Mild hypothermia neuroprotective effects

The neuroprotective properties of mild hypothermia have been demonstrated in numerous experimental animal models. Research in this area has been conducted for many years, yet the mechanisms of cerebral protection by mild hypothermia remain unclear and continue to be the subject of intense investigation. The neuroprotective effects of mild hypothermia have been attributed to alterations in metabolic rate (24), neurotransmitter release (25-27), activity of protein kinases (28), resynthesis of cellular repair proteins (29), cerebral blood flow (30), preservation of the blood-brain barrier (BBB) (31), attenuation of inflammatory processes (32,33), and decreases in free radical production (34). Although these may all be components of a complex cascade leading to neurologic injury, it has become increasingly clear that the primary mechanism of action of hypothermia may be different at various temperatures as well as under different ischemic and traumatic conditions. 

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. 

When mild hypothermia was first shown to be beneficial, the assumption was that a substantial portion of its neuroprotective effect stemmed from a reduction in cerebral metabolism. However, studies on cerebral metabolic rate (CMR) made it clear that the degree of neuro-pathological injury following ischemia with mild hypothermic treatment did not correlate with the magnitude of metabolic depression observed (42). A reduction in temperature from 37°C to 34°C produces a 15-20% reduction in cerebral metabolism (approx 5-7% per °C), which is far less than the 50% decrease seen with electroencephalogram (EEG) silence. Furthermore, reductions in metabolism produced by anesthetics vs hypothermia are not equally neuroprotective (43). Thus, hypothermic neuroprotection cannot be explained by alterations in metabolic rate alone. 

Deliberate mild hypothermia has been shown to be an extremely effective means of neuroprotection during periods of ischemia in experimental models. Intraoperative mild hypothermia has become a standard of practice for many neurosurgeons performing complex intracranial procedures. Recent findings of neurologic benefit in prospective, randomized, controlled clinical studies of cardiac arrest patients are encouraging, but more research is required to confirm and extend these positive results to other patients with stroke and traumatic insults. Further investigation must be completed to establish the optimal time and duration when treatment should be instituted to offer the optimal protection for patients with acute ischemic and traumatic injuries. 

Resurgence of Hypothermia as a Treatment for Brain Injury. The Effects of Hypothermia and Hyperthermia in Global Cerebral Ischemia. Mild Hypothermia in Experimental Focal Cerebral Ischemia. Hypothermic Protection in Traumatic Brain Injury. Postischemic Hypothermia Provides Long-Term Neuroprotection in Rodents. Combination Therapy With Hypothermia and Pharmaceuticals for the T reatment of Acute Cerebral Ischemia. Intraoperative and Intensive Care Management of the Patient Undergoing Mild Hypothermia. Management of Traumatic Brain Injury With Moderate Hypothermia. Hypothermia Clinical Experience in Stroke Patients. Hypothermia Therapy Future Directions in Research and Clinical Practice. Index. 

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