Neuroprotective strategies in nature - Novel clues for the treatment of stroke and trauma

A myriad of mediators and mechanisms have been implicated as participants i n the propagation of damage following stroke and traumatic brain injury. Ef fective neuroprotection for these conditions, however, remains elusive at t he clinical level. Adaptive strategies of animal species that naturally end ure severe reductions in nutrient perfusion to the brain may reveal new mec hanisms of homeostatic control and tolerance with potential clinical useful ness. A variety of species appear to qualify as models of tolerance, includ ing those that are anoxia tolerant and species capable of hibernation. Mamm alian hibernation represents a state in which global physiologic functions are virtually arrested and delivery of glucose and oxygen is minimal, yet h omeostatic control is maintained. The profound reduction of cerebral perfus ion in hibernation would lead to rapid autolysis of brain tissue in an unpr otected stare, but has no adverse effects on hibernators and brain damage d oes not occur. In fact, even hippocampal slices from hibernating ground squ irrels and cerebellar slices from anoxia-tolerant turtles show increased to lerance to a superimposed insult of aglycemia and hypoxia. Surprisingly, th e cellular mechanisms and signals that trigger and maintain these adaptatio ns remain unknown. Main targets of current investigations are the regulatio n of the controlled metabolic suppression in hibernation and the mechanisms of preservation of cell structure and membrane functions and integrity des pite reduced energy supplies. The possibility of induction of a similar tol erant state in humans by activation of natural mechanisms of reversible cel lular arrest employed by hibernators and other tolerant states would have p otentially far-reaching clinical implications. This includes prevention of secondary brain damage following brain trauma and ischemia as well as induc tion of a state of neuroprotection under conditions of anticipated reductio n in cerebral perfusion pressure, such as arterial vasospasm after subarach noid hemorrhage, or during surgical procedures that require temporary circu latory arrest. Induction of a resistant state could also provide additional time until specialized treatment to re-open occluded blood Vessels in stro ke patients could be administered.