Effects of an analogue of thyrotrophin-releasing hormone, RX77368, on infarct size and cerebral blood flow in focal cerebral ischaemia in the rat

Abstract

Effects of a stable analogue of thyrotrophin-releasing hormone, RX77368, on cerebral blood flow and infarct size have been studied in an acute model of cerebral ischaemia in the rat. Two hours after electrocoagulation of the left middle cerebral artery (MCA), the mean area of ischaemia (± SEM), determined histochemically, was 11.5 ± 2.2% of a single hemisphere and blood flow, determined using radiolabeled microspheres, was reduced by 40% in the left forebrain (p < 0.001 compared with sham-operated animals). Administration of RX77368 (50 μg/kg, intracerebroventricularly) within 10 min of arterial occlusion caused a significant (p < 0.01) reduction in mean lesion size to 3.7 ± 1.8% and stimulation of blood flow to the left ischaemic forebrain (60% above saline treated). Peripheral administration of RX77368 (1 mg/kg intraperitoneally) also significantly stimulated blood flow to the ischaemic forebrain and caused an apparent decrease in frequency of large infarcted areas of brain tissue, although mean lesion size was not significantly affected. These findings indicate that RX77368 ameliorates tissue damage in acute focal cerebral ischaemia. Such effects may be related to stimulation of cerebral blood flow.Key words: middle cerebral artery, focal cerebral ischaemia, cerebral blood flow, thyrotrophin-releasing hormone analogue.