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NEUROSURGICAL ANESTHESIA

The Time Course of Acquisition of Ischemic Tolerance and Induction of Heat Shock Protein 70 after a Brief Period of Ischemia in the Spinal Cord in Rabbits

Department of Anesthesiology-Resuscitology, Yamaguchi University School of Medicine, Ube, Japan

Address correspondence and reprint requests to Mishiya Matsumoto, MD, Department of Anesthesiology-Resuscitology, Yamaguchi University School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan.

We examined the time course of development of ischemic tolerance in the spinal cord and sought its mechanism exploring the expression of heat shock protein 70 (HSP70). Spinal cord ischemia was produced in rabbits by occlusion of the abdominal aorta. In Experiment 1, neurologic and histopathologic outcome was evaluated 48 h after prolonged ischemia (20 min) that was given 2 days, 4 days, or 7 days after a short period of ischemia (ischemic pretreatment) sufficient to abolish postsynaptic component of spinal cord evoked potentials. Control animals were given prolonged ischemia 4 days after sham operation. In Experiment 2, HSP70 expression in motor neurons after pretreatment without exposure to prolonged ischemia was examined by immunohistochemical staining. Ischemic pretreatment 4 days (but not 2 days or 7 days) before 20 min ischemia exhibited protective effects against spinal cord injury. In the cytoplasm, HSP70 immunoreactivity was mildly increased after 2, 4, and 7 days of ischemic pretreatment. However, the incidence of nuclear HSP70 immunoreactivity 2 days, 4 days, and 7 days after ischemic pretreatment was 2 of 6 animals, 4 of 6 animals, and 1 of 6 animals, respectively (none in the control group). These results suggest that ischemic tolerance is apparent 4 days after ischemic pretreatment and that HSP70 immunoreactivity in the nucleus may provide some insight into the mechanisms of ischemic tolerance in the spinal cord.

Implications: Ischemic tolerance in the spinal cord is induced in 4 days, not yet induced in 2 days but gone by 7 days, after ischemic pretreatment. The amount of heat shock protein 70 (HSP70) in the cytoplasm does not explain this temporal profile, but HSP70 in the nucleus might play a role in the acquisition of ischemic tolerance.

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