Neuroprotective effects of minocycline and progesterone on white matter injury after focal cerebral ischemia

Abstract

Stroke induced white matter injury can induce marked neurological deficits even after relatively small infarcts, due to the tightly packed nature of white matter tracts especially in certain areas in the brain. Many drugs which were successful in the pre-clinical trials failed in clinical trials, which was attributed in part to the focus on grey matter injury completely and ignoring their effect on white matter. In this work we selected two known neuroprotective drugs (minocycline and progesterone) and examined their effect on white matter injury after focal cerebral ischemia/reperfusion injury in rats. Focal cerebral ischemia was induced in male Wistar rats (one-hour ischemia followed by reperfusion). Progesterone and minocycline were administered immediately after reperfusion onset. Infarct size, microglial activation and white matter injury were assessed and compared between the treatment and no-treatment groups and Sham operated animals. Our data showed that both progesterone and minocycline reduced infarct size, microglial activation and white matter injury. This work shows a new neuroprotective mechanism of both drugs, via white matter injury reduction, that can be exploited for stroke management. While the utility of either drugs as a sole agent in the management of stroke is questionable, there is a value of using either drugs as an adjuvant therapy to traditional stroke therapy, making use of the white matter protective effect that would improve outcome and facilitate healing after stroke.