Gcp Ii Inhibitors Provide Neuroprotection

The efficacy of GCP II inhibition by 2-PMPA (100 mg/kg, i.p.) was assessed in the middle cerebral artery occlusion (MCAO) model of ischemic stroke. Focal ischemia was induced in rats by MCAO for 2 hours, followed by 22 hours of reperfusion.19 The rats were then sacrificed and their brains removed and evaluated by TTC (2,3,5-triphenyltetrazolium chloride) staining to determine brain injury volumes. 2-PMPA, when dosed at 1 hour following the beginning of the ischemia, significantly reduced the total brain injury volume, with predominant and significant effects in the cortical hemisphere19 (Fig. 4A). Similar efficacy was observed with 2-MPPA administered at 2 hours post onset of MCAO (30 mg/kg, i.v.) (Fig. 4B).

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