Microsurgical approach for experimental ischaemia

Abstract

Sudden occlusion of the middle cerebral artery (MCA) is one of the common strokes in humans which causes ischaemic brain damage and neurological deficit. Although a number of experimental approaches to produce MCA occlusion were performed using larger animals such as monkeys and cats, MCA occlusion in rats which was originally devised in Glasgow (Tamura et al., 1981) provided a useful means to investigate the pathophysiology of focal cerebral ischaemia particularly when combined with the autoradiographic techniques because of the reduced requirement of expensive radioisotopes in small animals. Through a subtemporal craniectomy under the operative microscope, the trunk of MCA was exposed. There was an important tiny arterial branch called lenticulostriate artery which arose from the very proximal part of the MCA and supplied circulation to the caudate nucleus. The circulatory and neuropathological consequences were quite different whether or not this artery was involved. The “proximal” occlusion which involved both the MCA and the lenticulostriate artery produced ischaemia and ischaemic brain damage in both cortex and the caudate nucleus, whereas the “distal” occlusion without occluding the lenticulostriate artery produced only cortical damage. Since the sites of occlusion for both types were so close, a careful microsurgical technique was required. The neuropathological consequence was found much more consistent and severe in proximal occlusion. Several autoradiographic investigations were carried out to investigate cerebral blood flow using (14C)-iodoantipyrine, cerebral glucose metabolism using (14C)-2-deoxyglucose, blood-brain barrier permeability using (14C)-aminoisobutyric acid and protein synthesis using (14C)-leucine. Heterogeneous alterations were found in each of the autoradiographic indices but these could be well correlated with a combined use of enzyme histochemistry for glycogen phosphorylase which could delineate the lesion. A greater interest was focused on the areas outside .the irreversibly damaged ischaemic core which were not yet dead and potentially salvageable. The autoradiographic investigations showed that this was an area with a metabolic activation through an enhanced anaerobic glycolysis. A model of reversible ischaemia was also established by utilizing a snare ligature in the trunk of the MCA. It was found that a short period of ischaemia for 30 minutes caused prolonged derangement in local cerebral circulation even after initial full restoration of cerebral perfusion. In conclusion, a small animal model of focal cerebral ischaemia can provide a sound basis for the study of ischaemic pathophysiology in the brain when a careful microsurgical technique is used.