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Byline: Xiao Y. Xia, Tomoaki Ikeda, Arturo Ota, Yi X. Xia, Hiroshi Sameshima, Tsuyomu Ikenoue, Kiyotaka Toshimori Keywords: Brain damage; developmental change; heat shock protein; hypoxia-ischemia; microtubule-associated protein 2; rat Abstract: Objective: This study was intended to investigate the temporal changes in heat shock protein 72 expression and microtubule-associated protein 2 disappearance in rat brain at 2 different ages after hypoxic-ischemic insult. Study Design: Both 5-day-old and 14-day-old Wistar rats were subjected to unilateral common carotid artery ligation and hypoxia in 8% oxygen for 2 hours at 33[degrees]C. Brain sections were examined sequentially for heat shock protein 72 expression at 0.5, 3, 6, 12, 24, 48, and 72 hours of recovery after hypoxia-ischemia and for microtubule-associated protein 2 disappearance at 0, 24, 48, and 72 hours of recovery and at 7 days of recovery after hypoxia-ischemia. Results of immunohistochemical staining for heat shock protein 72 and microtubule-associated protein 2 were used as markers for detection of early hypoxic-ischemic brain damage. Permanent neuronal damage was assessed with hematoxylin and eosin staining at 7 days after hypoxia. Results: In 5-day-old rats microtubule-associated protein 2 expression was lost as early as 0 hours after hypoxia-ischemia in the cerebral cortex and hippocampus, with a peak at 48 hours after which expression recovered. Expression of heat shock protein 72 was detected in the ligated hemisphere at 0.5 hours after hypoxia-ischemia and peaked at 6 to 24 hours of recovery. In 14-day-old rats microtubule-associated protein 2 was stained in the cortex at 0 hours after hypoxia-ischemia but gradually disappeared in the cerebral cortex and hippocampus after 24 hours of recovery. The expression of heat shock protein 72 was not detected by 6 hours of recovery in the cerebral cortex and by 3 to 12 hours of recovery in the hippocampus, but heat shock protein 72 was persistently expressed in the cortex and hippocampus after 48 hours of recovery. Neuronal damage was significantly less in 5-day-old rats than in 14-day-old rats. Conclusion: In 5-day-old rats hypoxia-ischemia causes earlier changes in heat shock protein 72 and microtubule-associated protein 2 immunostaining results and causes less severe brain damage than in 14-day-old rats. (Am J Obstet Gynecol 1999;180:1254-62.) Author Affiliation: Miyazaki, Japan From the Department of Obstetrics and Gynecology.sup.a and the First Department of Anatomy,.sup.b Miyazaki Medical College Article History: Received 3 June 1998; Revised 28 December 1998; Accepted 14 January 1999 Article Note: (footnote) [star] Reprint requests: Tsuyomu Ikenoue, MD, Department of Obstetrics and Gynecology, Miyazaki Medical College, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan., [star][star] 0002-9378/99 $8.00 + 0 6/1/97170

Byline: Arturo Ota, Tomoaki Ikeda, Tsuyomu Ikenoue, Kiyotaka Toshimori Keywords: Hypoxia-ischemia; newborn rat brain; heat shock protein-72; microtubule-associated protein-2 Abstract: Objective: Our purpose was to study the neuronal responses of heat shock protein-72 (a stress-inducible protein) and microtubule-associated protein-2 (a constitutive protein of the neuronal cytoskeleton) after hypoxia-ischemia and their relationship with permanent damage in the newborn rat brain. Study design: Seven-day-old rats were exposed to unilateral carotid artery ligation followed by 2 hours of hypoxia (8% oxygen/92% nitrogen) and then killed at time points ranging from 1 to 72 hours after injury. Brains were removed for immunohistochemical and routine staining. Results: Heat shock protein-72 appearance and microtubule-associated protein-2 disappearance occurred from 1 hour after injury, mainly in the dentate gyrus of the hippocampal formation and the cerebral cortex. Such alterations reached maximal levels at 24 hours for both proteins. Microtubule-associated protein-2 staining recovered in almost all parts of the brain. However, the hippocampal CA3 showed a delay in the responses for both proteins, and microtubule-associated protein-2 did not recover the response to immunostaining. Histologic evaluation at 72 hours after hypoxia by routine methods showed predominant damage in the hippocampal CA3. Conclusion: Our results show that delayed responses of heat shock protein-72 and microtubule-associated protein-2 are related to a high incidence of neuronal cell loss in the hippocampal CA3 region. Author Affiliation: Miyazaki, Japan Article History: Received 6 August 1996; Revised 6 March 1997; Accepted 16 April 1997 Article Note: (footnote) [star] From the Department of Obstetrics and Gynecologya and the First Department of Anatomy,b Miyazaki Medical College., [star][star] Reprint requests: Arturo Ota, MD, Department of Obstetrics and Gynecology, Miyazaki Medical College, 5200 Kihara, Kiyotake, Miyazaki 889-16, Japan., a 0002-9378/97 $5.00 + 0, aa 6/1/82776