Selective neuronal vulnerability following mild focal brain ischemia in the mouse.
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.
Katchanov
Juri
J
Klinik und Poliklinik für Neurologie, Charité Campus Mitte, Humboldt-Universität zu Berlin, Germany.
Waeber
Christian
C
Gertz
Karen
K
Gietz
Andrea
A
Winter
Benjamin
B
Brück
Wolfgang
W
Dirnagl
Ulrich
U
Veh
Rüdiger W
RW
Endres
Matthias
M
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
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