Intracerebroventricular prostaglandin administration increases the neural damage evoked by global hemispheric hypoxic ischemia.
This study was designed to determine if central (intracerebroventricular, i.c.v.) administration of prostaglandin E2 (PGE2, mediator of core temperature elevation following exogenous or endogenous pyrogen administration) worsens the neural damage of anesthetized rats to global hemispheric hypoxic-ischemia (GHHI) from damage seen in normothermic, i.c.v. saline control groups. The first study (no GHHI) showed that 10 or 50 ng PGE2 given i.c.v. to groups of anesthetized Long-Evans rats evoked dose-related increases in colonic (systemic core) temperature but no neural damage. In the second study anesthetized rats were given an i.c.v. injection of sterile saline or PGE2 plus GHHI (ligation of the right common carotid artery plus 35 min of 12% O2) at the peak of the temperature response. Thermal response indices (TRI, degrees C x min), determined from brain (temporalis muscle, ipsilateral and contralateral to ligation) and core (colonic) temperatures, showed significant increases in the 50-ng PGE2 group compared to the TRIs of the 10-ng PGE2 or saline control group. The 50-ng PGE2, GHHI group had a higher mortality rate and showed greater ipsilateral hemispheric neural damage than the saline-treated group given the same insult, especially due to increased damage to the cortex. The results show that i.c.v. PGE2 administration significantly increases the neural damage caused by GHHI, possibly due to the associated rise in core temperature.
Thornhill
J
J
Department of Physiology and Saskatchewan Stroke Research Center, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK S7N 5E5, Canada.
Smith
M
M
D000818:Animals; D002545:Brain Ischemia / Q000401:mortality / Q000473:pathology*; D015232:Dinoprostone / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005334:Fever / Q000139:chemically induced / Q000473:pathology; D002534:Hypoxia, Brain / Q000401:mortality / Q000473:pathology*; D007276:Injections, Intraventricular; D008297:Male; D009474:Neurons / Q000473:pathology*; D051381:Rats
D015232:Dinoprostone