Focal cerebral ischemia delayed hypothermia

The concept of neuroprotection relies on the fact that delayed neuronal injury occurs after ischemia, and each step along the ischemic cascade provides a target for therapeutic intervention. Thus, understanding the cellular and molecular mechanisms that underlie the development of neuronal and vascular injury is critical to optimize treatment. This chapter reviews experimental evidence from studies on focal cerebral ischemia and mild hypothermia, as well as the mechanisms involved in mild hypothermic neuroprotection. 

We recently carried out a study (40) to determine the effects of delaying induction of mild hypothermia after transient focal cerebral ischemia and to ascertain whether the neuroprotective effects of mild hypothermia induced during the ischemic period are sustained over... 

KaribeH.,ZarowG. J., GrahamS. H., and WeinsteinP.R. (1994) Mild intraischemic hypothermia reduces postischemic hyperperfusion, delayed postischemic hypoperfusion, blood-brain barrier disruption, brain edema, and neuronal damage volume after temporary focal cerebral ischemia in rats. J. Cereb. Blood Flow Metab. 14, 620-627. 

Kollmar R., Schabitz W. R., Heiland S., et al. (2002) Neuroprotective effect of delayed moderate hypothermia after focal cerebral ischemia an MRI study. Stroke 33, 1899-1904. 

KEY STUDIES OF DELAYED HYPOTHERMIA IN FOCAL CEREBRAL ISCHEMIA... 

Maier C. M., Sun G. H., Kunis D., Yenari M. A., and Steinberg G. K. (2001) Delayed induction and long-term effects of mild hypothermia in a focal model of transient cerebral ischemia neurological outcome and infarct size. J. Neurosurg. 94, 90-96. 

The mechanism of delayed neuronal injury following TBI includes apoptosis (63,64). Experimental data after cerebral hypoxic-ischemic injury indicate that moderate postinsult hypothermia (34°C) reduced the fraction of apoptotic cells but not cells undergoing necrosis (65). In another study, intraischemic hypothermia reduced the number of transferase dUTP nick-end labeling (TUNEL)-positive cells after transient focal ischemia (66). Thus, it will be important in future studies to determine whether hypothermia inhibits apoptotic neuronal cell death in models of TBI. 

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