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Published on: July 27, 2014
Neuroprotection of VEGF-expression neural stem cells in neonatal cerebral palsy rats
Xiang-Rong Zheng1, Shan-Shan Zhang, Fei Yin
1Department of Pediatrics, Xiangya Hospital, Central South University, Xiangya Road, Changsha City, Hunan Province, 410008, PR China. zxr 168@126.com
Insights
Neural stem cells (NSCs) transplantation shows promise for treating cerebral palsy (CP). VEGF-transfected NSCs partially prevented brain damage and improved outcomes in newborn rats with CP.
Area of Science:
- Neuroscience
- Regenerative Medicine
- Developmental Biology
Background:
- Cerebral palsy (CP) is a common neurological disorder causing physical disability.
- Current treatments for CP are limited, necessitating novel therapeutic strategies.
Purpose of the Study:
- To investigate the neuroprotective effects of vascular endothelial growth factor (VEGF)-transfected neural stem cells (NSCs) in a rat model of CP.
- To evaluate the impact of NSC transplantation on neural development, apoptosis, and behavioral outcomes in CP.
Main Methods:
- A CP model was established in newborn Sprague-Dawley rats using unilateral carotid artery occlusion and hypoxia.
- Rats received stereotactic injections of PBS, NSCs, or VEGF-transfected NSCs in the sensory-motor cortex.
- Neuroprotection, neural cell growth, apoptosis, brain development, and behavior were assessed up to 35 days of age.
Main Results:
- CP induction led to impaired growth, increased neuronal apoptosis, reduced micro-vessel density, and behavioral deficits.
- NSC transplantation increased VEGF protein expression and mitigated behavioral and pathological impairments associated with CP.
- VEGF-transfected NSCs demonstrated a marginally superior effect compared to un-transfected NSCs.
Conclusions:
- NSC transplantation offers a potential therapeutic approach for CP by partially preventing or slowing brain damage.
- VEGF-transfected NSCs may provide enhanced neuroprotective benefits in CP treatment strategies.
Abstract:
Cerebral palsy (CP) is a very common neural system development disorder that can cause physical disability in human. Here, we studied the neuroprotective effect of vascular endothelial growth factor (VEGF)-transfected neural stem cells (NSCs) in newborn rats with cerebral palsy (CP). Seven-day-old Sprague-Dawley rats were randomly divided into four groups: sham operation (control group), PBS transplantation (PBS group), VEGF+NSCs transplantation (transgene NSCs group) and NSCs transplantation groups (NSCs group). PBS, Transgene NSCs and NSCs groups respectively received stereotactic injections of PBS, lentiviral vector (pGC-FU-VEGF) infected NSCs or a NSCs suspension in the left sensory-motor cortex 3 days after CP model was established. The NSCs activity, their impacts on neural cell growth and apoptosis, brain development and animal behaviors were examined on the animals up to age 35-days. As expected, unilateral carotid artery occlusion plus hypoxia (cerebral palsy model) resulted in severe neural developmental disorders, including slowed growth, increased in cortical neuron apoptosis, decreased cerebral cortex micro-vessel density and retarded behavior developments. Transplantation of NSCs not only resulted in increases in VEGF protein expression in rat brains, but also largely prevented the behavioral defects and brain tissue pathology that resulted from cerebral palsy procedure, with animals received VEGF transfected NSCs always being marginally better than these received un-transfected cells. In conclusion, NSCs transplantation can partially prevent/slow down the brain damages that are associated with CP in the newborn rats, suggesting a new possible strategy for CP treatment.
