Rethinking Neuroprotection in Severe Traumatic Brain Injury: Toward Bedside Neuroprotection

Abstract

Neuroprotection after traumatic brain injury (TBI) is an important goal pursued strenuously in the last 30 years. The acute cerebral injury triggers a cascade of biochemical events that may worsen the integrity, function, and connectivity of the brain cells and decrease the chance of functional recovery. A number of molecules acting against this deleterious cascade have been tested in the experimental setting, often with preliminary encouraging results. Unfortunately, clinical trials using those candidate neuroprotectants molecules have consistently produced disappointing results, highlighting the necessity of improving the research standards. Despite repeated failures in pharmacological neuroprotection, TBI treatment in neurointensive care units has achieved outcome improvement. It is likely that intensive treatment has contributed to this progress offering a different kind of neuroprotection, based on a careful prevention and limitations of intracranial and systemic threats. The natural course of acute brain damage, in fact, is often complicated by additional adverse events, like the development of intracranial hypertension, brain hypoxia, or hypoperfusion. All these events may lead to additional brain damage and worsen outcome. An approach designed for early identification and prompt correction of insults may, therefore, limit brain damage and improve results.

Efficacy and safety of erythropoietin for traumatic brain injury

“…In laboratory studies, EPO can be administered as early as 5 minutes after injury [35], while this short time to intervention is not always possible in the clinical setting. However, the dose and timing of EPO injections varied greatly across RCTs in our study, and the current evidence is not strong enough to draw the conclusion that early intervention delivers better prognosis [36].…”

Targeted temperature management in patients with intracerebral haemorrhage, subarachnoid haemorrhage, or acute ischaemic stroke: consensus recommendations

“…3 All panel members accepted that poor outcomes are associated with neurogenic fever in these patients, given the weight of published evidence, for example, by Scaravilli and colleagues 6 and Kramer and colleagues 9 on SAH, Leira and colleagues 10 on ICH, and Rincon and colleagues 3 and Greer and colleagues 4 on all strokes and TBI. Fever can increase the brain's metabolic demand, exacerbating ischaemic injury and leading to cerebral vessel vasodilation, ultimately worsening the intracranial pressure (ICP) 13 ; therefore, it should be avoided or treated.…”

Virtual Reality for Traumatic Brain Injury

“…The search for neuroprotective therapies for severe TBI has been extensive but unfruitful over the last few decades, testified by more than 30 failed clinical trials, and we still have no specific neuroprotective therapy, that is, effective in clinical TBI. The burden of mortality and residual disability calls for new approaches to promote recovery of function of TBI patients in the acute and chronic phase ( 2 , 3 ).…”