Molecular alterations in the hippocampus after experimental subarachnoid hemorrhage.
Patients with aneurysmal subarachnoid hemorrhage (SAH) frequently have deficits in learning and memory that may or may not be associated with detectable brain lesions. We examined mediators of long-term potentiation after SAH in rats to determine what processes might be involved. There was a reduction in synapses in the dendritic layer of the CA1 region on transmission electron microscopy as well as reduced colocalization of microtubule-associated protein 2 (MAP2) and synaptophysin. Immunohistochemistry showed reduced staining for GluR1 and calmodulin kinase 2 and increased staining for GluR2. Myelin basic protein staining was decreased as well. There was no detectable neuronal injury by Fluoro-Jade B, TUNEL, or activated caspase-3 staining. Vasospasm of the large arteries of the circle of Willis was mild to moderate in severity. Nitric oxide was increased and superoxide anion radical was decreased in hippocampal tissue. Cerebral blood flow, measured by magnetic resonance imaging, and cerebral glucose metabolism, measured by positron emission tomography, were no different in SAH compared with control groups. The results suggest that the etiology of loss of LTP after SAH is not cerebral ischemia but may be mediated by effects of subarachnoid blood such as oxidative stress and inflammation.
Division of Neurosurgery, St Michael's Hospital, Labatt Family Centre of Excellence in Brain Injury and Trauma Research, Keenan Research Centre of the Li Ka Shing Knowledge Institute of St Michael's Hospital, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
Sang Myung
SM
Han
Division of Neurosurgery, St Michael's Hospital, Labatt Family Centre of Excellence in Brain Injury and Trauma Research, Keenan Research Centre of the Li Ka Shing Knowledge Institute of St Michael's Hospital, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
Hoyee
H
Wan
STTARR Innovation Centre, Department of Radiation Oncology, Princess Margaret Hospital, Toronto, Ontario, Canada.
Gen
G
Kudo
1] STTARR Innovation Centre, Department of Radiation Oncology, Princess Margaret Hospital, Toronto, Ontario, Canada [2] Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada.
Warren D
WD
Foltz
1] STTARR Innovation Centre, Department of Radiation Oncology, Princess Margaret Hospital, Toronto, Ontario, Canada [2] Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada.
Douglass C
DC
Vines
STTARR Innovation Centre, Department of Radiation Oncology, Princess Margaret Hospital, Toronto, Ontario, Canada.
David E
DE
Green
Division of Neurosurgery, St Michael's Hospital, Labatt Family Centre of Excellence in Brain Injury and Trauma Research, Keenan Research Centre of the Li Ka Shing Knowledge Institute of St Michael's Hospital, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
Tommaso
T
Zoerle
Division of Neurosurgery, St Michael's Hospital, Labatt Family Centre of Excellence in Brain Injury and Trauma Research, Keenan Research Centre of the Li Ka Shing Knowledge Institute of St Michael's Hospital, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
Asma
A
Tariq
Division of Neurosurgery, St Michael's Hospital, Labatt Family Centre of Excellence in Brain Injury and Trauma Research, Keenan Research Centre of the Li Ka Shing Knowledge Institute of St Michael's Hospital, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
Shakira
S
Brathwaite
Division of Neurosurgery, St Michael's Hospital, Labatt Family Centre of Excellence in Brain Injury and Trauma Research, Keenan Research Centre of the Li Ka Shing Knowledge Institute of St Michael's Hospital, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
Josephine
J
D'Abbondanza
Division of Neurosurgery, St Michael's Hospital, Labatt Family Centre of Excellence in Brain Injury and Trauma Research, Keenan Research Centre of the Li Ka Shing Knowledge Institute of St Michael's Hospital, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
Jinglu
J
Ai
Division of Neurosurgery, St Michael's Hospital, Labatt Family Centre of Excellence in Brain Injury and Trauma Research, Keenan Research Centre of the Li Ka Shing Knowledge Institute of St Michael's Hospital, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
R Loch
RL
Macdonald
D000818:Animals; D056547:CA1 Region, Hippocampal / Q000378:metabolism / Q000503:physiopathology / Q000648:ultrastructure*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D004195:Disease Models, Animal; D017774:Long-Term Potentiation / Q000502:physiology; D008279:Magnetic Resonance Imaging; D008297:Male; D046529:Microscopy, Electron, Transmission; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D004676:Myelin Basic Protein / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism; D013345:Subarachnoid Hemorrhage / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology
D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D008869:Microtubule-Associated Proteins; D004676:Myelin Basic Protein; D018091:Receptors, AMPA; C489787:MAP2 protein, rat; C104722:glutamate receptor ionotropic, AMPA 2