Neuroprotective efficacy of minocycline after intracerebral hemorrhage and possible Kv1.3, Kv1.5, HERG and alpha7 nAChR channels as targets for regulating secondary brain injury in hemorrhagic and ischemic stroke.

摘要

Infiltrating leukocytes and activated microglia were found to release cytotoxic mediators contributing to secondary brain injury after intracerebral hemorrhage. Because the inflammatory response is a delayed process, the molecules participating in this secondary response, are potential targets for human therapy with a sufficiently wide therapeutic window. Minocycline is a semi-synthetic second-generation tetracycline that exerts anti-inflammatory effects completely from its antimicrobial action. We tested the hypothesis that minocycline would have neuroprotective effects in a rat model of intracerebral hemorrhage. In addition, previous studies have indicated that the voltage gated potassium channels Kv1.3, Kv1.5, HERG and the nicotinic acetylcholine receptors alpha7 unit are important regulators of T cells, microglia and macrophages, and these channels have become potential therapeutic targets for immunosuppression and for controlling brain inflammation. Thus, we tested the hypothesis that Kv1.3, Kv1.5, HERG and alpha7 channels are expressed in neutrophils, using immunohistochemical methods following intracerebral hemorrhage induced by injecting bacterial collagenase into rat striatum. (Abstract shortened by UMI.)