Reversing coma by senolytics and stem cells: the future is now.

Global cerebral ischemia (GCI) caused by impaired blood flow to the brain-typically following cardiac arrest or traumatic brain injury-remains the leading cause of coma and disorders of consciousness (DoC). In certain cases, the recovery potential of these patients may be significantly underestimated. Historically, these patients were often given little hope for recovery, particularly due to longstanding, outdated dogmatic views such as the presumed absence of adult neurogenesis. However, recent advances suggest that we have been discounting ongoing mental activity in comatose patients; additionally, emerging evidence shows that some patients in coma retain the capacity for communication through non-traditional means. The authors believe that the exponential progress in the field and the increase of our understanding in neurophysiology, regenerative medicine, and the biology of cellular senescence now makes it plausible to initiate experimental interventions that offer a realistic chance of reversing disorders of consciousness. The proposed strategy involves a two-step therapeutic paradigm: first the use of senolytic approaches to remove senescent cells and reduce neuroinflammatory burden ("clear the debris"); second, stimulation of neural regeneration through stem cell therapies, combined with electrophysiologic/pharmacological stimulation. The authors propose, that this integrated approach offers a novel treatment paradigm to address the previously insurmountable challenge of coma reversal.