Quantitative assessment of ischemic pathology in axons, oligodendrocytes, and neurons: Attenuation of damage after transient ischemia

Axone and oligodendrocytes are vulnerable to cerebral ischemia. The absence of quantitative methods for assessment of white matter pathology in ischem ia has precluded in vivo evaluation of therapeutic interventions directed a t axons and oligodendrocytes. The authors demonstrate here that the quantit ative extent of white matter pathology was reduced by restoration of cerebr al blood flow after 2 hours of middle cerebral artery occlusion. Focal isch emia was induced in anesthetized rats by intraluminal thread placement, eit her transiently (for 2 hours) or permanently. At 24 hours after induction o f ischemia. axonal damage was determined by amyloid precursor protein (APP) immunohistochemistry, and the ischemic insult to oligodendrocytes was asse ssed by Tau-1 immunostaining in the same sections. In adjacent sections, is chemic damage to neuronal perikarya was defined histologically. The hemisph eric extent of axonal damage was reduced by 70% in the transiently occluded animals from that in permanently occluded animals. The volumes of oligoden drocyte pathology and of neuronal perikaryal damage were reduced by 62% and 58% respectively, in the transiently occluded animals. These results demon strate that this methodologic approach for assessing ischemic damage in axo ns and oligodendrocytes can detect relative alterations in gray and white m atter pathology with intervention strategies.