Selective Epac2 antagonist attenuates cerebral infarction induced by secondary brain injury in rats.

The impact of 1,3,5-trimethyl-2-[(4-methylphenyl)sulfonyl]-benzene (ESI-05), a specific antagonist of exchange protein directly activated by cyclic adenosine monophosphate 2 (Epac2), in mitigating secondary brain injury following cerebral hemorrhage and trauma has been established. However, to the best of our knowledge, the precise influence of ESI-05 on apoptosis and cell death after cerebral infarction remains uncertain. The present study investigated the involvement of ESI-05 in apoptosis and cell death using a rodent model of cerebral infarction induced by permanent middle cerebral artery (MCA) occlusion. Before permanent MCA occlusion, ESI-05 was administered intraperitoneally at 8 mg/kg. Stroke volume, brain edema, and the levels of Epac2, phospho-p38 and cleaved caspase 3 were evaluated. Apoptosis was detected by TUNEL staining. ESI-05 administration reduced the infarct volume and water content, and reduced the levels of Epac2, phospho-p38 and cleaved caspase 3 in the ischemic penumbra. Immunohistochemical staining confirmed that ESI-05 attenuated apoptosis around the ischemic core. ESI-05 administration reduced apoptosis and cell death around the ischemic core, resulting in amelioration of cerebral edema.