A three-dimensional matrix system containing melatonin and neural stem cells repairs damage from traumatic brain injury in rats

Brain lesions can cause neural stem cells to activate,proliferate,diffe rentiate,and migrate to the injured area.However,after traumatic brain injury,brain tissue defects and microenvironment changes greatly affect the survival and growth of neural stem cells;the resulting reduction in the number of neural stem cells impedes effective repair of the injured area.Melatonin can promote the survival,proliferation,and differentiation of neural stem cells under adverse conditions such as oxidative stress or hypoxia that can occur after traumatic brain injury.Therefore,we investigated the therapeutic effects of melatonin combined with neural stem cells on traumatic brain injury in rats.First,in vitro studies confirmed that melatonin promoted the survival of neural stem cells deprived of oxygen and glucose.Then,we established a three-dimensional Matrigel-based transplantation system containing melatonin and neural stem cells and then used it to treat traumatic brain injury in rats.We found that treatment with the Matrigel system containing melatonin and neural stem cells decreased brain lesion volume,increased the number of surviving neuro ns,and improved recove ry of neurological function compared with treatment with Matrigel alone,neural stem cells alone,Matrigel and neural stem cells combined,and Matrigel and melatonin combined.Our findings suggest that the three-dimensional Matrigelbased transplantation system containing melatonin and neural stem cells is a potential treatment for traumatic brain injury.

Ischemic postconditioning protects against ischemic brain injury by up-regulation of acid-sensing ion channel 2a

Ischemic postconditioning renders brain tissue tolerant to brain ischemia,thereby alleviating ischemic brain injury.However,the exact mechanism of action is still unclear.In this study,a rat model of global brain ischemia was subjected to ischemic postconditioning treatment using the vessel occlusion method.After 2 hours of ischemia,the bilateral common carotid arteries were blocked immediately for 10 seconds and then perfused for 10 seconds.This procedure was repeated six times.Ischemic postconditioning was found to mitigate hippocampal CA1 neuronal damage in rats with brain ischemia,and up-regulate acid-sensing ion channel 2a expression at the m RNA and protein level.These findings suggest that ischemic postconditioning up-regulates acid-sensing ion channel 2a expression in the rat hippocampus after global brain ischemia,which promotes neuronal tolerance to ischemic brain injury.

Neuroprotection by cattle encephalon glycoside and ignotin beyond the time window of thrombolysis in ischemic stroke

Cattle encephalon glycoside and ignotin(CEGI)injection is known as a multi-target neuroprotective drug that contains numerous liposoluble molecules,such as polypeptides,monosialotetrahexosyl ganglioside(GM-1),free amino acids,hypoxanthine and carnosine.CEGI has been approved by the Chinese State Food and Drug Administration and widely used in the treatments of various diseases,such as stroke and Alzheimer's disease.However,the neuroprotective effects of CEGI beyond the time window of thrombolysis(within 4.5 hours)on acute ischemic stroke remain unclear.This study constructed a rat middle cerebral artery occlusion model by suture-occluded method to simulate ischemic stroke.The first daily dose was intraperitoneally injected at 8 hours post-surgery and the CEGI treatments continued for 14 days.Results of the modified five-point Bederson scale,beam balance test and rotameric test showed the neurological function of ischemic stroke rats treated with 4 m L/kg/d CEGI improved significantly,but the mortality within 14 days did not change significantly.Brain MRI and 2,3,5-triphenyltetrazolium chloride staining confirmed that the infarct size in the 4 m L/kg/d CEGI-treated rats was significantly reduced compared with ischemic insult only.The results of transmission electron microscopy and double immunofluorescence staining showed that the hippocampal neuronal necrosis in the ischemic penumbra decreased whereas the immunopositivity of new neuronal-specific protein doublecortin and the percentage of Ki67/doublecortin positive cells increased in CEGI-treated rats compared with untreated rats.Our results suggest that CEGI has an effective neuroprotective effect on ischemic stroke when administered after the time window of thrombolysis.The study was approved by the Animal Ethics Committee of The Third Military Medical University,China.