The distribution of ischaemic damage and cerebral blood flow after unilateral carotid occlusion and hypotension in the rat.

Abstract

We have developed a model of haemodynamic cerebral ischaemia by inducing haemorrhagic hypotension (40-50 mmHg mean blood pressure) following unilateral common carotid occlusion, with external carotid ligation, in anaesthetised rats. The neuropathological pattern of ischaemic brain damage was correlated with the distribution of change in cerebral blood flow using the 14C-iodoantypyrine autoradiographic technique. Whereas hypotension alone (40-50 mmHg) resulted in neither ischaemic brain damage nor significant alterations in cerebral blood flow, the combination of this degree of hypotension with unilateral carotid occlusion produced predominantly unilateral ischaemic brain damage which correlated with regions of reduced cerebral blood flow. With this type of haemodynamically induced oligaemia, the most vulnerable areas were the lateral neocortex, the caudate nucleus, the hippocampus and the thalamus. Within the cortex, the greatest reductions in blood flow occurred in the deeper cortical layers, and this was the most frequent site of ischaemic cell change. These data support the concept of a haemodynamic mechanism in the pathogenesis of some transient cerebral ischaemic attacks in man.

The CBF Threshold and Dynamics for Focal Cerebral Infarction in Spontaneously Hypertensive Rats

“…Pollowing permanent common carotid artery occlusion and transient (30 min) hy potension, pathological changes 2.5 h after ischemia onset were correlated to CBP values averaging slightly less than 50 mll00 g-I min -I (measured 15 min after ischemia onset) in the deepest layers of the cortex (Mendelow et al, 1984). Moreover, CBP values in the 40-50 ml 100 g -I min -I range (mea sured 2-2.5 h after the onset of focal ischemia) pro voke major changes in protein synthesis (Mies et al, 1991) the expression of heat shock proteins (Jacewicz et al, 1986), and cerebral acidosis (Nakai et aI., 1988;Kaplan et aI., unpublished observa tions).…”

Endogenous Nitric Oxide Synthesis Differentially Modulates Pressure-Flow and Pressure-Conductance Relationships in the Internal and External Carotid Artery Circulations of the Rat

“…This observation suggests that flow-induced NO release may exaggerate functional differences in the dynamic control mechanisms that regulate the two circulations and/or anatomical differences in their vascular architectures, including collateral pathways that might influence the P-Q characteristics of these beds. For example, the circle of Willis allows equalization of pressures throughout the intracerebral circulation, 1,2,24,39) and the present findings raise the possibility that the hydraulic consequences of this anastomotic network are influenced by NO-mediated flow-dependent dilation. Despite substantial intrinsic differences in the P-Q characteristics of the ICA and ECA territories at intermediate flow rates, their asymptotic high-flow properties may nevertheless both be considered as equivalent to those of networks of``rigid'' vessels.…”

“…10) Since the ICA gives rise to the pterygopalatine artery before passing intracranially to enter the circle of Willis in the rat, a fraction of the ICA blood flow runs into the ECA territory. 1,2,24,39) It is therefore likely that the ability of the intracerebral circulation to stabilize perfusion pressure in the presence of NO synthesis may in practice be greater than suggested by the present findings.…”

Animal Models of Cerebral Ischemia. 2. Rat Models

“…artery: iCCAO -occlusion of ipsilateral common carotid artery; cCCAO = occlusion of Levine developed a model of anoxic-ischemic encepha lopathy consisting of unilateral CCA occlusion followed by gradual exposure to anoxic anoxia [12]. A model of hemodynamic cerebral ischemia induced by hemorrhagic hypotension following unilateral CCA occlusion and ex ternal carotid ligation has also been developed [13]. These physiologic stresses, in addition to focal ischemia, may introduce important metabolic changes in the con tralateral hemisphere and damage organs (heart, kidney) other than brain.…”