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(Stroke. 1997;28:1451-1457.)
© 1997 American Heart Association, Inc.

Articles

A Near-Infrared Spectroscopic Study of Cerebral Ischemia and Ischemic Tolerance in Gerbils

Ji-Yao Li, MD; Hirokazu Ueda, MD, PhD; Akitoshi Seiyama, PhD; Misa Nakano, MD; Masayasu Matsumoto, MD, PhD; Takehiko Yanagihara, MD

From the Departments of Neurology (J-Y.L., H.U., M.N., M.M., T.Y.), Physiology I (A.S.), and Internal Medicine I (M.M.), Osaka University Medical School (Japan).

Background and Purpose To explore the physiological mechanism of ischemic tolerance, we studied intracerebral oxygenation states noninvasively using near-infrared spectroscopy after bilateral common carotid artery occlusion (BCO) in gerbils with and without ischemic pretreatment.

Methods Under ether anesthesia, gerbils with sham operation (S group, n=8) and those with pretreatment consisting of BCO for 2 minutes, twice at 3 days and 2 days earlier (T group, n=8), were again subjected to BCO for 5 minutes. Changes in oxyhemoglobin (HbO₂), deoxyhemoglobin (Hb), and total hemoglobin (HbT) as well as reduction in cytochrome oxidase (cyt.aa₃) were calculated from the absorbance changes of the light transmitted through the brain. Seven days after the ischemic study, immunohistochemical examination was performed with an antiserum against microtubule-associated proteins.

Results In both groups, the increase of Hb and decrease of HbO₂ and HbT proceeded rapidly after BCO, and the maximal deoxygenation of hemoglobin occurred within 2.5 minutes. Reduction of cyt.aa₃ also ensued rapidly and reached the maximal reduction within 3 minutes in both groups. In the T group, however, both deoxygenation of hemoglobin and reduction of cyt.aa₃ progressed more slowly than in the S group. The time (seconds) necessary for a maximal change for cyt.aa₃ was significantly longer in the T group (203.8±34.0 [mean±SD]; P<.01) than in the S group (68.0±14.7). The time necessary for a half-maximal change was also significantly longer in the T group than in the S group for both Hb (22.0±7.5 and 13.5±4.0, respectively; P<.05) and cyt.aa₃ (23.9±5.7 and 11.6±4.3; P<.01). After recirculation for 7 days, all gerbils in the S group were found to have neuronal death in the hippocampus, while those in the T group did not.

Conclusions The present study indicated that mild ischemic stress can induce improvement in oxygen metabolism during subsequent ischemia, which might be causally related to the phenomenon known as "ischemic tolerance," in which a protective effect toward ischemic/postischemic injury is induced by earlier mild ischemic pretreatment.

Key Words: hemoglobin • immunohistochemistry • near-infrared spectroscopy • neuroprotection • oxygen • gerbils

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