Temperature Modulation in the Ischemic Maturation Phenomenon

Brief global cerebral ischemia can result in a marked loss of hippocampal CA1 neurons which is typically delayed for a 24- to 72-h period — delayed neuronal death (DND). While CA1 necrosis is substantially reduced by intraischemic cooling, the effectiveness of postischemic hypothermia is controversial as it is thought that protection may only be transient (i.e., slow maturation). Mongolian gerbils were subjected to a severe episode (3 or 5 min) of forebrain ischemia followed, in some, by either 12h or 24h of hypothermia (32°C) which was initiated at 1 h following ischemia. Behavioral (memory) and histological (CA1 counts) endpoints were assessed up to 6 months postischemia. Delayed postischemic hypothermia substantially and persistently reduced both CA1 loss (especially against 3-min ischemia) and associated behavioral abnormalities. However, the 12-h cooling period was significantly less protective than the 24-h duration. In addition, some CA1 necrosis in the 12- and 24-h-treated animals occurred much later than the classical time frame expected of DND. While protracted postischemic cooling is remarkably beneficial, the amount and perhaps nature of this depends upon the duration of ischemia and cooling as well as the survival time.