Abstract

To observe the efficacy of phosphocreatine pre-administration (PCr-PA) on X-linked inhibitor of apoptosis protein (XIAP), the second mitochondia-derived activator of caspase (Smac) and apoptosis in the ischemic penumbra of rats with focal cerebral ischemia-reperfusion injury (CIRI). A total of 60 healthy male Sprague Dawley (SD) rats were randomly divided into three groups (n=20): group A (the sham operation group), group B <intraperitoneally injected with 20 mg/kg (10 mg/ml) of saline before preparing the ischemia-reperfusion (IR) model>, and group C <intraperitoneally injected with 20 mg/kg (10 mg/ml) of PCr immediately before preparing the IR model>. After 24 h for reperfusion, the neurological function was evaluated and the tissue was sampled to detect expression of XIAP, Smac and caspase-3 positive cells in the ischemic penumbra so as to observe the apoptosis. Compared with group B, neurological deficit scores, numbers of apoptotic cells, expression of Smac,caspase-9 and the numbers of Caspase-3 positive cells were decreased while expression of XIAP were increased in the ischemic penumbra of group C. Phosphocreatine pre-administration may elicit neuroprotective effects in the brain by increasing expression of X-linked inhibitor of apoptosis protein, reducing expression of second mitochondia-derived activator of caspase, and inhibiting the apoptosis in the ischemic penumbra.

Highlights

  • The key to treating ischemic stroke lies in recanalizing partial vessels or thrombolytic therapy, which can rescue or reduce neuronal apoptosis in the ischemic penumbra in a timely manner[1,2]

  • The current study investigated the efficacy of phosphocreatine pre-administration (PCr-PA) on X-linked inhibitor of apoptosis protein (XIAP), second mitochondia-derived activator of caspase (Smac) and apoptosis in the ischemic penumbra of rats a focal cerebral ischemiareperfusion injury (CIRI), with the aim of exploring the possible mechanism by which PCr can protect the brain

  • The results showed that PCr can increase the expression of XIAP and reduce the expression of Smac in infarcted core region to a certain extent, the striatum was the tissue firstly involved in the infarcted core area; so PCr could not reverse serious injury of the striatum and could only reduce the injury in partial parietal cortex and frontal cortex

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Summary

Introduction

The key to treating ischemic stroke lies in recanalizing partial vessels or thrombolytic therapy, which can rescue or reduce neuronal apoptosis in the ischemic penumbra in a timely manner[1,2]. The ischemic cerebral tissue outside and surrounding the focal central infarction area is called the ischemic penumbra. Since it is a reverse injury area, its function can be restored if treated timely and effectively[3,4]. A type of apoptosis-promoting protein,can antagonize caspase-inhibiting XIAP, accelerating the process of cell apoptosis[9]. Studies have showed that PCr has effects of brain protection, but the specific mechanism is not clear yet[10,11]. The current study investigated the efficacy of PCr-PA on XIAP, Smac and apoptosis in the ischemic penumbra of rats a focal CIRI, with the aim of exploring the possible mechanism by which PCr can protect the brain

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