Somatostatin, cortistatin and sst receptors are abundantly expressed in the cerebral cortex. However, little is known about their status after focal cerebral ischemia. In the present study, the distribution of somatostatin, cortistatin, somatostatin receptors was analyzed in the cerebral cortex at the mRNA and protein levels under both physiological conditions and after permanent unilateral occlusion of the middle cerebral artery (MCAO). Using double-labelling strategies, neurochemical phenotypes of neurons expressing somatostatin, cortistatin and sst2 receptors were identified. Spatial and temporal patterns of sst2a internalization after MCAO were analyzed to identify the sites of sst2a activation. Our results revealed that somatostatin and cortistatin mRNAs are constitutively expressed in the cortex, where they exhibit a partially overlapping distribution. Both sst2 and sst4 receptors are assigned to vast majority of glutamatergic pyramidal cells at protein and mRNA levels. From 3 hr to 24 hr after focal ischemia, a decrease in somatostatin-LIR and internalization of sst2a in the peri- and exofocal areas were observed, indicating activation of sst2a after ischemic brain damage. In addition, a robust increase in sst2 mRNA levels was shown in the cortical penumbra at 6 hr after MCAO. sst2 mRNA was upregulated selectively in glutamatergic neurons. From 2 d to 4 d after focal ischemia, opposite gene regulation of somatostatin and cortistatin was seen in non-lesioned areas of the cortex. In particular, levels of somatostatin mRNA were slightly increased, while cortistatin mRNA levels were massively decreased. Co-expression analysis after MCAO showed that cortistatin mRNA levels were below the detection limit in the vast majority of parvalbumin-positive GABAergic neurons, while cortistatin expression was still detectable in numerous somatostatin-positive neurons. Together, our results provide evidence that the somatostatinergic system, in particular, sst2, is involved in the pathophysiology of focal ischemia, which is proposed to be of potential therapeutic value for cerebrovasicular diseases.
somatostatin, cortistatin, focal cerebral ischemia, immunohistochemistry and internalization