The Cortical Ischaemic Penumbra Associated with Occlusion of the Middle Cerebral Artery in the Cat: 2. Studies of Histopathology, Water Content, and in vitro Neurotransmitter Uptake

Abstract

The nature of the ischaemic penumbra, as defined by suppression of electroencephalogram amplitude in the absence of increase in steady state pial surface potassium activity in excess of 13 m M, was examined in the marginal gyrus of cats subjected to middle cerebral artery occlusion. In vitro synaptosomal neurotransmitter uptake, water content (specific gravity), and histopathology at the light and electron microscopic level were studied and the results compared with those obtained at deeper, critical levels of ischaemia (less than 15 ml 100 g⁻¹ min⁻¹). [³H]4-Aminobutyric acid uptake was 104% of control in the marginal gyrus (NS), and 61 and 48% (p < 0.05) in critical ischaemia. It is concluded that impairment of in vivo synaptosomal uptake is a marker of simultaneous widespread damage to neurones, rather than of a change restricted to the synaptic compartment, although the present findings cannot exclude reversible, substrate-limited impairment of uptake in vivo. Reductions in specific gravity were seen only with critical ischaemia. In 5 of 6 experiments, early or classical ischaemic neuronal cell changes and reactive glia were seen on light microscopy in restricted areas in the marginal gyrus, either in microfoci or scattered more diffusely. Ultrastructural changes were more frequent but were considered to affect only a minority of neurones. Hypotheses for selective electrophysiological suppression in penumbra are discussed.