An Investigation Into the Pathophysiology of a New Model of Transient Focal Cerebral Ischaemia in the Rat

This study aimed to investigate the consequences of a transient focal ischaemic insult using a novel model of transient focal cerebral ischaemia that utilises the vasoconstrictor peptide endothelin-1 to induce temporary occlusion of the left middle cerebral artery (MCA) in the rat. Quantitative histopathology and in vivo autoradiographical techniques were used to assess this model and compare it to the standard model of permanent MCA occlusion originally developed in these laboratories (Tamura et al. 1981a). In vivo double-label autoradiography using the blood flow tracers [14C]iodoantipyrine (IAP) and [993Tc]hexamethylpropylamine oxime (HMPAO) revealed that application of endothelin-1 (2.5 nmol in 25 mul) to the MCA in the halothane-anaesthetised rat resulted in profound reductions in local cerebral blood flow throughout the territory of the MCA 5 min post-endothelin-1 application (measured by [99mTc]HMPAO). In the same animals reperfusion (measured by [14C]IAP) was apparent 2 h post-endothelin-1 application in both the cerebral cortex and caudate nucleus. Thus in this model endothelin-1 induces a period of profound ischaemia followed by gradual, spontaneous reperfusion