CONSEQUENCES OF TRANSIENT FOCAL CEREBRAL-ISCHEMIA FOR 2ND MESSENGER AND NEUROTRANSMITTER BINDING IN THE RAT - QUANTITATIVE AUTORADIOGRAPHICANALYSIS OF FORSKOLIN, DOPAMINE D-1 RECEPTOR-BINDING AND CEREBRAL BLOOD-FLOW CHANGES

In order to study the consequences of reperfusion for ischaemic brain injury, quantitative ligand binding autoradiography was carried out in a model of reversible focal cerebral ischaemia. Endothelin-l applied to the abluminal surface of the middle cerebral artery in anaesthetize d Sprague-Dawley rats induced severe focal ischaemia and subsequent re perfusion (assessed by blood flow tracers [Tc-99m]HMpAO and [C-14]iodo antipyrine respectively) by 2 h after insult. Ligand binding autoradio graphy on consecutive sections demonstrated these blood flow changes t o be associated with a significant reduction in forskolin binding thro ughout the middle cerebral artery territory (e.g. 25% in parietal cort ex, 11% in dorsolateral caudate nucleus). The most marked losses in fo rskolin binding were in areas where ischaemia was severe and reperfusi on was poor, However, the same changes in cerebral blood flow had no s ignificant effect on D-1 dopamine receptor binding (e,g. <2% reduction in the caudate nucleus). These data demonstrate that ligand binding c haracteristics are significantly affected as early as 2 h after insult , with evidence of differential sensitivity for forskolin and D-1 dopa mine binding. With regard to the consequences of reperfusion, comparis on with our previous study of 2 h maintained ischaemia demonstrates re perfusion-related salvage of dopamine and forskolin binding in the cau date nucleus but possible exacerbation of forskolin binding loss in th e cortex.