Mild hypothermia has no long-term impact on postischemic neurogenesis in rats.
BACKGROUND
Postischemic improvement of functional outcome by therapeutic hypothermia may be related to cerebral regeneration by postischemic neurogenesis. We investigated whether mild peri-ischemic hypothermia leads to a long-term increase in postischemic neurogenesis.


METHODS
Seventy male sevoflurane-anesthetized Sprague Dawley rats were randomly assigned to the following treatment groups: normothermic ischemia, intraischemic hypothermia, and postischemic hypothermia with corresponding sham-operated controls. Fifteen naïve rats were investigated as reference for natural neurogenesis. Forebrain ischemia was induced by bilateral common carotid artery occlusion and hemorrhagic hypotension. In normothermic groups, the pericranial temperature was maintained at 37.5 degrees C. Animals in the hypothermic groups were cooled to a pericranial temperature of 33 degrees C for 45 min. All animals received 5-bromo-2-deoxyuridine for 7 days. Histopathological damage and 5-bromo-2-deoxyuridine-positive neurons of the hippocampus were analyzed after 28 days.


RESULTS
Hypothermia had no impact on natural neurogenesis. Cerebral ischemia increased the number of new neurons regardless of pericranial temperature. Forty-five minutes of hypothermia beginning before ischemia diminished hippocampal injury to <10% in the CA1 and CA3 regions, whereas 45 min of postischemic hypothermia beginning after reperfusion did not reduce neuronal injury compared with normothermia.


CONCLUSIONS
Neither intraischemic nor postischemic hypothermia affected the ischemia-induced increase in endogenous neurogenesis. Intraischemic hypothermia reduced hippocampal damage, whereas postischemic hypothermia as applied here did not prevent formation of histopathological injury. This indicates that, 28 days after cerebral ischemia, postischemic neurogenesis is not significantly increased by mild peri-ischemic hypothermia and not affected by the severity of histopathological damage.
Department of Anesthesiology, Medical Center of the Johannes Gutenberg-University, Mainz, Germany. lasarzik@uni-mainz.d
Irina
I
Lasarzik
Uta
U
Winkelheide
Serge C
SC
Thal
Natascha
N
Benz
Matthias
M
Lörscher
Antje
A
Jahn-Eimermacher
Christian
C
Werner
Kristin
K
Engelhard
D000818:Animals; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D049109:Cell Proliferation; D018891:Dentate Gyrus / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D007036:Hypothermia, Induced; D008297:Male; D009410:Nerve Degeneration / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D055495:Neurogenesis; D009474:Neurons / Q000473:pathology*; D016548:Prosencephalon / Q000098:blood supply*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D013997:Time Factors