The Consequences of Reperfusion on Cerebral Ischaemic Damage

The aim of this PhD thesis was to investigate the consequences of reperfusion on cerebral ischaemic damage using a new model of transient focal cerebral ischaemia developed at the Wellcome Surgical Institute. The model involves the abluminal application of the potent vasoconstrictor peptide endothelin-1 (ET-1) to the exposed MCA of the anaesthetised rat. Previous studied using the hydrogen clearance CBF technique and quantitative autoradiographic and histopathological procedures, revealed that ET-1 application to the MCA produced a profound ischaemia followed by a gradual, spontaneous reperfusion resulting in a reproducible lesion (within the cortex and caudate nucleus) by 4h post insult. The object of this thesis was to further characterise the pathological mechanisms associated with this model of transient cerebral ischaemia by investigating such parameters as CBF, brain tissue swelling, microvascular permeability, free radical damage and neurotransmitter transduction systems and second messengers