Post-insult Ibuprofen Treatment Attenuates Damage to the Serotonergic System After Hypoxia-Ischemia in the Immature Rat Brain

Cerebral hypoxia-ischemia produces major alterations in energy metabolism and glucose utilization in brain. The facilitative glucose transporter proteins mediate the transport of glucose across the blood–brain barrier (BBB) (55 kDa GLUT1) and into the neurons and glia (GLUT3 and 45 kDa GLUT1). Glucose uptake and utilization are low in the immature rat brain, as are the levels of the glucose transporter proteins. This study investigated the effect of cerebral hypoxia-ischemia in a model of unilateral brain damage on the expression of GLUT 1 and GLUT3 in the ipsilateral (damaged, hypoxic-ischemic) and contralateral (undamaged, hypoxic) hemispheres of perinatal rat brain. Early in the recovery period, both hemispheres exhibited increased expression of BBB GLUT1 and GLUT3, consistent with increased glucose transport and utilization. Further into recovery, BBB GLUT1 increased and neuronal GLUT3 decreased in the damaged hemisphere only, commensurate with neuronal loss.

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Hypoxia—Ischemia Induces a Rapid Elevation of Ubiquitin Conjugate Levels and Ubiquitin Immunoreactivity in the Immature Rat Brain

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/00004647-199804000-00005 ◽

1998 ◽

Vol 18 (4) ◽

pp. 376-385 ◽

Cited By ~ 24

Author(s):

Susan J. Vannucci ◽

Rosemary Mummery ◽

Richard B. Hawkes ◽

Christopher C. Rider ◽

Philip W. Beesley

Keyword(s):

Rat Brain ◽

Control Level ◽

Artery Ligation ◽

Western Blots ◽

Immature Rat ◽

Carotid Artery Ligation ◽

Hypoxia Ischemia ◽

The Right ◽

Ubiquitin Conjugate ◽

Postnatal Rats

Postnatal rats at 7 and 21 days of age were subjected to unilateral hypoxia—ischemia (H/I) by right carotid artery ligation followed by 1.5 to 2 hours of hypoxia (8% oxygen). Brains were frozen at specific intervals of recovery from 0 to 24 hours. Western blots of samples of right and left forebrain were immunodeveloped with a monoclonal antibody specific for ubiquitin, RHUb 1. An elevation of ubiquitin conjugate levels in the right compared with the left forebrain of 7-day-old animals was detectable immediately following H/I and increased by close to 60% of control level within 1 hour of recovery. The conjugate immunoreactivity remained at this level for 6 hours but had declined to control levels by 24 hours of recovery. No such increase was observed in response to hypoxia alone. Similar changes were observed in samples from the 21-day-old rat brain. However, the elevation of ubiquitin conjugate levels was of slower onset and persisted longer than observed for the 7-day-old animals. Immunocytochemical studies of brain fixed by immersion in formaldehyde/acetone/methanol showed that ubiquitin-like immunoreactivity was increased in the right, but not left, cerebral cortex and hippocampus of animals subjected to H/I. The data suggest that elevated ubiquitination may represent a neuroprotective response to H/I.

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