Delayed cell death related to acute cerebral blood flow changes following subarachnoid hemorrhage in the rat brain.
OBJECTIVE
The authors tested the hypotheses that subarachnoid hemorrhage (SAH) leads to delayed cell death with the participation of apoptotic-like mechanisms and is influenced by the degree of acute decrease in the cerebral blood flow (CBF) following hemorrhage.


METHODS
Subarachnoid hemorrhage was induced in rats by endovascular perforation of the internal carotid artery or injection of blood into the prechiasmatic cistern. Cerebral blood flow was measured using laser Doppler flowmetry for 60 minutes. Brain sections stained with terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) showed DNA fragmentation at 2 and 7 days after both methods of inducing SAH in one third to two thirds of the surviving animals in the different experimental groups. More than 80% of the TUNEL-positive cells were neuron-specific nuclear protein-positive (neurons), but immunoreactivity to glial fibrillary acidic protein (astrocytes) and transferrin (oligodendrocytes) were markedly decreased in TUNEL-positive areas. Most of the TUNEL-positive cells displayed chromatin condensation and/or blebs and immunostained for increased Bax; approximately 50% of them were immunoreactive to cleaved caspase-3 and a few to Bcl-2. The duration of the acute CBF decrease below 30% of the baseline level was related to the degree of TUNEL staining.


CONCLUSIONS
Subarachnoid hemorrhage resulted in delayed cell death in a large proportion, but not all, of the surviving animals. The acute CBF decrease was related to the degree of subsequent cell death. These findings indicated the relevance of apoptotic-like pathways. There appears to be a temporal therapeutic window during which adequate treatment might reduce the final damage following SAH.
Prunell
Giselle F
GF
Department of Clinical Neuroscience, Section for Neurosurgery, Karolinska Institutet, Stockholm, Sweden. gfp2102@columbia.edu
Svendgaard
Niels-Aage
NA
Alkass
Kanar
K
Mathiesen
Tiit
T
D000208:Acute Disease; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001921:Brain / Q000098:blood supply / Q000473:pathology; D002470:Cell Survival / Q000502:physiology; D002536:Cerebral Arteries / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000502:physiology*; D004195:Disease Models, Animal; D020287:In Situ Nick-End Labeling; D017078:Laser-Doppler Flowmetry; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013345:Subarachnoid Hemorrhage / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology*; D014463:Ultrasonography