Abstract
Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. In the last 30 years several neuroprotective agents, attenuating the downstream molecular and cellular damaging events triggered by TBI, have been extensively studied. Even though many drugs have shown promising results in the pre-clinical stage, all have failed in large clinical trials. Mesenchymal stromal cells (MSCs) may offer a promising new therapeutic intervention, with preclinical data showing protection of the injured brain. We selected three of the critical aspects identified as possible causes of clinical failure: the window of opportunity for drug administration, the double-edged contribution of mechanisms to damage and recovery, and the oft-neglected role of reparative mechanisms. For each aspect, we briefly summarized the limitations of previous trials and the potential advantages of a newer approach using MSCs.
Highlights
Traumatic brain injury (TBI) is the leading cause of mortality and morbidity across all ages in all countries
The relative positive or negative effects of inflammation in relation to time from injury are still far from certain, and a threat of neurodegeneration associated with late microglia inhibition has recently been reported in TBI subjects chronically treated with minocycline, an antibiotic that can inhibit microglia activation [45]
The analysis confirms Mesenchymal stromal cells (MSCs) efficacy when infused from 2 h up to 7 days, with no significant differences in effect sizes relative to the time from TBI to intervention
Summary
Traumatic brain injury (TBI) is the leading cause of mortality and morbidity across all ages in all countries. Treatment of TBI patients has not changed much in the last 20 years, consisting only in supportive therapy directed at prevention, early detection and treatment of second insults, since all pharmacological trials testing neuroprotective agents have failed [2,3,4,5]. This translational defeat may have several explanations, analyzed in numerous papers [6,7,8]. Many factors were identified at preclinical and clinical levels as area of improvement
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