Cerebral ischemia hypothermia

Markarian GZ, Lee JH, Stein DJ, Hong SC. Mild hypothermia therapeutic window after experimental cerebral ischemia. Neurosurgery 1996 38 542-550 [discussion 551]. 

From Hypothermia and Cerebral Ischemia Mechanisms and Clinical Applications... 

In 1987, however, a study by Busto et al. (5) showed that small decreases in brain temperature (as little as 2-5°C below normal brain temperature) conferred a marked protective effect against experimental global cerebral ischemia. This finding, as well as subsequent animal studies that modeled neurodegenerative diseases and CNS injury, led to a resurgence of interest in mild hypothermia as a method of cerebral protection. 

Chopp M., Knight R., Tidwell C. D., Helpern J. A., Brown E., and Welch K. M. (1989) The metabolic effects of mild hypothermia on global cerebral ischemia and recirculation in the cat comparison to normothermia and hyperthermia. J. Cereb. Blood Flow Metab. 9, 141-148. 

Maier C. M., Sun G. H., Cheng D., Yenari M. A., Chan P. H., and Steinberg G. K. (2002) Effects of mild hypothermia on superoxide anion production, superoxide dismutase expression, and activity following transient focal cerebral ischemia. Neurobiol. Dis. 11, 28 -2. 

Huh P. W., Belayev L., Zhao W., Koch S., Busto R., and Ginsberg M. D. (2000) Comparative neuroprotective efficacy of prolonged moderate intraischemic and postischemic hypothermia in focal cerebral ischemia. J. Neurosurg. 92,91-99. 

The Effects of Hypothermia and Hyperthermia in Global Cerebral Ischemia... 

From Hypothermia and Cerebral Ischemia Mechanisms and Clinical Applications Edited by C. M. Maier and G. K. Steinberg Humana Press Inc., Totowa, NJ... 

Connoly J. E., Boyd R. J., and Calvin J. W. (1962) The protective effect of hypothermia in cerebral ischemia experimental and clinical application by selective brain cooling in the human. Surgery 52, 15-24. 

Horn M., Schlote W., and Henrich H. A. (1991) Global cerebral ischemia and subsequent selective hypothermia. A neuiopathological andmorphometrical study on ischemic neuronal damage in cat. Acta Neuropathol. (Berl.) 81,443-449. 

Coimbra C. and Wieloch T. (1994) Moderate hypothermia mitigates neuronal damage in the rat brain when initiated several hours following transient cerebral ischemia. Acta Neuropathol. 87,325-331. 

Green E. J., Dietrich W. D., van Dijk F., et al. (1992) Protective effects of brain hypothermia on behavior and histopathology following global cerebral ischemia in rats. Brain Res. 580, 197-204. 

BlievichU. M Zomow M. H Choi K. T Stmat M. A., and ScheBerM. S. (1994) Effects of hypothermia or anesthetics on hippocampal glutamate and glycine concentrations after repeated transient global cerebral ischemia. Anesthesiology 80, 177-186. 

Boris-Moller F., Kamme F., and Wieloch T. (1998) The effect of hypothermia on the expression of neurotrophin mRNA in the hippocampus following transient cerebral ischemia in the rat. Brain Res. Mol. Brain Res. 63, 163-173. 

The mechanisms whereby brain cells die during ischemia are not fully understood. Experimental evidence points to a complex array of parallel hemodynamic, biochemical, and electrophysiological events that combine to produce neuronal damage. In experimental cerebral ischemia, the severity of this damage can be significantly reduced by treatment with mild hypothermia (2-5°C below normal brain temperature). 

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. 

Mild hypothermia has been shown to reduce neurological deficits if started before, during, or after cerebral ischemia, but few studies have examined functional outcome in detail after experimental cerebral ischemia with hypothermia (29-33). 

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... 

The main role of mild hypothermia against stroke may, perhaps, be to extend the therapeutic window of other treatment modalities. On the other hand, hypothermia is by far the most potent neuroprotectant available against experimental cerebral ischemia, and new technological advances are now facilitating its implementation in the clinical setting. Understanding the mechanisms by which mild hypothermia exerts its neuroprotective effects will allow us to optimize its use as a therapeutic strategy. 

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. 

Huang F. and Zhou L. (1998) Effect of mild hypothermia on the changes of cerebral blood flow, brain blood barrier and neuronal injuries following reperfusion of focal cerebral ischemia in rats. Chin. Med. J. (Engl.) Ill, 368-372. 

Kollmar R., Frietsch T., Georgiadis D., et al. (2002) Early effects of acid-base management during hypothermia on cerebral infarct volume, edema, and cerebral blood flow in acute focal cerebral ischemia in rats. Anesthesiology 97, 868-874. 

Huang F. P., Zhou L. F., and Yang G. Y. (1998) Effects of mild hypothermia on the release of regional glutamate and glycine during extended transient focal cerebral ischemia in rats. Neurochem. Res. 23,991-996. 

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. 

MoriK., Miyazaki M., IwaseH., and MaedaM. (2002) Temporal profile of changes in brain tissue extracellular space and extracellular ion (Na(+), K(+)) concentrations after cerebral ischemia and the effects of mild cerebral hypothermia. J. Neurotrauma 19, 1261-1270. 

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