Background: In rat focal ischemia, the permanently depolarizing ischemic core has been suggested to result in infarction, and it is well known that NADH concentration is increased by ischemia. In the present study, we examined changes in cortical NADH fluorescence and DCpotential to determine whether intraischemic hypothermia results in repolarization of the area showing persistent depolarization. Methods: Three male spontaneously hypertensive rats weighing 300±20 g were used in this study. Anesthesia was maintained with 1% halothane in a mixture of 30% O2 and 70% N2O. Focal ischemia was initiated by occlusion of the left common carotid artery and middle cerebral artery (MCA). Hypothermia was initiated at 15 minutes after occlusion of the MCA using a nasopharyngeal cooling method described by Hagioka et al. (1) Brain temperature decreased to 25°C within 15 minutes and was maintained at that temperature for 2 hours. Rectal temperature was maintained at over 34°C during hypothermia. A large cranial window was made on the left parietal-temporal bone, and two glass microelectrodes (for monitoring DCpotential) were placed in this window. One was placed 3 mm posterior to the bregma and 3 mm lateral from the sagittal line, and the other was placed 5 mm posterior to the bregma and 3 mm lateral from the sagittal line. We observed changes in DCpotential and cortical NADH fluorescence using an in vivo fluorescence imaging technique described by Higuchi et al. (2) Results: At the DC recording sites, persistent depolarization was observed for the first 15 minutes in all rats. After starting hypothermia, recovery of DC potentials was observed in two of the three rats. In the two rats in which recovery of DC potentials was observed, the number of pixels showing more than 120% NADH fluorescence, which we call the "ischemic core", had decreased from 5000 to 4000 and 4800 to 3800, respectively, at 10 minutes after starting hypothermia. Conclusion: Hypothermia induced 15 minues after focal brain ischemia by nasopharyngeal cooling repolarized the area showing persistent depolarization and reduced the ischemic core in NADH fluorescence images. Our results suggest that hypothermia induced by nasopharyngeal cooling repolarizes neural cells by changing the mitochondrial NADH redox state and improving the energy metabolism of neural cells.
|Journal||Journal of Cerebral Blood Flow and Metabolism|
|Issue number||SUPPL. 1|
|Publication status||Published - Nov 13 2007|
ASJC Scopus subject areas
- Clinical Neurology
- Cardiology and Cardiovascular Medicine