Intracerebroventricular prostaglandin administration increases the neural damage evoked by global hemispheric hypoxic ischemia

Abstract

This study was designed to determine if central (intracerebroventricular, i.c.v.) administration of prostaglandin E 2 (PGE 2, 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 PGE 2 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 PGE 2 plus GHHI (ligation of the right common carotid artery plus 35 min of 12% O 2) at the peak of the temperature response. Thermal response indices (TRI, °C×min), determined from brain (temporalis muscle, ipsilateral and contralateral to ligation) and core (colonic) temperatures, showed significant increases in the 50-ng PGE 2 group compared to the TRIs of the 10-ng PGE 2 or saline control group. The 50-ng PGE 2, 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. PGE 2 administration significantly increases the neural damage caused by GHHI, possibly due to the associated rise in core temperature.