Very brief focal ischemia simulating transient ischemic attacks (TIAs) can injure brain and induce Hsp70 protein

This study examined very brief focal ischemia that simulates transient ischemic attacks (TIAs) that occur in humans. Adult rats were subjected to sham operations or 5 min, 10 min, or 2 h of middle cerebral artery (MCA) ischemia using the suture (thread) model. Hsp70 protein was induced 24 h, 48 h and 72 h later in neurons throughout the entire MCA territory in many but not all animals. Following 5- and 10-minute MCA occlusions, 9 of 32 animals (28%) had microinfarcts mostly in dorsal lateral striatum. Uncommon Hsp70 stained intracellular cytoplasmic inclusions, some of which co-localized with activated caspase-3, were detected in microglia, macrophages, astrocytes and oligodendrocytes. Hsp70 stained neurons were TUNEL negative at 24 h and 48 h whereas some Hsp70 stained neurons were TUNEL positive at 72 h after reperfusion. Hsp70 positive, activated “bushy” microglia and Hsp70 negative, activated “polarized” or rod-shaped microglia were located outside of the microinfarcts. Thus, experimental focal ischemia simulating TIAs can: induce Hsp70 protein throughout the ischemic vessel territory; produce Hsp70 protein positive glial inclusions; activate Hsp70 positive and negative microglia; and cause microinfarcts in some animals.