Neuroprotection and neurogenesis: modulation of cornus ammonis 1 neuronal survival after transient forebrain ischemia by prior fimbria-fornix deafferentation.
Severe transient forebrain ischemia causes selective neuronal death in the hippocampal cornus ammonis 1 region. We tested the hypothesis that fimbria-fornix deafferentation can provide long-term protection to cornus ammonis 1 neurons and modulate neurogenesis following ischemia. Fimbria-fornix lesion or sham-fimbria-fornix lesion was performed on Wistar rats 13 days prior to 10 min forebrain ischemia or sham ischemia. Temperature was regulated and rats survived for 7, 14 or 28 days. Immunofluorescent bromodeoxyuridine and neuron specific nuclear protein staining and immunochemistry terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling staining were performed. At 7 days after ischemia, 73%+/-14% of cornus ammonis 1 neurons were damaged, while deafferentation reduced the injury to 36%+/-17% of cornus ammonis 1 neurons. This protection persisted for at least 28 days. Ischemia significantly increased the number of bromodeoxyuridine-positive cells (85-90 cells/section in stroke group vs. 6 to 11 cells/section in normal or sham stroke group), with very few terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling-stained cells adjacent to the hippocampal cornus ammonis 1. Fimbria-fornix lesioning followed by ischemia increased the percentage of new neurons 13-fold over ischemia alone and 6.5-fold over sham lesion plus ischemia. The results indicate that fimbria-fornix deafferentation provides long-term neuroprotection in cornus ammonis 1 following forebrain ischemia and promotes neurogenesis after ischemic insults.
Calgary Stroke Program, Hotchkiss Brain Institute and Department of Clinical Neurosciences, University of Calgary, 3330 Hospital Drive NW, Calgary, AB T2N 4N1, Canada.
Z
Z
Zhao
P
P
Sun
N
N
Chauhan
J
J
Kaur
M D
MD
Hill
M
M
Papadakis
A M
AM
Buchan
D000704:Analysis of Variance; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology; D004195:Disease Models, Animal; D020712:Fornix, Brain / Q000293:injuries / Q000502:physiology*; D006624:Hippocampus / Q000473:pathology*; D007150:Immunohistochemistry / Q000379:methods; D002546:Ischemic Attack, Transient / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D018613:Microscopy, Confocal / Q000379:methods; D009474:Neurons / Q000473:pathology*; D038081:Organogenesis / Q000502:physiology; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D010751:Phosphopyruvate Hydratase; D001973:Bromodeoxyuridine