Delayed activin A administration attenuates tissue death after transient focal cerebral ischemia and is associated with decreased stress-responsive kinase activation.
Delayed activin A administration attenuates tissue death after transient focal cerebral ischemia and is associated with decreased stress-responsive kinase activation.
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DOI：
10.1111/j.1471-4159.2009.06406.x
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发表时间：
2009-12
影响因子：
4.7
通讯作者：
Hall AK
中科院分区：
文献类型：
--
作者：
Mukerji SS;Rainey RN;Rhodes JL;Hall AK
局灶性脑缺血和再灌注引发复杂的细胞和分子相互作用，导致细胞修复或破坏。在早期的工作中，我们发现激活素A是对脑缺血的早期基因反应，并支持体外皮质神经元存活。在这项研究中，在成年小鼠中测试了外源性激活素A减轻短暂性大脑中动脉闭塞（MCAO）损伤的能力。在MCAO前脑室内给予激活素A可减少实验性卒中后一天明显的梗死体积。在缺血/再灌注后6小时单次给予激活素A减少了第1天和第3天的病变体积，并导致神经行为改善。此外，激活素A治疗保留了缺血半球内的神经元，并导致小胶质细胞活化的伴随减少。激活素A治疗后，与卒中后神经元凋亡有关的应激反应激酶p38和c-Jun N-末端激酶的激活减少。总之，这些发现表明，激活素A促进局灶性脑缺血/再灌注后的组织存活，具有延长的治疗窗。
Focal cerebral ischemia and reperfusion initiates complex cellular and molecular interactions that lead to either cell repair or destruction. In earlier work, we found that Activin A is an early gene response to cerebral ischemia and supports cortical neuron survival in vitro. In this study, the ability of exogenous activin A to attenuate injury from transient middle cerebral artery occlusion (MCAO) was tested in adult mice. Intracerebroventricular administration of activin A prior to MCAO reduced infarct volume apparent one day after experimental stroke. A single Activin A administration at 6 hr following ischemia/reperfusion reduced lesion volumes at 1 and 3 days and led to improved neurobehavior. Moreover, activin A treatment spared neurons within the ischemic hemisphere and led to a concomitant reduction in microglial activation. Activation of the stress-responsive kinases p38 and c-Jun N-terminal kinase implicated in neuronal apoptosis after stroke was reduced following activin A treatment. Together these findings suggest that activin A promotes tissue survival after focal cerebral ischemia/reperfusion with an extended therapeutic window.
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