Delayed administration of JTP-2942, a novel thyrotropin-releasing hormone analogue, improves cerebral blood flow and metabolism in rat postischaemic brain.

Abstract

1. The aim of the present study was to examine the central nervous system action of JTP-2942, a novel thyrotropin-releasing hormone (TRH) analogue, from the point of view of cerebral blood flow (CBF) and metabolism in the postischaemic brain. 2. Left middle cerebral artery ischaemia was induced for 90 min followed by reperfusion. 3. Animals were separated into four groups: (i) low-dose (0.003 mg/kg) JTP-2942; (ii) high-dose (0.03 mg/kg) JTP-2942; (iii) cystidine diphosphate choline (500 mg/kg); and (iv) saline. The test drug or saline was administered intravenously 1 week after ischaemia. 4. Local CBF and local cerebral glucose utilization were measured autoradiographically, adjacent sections were stained with haematoxylin-eosin and infarction size was measured. 5. JTP-2942 ameliorated the reduction of local CBF and glucose utilization except in the ischaemic core. In particular, the higher dose (0.03 mg/kg) of JTP-2942 significantly increased local CBF and glucose utilization not only in peri-infarcted areas, but also in distal and contralateral areas. 6. These results suggest that JTP-2942 treatment may be beneficial for improving cerebral circulation and metabolism in the postischaemic brain.