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Long-term treatment with PP2 after spinal cord injury resulted in functional locomotor recovery and increased spared tissue

查看全文 作　　者：Odrick [1]R.Rosas;Aranza [1]I.Torrado;Jose [2]M.Santiago;Ana [1]E.Rodriguez;Iris [1]K.Salgado;Jorge [1]D.Miranda 高影响力作者 机构地区：[1]Department of Physiology, School of Medicine, University of Puerto Rico Medical Sciences Campus;[2]Department of Natural Sciences, University of Puerto Rico Carolina Campus高影响力机构 出　　处：《Neural Regeneration Research》索引2014年第9卷第24期,共10页高影响力期刊 基　　金：partially supported by the MBRS-RISE Program(R25 GM061838);MBRS-SCORE(SO6-GM08224);COBRE(5P20-GM103642);SNRP(NS39405);RCMI(8G12MD007600) 摘　　要：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 field test, round and square beam crossing tests. In addition, an increase in white matter spared tissue and serotonin fiber density was observed in animals treated with PP2. However, blockade of SFK activity did not change the astrocytic response or infiltration of cells from the immune system at 28 days post-injury. Moreover, a reduced SFK activity with PP2 diminished Ephexin(a guanine nucleotide exchange factor) phosphorylation in the acute phase(4 days post-injury) after trauma. Together, these findings 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 pathophysiology 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. 关 键 词：脊髓损伤 运动功能 组织 治疗 中枢神经系统损伤 选择性抑制剂 现场测试 细胞反应
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