolecules such as DNA, proteins and lipids, leading to neuron vulnerability and eventual death. However, the underlying molecular mechanism of the ROS regulation is not fully elucidated. Recently, an increasing number of studies suggest that microRNAs (miRNAs) emerge as the targets in regulating oxidative stress. We recently reported the neuroprotective effect of miR-137-3p for brachial plexus avulsion-induced motoneuron death. The present study is sought to investigate whether miR-137-3p also could protect PC12 cells against hydrogen peroxide (H2O2) induced neurotoxicity. By using cell viability assay, ROS assay, gene and protein expression assay, we found that PC-12 cells exposed to H2O2 exhibited decreased cell viability, increased expression levels of calpain-2 and neuronal nitric oxide synthase (nNOS), whereas a decreased miR-137-3p expression. Importantly, restoring the miR-137-3p levels in H2O2 exposure robustly inhibited the elevated nNOS, calpain-2 and ROS expression levels, which subsequently improved the cell viability. Furthermore, the suppressive effect of miR-137-3p on the elevated ROS level under oxidative stress was considerably blunted when we mutated the binding site of calpain-2 targted by miR-137-3p, suggesting the critical role of calpain-2 involving the neuroprotective effect of miR-137-3p. Collectively, these findings highlight the neuroprotective role of miR-137-3p through down-regulating calpain and NOS activity, suggesting its potential role for combating oxidative stress insults in the neurodegenerative diseases.
About the journal
Ji-Feng Zhang, Prince Last Mudenda Zilundu, Lihua Zhou, Guo-Qing Guo, Supplementary Regional Anatomy Teaching by Surgeons Enhances Medical Students Mastery of Anatomical Knowledge and Positively Impacts Their Choice of Future Career, Journal of Surgical Education, May 2020
Background: Anatomy is fundamental to the practice of medicine and surgery. Anatomy is also increasingly being taught by basic medical scientists or postclinical practice surgeons, thereby potentially detaching it from ongoing clinical realities. Objective: To evaluate whether supplementing regional anatomy teaching using surgeons enhances medical students' mastery of anatomical knowledge and how it impacts their choice of a future career. Design: This was a descriptive study. Setting: An integrated tuition model in which basic regional anatomy was supplemented with clinical correlates taught by surgeons was devised and implemented at Jinan University Medical School. Participants: Soon after the third-year medical students finished dissecting each region (e.g., head and neck, limbs, etc.) of the human body, the surgeons from relevant specialties and sub-specialties were invited to give clinical application lectures. A self-administered questionnaire was used to evaluate all the students' perceptions of the integrated teaching model, perceived mastery of anatomical knowledge and determinants of future career choice. Results: More than half of the students believe that regional anatomy is more closely related to surgery than systemic anatomy. Over 70% of the students have a positive attitude towards this teaching model where surgeons supplement regional anatomy with clinical correlates, and 98% of the students are in favor of integrating human body structural knowledge into clinical problems to learn anatomy. In addition, 78% of the students believe that the surgeons' participation in the teaching of regional anatomy helps them better understand human body structures and their clinical significance. However, some of their responses point towards the clinical correlate disconnection from the basic anatomy content. Furthermore, the majority of the students plan to become clinical doctors. After studying regional anatomy, the proportion of students who elected to be surgeons decreased slightly. However, the number of students who affirmatively planned to become surgeons in the future increased slightly, and 90% of these students were able to specify a chosen and preferred subspecialty of surgery. Conclusions: Surgeons' involvement in regional anatomy is of major benefit to students in understanding the human anatomy and its clinical significance, as well as positively impact on the decision to pursue a career in surgery.
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Zhou LN, Wang JC, Zilundu PLM, Wang YQ, Guo WP, Zhang SX, Luo H, Zhou JH, Deng RD, Chen DF, A comparison of the use of adipose-derived and bone marrow-derived stem cells for peripheral nerve regeneration in vitro and in vivo, Stem Cell Research And Therapy, Apr 2020
Background: To date, it has repeatedly been demonstrated that infusing bone marrow-derived stem cells (BMSCs) into acellular nerve scaffolds can promote and support axon regeneration through a peripheral nerve defect. However, harvesting BMSCs is an invasive and painful process fraught with a low cellular yield. Methods: In pursuit of alternative stem cell sources, we isolated stem cells from the inguinal subcutaneous adipose tissue of adult Sprague-Dawley rats (adipose-derived stem cells, ADSCs). We used a co-culture system that allows isolated adult mesenchymal stem cells (MSCs) and Schwann cells (SCs) to grow in the same culture medium but without direct cellular contact. We verified SC phenotype in vitro by cell marker analysis and used red fluorescent protein-tagged ADSCs to detect their fate after being injected into a chemically extracted acellular nerve allograft (CEANA). To compare the regenerative effects of CEANA containing either BMSCs or ADSCs with an autograft and CEANA only on the sciatic nerve defect in vivo, we performed histological and functional assessments up to 16 weeks after grafting. Results: In vitro, we observed reciprocal beneficial effects of ADSCs and SCs in the ADSC-SC co-culture system. Moreover, ADSCs were able to survive in CEANA for 5 days after in vitro implantation. Sixteen weeks after grafting, all results consistently showed that CEANA infused with BMSCs or ADSCs enhanced injured sciatic nerve repair compared to the acellular CEANA-only treatment. Furthermore, their beneficial effects on sciatic injury regeneration were comparable as histological and functional parameters evaluated showed no statistically significant differences. However, the autograft group was roundly superior to both the BMSC- or ADSC-loaded CEANA groups. Conclusion: The results of the present study show that ADSCs are a viable alternative stem cell source for treating sciatic nerve injury in lieu of BMSCs.
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Guangyin Yu, Prince Last Mudenda Zilundu, Linlin Liu, Ke Zhong, Ying Tang, Zemin Ling, Li-Hua Zhou, ERRγ is downregulated in injured motor neuron subpopulations following brachial plexus root avulsion, Experimental and Therapeutic Medicine, Nov 2019
Estrogen-related receptor γ (ERRγ) is a member of a small group of orphan nuclear receptor transcription factors that have been implicated in several physiological and pathological processes, including placental development, regulation of metabolic genes or disease. The pattern of expression of ERRγ, its role in neuronal injury and its co-localization with other transcription factors in the spinal cord of rats with brachial plexus injury has not been determined. The expression profile of ERRγ and its co-localization with RNA binding protein fox-1 homolog 3 (NeuN) or cyclic AMP-dependent transcription factor 3 (ATF-3) in the motor neurons of rats that underwent brachial plexus root avulsion were assessed using western blot analysis, immunohistochemistry and immunofluorescence. Fluorogold (FG) was used to mark neurons whose axons were severed. ATF-3 was expressed in the nuclei of motor neurons whose axons were severed by root avulsion. On day 3 post-avulsion, FG and ATF-3 were all co-localized in the injured motor neurons. The level of ERRγ protein in the ipsilateral half of injured spinal cords was significantly decreased compared with that in the contralateral half on days 3, 14 and 28 post-avulsion (all P
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Guangyin Yu, Prince Last Mudenda Zilundu, Xiaoying Xu, Yingqin Li, Yingying Zhou, Ke Zhong, Rao Fu, Li-Hua Zhou, The temporal pattern of brachial plexus root avulsion-induced lncRNA and mRNA expression prior to the motoneuron loss in the injured spinal cord segments, Neurochemistry International, Nov 2019
The neuronal mechanisms underlying brachial plexus roots avulsion-induced motoneuron death are unknown. Our previous studies showed that the avulsion induced obvious temporal and spatial expression of both degenerative and regenerative genes in the injured spinal cord tissue. Therefore, we hypothesized that lncRNAs (responsible for epigenetic molecular mechanisms) are altered (resulting in altered gene expression patterns) at days 3 and 14 after avulsion. In the present microarray study, 121 lncRNAs (83 up/38 down) and 844 mRNAs (726 up/118 down) were differentially expressed (ipsilateral vs contralateral) after avulsion. We further used qRT-PCR as a validation tool to confirm the expression patterns of 5 lncRNAs and 5 mRNAs randomly selected from our microarray analysis data. The gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to identify the critical biological processes and pathways. The noted downregulation of the AF128540 (which targets the nNOS gene) is consistent with the high expression of nNOS protein observed at day 14 post-avulsion. The downregulation of MRAK034299, whose target is the Adra1d gene, is consistent with the downregulation of Adra1d mRNA and protein at days 3 and 14 post avulsion. Immunofluorescence evaluation showed cytoplasmic translocation of ECEL1 after avulsion injury. Moreover, we also found that IL6 and Rac2 are the core genes at days 3 and 14 after unilateral brachial plexus roots avulsion, respectively. Overall, our present data suggest that the altered LncRNAs (avulsion-induced), via unknown epigenetic mechanisms, certainly contribute to the molecular mechanism underpinning motoneuron death or survival. Therefore, the avulsion-induced differentially expressed lncRNAs and mRNAs may offer potential diagnostic and therapeutic targets for BPRA.
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Xiao Cheng, Patrick K K Yeung, Ke Zhong, Prince L M Zilundu, Lihua Zhou, Sookja K Chung, Astrocytic endothelin-1 overexpression promotes neural progenitor cells proliferation and differentiation into astrocytes via the Jak2/Stat3 pathway after stroke, Journal of Neuroinflammation, Nov 2019
Background: Endothelin-1 (ET-1) is synthesized and upregulated in astrocytes under stroke. We previously demonstrated that transgenic mice over-expressing astrocytic ET-1 (GET-1) displayed more severe neurological deficits characterized by a larger infarct after transient middle cerebral artery occlusion (tMCAO). ET-1 is a known vasoconstrictor, mitogenic, and a survival factor. However, it is unclear whether the observed severe brain damage in GET-1 mice post stroke is due to ET-1 dysregulation of neurogenesis by altering the stem cell niche. Methods: Non-transgenic (Ntg) and GET-1 mice were subjected to tMCAO with 1 h occlusion followed by long-term reperfusion (from day 1 to day 28). Neurological function was assessed using a four-point scale method. Infarct area and volume were determined by 2,3,5-triphenyltetra-zolium chloride staining. Neural stem cell (NSC) proliferation and migration in subventricular zone (SVZ) were evaluated by immunofluorescence double labeling of bromodeoxyuridine (BrdU), Ki67 and Sox2, Nestin, and Doublecortin (DCX). NSC differentiation in SVZ was evaluated using the following immunofluorescence double immunostaining: BrdU and neuron-specific nuclear protein (NeuN), BrdU and glial fibrillary acidic protein (GFAP). Phospho-Stat3 (p-Stat3) expression detected by Western-blot and immunofluorescence staining. Results: GET-1 mice displayed a more severe neurological deficit and larger infarct area after tMCAO injury. There was a significant increase of BrdU-labeled progenitor cell proliferation, which co-expressed with GFAP, at SVZ in the ipsilateral side of the GET-1 brain at 28 days after tMCAO. p-Stat3 expression was increased in both Ntg and GET-1 mice in the ischemia brain at 7 days after tMCAO. p-Stat3 expression was significantly upregulated in the ipsilateral side in the GET-1 brain than that in the Ntg brain at 7 days after tMCAO. Furthermore, GET-1 mice treated with AG490 (a JAK2/Stat3 inhibitor) sh owed a significant reduction in neurological deficit along with reduced infarct area and dwarfed astrocytic differentiation in the ipsilateral brain after tMCAO. Conclusions: The data indicate that astrocytic endothelin-1 overexpression promotes progenitor stem cell proliferation and astr ocytic differentiation via the Jak2/Stat3 pathway.
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The applied anatomy and clinical significance of the proximal, V1 segment of vertebral artery, Folia Morphologica (Warsz), Apr 2019
Background: The aim of the study was to probe the morphological features of the proximal segment (V1) of vertebral artery (VA) in a sample of Chinese cadavers. Materials and methods: The origin, course and outer diameter at origin of the pre-vertebral part of the VAs were evaluated in 119 adult cadavers. Results: It was found that 94.12% of the VAs originated from the subclavian arteries, bilaterally. The variant origins were present in 5.88% of the cadavers and all originated directly from the arch of the aorta. All the variations were observed on the left side of male cadavers. The average outer diameters at origin of the normal and variation groups were 4.35 ± 1.00 mm and 4.82 ± ± 1.42 mm, respectively, p = 0.035. In the normal group, but not in the variation group, the average diameter in the males was significantly larger than that in the females (4.50 ± 0.99 mm, 3.92 ± 0.92 mm, respectively, p = 0.000). In addition, only 5 cadavers in the normal group had hypoplastic VAs (4.20%, 4 males, 3 right-sided). Vertebral artery dominance (VAD) was present in 91 (69 males) out of 112 cadavers and more common on the left (n = 48). In addition, 3 cadavers satisfied conditions for coexistence of VAD and vertebral artery hypoplasia. All 7 cadavers in the variation group exhibited VAD, which was more common on the right side (n = 5). Conclusions: The morphologic variations and frequencies described above have implications for the early prevention, abnormal anatomy detection, accurate diagnosis, safe surgery and endovascular treatment of cardiovascular and neurological disease.
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Qiu Y, Wu X, Zhuang Z, Li X, Zhu L, Huang C, Zhuang H, Ma M, Ye F, Chen J, Wu Z, Yu X, An M, Chen R, Chen J, Guan L, Sang H, Ye Y, Han Y, Chen Z, Qin H, Zhu H, Zhou Y, Zilundu PLM, Xu D, Zhou L., Anatomical variations of the aortic arch branches in a sample of Chinese cadavers: embryological basis and literature review, Interactive CardioVascular and Thoracic Surgery, Nov 2018
Objectives: The aim of this study is to determine the incidence and explore the types of aortic arch branch variations found in our cadavers. Methods: The types and incidence of aortic branch variations in 120 cadavers were analysed after careful dissection. Results: One hundred and six of 120 cadavers had normal aortic arch branches and gave rise to usual branches, namely the brachiocephalic trunk, the left common carotid artery and the left subclavian artery. The remaining 14 cadavers had 2 basic types of branch variations, thus accounting for an incidence of 11.67%. A total of 9 aortic arches emitted 4 branches; the brachiocephalic trunk, the left common carotid artery, the left vertebral artery and the left subclavian artery (incidence 7.5%). The second subgroup of 5 cadavers also emitted 4 aortic branches: the right common carotid artery, the left common carotid artery, the left subclavian artery and the right subclavian artery (incidence 4.16%). In this group, the right subclavian artery sprung as a distal branch of the aortic arch (descending), thus making a vascular ring that takes a superoposterior course round the back of the trachea and the oesophagus to reach the right side. There was a single cadaver, different from the other 4 aortic branches of the second group which had a common origin for the common carotid arteries, while the left subclavian artery and distally placed right subclavian artery were present. We did not observe any Kommerell's aortic diverticula. Conclusions: The variations of aortic arch branching are complex and diverse due to varied possible alterations in the embryological processes. There is an imperative need for further research on these variations to elucidate the possible relationships with clinical diagnostic or surgical events.
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Sun JB, Li Y, Cai YF, Huang Y, Liu S, Yeung PK, Deng MZ, Sun GS, Zilundu PLM, Hu QS, An RX, Zhou LH, Wang LX, Cheng X., Scutellarin protects oxygen/glucose-deprived astrocytes and reduces focal cerebral ischemic injury, Neural Regeneration Research, Aug 2018
Scutellarin, a bioactive flavone isolated from Scutellaria baicalensis, has anti-inflammatory, anti-neurotoxic, anti-apoptotic and anti-oxidative effects and has been used to treat cardiovascular and cerebrovascular diseases in China. However, the mechanisms by which scutellarin mediates neuroprotection in cerebral ischemia remain unclear. The interaction between scutellarin and nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) was assessed by molecular docking study, which showed that scutellarin selectively binds to NOX2 with high affinity. Cultures of primary astrocytes isolated from the cerebral cortex of neonatal Sprague-Dawley rats were pretreated with 2, 10 or 50 μM scutellarin for 30 minutes. The astrocytes were then subjected to oxygen/glucose deprivation by incubation for 2 hours in glucose-free Dulbecco's modified Eagle's medium in a 95% N2/5% CO2 incubator, followed by simulated reperfusion for 22 hours. Cell viability was assessed by cell counting kit-8 assay. Expression levels of NOX2, connexin 43 and caspase-3 were assessed by western blot assay. Reactive oxygen species were measured spectrophotometrically. Pretreatment with 10 or 50 μM scutellarin substantially increased viability, reduced the expression of NOX2 and caspase-3, increased the expression of connexin 43, and diminished the levels of reactive oxygen species in astrocytes subjected to ischemia-reperfusion. We also assessed the effects of scutellarin in vivo in the rat transient middle cerebral artery occlusion model of cerebral ischemia-reperfusion injury. Rats were given intraperitoneal injection of 100 mg/kg scutellarin 2 hours before surgery. The Bederson scale was used to assess neurological deficit, and 2,3,5-triphenyltetrazolium chloride staining was used to measure infarct size. Western blot assay was used to assess expression of NOX2 and connexin 43 in brain tissue. Enzyme-linked immunosorbent assay was used to detect 8-hydroxydeoxyguanosine (8-OHdG), 4-hydroxy-2-nonenal (4-HNE) and 3-nitrotyrosin (3-NT) in brain tissue. Immunofluorescence double staining was used to determine the co-expression of caspase-3 and NeuN. Pretreatment with scutellarin improved the neurological function of rats with focal cerebral ischemia, reduced infarct size, diminished the expression of NOX2, reduced levels of 8-OHdG, 4-HNE and 3-NT, and reduced the number of cells co-expressing caspase-3 and NeuN in the injured brain tissue. Furthermore, we examined the effect of the NOX2 inhibitor apocynin. Apocynin substantially increased connexin 43 expression in vivo and in vitro. Collectively, our findings suggest that scutellarin protects against ischemic injury in vitro and in vivo by downregulating NOX2, upregulating connexin 43, decreasing oxidative damage, and reducing apoptotic cell death.
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Li YQ, Song FH, Zhong K, Yu GY, Zilundu PLM, Zhou YY, Fu R, Tang Y, Ling ZM, Xu X, Zhou LH, Pre-Injection of Small Interfering RNA (siRNA) Promotes c-Jun Gene Silencing and Decreases the Survival Rate of Axotomy-Injured Spinal Motoneurons in Adult Mice, Journal of Molecular Neuroscience, Jul 2018
Brachial plexus injury is a common clinical peripheral nerve trauma. A series of genes in motoneurons were activated in the corresponding segments of the spinal cord after brachial plexus roots axotomy. The spatial and temporal expression of these genes directly affects the speed of motoneuron axon regeneration and precise target organ reinnervation. In a previous study, we observed the overexpression of c-Jun in motoneurons of the spinal cord ventral horn after brachial plexus injury in rats. However, the relevance of c-Jun expression with respect to the fate of axotomy-induced branchial plexus injury in adult mice remains unknown. In the present study, we explored the function of c-Jun in motoneuron recovery after axotomy. We pre-injected small interfering RNA (siRNA) to knockdown c-Jun expression in mice and examined the effects of the overexpression of c-Jun in motoneurons after the axotomy of the brachial plexus in vivo. Axotomy induced c-Jun overexpression in the ventral horn motoneurons of adult mice from 3 to 14 days after injury. In addition, the pre-injection of siRNA transiently inhibited c-Jun expression and decreased the survival rate of axotomy-injured motoneurons. These findings indicate that the axotomy-induced overexpression of c-Jun plays an important role in the survival of ventral horn motoneurons in adult mice. In addition, the pre-injection of c-Jun siRNA through the brachial plexus stem effectively adjusts c-Jun gene expression at the ipsilateral side.
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Li XZ, Chen J, Zhuang ZK, Ma MJ, Zhuang HJ, Qiu YM, Ye F, Wu XX, Prince LM Zilundu, Zhou LH, XuDZ., A rare case of the dual origin of the right vertebral artery with an aortic arch origin of the left vertebral artery, The European Journal of Anatomy, Jun 2018
In clinical practice, rare structural vascular variations pose important risks for clinical procedures such as diagnostic vascular interventions or surgical treatment. The authors herein describe a rare case of an unusual origin of both vertebral arteries in a singular adult male cadaver. The two right vertebral arteries independently originated from the right subclavian artery, while the left vertebral artery took origin from the aortic arch. The left vertebral artery entered the 5th transverse foramen while the two right vertebral arteries entered the 4th and 6th transverse foramen, respectively.
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Zilundu PLM, Zhou LH, Gene Therapy for Brachial Plexus Root Avulsion and Spinal Cord Injuries: A Review, Journal of Jinan University (Natural Science & Medicine Edition), Mar 2017, doi: DOI: 10.11778/j.jdxb.2017.01.001
Brachial plexus root avulsion and spinal cord injuries are very important clinical entities that have vexed scientists and clinicians for a long time. Many treatments have been designed and applied clinically but none of them has successfully cured paralysis or chronic pain that comes with these conditions in the clinical area. In pursuit of a solution to root avulsion and spinal cord injuries, gene therapy has emerged as a powerful tool that could potentially mitigate the impact on patients, families, health-care resources and world economies. Clinical trials involving gene therapy in other conditions such as cancer have unravelled a lot of promises and challenges that have served as pointers to guide the imminent scaling up of spinal cord targeted gene therapy from the experimental work to everyday clinical utility.This review discusses the brachial plexus anatomy, roots avulsion and spinal cord injuries-related pathobehaviour of the blood spinal cord barrier, types of gene therapy and the gene cargo delivery vectors currently being exploited in the management of these injuries. Major highlights of the viral and non viral gene delivery routes are explored while pointing out areas where they have been found wanting, thereby warranting much more exploration. It is clear that gene therapy targeted at the spinal cord has come a long way but still has more basic science research needed, especially for the potentially transduction-efficient viral vectors. Until the safety and design issues raised about the viral vectors are taken care of, clinical translation will remain a dream at the horizon.
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Conference Presentation
- ISN-ESN 2017 Meeting, Paris, France, Poster: The ERR gene expression on spinal cord after brachial plexus root avulsion
- Chinese Society of Anatomy 2019 Annual Conference: Anatomical variations of the aortic arch branches in a sample of Chinese cadavers: embryological basis and literature review
ISN-ESN 2017 Meeting, Paris, France, Poster: The ERR gene expression on spinal cord after brachial plexus root avulsion
Chinese Society of Anatomy 2019 Annual Conference: Anatomical variations of the aortic arch branches in a sample of Chinese cadavers: embryological basis and literature review
Memberships, Awards and Honors
- University of Zimbabwe Book Prince: 2004
- Member of American Association for Anatomy
- Member of Zimbabwe Association of Occupational Therapists