Long-term treatment with PP2 after spinal cord injur y resulted in functional locomotor recover y and increased spared tissue
Odrick R Rosas
Aranza I Torrado
Jose M Santiago
Ana E Rodriguez
Iris K Salgado
Jorge D Miranda
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 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.
机标关键词：spinal cord injurycentral nervous systemlocomotor activityimmune system
资助基金：The project was partially supported by the MBRS-RISE Program(R25 GM061838)MBRS-SCORE(SO6-GM08224)COBRE(5P20-GM103642)SNRP(NS39405)RCMI(8G12MD007600)
论文发表日期：2014-01-01
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：10( 2164-2173 )
英文信息