Liu Da-Zhi, Sharp Frank R
Department of Neurology and the MIND Institute, University of California at Davis Medical Center, Sacramento, CA 95817, USA.
Acta Neurochir Suppl. 2011;111:77-81. doi: 10.1007/978-3-7091-0693-8_13.
Src kinase signaling has been implicated in multiple mechanisms of intracerebral hemorrhage (ICH). These include (1) thrombin-mediated mitogenic stress, (2) excitatory amino acid (AA)-mediated excitatory toxicity, (3) vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs)-mediated changes of vascular permeability, (4) cytokines-mediated inflammatory responses, and (5) others. These work together after ICH, causing brain injuries in the acute stage and self-repair in the recovery stage. We found that acute administration of the Src inhibitor, PP2, blocks the blood-brain barrier (BBB) breakdown and brain edema that occurs after ICH. However, delayed and chronic administration of PP2 prevents the BBB repair and edema resolution after ICH. These results led us to suggest that the two contradictory findings share the same principles at least in part via activation of Src kinases in acute or recovery stages after ICH. Acute Src kinase activation after ICH leads to BBB damage, and chronic Src kinase activation after ICH leads to BBB repair.
Src激酶信号传导与脑出血（ICH）的多种机制有关。这些机制包括：（1）凝血酶介导的促有丝分裂应激；（2）兴奋性氨基酸（AA）介导的兴奋性毒性；（3）血管内皮生长因子（VEGF）和基质金属蛋白酶（MMPs）介导的血管通透性变化；（4）细胞因子介导的炎症反应；以及（5）其他机制。这些机制在脑出血后共同作用，在急性期导致脑损伤，在恢复期促进自我修复。我们发现，急性给予Src抑制剂PP2可阻断脑出血后发生的血脑屏障（BBB）破坏和脑水肿。然而，延迟和长期给予PP2会阻碍脑出血后血脑屏障的修复和水肿的消退。这些结果使我们认为，这两个相互矛盾的发现至少部分地通过脑出血后急性期或恢复期Src激酶的激活而遵循相同的原理。脑出血后急性Src激酶激活导致血脑屏障损伤，而脑出血后慢性Src激酶激活则导致血脑屏障修复。
