Hypothermic reperfusion after cardiac arrest augments brain-derived neurotrophic factor activation
Hypothermic reperfusion after cardiac arrest augments brain-derived neurotrophic factor activation
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DOI：
10.1097/00004647-200207000-00009
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发表时间：
2002-07-01
影响因子：
6.3
通讯作者：
Callaway, CW
中科院分区：
文献类型：
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作者：
D'Cruz, BJ;Fertig, KC;Callaway, CW
诱导亚低温改善全脑缺血后的神经功能预后。本研究测量了常温窒息心脏骤停8分钟复苏后大鼠海马组织中脑源性神经营养因子（BDNF）和神经生长因子（NGF）的水平。复苏后，将大鼠保持在正常温度（37 ℃）或冷却至轻度低温（33 ℃，复苏后60分钟开始）。12或24小时后，通过免疫印迹法测量海马中的神经营养因子水平。缺血再灌注后海马BDNF水平升高。再灌注期间诱导低温在24小时后增强了BDNF的增加，但在12小时后没有。复苏后低温不增加NGF水平。低温还增加了组织水平和TrkB（BDNF受体）的酪氨酸磷酸化。BDNF水平的增加与细胞外调节激酶（ERK）的激活相关，ERK是BDNF诱导的信号转导级联反应的下游元件。在缺血和再灌注过程中，许多有害的过程被诱导的低温抑制，与此相反，增加BDNF水平是一个潜在的恢复过程，增强。脑源性神经营养因子信号的激活增加是一种可能的机制，通过这种机制，轻度低温能够减少心脏骤停后通常发生的神经元损伤。
Induction of mild hypothermia improves neurologic outcome after global cerebral ischemia. This study measured levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in hippocampal tissue of rats after resuscitation from 8 minutes of normothermic, asphyxial cardiac arrest. After resuscitation, rats were maintained either at normal temperature (37degreesC) or cooled to mild hypothermia (33degreesC, beginning 60 minutes after resuscitation). After 12 or 24 hours, neurotrophin levels in hippocampus were measured by immunoblotting. Ischemia and reperfusion increased hippocampal levels of BDNF. Induction of hypothermia during reperfusion potentiated the increase in BDNF after 24 hours, but not after 12 hours. Levels of NGF were not increased by postresuscitation hypothermia. Hypothermia also increased tissue levels and tyrosine phosphorylation of TrkB, the receptor for BDNF. Increased BDNF levels were correlated with activation of the extracellularly regulated kinase (ERK), a downstream element in the signal transduction cascade induced by BDNF. In contrast to the many deleterious processes during ischemia and reperfusion that are inhibited by induced hypothermia, increasing BDNF levels is a potentially restorative process that is augmented. Increased activation of BDNF signaling is a possible mechanism by which mild hypothermia is able to reduce the neuronal damage typically occurring after cardiac arrest.