Role of MC-1 alone and in combination with tissue plasminogen activator in focal ischemic brain injury in rats.

Abstract

OBJECT: Pyridoxal-5-phosphate (PLP), the biologically active form of pyridoxine, can rescue neurons from death in vitro and in vivo. In the present project, the authors have studied whether MC-1, an analog of PLP, alone or in combination with the thrombolytic agent tissue plasminogen activator (tPA), can protect the brains of rats injured by ischemia. METHODS: Ischemic brain injury was induced in rats by injecting a preformed blood clot in the middle cerebral artery (MCA). Neurological deficits and infarct volumes caused by the embolus were measured to evaluate the effects of MC-1 on the ischemic injury. Systemic blood pressure and local brain blood flow were also monitored. Administration of different doses of MC-1 1 hour after embolization significantly reduced the infarct volume and improved functional recovery. Injection of MC-1 (40 mg/kg) at 3 or 6 hours after embolization also reduced the volume of the infarct significantly and improved functional recovery. Combined treatment with MC-1 and tPA was also neuroprotective, although it was not superior to treatment involving either MC-1 or tPA alone. Treatment with MC-1 did not result in significant changes in either systemic blood pressure or local blood flow in the ischemic brain. CONCLUSIONS: These data support the hypothesis that in the focal embolic stroke model in rats MC-1 is a neuroprotective agent. The neuroprotection this compound provides still exists when MC-1 administration is delayed up to 6 hours after ischemic injury.