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

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-I 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.