Microtubule-associated protein 2, an early blood marker of ischemic brain injury

The aim of this study was to develop a sensitive and rapid blood marker to detect ischemic brain injury, because imaging techniques have a limited capacity to identify lesions during the first crucial hours without massive tissue destruction. Rats were subjected to middle cerebral artery occlusion for various durations (0.5-3 hr), followed by reperfusion. At different time points after ischemia and/or ischemia-reperfusion, the amounts of glial fibrillary acidic protein (GFAP) and microtubule-associated protein 2 (MAP2) in the cerebrospinal fluid (CSF) and serum were analyzed by Western blotting. Brain infarction was observed in an ischemia-duration-dependent manner. GFAP was drastically increased in the CSF 24 and 48 hr after reperfusion, without change in the serum level. Serum levels of MAP2 remarkably increased as early as 0.5 hr of ischemia, much earlier than the observation of minimal tissue injury 3 hr following occlusion. The serum MAP2 level was further increased by a short period (2 hr) of reperfusion, even in 0.5- and 1-hr ischemic rats, despite not observing any typical tissue injuries 24 hr after reperfusion. These results indicate that the MAP2 protein may be able to detect early neuronal injuries, because the level of this protein in the blood spikes before the appearance of visible macrolesions. Therefore, MAP2 could potentially be used as a novel early marker for the detection of a neurotoxic insult.