Multifactorial neuroprotection: Does the brain have an answer

Massive research efforts to develop effective neuroprotective therapy against stroke until now produced unsatisfactory results. It has been suggested that monotherapeutic approaches may not be sufficient. Investigations over the last three decades convincingly demonstrated the existence of powerful endogenous protective mechanisms. One of the innate protective mechanisms includes several brain structures, which when activated render the brain tolerant to various damaging stimuli. The best studied today is the cerebellar fastigial nucleus, neurons of which when activated, initiate coordinated multifactorial response providing long lasting neuroprotection. Numerous protective mechanisms induced by fastigial nucleus stimulation and other conditioning maneuvers are shared. In this review we summarize current knowledge of the neurogenic neuroprotection system related to the cerebellar fastigial nucleus and its commonalities with other forms of conditioning. Unveiling the systemic neuroprotective mechanisms will allow development of therapeutic approaches targeted toward activation/amplification of innate protective multifactorial mechanisms.