Neuroprotection Trials in Traumatic Brain Injury

Abstract

Traumatic brain injury (TBI) is a significant cause of mortality and morbidity worldwide. Current treatment of acute TBI includes surgical intervention when needed, followed by supportive critical care such as optimizing cerebral perfusion, preventing pyrexia, and treating raised intracranial pressure. While effective in managing the primary injury to the brain and skull, these treatment modalities do not address the complex secondary cascades that occur at a cellular level following initial injury and greatly affect the ultimate neurologic outcome. These secondary processes involve changes in ionic flux, disruption of cellular function, derangement of blood flow and the blood-brain barrier, and elevated levels of free radicals. Over the past few decades, numerous pharmacologic agents and modalities have been investigated in an attempt to interrupt these secondary processes. No neuroprotective agents currently exist that have been proven to improve neurologic outcome following TBI. However, these trials have contributed significantly to the understanding of the clinical sequelae of TBI and to improvements in the quality of care for TBI. With the experience and insights that have been accrued with the trials to date, we will be able to optimize future trial designs and refine established neurologic endpoints to better identify new therapeutic agents and further improve neurologic outcomes from this often devastating condition.

Pathophysiology and Treatment of Memory Dysfunction After Traumatic Brain Injury

“…have not been translated into successful phase 3 clinical trials. The reasons for the failure to translate bench research to bedside clinical practice are multi-fold and a recent review authored by Chakraborty et al 2016 analyzes in detail potential different causes of this failure [123][123]. However, even with unsuccessful clinical trial results, we believe that some of those therapies can be useful in TBI treatment if they would be designed to guide the pathophysiology.…”

The use of antioxidants in the treatment of traumatic brain injury

“…These conditions contribute to the cascade of events that occurs following the initial impact and to the pathophysiologic, neurobehavioural and histopathological changes (Chakraborty et al . ).…”

Neuroimmunology of Traumatic Brain Injury: Time for a Paradigm Shift

“…No single model can fully recapitulate all types of primary and secondary damage observed following human TBI, as well as the complex diversity of injury mechanisms and other factors that contribute to outcome in a given individual (Saatman et al, 2008). Inadequate modeling of TBI may be one reason why therapies that showed promise in preclinical studies have failed in clinical trials (Chakraborty et al, 2016; Hawryluk and Bullock, 2016; Marklund et al, 2006; Simon et al, 2017), as diverse pathoanatomic injury subtypes make it challenging to stratify patients in clinical trials (Margulies et al, 2009) and devise effective therapies.…”