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Long‐term effects of hypothermia on neuronal cell death and the concentration of apoptotic proteins after incomplete cerebral ischemia and reperfusion in rats
Author(s) -
Eberspächer E.,
Werner C.,
Engelhard K.,
Pape M.,
Laacke L.,
Winner D.,
Hollweck R.,
Hutzler P.,
Kochs E.
Publication year - 2005
Publication title -
acta anaesthesiologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.738
H-Index - 107
eISSN - 1399-6576
pISSN - 0001-5172
DOI - 10.1111/j.1399-6576.2005.00649.x
Subject(s) - medicine , hypothermia , isoflurane , ischemia , apoptosis , anesthesia , hippocampal formation , neuroprotection , fentanyl , pharmacology , biochemistry , biology
Background: The present study investigates the long‐term effects of postischemic hypothermia on neuronal cell damage and concentration changes of apoptotic proteins after cerebral ischemia. Methods: Sixty‐four Sprague‐Dawley rats were anesthetized, intubated and ventilated with 2.0 Vol% isoflurane and 70% N 2 O/O 2 . After preparation the animals were randomly assigned to the following groups: group 1 (n = 32, fentanyl‐N 2 O/normothermia 37.5°C), and group 2 (n = 32, fentanyl‐N 2 O/hypothermia 34.0°C. Ischemia (45 min) was induced by common carotid artery occlusion plus hemorrhagic hypotension (MAP = 40 mmHg). Arterial blood gases and pH were maintained constant. After 1, 3, 7, or 28 days (each n = 8) the brains were removed, frozen and cut. Neuronal damage was assessed by analyzing Bax, Bcl‐2, p53, and Mdm‐2 proteins, activated caspases‐3‐positive and eosinophilic cells. A third group (n = 8) of untreated animals served as naive controls. Results: In hypothermic animals, Bax concentration was decreased by 50–70% over time compared to normothermia. On days 1 and 3, Bcl‐2 was increased by 50% with hypothermia. The amount of activated caspase‐3‐positive cells in the ischemic hemisphere was 0.5% in the hypothermic and 1–2% in the normothermic animals. Of the hippocampal cells, 10–25% were eosinophilic in both groups over time. Conclusion: The present data show that hypothermia prevents an ischemia‐induced increase of the pro‐apoptotic protein Bax for as long as 28 days and increases the concentration of the antiapoptotic protein Bcl‐2 up to 3 days compared to normothermic animals. Therefore, after cerebral ischemia, hypothermia has the sustained neuroprotective potential to shift apoptosis‐related proteins towards neuronal cell survival.