Dexmedetomidine and Phosphocreatine Post-treatment Provides Protection against Focal Cerebral Ischemia-reperfusion Injury in Rats.

Abstract

In this study we investigated the neuroprotective efficacy of dexmedetomidine (Dex) and phosphocreatine (PCr) alone or in combination in a rat model of focal cerebral ischemia-reperfusion injury (I/R). I/R was induced by intraluminal middle cerebral artery occlusion (MCAO) and reperfusion. Male Sprague-Dawley rats were randomly allocated to the Sham group and I/R group, and the I/R group was further divided into three subgroups: Dex (9 μg.kg^-1 Dex), PCr (180 mg.kg^-1 PCr) and Dex + PCr (9 μg.kg^-1 Dex + 180 mg.kg^-1 PCr). All treatments were given intravenously at the onset of reperfusion. After 24 hr of reperfusion, the neurological deficit score (NDS) was determined and a magnetic resonance imaging (MRI) scan was performed. Serum concentrations of malonaldehyde (MDA) and 4-hydroxynonenal (4-HNE) were measured and cerebral infarct volume was estimated by triphenyl tetrazolium chloride (TTC) staining. Blood brain barrier, neuronal and mitochondrial damage was assessed by optical and electron microscopy. Neuronal injury was further assessed using double cleaved caspase-3 and NeuN immunofluorescent staining. Compared with group I/R, Dex and PCr significantly reduced the neurological deficit score (P < 0.01), infarct volume (P < 0.01), and brain blood barrier, neuronal and mitochondrial damage. The level of oxidative stress (P < 0.001) and neuronal injury (P < 0.001) also decreased and surviving neurons increased (P < 0.001). Compared with Dex or PCr alone, the combination treatment had overall greater effects (P < 0.05). These results indicate that posttreatment with Dex or PCr decreases focal cerebral I/R injury and that these agents in combination have greater protective effects than each alone.