cgp-39653 and Disease-Models--Animal

The evolution of cellular damage over time and the selective vulnerability of different neuronal subtypes was characterized in the striatum following 30-minute middle cerebral artery occlusion and reperfusion in the mouse. Using autoradiography we found an increase in the density of [3H]PK11195 binding sites--likely reflecting microglial activation--in the lesion border at 3 days and in the whole striatum from 10 days to 6 weeks. This was accompanied by a distinct loss of [3H]flumazenil and [3H]CGP39653 binding sites from 10 days up to 6 weeks reflecting neuronal loss. Brain ischemia resulted in a substantial loss of medium spiny projection neurons as seen at three days by Nissl staining, TUNEL and immunocytochemistry using antibodies against microtubule-associated protein (MAP2), NeuN, mu-opioid receptors, substance P, L-enkephalin, neurokinin B, choline acetyltransferase, parvalbumin, calretinin and somatostatin. Both patch and matrix compartments were involved in ischemic damage. In contrast, the numbers of cholinergic, GABAergic, and somatostatin-containing interneurons in the ischemic striatum were not different from those in the contralateral hemisphere at 3 and 14 days. A low density of glutamate receptors, the ability to sequester calcium by calcium-binding proteins and other hitherto unidentified factors may explain this relative resistance of interneurons to acute ischemia.

Topics: 2-Amino-5-phosphonovalerate; Animals; Antidotes; Antineoplastic Agents; Autoradiography; Binding Sites; Brain Ischemia; Calbindin 2; Cell Count; Cell Survival; Choline O-Acetyltransferase; Corpus Striatum; Disease Models, Animal; Excitatory Amino Acid Antagonists; Flumazenil; Functional Laterality; Immunohistochemistry; In Situ Nick-End Labeling; Infarction, Middle Cerebral Artery; Isoquinolines; Mice; Neurons; Parvalbumins; Phosphopyruvate Hydratase; S100 Calcium Binding Protein G; Somatostatin; Staining and Labeling; Time Factors; Tritium