Abstract
BackgroundBrain edema is a significant challenge facing clinicians managing severe traumatic brain injury (TBI) in the acute period. If edema reaches a critical point, it leads to runaway intracranial hypertension that, in turn, leads to severe morbidity or death if left untreated. Clinical data on the efficacy of standard interventions is mixed. The goal of this study was to validate a novel therapeutic strategy for reducing post-traumatic brain edema in a mouse model. Prior in vitro work reported that the brain swells due to coupled electrostatic and osmotic forces generated by large, negatively charged, immobile molecules in the matrix that comprises brain tissue. Chondroitinase ABC (ChABC) digests chondroitin sulfate proteoglycan, a molecule that contributes to this negative charge. Therefore, we administered ChABC by intracerebroventricular (ICV) injection after controlled cortical impact TBI in the mouse and measured associated changes in edema.ResultsAlmost half of the edema induced by injury was eliminated by ChABC treatment.ConclusionsICV administration of ChABC may be a novel and effective method of treating post-traumatic brain edema in the acute period.
Highlights
Brain edema is a significant challenge facing clinicians managing severe traumatic brain injury (TBI) in the acute period
Reported values for edema in this injury model range from 1 to 3 % [21,22,23,24]. These values are small because controlled cortical impact induces a focal lesion so only a small domain in the tissue sample tested has increased water content
Smaller tissue samples excised at the lesion site in a controlled cortical impact model showed a greater change in water content [25]
Summary
Brain edema is a significant challenge facing clinicians managing severe traumatic brain injury (TBI) in the acute period. Traumatic brain injury (TBI) is responsible for 36 % of deaths among children 1–14 years old and is a leading cause of death among those in the 15–45 year agebracket [1]. It is responsible for 40 % of combat deaths among US military personnel [2]. Brain edema within the rigid confines of the skull elevates intracranial pressure (ICP) [3] and, in severe cases, leads to herniation of the brain tissue which is frequently fatal [4].
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