Mild hypothermia (33 degrees C) reduces intracranial hypertension and improves functional outcome after subarachnoid hemorrhage in rats.
OBJECTIVE
After a subarachnoid hemorrhage (SAH), the primary cause of mortality is secondary brain injury occurring within the first 48 hours after the initial bleeding. Because of the unknown pathophysiology of these early events, therapeutic approaches are scarce. Because mild hypothermia (33 degrees C) is among the strongest neuroprotectants known so far, the aim of this study was to investigate acute and delayed effects of hypothermia if applied after SAH.


METHODS
Male Sprague-Dawley rats were subjected to SAH and randomly assigned to the following groups: 1) SAH under normothermia, 2) SAH followed by 2 hours of hypothermia starting 1 hour after the bleeding, and 3) SAH followed by 2 hours of hypothermia starting 3 hours after the bleeding. Cerebral blood flow and intracranial pressure were continuously measured up to 6 hours after SAH. Mortality, neurological deficits, and body weight were assessed from postoperative day 1 to day 7. Brain water content and morphological brain damage were quantified 24 hours and 7 days after SAH, respectively.


RESULTS
Mild hypothermia reduced intracranial pressure (P < 0.001) and posthemorrhagic neurological deficits (P < 0.05) and improved postoperative weight gain significantly (P < 0.05). Mortality, cerebral blood flow, and the formation of cerebral edema were not significantly influenced by mild hypothermia.


CONCLUSIONS
The current results show that mild hypothermia (33 degrees C) exhibits sustained neuroprotection if applied up to 3 hours after SAH. Overall, mild hypothermia seems to be an effective neuroprotective strategy after SAH and should therefore be evaluated as a treatment option for SAH in patients.
Török
Elisabeth
E
Institute for Surgical Research, University of Munich Medical Center, Grosshadern, Ludwig-Maximilians University, Munich, Germany.
Klopotowski
Mariusz
M
Trabold
Raimund
R
Thal
Serge C
SC
Plesnila
Nikolaus
N
Schöller
Karsten
K
D000818:Animals; D001831:Body Temperature / Q000502:physiology*; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000503:physiopathology*; D020520:Brain Infarction / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D002560:Cerebrovascular Circulation / Q000502:physiology; D004195:Disease Models, Animal; D004632:Emergency Medical Services / Q000379:methods / Q000592:standards; D007036:Hypothermia, Induced / Q000379:methods*; D019586:Intracranial Hypertension / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D013997:Time Factors; D016896:Treatment Outcome