This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Lasarzik, I. Articles by Engelhard, K. PubMed PubMed Citation Articles by Lasarzik, I. Articles by Engelhard, K. Related Collections Mechanisms Neuroanesthesia Complications

---

NEUROSURGICAL ANESTHESIOLOGY AND NEUROSCIENCE

Mild Hypothermia Has No Long-Term Impact on Postischemic Neurogenesis in Rats

Irina Lasarzik, MD^*, Uta Winkelheide, DVM^*, Serge C. Thal, MD^*, Natascha Benz, MD^*, Matthias Lörscher, MD^*, Antje Jahn-Eimermacher, Dipl Math, Christian Werner, MD, PhD^*, and Kristin Engelhard, MD, PhD^*

From the *Department of Anesthesiology, and Institute of Medical Biostatistics, Epidemiology and Informatics, Medical Center of the Johannes Gutenberg-University, Mainz, Germany.

Address correspondence to Irina Lasarzik, MD, Department of Anesthesiology, Medical Center of the Johannes Gutenberg-University, Langenbeckstr 1, Mainz 55131, Germany. Address e-mail to lasarzik{at}uni-mainz.de.

Abstract

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°C. Animals in the hypothermic groups were cooled to a pericranial temperature of 33°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.