Induction of heat shock protein 70 in the rat brain following intracisternal infusion of autologous blood: evaluation of acute neuronal damage.
OBJECTIVE
Investigation into a potential treatment for the acute period following onset of spontaneous subarachnoid hemorrhage (SAH) is hampered by the lack of a standardized experimental model. For that purpose the authors elaborated on a small-animal model in which computer-controlled intracisternal blood infusion is used and investigated whether this model can reliably reproduce acute neuronal injury after SAH.


METHODS
Whole autologous blood (blood-infused group) or isotonic saline (control group) was infused into the cisterna magna or olfactory cistern of rats. The infusions decreased exponentially during a 5-minute period. Throughout the infusion period, intracranial pressure (ICP) was monitored. Neuronal injury was quantified by observing tissue immunoreactivity to a 70-kD heat shock protein (HSP70) and comparing this with the tissue's reaction to hematoxylin and eosin staining. On Days 1, 3, and 5, the CA1, CA3, and dentate gyrus regions of the hippocampus were analyzed, respectively. During saline infusion ICP increased within seconds beyond 80 mm Hg and afterward decreased in accordance with the infusion rate. During the infusion of blood, the same initial pressure peak was found, but the ICP remained increased beyond this pressure level throughout the 5-minute infusion period. The HSP70 immunoreactivity in the saline-infused group was found only on Day 1 in the CA1 region and the dentate gyrus, but not in the CA3. After injection of whole blood, there was HSP70-positive staining in the CA1, CA3, and dentate gyrus regions throughout the observation period.


CONCLUSIONS
The controlled cisternal infusion of blood caused neuronal injury that resembled that of previous experimental models that produce SAH by rupture of intracranial vessels with endovascular techniques. Unlike those experiments, the intracisternal infusion technique presented by the authors provides more standardized bleeding with regard to ICP, the volume of subarachnoid blood, and the extent of acute cellular injury.
Klinge
P M
PM
Department of Neurosurgery, Nordstadt Hospital, Hannover, Germany.
Beck
H
H
Brinker
T
T
Walter
G F
GF
Samii
M
M
D000818:Animals; D000906:Antibodies; D001803:Blood Transfusion; D002545:Brain Ischemia / Q000503:physiopathology; D002946:Cisterna Magna; D004396:Coloring Agents; D018891:Dentate Gyrus / Q000098:blood supply / Q000737:chemistry / Q000378:metabolism*; D004195:Disease Models, Animal; D004801:Eosine Yellowish-(YS); D018840:HSP70 Heat-Shock Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000276:immunology; D006416:Hematoxylin; D007276:Injections, Intraventricular; D007427:Intracranial Pressure; D009410:Nerve Degeneration / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D012965:Sodium Chloride; D013345:Subarachnoid Hemorrhage / Q000503:physiopathology*
D000906:Antibodies; D004396:Coloring Agents; D018840:HSP70 Heat-Shock Proteins; D012965:Sodium Chloride; D004801:Eosine Yellowish-(YS); D006416:Hematoxylin