Neuronal and astrocytic apoptosis after subarachnoid hemorrhage: a possible cause for poor prognosis.
Clinical evidence suggests that factors other than cerebral vasospasm, such as delayed neuronal and astrocytic cell death, may play a role in the poor prognosis of patients with subarachnoid hemorrhage (SAH). Here we examined this using immunohistochemistry and confocal microscopy in 3 different brain areas in a dog model of SAH. Using antibodies against neuronal marker neuronal nuclear protein (NeuN) and astrocyte marker glial fibrillary acidic protein (GFAP) in conjunction with apoptosis marker (cleaved caspase-3), we quantified neurons and astrocytes to monitor the degree of apoptosis in both groups. Experimental SAH group showed 44 +/- 1% caspase-3 positive neurons in comparison to the 2.0 +/- 0.1% in the control group (P < 0.001, 6 animals each group). For astrocytes, a total 25 +/- 1% were caspase-3 positive in day 7 SAH group, as compared to 0.40 +/- 0.01% for controls (P < 0.001). Regional analysis revealed that neuronal caspase-3 immunoreactivity in all 3 regions were significantly higher (P < 0.001) in SAH animals than that in the control animals. However, the analysis of total area, size and signal co-localization of GFAP with caspase-3 indicated that astrocytic reactivity and proliferation are seen primarily in the hippocampal area, with the least changes detectable in the brainstem. We conclude that in the dog model, there was a significant increase of neuronal and astrocytic cleaved caspase-3, possibly reflecting apoptosis, following SAH induction. These changes coupled with neurological deterioration seen in patients may present a possible reason for the poor outcome in SAH patients.
Sabri
Mohammed
M
Division of Neurosurgery, St Michael's Hospital, Keenan Research Centre in the Li Ka Shing Knowledge Institute of St Michael's, Toronto, Ontario, Canada.
Kawashima
Ayako
A
Ai
Jinglu
J
Macdonald
R Loch
RL
D000818:Animals; D034961:Antigens, Nuclear / Q000096:biosynthesis; D017209:Apoptosis / Q000502:physiology*; D001253:Astrocytes / Q000473:pathology*; D001921:Brain / Q000473:pathology; D053148:Caspase 3 / Q000096:biosynthesis; D004285:Dogs; D005260:Female; D005455:Fluorescent Antibody Technique; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D009474:Neurons / Q000473:pathology*; D011379:Prognosis; D013345:Subarachnoid Hemorrhage / Q000473:pathology*
D034961:Antigens, Nuclear; D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; C506808:neuronal nuclear antigen NeuN, human; D053148:Caspase 3
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