Protective effects of brief intra- and delayed postischemic hypothermia in a transient focal ischemia model in the neonatal rat

Abstract

Hypothermia provides neuroprotection in virtually all animal models of ischemia, including adult stroke models and the neonatal hypoxic–ischemic (HI) model. In these studies, brief periods of hypothermia are examined in a neonatal model employing transient focal ischemia in a 7-day-old rat pup. Pups underwent permanent middle cerebral artery (MCA) occlusion coupled with a temporary (1 h) occlusion of the ipsilateral common carotid artery (CCA). This study included five treatment groups: (1) normothermic (Normo)—brain temperature was maintained at 37 °C; (2) intraischemic hypothermia (IntraH)—28 °C during the 1-h ischemic period only; (3) postischemic hypothermia (PostH)—28 °C for the second hour of reperfusion only; (4) late-onset postischemic hypothermia (LPostH) cooled to 28 °C for the fifth and sixth hours of reperfusion only; and (5) Shams. After various times (3 days–6 weeks), the lesion was assessed using 2,3,5-triphenyltetrazolium chloride (TTC) or hematoxylin and eosin (H&E) stains. Intraischemic hypothermia resulted in significant protection in terms of survival, lesion size, and histology. Postischemic hypothermia was not effective in reducing lesion size early after ischemia, but significantly reduced the eventual long-term damage (2–6 weeks). Late-onset postischemic hypothermia did not reduce infarct volume. Therefore, both intraischemic and postischemic hypothermia provided neuroprotection in the neonatal rat, but with different effects on the degenerative time course. While there were no observable differences in simple behaviors or growth, all hypothermic conditions significantly reduced mortality rates. While the protection resulting from intraischemic hypothermia is similar to what is observed in other models, the degree of long-term ischemic protection observed after 1 h of postischemic hypothermia was remarkable and distinct from what has been observed in other adult or neonatal models.