Emerging treatments for traumatic brain injury

Abstract

Background This review summarizes promising approaches for the treatment of traumatic brain injury (TBI), which are either in preclinical or clinical trials. Objective The pathophysiology underlying neurological deficits after TBI is described. An overview of select therapies for TBI with neuroprotective and neurorestorative effects is presented. Methods A literature review of pre-clinical TBI studies and clinical TBI trials related to neuroprotective and neurorestorative therapeutic approaches is provided. Results/conclusion Nearly all phase II/III clinical trials in neuroprotection have failed to show any consistent improvement in outcome for TBI patients. The next decade will witness an increasing number of clinical trials which seek to translate preclinical research discoveries to the clinic. Promising drug- or cell-based therapeutic approaches include erythropoietin and its carbamylated form, statins, bone marrow stromal cells, stem cells singularly or in combination or with biomaterials to reduce brain injury via neuroprotection and promote brain remodeling via angiogenesis, neurogenesis, and synaptogenesis with a final goal to improve functional outcome of TBI patients. In addition, enriched environment and voluntary physical exercise show promise in promoting functional outcome after TBI, and should be evaluated alone or in combination with other treatments as therapeutic approaches for TBI.

Diffusion-Derived Magnetic Resonance Imaging Measures of Longitudinal Microstructural Remodeling Induced by Marrow Stromal Cell Therapy after Traumatic Brain Injury

“…Instead of a single unique location, however, ameliorative structural change occurs in multiple sites in the brain after TBI. 9,26,60 Supporting this multi-site cerebral remodeling post-TBI, our data demonstrate that entropy, not FA, identifies structural plasticity within tissue regions with crossing fibers (Fig. 4), in addition to the narrow boundary region consisting of highly parallel fibers (Fig.…”

“…[5][6][7] However, recent investigations show that cell transplantation, which amplifies endogenous regenerative and restorative processes, has potential as a therapeutic strategy to attenuate devastating secondary pathological processes and meanwhile, to enhance brain plasticity. [8][9][10] As the key mechanism of damage, axonal injury is directly associated with neurobehavioral outcome, 11,12 whereas axonal remodeling, an adaptive brain response to trauma, which compensates for loss of function and could be promoted by cell engraftment, [13][14][15] has received increasing attention. These structural alterations within the injured brain can be revealed by magnetic resonance imaging (MRI), especially diffusion measurements.…”

Midbrain Raphe Stimulation Improves Behavioral and Anatomical Recovery from Fluid-Percussion Brain Injury

“…For example, some treatments attempt to augment axonal sprouting, remyelination, or neurogenesis in zones that contain progenitor cells. [3][4][5][6] Alternatively, the suppression of secondary detrimental events can be attempted; these include toxicity from excess glutamate, production of reactive oxygen species, inhibitory effects on fiber growth from the breakdown products of myelin, inflammatory responses, apoptosis, and glial scarring. 7 Not all endogenous reactions, however, are unequivocally beneficial or harmful.…”

Brain Plasticity Following Ischemia: Effect of Estrogen and Other Cerebroprotective Drugs

“…Angiogenesis is related to hypoxia and results in new capillaries from the pre-existing vessels, whereas arteriogenesis is induced most importantly by increased shear stress that results in newly formed blood vessels (Heil and Sharper, 2004;Heil et al, 2006;Schierling et al, 2009;Xiong et al, 2010); however, the differences in the cause and the result is usually are not this clear cut. Angiogenesis has a major role in brain regeneration after ischemia as increased blood supply directly enhances cell survival and regenerative processes (Font et al, 2010).…”