The spinal cord has the ability to regenerate but the microenvironment generated after trauma reduces that capacity. An increase in Src family kinase (SFK) activity has been implicated in neuropathological conditions associated with central nervous system trauma. Therefore, we hypothesized that a decrease in SFK activation by a long-term treatment with 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyramidine (PP2), a selective SFK inhibitor, after spinal cord contusion with the New York University (NYU) impactor device would generate a permissive environment that improves axonal sprouting and/or behavioral activity. Results demonstrated that long-term blockade of SFK activation with PP2 increases locomotor activity at 7, 14, 21 and 28 days post-injury in the Basso, Beattie, and Bresnahan open ifeld test, round and square beam crossing tests. In addition, an increase in white matter spared tissue and sero-tonin ifber density was observed in animals treated with PP2. However, blockade of SFK activity did not change the astrocytic response or inifltration of cells from the immune system at 28 days post-injury. Moreover, a reduced SFK activity with PP2 diminished Ephexin (a guanine nucle-otide exchange factor) phosphorylation in the acute phase (4 days post-injury) after trauma. Together, these ifndings suggest a potential role of SFK in the regulation of spared tissue and/or axonal outgrowth that may result in functional locomotor recovery during the pathophysiolo-gy generated after spinal cord injury. Our study also points out that ephexin1 phosphorylation (activation) by SFK action may be involved in the repulsive microenvironment generated after spinal cord injury.

Traumatic brain injury (TBI) is the leading cause of death and disability of persons under 45 years old in the United States, affecting over 1.5 million individuals each year. It had been th ought that recovery from such injuries is severely limited due to the inability of the adult bra in to replace damaged neurons. However, recent studies indicate that the mature mammalian central nervous system (CNS) has the potential to replenish damaged neurons by proliferation and neuronal differentiation of adult neural stem/progenitor cells residing in the neurogenic regions in the brain. Furthermore, increasing evidence indicates that these endogenous stem/progenitor cells may play regenerative and reparative roles in response to CNS injuries or diseases. In support of this notion, heightened levels of cell proliferation and neurogenesis have been ob-served in response to brain trauma or insults suggesting that the brain has the inherent potential to restore populations of damaged or destroyed neurons. This review will discuss the potential functions of adult neurogenesis and recent development of strategies aiming at harnessing this neurogenic capacity in order to repopulate and repair the injured brain.

In the field of developmental neurobiology, accurate and ordered regulation of the cel cycle and apoptosis are crucial factors contributing to the normal formation of the neural tube. Preliminary studies identified several genes involved in the development of neural tube defects. In this study, we established a model of developmental neural tube defects by administration of retinoic acid to pregnant rats. Gene chip hybridization analysis showed that genes related to the cel cycle and apoptosis, signal transduction, transcription and translation regulation, energy and metabolism, heat shock, and matrix and cytoskeletal proteins were al involved in the formation of developmental neural tube defects. Among these, cel cycle-related genes were predominant. Retinoic acid ment caused differential expression of three cel cycle-related genes p57kip2, Cdk5 and Spin, the expression levels of which were downregulated by retinoic acid and upregulated during normal neural tube formation. The results of this study indicate that cel cycle-related genes play an im-portant role in the formation of neural tube defects. P57kip2, Cdk5 and Spin may be critical genes in the pathogenesis of neural tube defects.

Molecular mechanisms of the Kr?uppel-like family of transcription factors (KLFs) have been studied more in proliferating cells than in post-mitotic cells such as neurons. We recently found that KLFs regulate intrinsic axon growth ability in central nervous system (CNS) neurons in-cluding retinal ganglion cells, and hippocampal and cortical neurons. With at least 15 of 17 KLF family members expressed in neurons and at least 5 structurally unique subfamilies, it is import-ant to determine how this complex family functions in neurons to regulate the intricate genetic programs of axon growth and regeneration. By characterizing the molecular mechanisms of the KLF family in the nervous system, including binding partners and gene targets, and comparing them to deifned mechanisms deifned outside the nervous system, we may better understand how KLFs regulate neurite growth and axon regeneration.

Experimental substantiation of the platelet-rich plasma usage in toxic hepatitis treatment

Research Highlight in Stroke

短暂脑缺血诱导成年大鼠纹状体内CRMP-4的表达

AIM: To study the expression of collapsing response mediated protein-4 (CRMP-4) and nestin in the ischemic adult rat brain following transient brain ischemia. METHODS: Brain ischemia was induced by transient left middle cerebral artery occlusion (MCAO) for 60 min in adult rats. The expression of CRMP-4, nestin and bromodeoxyuridine (BrdU) was analyzed by immunohistochemical method. The co-localization of CRMP-4 and nestin or BrdU was analyzed by double staining combined with confocal laser scanning microscopy. RESULTS: CRMP-4, a marker of immature neuron, could be expressed in the ipsilateral striatum and cerebral cortex at 1st and 2nd week after the ischemia-reperfusion; nestin, a marker of neural stem cell, occurred in above regions from several hours to 2 weeks. CRMP-4 costained with nestin and with BrdU incorporation. CONCLUSION: Neural stem cells may present in the striatum and cerebral cortex of adult rat and can be triggered to differentiate into newborn neuron there by ischemic brain trauma.

Objective: To study the effect of compound injectionof Radix Hedysari on peripheral nerve regeneration in rats.Methods: Seventy-five healthy adult SD male rats,weighing 150 g, were randomized into 5 groups (15 rats ineach group). The bilateral sciatic nerves of the rats wereexposed and clamped with a smooth clamp to make aninjury area of 2 mm. After clamp operation Group 1 wasinjected with compound injection of radix Hedysari (CIRH)1.5 ml/day, Group 2 with CIRH 1.0 md/day, Group 3 withCIRH 0.5 ml/day, Group 4 with nerve growth factor(NGF) 50 U/day, and Group 5 was taken as the controlgroup without any management. The bilateral sciatic nervewas taken out at 3 days, 1, 2 and 4 weeks after clamping,stained with osmic acid and observed microscopically. Themyelinated nerve fibers were counted. The nerveconduction velocity was determined 2 and and 4 weeksbefore sample taking the sciatic nerve function index wasmeasured 4 weeks before sample taking.Results: The results of nerve conduction velocity, themyelinated nerve fiber count and the sciatic functuion indexin the CIRH treated groups were better than those in thecontrol group. The results of the nerve conduction velocityand the myelinated nerve fiber count at 2 weeks and thenerve conduction velocity at 4 weeks in Group 1 were betterthan those of Group 4. Biological observation showed thatdegenerated and necrotic myelin sheath in CIRH treatedGroups at 2 and 4 weeks decreased remarkably compared to the NGF treated group.ConcIusions: CIRH can promote regeneration ofperipheral nerves and absorption of degenerated andnecrotic injured nerves. It has the same effect as NGF.

神经胶质细胞的活化和成人听觉损伤后神经再生及自我修复

螺旋神经节细胞是将信息从耳蜗神经传递到枢听觉系统的主要传入细胞.施万细胞、卫星细胞和少突胶质细胞等各种神经胶质细胞与外周和中枢神经元信息处理这一活动密切相关.中枢神经系统的神经胶质细胞在脑损伤后调节组织稳态、控制神经再生起重要作用,但在成人听神经损伤后神经再生和修复过程不为所知.Sox2是一种主要的神经发生调节器,在维持神经干/祖细胞的增殖必不可少.近在急性螺旋神经节退行性变动物模型中发现在神经元死亡后很快Sox2阳性亚群神经胶质细胞表达BrdU,表明成熟细胞在经历急性耳蜗损伤后可以改变它们的静态表型并重新进入细胞周期.耳蜗病变某些病理条件下,活化的Sox2阳性胶质细胞可能对于听神经再生和自我修复是一个重要的调节物质.