The concepts of thresholds of ischaemia in relation to brain structure and function.

Abstract

The relationship between the blood supply of a neurone and its capacity to function and survive remains of fundamental importance in the study of cerebral vascular disease from both the surgical and the medical standpoint. Thus it has been assumed that a matter of only a few minutes is necessary to cause complete and permanent loss of function of key neurones in the primate nervous system (Dennis and Kabat, 1939; Weinberger et al, 1940; Grenell, 1946; Boyd and Connolly, 1962), but everyday clinical experience confirms that dense neurological deficits following soon after a cerebral ischaemic episode may gradually resolve and finally even disappear. It has long been an intriguing clinical question whether such resolution of neurological deficits relates to the recovery of neurones so damaged following the ischaemic episode as to cease functioning, yet subsequently recover, or whether associated areas outwith the zone of immediate ischaemia are capable of assuming the function of structures rendered irreversibly damaged by the ischaemic event. The theory that certain cells probably survive in a state of structural integrity but functional paralysis has seemed to us for some years most likely, while possible explanations for the recovery of neurones have been either improvement in residual circulation with expansion of the collateral vessels from neighbouring cerebrovascular beds, or modification of the neuronal metabolism itself so that function may be resumed at a lower basal level of blood flow. The experimental findings in this paper relate attempts to elucidate the relationship between structure, function and blood supply in the nervous system. They have been stimulated by surgical rather than medical phenomena, since the occlusion of vessels during the excision of basal tumours, or the occlusion of portions of the cerebral circulation in the treatment of intracranial aneurysm, generally gives a human preparation less clouded by incidental vascular disease than occlusion in the course of the development of atherosclerosis with its attendant impairment of function of collateral vessels, and, possibly, disorder reactivity of the vascular system as a whole. In the experimental analysis of these phenomena the experimental stroke model described elsewhere has been used (Symon et al, 1971; Symon, 1975), in which the middle cerebral artery is occluded either by an intracranial approach along the sphenoidal wing, or by a transorbital approach after removal of the contents of the orbit and dissection through the enlarged superior orbital fissure. Temporary occlusion of the vessel in acute experiments is performed with a small spring clip such as a Scoville clip, while for permanent occlusion the artery is divided between two small 'haemo' clips. The site of occlusion used in this model is the first millimetre of the middle cerebral which, as Shellshear (1921) and Abbie (1934) have indicated, is free from perforating vessels. The intensity of ischaemia in the basal ganglia may be increased by simultaneous occlusion of the perforating vessels.