Focal cerebral ischemia preferentially affects neurons distant from their neighboring microvessels

Developing cerebral infarction obscures the relationship of neurons to their local supply microvessels. We tested the notion that in the basal ganglia (i) an ordered relationship between neurons and their nearest neighboring microvessel exists, and (ii) focal ischemia predictably affects neuron integrity based on microvessel-neuron proximity. Distances between individual microvessels and their nearest neurons ([m-n distance]s) were measured in normal primates and ischemic subjects undergoing middle cerebral artery occlusion for 2 hours. An ordered microvessel-neuron relationship exists in the normal nonischemic basal ganglia within the early hours of focal ischemia. During ischemia normal (n) and sensitive (n*) neurons are interspersed. On average, neurons more distant from their nearest microvessel are most sensitive ([m-n distance]=16.2+/-11.2 microm versus [m-n* distance]=22.2+/-13.0 microm, 2P<0.00000001). Neurons not expressing glutamic acid decarboxylase were more likely to be sensitive than those with a normal microvessel-neuron relationship. In contrast, the [m-n distance] distribution of injured tyrosine hydroxylase-containing neurons was similar to those without tyrosine hydroxylase. Hence, the [m-n distance] relationship in the normal and ischemic basal ganglia is highly ordered, and distant neurons are consistently perturbed by ischemia, although this is not uniformly dependent on neurotransmitter type.