Src kinase inhibition decreases thrombin-induced injury and cell cycle re-entry in striatal neurons

Abstract

Since Src kinase inhibitors decrease brain injury produced by intracerebral hemorrhage (ICH) and thrombin is activated following ICH, this study determined whether Src kinase inhibitors decrease thrombin induced brain injury. Thrombin injections into adult rat striatum produced focal infarction and motor deficits. The Src kinase inhibitor PP2 decreased thrombin-induced Src activation, infarction in striatum and motor deficits in vivo. Thrombin applied to cultured post-mitotic striatal neurons caused: injury to axons and dendrites; many TUNEL positive neuronal nuclei; and re-entry into the cell cycle as manifested by cyclin D1 expression, induction of several other cell cycle genes and cyclin-dependent kinase 4 activation. PP2 dose-dependently attenuated thrombin-induced injury to the cultured neurons; and attenuated thrombin-induced neuronal cell cycle re-entry. These results are consistent with the hypotheses that Src kinase inhibitors decrease injury produced by ICH by decreasing thrombin activation of Src kinases and, at least in part, by decreasing Src induced cell cycle re-entry.

Systemic hemin therapy attenuates blood–brain barrier disruption after intracerebral hemorrhage

“…Left and right swings were recorded by a blinded observer over 45 seconds and the percentage of left swings was calculated. A right striatal lesion produces a leftward swinging bias (Liu et al, 2008). …”

A Truncated Fragment of Src Protein Kinase Generated by Calpain-mediated Cleavage Is a Mediator of Neuronal Death in Excitotoxicity

“…from Ischemic Stroke-Although Src inhibitors can reduce stroke-induced brain damage in rodent models (16,17,54), their use may adversely affect the recovery of brain cells from the damage. Relevant to this, Takadera et al (19) demonstrated that treatment with Src kinase inhibitors induces apoptosis in cultured cortical neurons.…”

Integrated analysis of mRNA and microRNA expression in mature neurons, neural progenitor cells and neuroblastoma cells

“…Mature neurons (MNs) were prepared from combined embryonic day 18 rat brain tissue as previously reported with minor modification (Liu et al, 2008). Briefly, tissue was triturated ten times to break up the brain tissue in 1 ml Hibernate medium (BrainBits, Springfield, IL) containing 2% B27.…”