Influence of chronic intermittent hypoxia on growth associated protein 43 expression in the hippocampus of young rats

This study aimed to explore the pathological change to hippocampal neurons and the expression of growth associated protein 43 in 21-day-old young rats following chronic intermittent hypoxia. Hematoxylin-eosin staining results showed varying degrees of degeneration and necrosis in hippocampal neurons depending on the modeling time. Immunohistochemistry revealed that growth associated protein 43 expression in young rats following chronic intermittent hypoxia decreased, but that levels were still higher than those of normal rats at each time point, especially 4 weeks after modeling. During 1 5 weeks after modeling, a slow growth in rat weight was observed. Experimental findings indicate that chronic intermittent hypoxia may induce growth dysfunction and necrosis of hippocampal neurons, as well as increase the expression of growth associated protein 43 in young rats.

Hippocampal expression of synaptic structural proteins and phosphorylated cAMP response element-binding protein in a rat model of vascular dementia induced by chronic cerebral hypoperfusion

The present study established a rat model of vascular dementia induced by chronic cerebral hypoperfusion through permanent ligation of bilateral common carotid arteries.At 60 days after modeling,escape latency and swimming path length during hidden-platform acquisition training in Morris water maze significantly increased in the model group.In addition,the number of accurate crossings over the original platform significantly decreased,hippocampal CA1 synaptophysin and growth-associated protein 43 expression significantly decreased,cAMP response element-binding protein expression remained unchanged,and phosphorylated cAMP response element-binding protein expression significantly decreased.Results suggested that abnormal expression of hippocampal synaptic structural protein and cAMP response element-binding protein phosphorylation played a role in cognitive impairment following chronic cerebral hypoperfusion.

Serum response factor promotes axon regeneration following spinal cord transection injury

Studies have snown that serum response factor is beneficaial for axonar regeneration of peripheral herves.However,Its role after central nervous system injury remains unclear. In this study,we established a rat model of T9-T10 spinal cord transection injury.We found that the expression of serum response factor in injured spinal cord gray matter neurons gradually increased with time,reached its peak on the 7^(th) day,and then gradually decreased.To investigate the role of serum response factor,we used lentivirus vecto rs to ove rexpress and silence serum response factor in spinal cord tissue.We found that overexpression of serum response factor promoted motor function recovery in rats with spinal cord injury.Qualitative observation of biotinylated dextran amine anterograde tra cing showed that ove rexpression of serum response factor increased nerve fibers in the injured spinal co rd.Additionally,transmission electron microscopy showed that axon and myelin sheath morphology was restored.Silencing serum response factor had the opposite effects of ove rexpression.These findings suggest that serum response factor plays a role in the recovery of motor function after spinal cord injury.The underlying mechanism may be related to the regulation of axonal regeneration.

Human bone marrow mesenchymal stem cell transplantation attenuates axonal injury in stroke rats

Previous studies have shown that transplantation of human bone marrow mesenchymal stem cells promotes neural functional recovery after stroke, but the neurorestorative mechanisms remain largely unknown. We hypothesized that functional recovery of myelinated axons may be one of underlying mechanisms. In this study, an ischemia/reperfusion rat model was established using the middle cerebral artery occlusion method. Rats were used to test the hypothesis that intravenous transplantation of human bone marrow mesenchyrnal stem cells through the femoral vein could exert neuroprotective effects against cerebral ischemia via a mechanism associated with the ability to attenuate axonal injury. The results of behavioral tests, infarction volume analysis and immunohistochemistry showed that cerebral ischemia caused severe damage to the myelin sheath and axons. After rats were intravenously transplanted with human bone marrow mesenchymal stem cells, the levels of axon and myelin sheath-related proteins, including microtubule-associated protein 2, myelin basic protein, and growth-associated protein 43, were elevated, infarct volume was decreased and neural function was improved in cerebral ischemic rats. These findings suggest that intravenously transplanted human bone marrow mesenchymal stem cells promote neural function. Possible mechanisms underlying these beneficial effects include resistance to demyelination after cerebral ischemia, prevention of axonal degeneration, and promotion of axonal regeneration.

7, 8-dihydroxycoumarin improves neurological function in a mouse model of sciatic nerve injury

In the present study, a mouse model of sciatic nerve injury was treated with intraperitoneal injection of 7, 8-dihydroxycoumarin （10, 5, or 2.5 mg/kg per day）. Western blot and real-time PCR results showed that growth associated protein 43 expression was significantly increased in the L4-6 segments of the spinal cord. The amplitude and velocity of motor nerve conduction in the sciatic nerve were significantly increased in model mice. In addition, the appearance of the myelin sheath in the injured sciatic nerve was regular, with an even thickness and clear outline, and the surrounding fibroplasia was not obvious. Our results indicate that 7, 8-dihydroxycoumarin can promote the repair of injured nerve by upregulating growth associated protein 43 expression in the corresponding spinal cord segments of mice with sciatic nerve injury.

Toxic effect of acrylamide on the development of hippocampal neurons of weaning rats

Although numerous studies have examined the neurotoxicity of acrylamide in adult animals,the effects on neuronal development in the embryonic and lactational periods are largely unknown.Thus,we examined the toxicity of acrylamide on neuronal development in the hippocampus of fetal rats during pregnancy.Sprague-Dawley rats were mated with male rats at a 1：1 ratio.Rats were administered 0,5,10 or 20 mg/kg acrylamide intragastrically from embryonic days 6–21.The gait scores were examined in pregnant rats in each group to analyze maternal toxicity.Eight weaning rats from each group were also euthanized on postnatal day 21 for follow-up studies.Nissl staining was used to observe histological change in the hippocampus.Immunohistochemistry was conducted to observe the condition of neurites,including dendrites and axons.Western blot assay was used to measure the expression levels of the specific nerve axon membrane protein,growth associated protein 43,and the presynaptic vesicle membrane specific protein,synaptophysin.The gait scores of gravid rats significantly increased,suggesting that acrylamide induced maternal motor dysfunction.The number of neurons,as well as expression of growth associated protein 43 and synaptophysin,was reduced with increasing acrylamide dose in postnatal day 21 weaning rats.These data suggest that acrylamide exerts dose-dependent toxic effects on the growth and development of hippocampal neurons of weaning rats.

Fine motor skill training enhances functional plasticity of the corticospinal tract after spinal cord injury

Following central nervous system injury, axonal sprouts form distal to the injury site and extend into the denervated area, reconstructing neural circuits through neural plasticity. How to facilitate this plasticity has become the key to the success of central nervous system repair. It remains controversial whether fine motor skill training contributes to the recovery of neurological function after spinal cord injury. Therefore, we established a rat model of unilateral corticospinal tract injury using a pyramidal tract cutting method. Horizontal ladder crawling and food ball grasping training procedures were conducted 2 weeks before injury and 3 days after injury. The neurological function of rat forelimbs was assessed at 1, 2, 3, 4, and 6 weeks after injury. Axon growth was observed with biotinylated dextran amine anterograde tracing in the healthy corticospinal tract of the denervated area at different time periods. Our results demonstrate that compared with untrained rats, functional recovery was better in the forelimbs and forepaws of trained rats. The number of axons and the expression of growth associated protein 43 were increased at the injury site 3 weeks after corticospinal tract injury. These findings confirm that fine motor skill training promotes central nervous system plasticity in spinal cord injury rats.

Protective effects of Achyranthes bidentata polypeptides on retinal ganglion cells post-optic nerve crush in rats

Achyranthes bidentata polypeptides（ABPP） have been reported to inhibit apoptosis of retinal ganglion cells（RGCs）.The present study investigated the protective effects of ABPP on RGCs in a rat model of optic nerve injury.With prolonged injury time,RGC densities were gradually decreased.ABPP（5 μg） significantly increased RGC densities and upregulated growth associated protein 43 expression in rats with optic nerve injury.Results demonstrate that ABPP can protect RGCs and promote axonal growth after optic nerve crush.

Neuroprotective effect of recombinant human erythropoietin on optic nerve injury in rats

Background Optic nerve injury, caused by retinal and optic nerve diseases, can eventually result in vision loss. To date, few effective treatments have been discovered to restore visual function. Previous studies showed that recombinant human erythropoietin （rhEPO） has a neuroprotective effect on the central nervous system, particularly in nerve injury. In this study, we investigated the effects of rhEPO on axonal regeneration and functional restoration following optic nerve injury. This was done by measuring the expression of growth associated protein 43 （GAP-43）, a marker for neuronal regeneration, on the retina and flash-visual evoked potential （F-VEP）. Methods Adult Wistar rats were randomly assigned to rhEPO and control （saline） groups. Optic nerve crush injury models were established and rhEPO or saline were immediately injected into the vitreous cavity. The expression of GAP-43 was detected by immunohistochemistry and the F-VEP was measured pre-injury, immediately after injury, 1 week and 2 weeks post-injury. Results No detectable staining for GAP-43 was observed in normal retina. In the control group, the level of GAP-43 expression was higher at 1 week post-injury, but decreased at 2 weeks. In the rhEPO group, the level of GAP-43 expression was notably higher at both 1 week and 2 weeks. At each time point post-injury, the expression of GAP-43 in rhEPO group was significantly higher than the control group （P 〈0.05）. Obvious changes in F-VEP examination were detected immediately after optic nerve injury, including significantly prolonged latency and decreased amplitude of the P1 wave. In the control group, the changes were still obvious at 1 week. The latency was decreased and the amplitude had slightly recovered to 28.23% of the normal value at 2 weeks. In rhEPO group, there was significantly more recovery than the control group at 1 week and 2 weeks post-injury （P 〈0.05）. The latency most close to the normal level and the amplitude had recovered to 65.51% of the normal value at 2 weeks. Conclusions rhEPO can prolong the expression of GAP-43 and increase its intensity after optic nerve injury, thereby promoting neural repair and axonal regeneration. Under the protection of rhEPO, the conduction velocity of the optic nerve recovered significantly. Therefore, rhEPO has neuroprotective effects on the optic nerve and promotes functional restoration of the optic nerve. Chin Med J 2009;122（17）：2008-2012