Identification of Compounds to Induce Suspended Animation or Hypometabolism

Suspended or reduced animation of brain and heart tissues during battle-field injury or during critical-care trauma may result in a significant protection from organ damage, systemic shock, and pain and may provide a prolonged window of opportunity fortreatment. Suspended or reduced animation of brain and heart tissues may be achieved by a complete suspension or suppression of neural activities (hypometabolism) in the CNS. The primary objective of this Phase I feasibility research is to identifyhypometabolic effects of serum and brain tissue extracts from hibernating Arctic ground squirrels (AGS) on human brain neurons and glia. Potential effects of AGS extracts on several different aspects of neuronal activity/metabolism will be quantified inorder to establish robust assays for high throughput screening of small molecule libraries as well as for purification of hibernation factor(s). Identification of the agents with hypometabolic efficacy on human brain cells in vitro would then lead tofurther testing of those agents for potential therapeutic values in animal models of various human disesaes, including traumatic brain injury, spinal injury, and ischemic stroke. Hypometabolic factors or small molecules with hypometabolic effects may beeffective in minimizing tissue damage during/after stroke, traumatic brain injury, spinal injury, and major surgeries. Effective agents will be further developed as commercial therapeutics for these and other indications. They may also have immediateapplication to sustaining viability and thus enhancing commercial potential of Neuralstem's cell lines during transport.