The utility of microtubule-associated protein 2 (MAP2) immunostaining as a marker of acute focal ischemic injury was investigated. Permanent middle cerebral artery occlusion (MCAO) elicited a rapid reduction in MAP2 immunostaining that was visible 1 h post-MCAO and that increased in intensity and area encompassed over time. The ischemic lesion borders were well defined by loss of MAP2 immunostaining, but alterations in staining within the lesion were more heterogeneous. Lesion volume increased significantly from 1 to 4 h post-MCAO (from 63.8 +/- 10.8 to 111.3 +/- 19.0 mm3, mean +/- SD). Thus, MAP2 immunostaining is a sensitive, quantifiable indicator of acute brain injury following focal ischemia.