Hippocampal Neurophysiologic Changes after Mild Traumatic Brain Injury and Potential Neuromodulation Treatment Approaches

Abstract

Traumatic brain injury (TBI) is the leading cause of death and disability in individuals below age 45, and five million Americans live with chronic disability as a result. Mild TBI (mTBI), defined as TBI in the absence of major imaging or histopathological defects, is responsible for a majority of cases. Despite the lack of overt morphological defects, victims of mTBI frequently suffer lasting cognitive deficits, memory difficulties, and behavioral disturbances. There is increasing evidence that cognitive and memory dysfunction is related to subtle physiological changes that occur in the hippocampus, and these impact both the phenotype of deficits observed and subsequent recovery. Therapeutic modulation of physiological activity by means of medications commonly used for other indications or brain stimulation may represent novel treatment approaches. This review summarizes the present body of knowledge regarding neurophysiologic changes that occur in the hippocampus after mTBI, as well as potential targets for therapeutic modulation of neurologic activity.

Function and Dysfunction of Adult Hippocampal Neurogenesis in Regeneration and Disease

“…30 The hippocampus is the most frequently affected site that contributes to many of the cognitive deficits found in patients. 31 Hippocampal neurogenesis is thought to partially mitigate this decline. Using rodent models, increases in proliferation and new neuron production occur as early as 2 days after injury.…”

Longitudinal, Multiparametric MRI Assessment of repetitive mild TBI in rats

“…Similar to human concussion, the present study found a marked decrease in CBF in ipsilateral gray matter (injury site) (IGM) of the brain. The reduced AD, increased MD in white matter, increased Glu and lactate are considered potential biomarkers for repetitive/ mTBI, [11,39,40]. The MRI based microstructural, metabolic and blood perfusion alterations are corroborated by immunohistological findings in repetitive mTBI studies in animals [41] and humans [42].…”

“…In the last few decades clinical, and preclinical research has identified potential neuroimaging biomarkers for repetitive/ mTBI [39,40], but until now an objective diagnostic test is not available due to immense heterogeneity of symptoms and/or inability to probe subtle metabolic, microstructural and pathophysiological alterations with traditional neuroimaging techniques. Early detection to probe metabolic, microstructural and pathophysiological alterations after repetitive/mTBI cases are crucial for treatment intervention and management.…”

Traumatic brain injury and methamphetamine: A double-hit neurological insult

“…The midbrain, which includes the VTA, represents another critical site of injury that sustains a decrease in white matter integrity post-TBI [42]. In addition, the hippocampus is one more highly vulnerable structural post brain trauma, with neurophysiological changes occurring weeks to months after TBI (see reviews [43,44]).…”