Suramin reduces infarct volume in a model of focal brain ischemia in rats.

摘要: Extracellular adenosine 5'-triphosphate (ATP) provides excitatory transmission in the central nervous system. Stimulation by ATP of ionotropic ligand-gated ion channel purinoceptors (P2X) leads to increased intracellular calcium levels, and activation P2X receptors may be involved process excitotoxic neuronal injury caused stroke. Suramin, as an agent that is known block at a specific concentration, was assessed for its neuroprotective potential model experimental stroke rat. We propose effectiveness suramin limited those concentrations where it effective receptor antagonist. Focal brain ischemia produced unilateral occlusion transection middle cerebral artery (MCAT) bilateral common carotid arteries (CCA). Thirty-four male Sprague-Dawley rats were randomly separated into five groups. Changes regional blood flow ischemic region verified laser Doppler flowmetry. All received, over period 30 min before MCAT, dose 0 (saline), 25, 50, 100, or 250 mg/kg intravenously volume 1 ml using infusion pump. Six hours after onset, evaluation neurologic status followed morphometric analysis infarct volume. During surgical procedure mean arterial pressure, gases (PaCO2, PaO2), pH monitored. A dose-dependent decrease (slope –0.049, SE 0.009, P<0.001) observed groups treated range 100 mg/kg (r 2=0.55). Suramin significantly decreased (n=9, edema (P=0.003). The effect supported improved score this group (median 0) compared with median 3 control animals (P=0.02). These findings indicate pre-treatment agent. As estimated concentration 10 µM (from McNally et al., 2000, Life Sci 67:1847–1857) IC50 suramin-mediated antagonism, these results suggest interference system could provide neuroprotection from ischemia.