title: Selective neuronal vulnerability following mild focal brain ischemia in the mouse.
abstract: 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.
authors.affiliation: Klinik und Poliklinik für Neurologie, Charité Campus Mitte, Humboldt-Universität zu Berlin, Germany.
authors.forename: Juri
authors.initials: J
authors.lastname: Katchanov
authors.forename: Christian
authors.initials: C
authors.lastname: Waeber
authors.forename: Karen
authors.initials: K
authors.lastname: Gertz
authors.forename: Andrea
authors.initials: A
authors.lastname: Gietz
authors.forename: Benjamin
authors.initials: B
authors.lastname: Winter
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Brück
authors.forename: Ulrich
authors.initials: U
authors.lastname: Dirnagl
authors.forename: Rüdiger W
authors.initials: RW
authors.lastname: Veh
authors.forename: Matthias
authors.initials: M
authors.lastname: Endres
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000818:Animals; D000931:Antidotes / Q000493:pharmacokinetics; D000970:Antineoplastic Agents / Q000493:pharmacokinetics; D001345:Autoradiography / Q000379:methods; D001665:Binding Sites; D002545:Brain Ischemia / Q000209:etiology / Q000503:physiopathology*; D064032:Calbindin 2; D002452:Cell Count / Q000379:methods; D002470:Cell Survival; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology*; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000493:pharmacokinetics; D005442:Flumazenil / Q000493:pharmacokinetics; D007839:Functional Laterality; D007150:Immunohistochemistry / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D007546:Isoquinolines / Q000493:pharmacokinetics; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D010320:Parvalbumins; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D013004:Somatostatin / Q000378:metabolism; D013194:Staining and Labeling; D013997:Time Factors; D014316:Tritium / Q000493:pharmacokinetics
chemical_list: D000931:Antidotes; D000970:Antineoplastic Agents; C576511:Calb2 protein, mouse; D064032:Calbindin 2; D018691:Excitatory Amino Acid Antagonists; D007546:Isoquinolines; D010320:Parvalbumins; D064030:S100 Calcium Binding Protein G; D014316:Tritium; C069052:CGP 39653; D005442:Flumazenil; D013004:Somatostatin; D015763:2-Amino-5-phosphonovalerate; D002795:Choline O-Acetyltransferase; D010751:Phosphopyruvate Hydratase; C037850:PK 11195