CHARACTERIZATION OF AN EXPERIMENTAL-MODEL OF STROKE PRODUCED BY INTRACEREBRAL MICROINJECTION OF ENDOTHELIN-1 ADJACENT TO THE RAT MIDDLE CEREBRAL-ARTERY

A novel experimental model of stroke has been developed using the powe rful vasoconstrictor peptide, endothelin-1, to occlude the middle cere bral artery (MCA) of anaesthetised rats. Intracerebral microinjections of endothelin-1 were administered under stereotaxic guidance adjacent to the MCA, and after 3 days rats were perfusion fixed for histopatho logical determination of ischaemic brain damage. The pattern of brain damage noted using this model was similar to that reported following p ermanent surgical occlusion of the MCA. Brain damage was apparent in t he dorsal and lateral neocortex (98 +/- 12 mm(3)) and striatum (32 +/- 3 mm(3)) ipsilateral to the insult. Rats anaesthetised with halothane and barbiturate exhibited a similar volume of brain damage. However, infarct volume increased when the duration of halothane anaesthesia wa s extended from 5 to 180 min post-occlusion. Neuroprotection studies d emonstrated that dizocilpine (5 mg/kg, i.p.), administered 30 min prio r to MCA occlusion, reduced the volume of cortical brain damage by 51% (P < 0.05) but did not alter the volume of striatal brain damage. The present results demonstrate that microinjections of endothelin-1 adja cent to the rat MCA result in a reproducible pattern of focal cerebral infarction which is sensitive to the duration of anaesthesia and can be reduced by dizocilpine.