Abstract 2058
Neuroprotective Strategies for Hypoxic-Ischemic Encephalopathy Platform, Sunday, 5/2
Introduction: Intra-ischemic hypothermia of only 3-6°C is accepted as a potent neuroprotective agent in both adult and newborn animal models. From a clinical perspective however, post - ischemic hypothermia would provide a far more practical and efficient method of brain protection. In previous studies we had found that brief post-ischemic hypothermia for 3 hrs. did not reduce brain damage in a model of severe perinatal HI (Ped. Res. 1993;34:525-529). Brief periods of post-ischemic hypothermia have been show, however, to delay though not completely ameliorate the brain damaging effects of a "moderate" HI insult (Brain & Dev. 1997;19:326-338, Ped Res. 1998;43:325A). The purpose of the present study was to define the duration of variable degrees of hypothermia required to effect neuropathologic outcome following a "moderate" HI insult in the immature rat. Methods: Seven-day postnatal rats were anesthetized with halothane (4% induction: 1% maintenance) during which they underwent unilateral common carotid artery ligation. Following a 2 hr period of recovery with their Dams, the animals were placed in 500 ml glass jars and exposed to hypoxia in 8% oxygen/balance nitrogen for a period of 90 min. (moderate injury), via inlet/outlet portals. Thermoregulation during HI was maintained by placing the jars in waterbaths held at 37°C. Animals were then recovered for varying periods of either 3, 6, 12, or 24 hrs in thermo-controlled waterbaths at 28, 31, 34, or 37°C or with their Dams (nesting temp - 34°C). In separate groups of animals, core (rectal) temperature was monitored continuously for up to 24 hrs in order to determine the effect of environmental temperature on true body and brain temp. Given that immature rat pups will become hypoglycemic and hyperketonemic (which has been also shown to be neuroprotective -Ped Res., 1993; 31:138-142) if away from their Dams for this length of time, the rat pups were supplemented with continuous subcutaneous infusions of 15% glucose. Subsequently the animals were returned to their Dams, and nurtured to 30 days of age, at which time brains were examined neuropathologically.
