Differential vulnerability of microtubule components in cerebral ischemia.

Differential vulnerability of the major components of microtubules was examined in ischemic gerbil brains by a light microscopic, immunohistochemical method using monoclonal antibodies for microtubule-associated protein (MAP) 1A and MAP2, polyclonal antibody for MAP1 and 2 as well as monoclonal antibody for alpha-tubulin. Progressive cerebral ischemia during unilateral carotid occlusion for 5, 15 and 120 min and reperfusion for 3, 12 and 48 h following bilateral carotid occlusion for 10 min were studied. Ischemic lesions in the subiculum-CA1 region were visualized by all antibodies after ischemia for 5 min but the antibody for alpha-tubulin was less sensitive. The antibody for alpha-tubulin was also less sensitive than antibodies for MAPs for detection of early postischemic lesions. Differential sensitivity was also observed in the cerebral cortex and other brain regions. Microtubules in myelinated axons were more stable than those in dendrites. The observed loss of immunohistochemical reactivities for MAPs and alpha-tubulin may have been caused by activation of calcium-dependent proteolytic enzymes such as calpains. The discrepancy between MAPs and alpha-tubulin could be due to differences in affinities or topographic distributions of these proteins within microtubules.