Journal of neurotrauma
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Journal of neurotrauma · Mar 2014
Serial Atlas-based DTI Study of Uncomplicated Mild Traumatic Brain Injury in Adults.
Abstract In this report, we applied diffusion tensor imaging (DTI) methods in 36 patients with uncomplicated mild traumatic brain injury (mTBI) and a comparison group of 37 participants with orthopedic injury. Our aim was to characterize regional and global macro- and microstructural attributes of white matter (WM), gray matter (GM), in addition to volume and diffusivity of cerebrospinal fluid (CSF) to identify and differentiate patterns of acute and short-term recovery. Given that previous DTI reports on mTBI in adults using a region-of-interest approach implicated the corona radiata (CR), corpus callosum, and hippocampus, we analyzed and quantified DTI metrics of these regions using atlas-based methods. ⋯ CR radial diffusivity was found to be elevated in the between-group comparison at baseline (mTBI1 vs. OC1), but did not differ in the within-group comparison (mTBI1 vs. mTBI2; N=19), suggesting the possible resolution of edema. Our analysis of the cross-sectional and follow-up data, which is uncorrected for multiple comparisons, demonstrates dissociation between volumetric (macrostructural) and tissue integrity (microstructural) attributes and shows the potential utility of DTI to capture transient edema in the CR.
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Journal of neurotrauma · Mar 2014
Neuroprotective efficacy of a proneurogenic compound after traumatic brain injury.
Traumatic brain injury (TBI) is characterized by histopathological damage and long-term sensorimotor and cognitive dysfunction. Recent studies have reported the discovery of the P7C3 class of aminopropyl carbazole agents with potent neuroprotective properties for both newborn neural precursor cells in the adult hippocampus and mature neurons in other regions of the central nervous system. This study tested, for the first time, whether the highly active P7C3-A20 compound would be neuroprotective, promote hippocampal neurogenesis, and improve functional outcomes after experimental TBI. ⋯ Five weeks after TBI, animals treated with P7C3-A20 showed significantly increased BrdU/NeuN double-labeled neurons and improved cognitive function in the Morris water maze, compared to TBI-control animals. These results suggest that P7C3-A20 is neuroprotective and promotes endogenous reparative strategies after TBI. We propose that the chemical scaffold represented by P7C3-A20 provides a basis for optimizing and advancing new pharmacological agents for protecting patients against the early and chronic consequences of TBI.
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Journal of neurotrauma · Mar 2014
The Cysteine Protease Cathepsin B is a Key Drug Target and Cysteine Protease Inhibitors are Potential Therapeutics for Traumatic Brain Injury.
There are currently no effective therapeutic agents for traumatic brain injury (TBI), but drug treatments for TBI can be developed by validation of new drug targets and demonstration that compounds directed to such targets are efficacious in TBI animal models using a clinically relevant route of drug administration. The cysteine protease, cathepsin B, has been implicated in mediating TBI, but it has not been validated by gene knockout (KO) studies. Therefore, this investigation evaluated mice with deletion of the cathepsin B gene receiving controlled cortical impact TBI trauma. ⋯ E64d treatment was effective even when administered 8 h after injury, indicating a clinically plausible time period for acute therapeutic intervention. These data demonstrate that a cysteine protease inhibitor can be orally efficacious in a TBI animal model when administered at a clinically relevant time point post-trauma, and that E64d-mediated improvement of TBI is primarily the result of inhibition of cathepsin B activity. These results validate cathepsin B as a new TBI therapeutic target.
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Journal of neurotrauma · Mar 2014
Neuroimaging, Behavioral, and Psychological Sequelae of Repetitive Combined Blast/Impact Mild Traumatic Brain Injury in Iraq and Afghanistan War Veterans.
Abstract Whether persisting cognitive complaints and postconcussive symptoms (PCS) reported by Iraq and Afghanistan war veterans with blast- and/or combined blast/impact-related mild traumatic brain injuries (mTBIs) are associated with enduring structural and/or functional brain abnormalities versus comorbid depression or posttraumatic stress disorder (PTSD) remains unclear. We sought to characterize relationships among these variables in a convenience sample of Iraq and Afghanistan-deployed veterans with (n=34) and without (n=18) a history of one or more combined blast/impact-related mTBIs. Participants underwent magnetic resonance imaging of fractional anisotropy (FA) and macromolecular proton fraction (MPF) to assess brain white matter (WM) integrity; [(18)F]-fluorodeoxyglucose positron emission tomography imaging of cerebral glucose metabolism (CMRglu); structured clinical assessments of blast exposure, psychiatric diagnoses, and PTSD symptoms; neurologic evaluations; and self-report scales of PCS, combat exposure, depression, sleep quality, and alcohol use. ⋯ Neuroimaging metrics did not differ between participants with versus without PTSD. Iraq and Afghanistan veterans with one or more blast-related mTBIs exhibit abnormalities of brain WM structural integrity and macromolecular organization and CMRglu that are not related to comorbid PTSD. These findings are congruent with recent neuropathological evidence of chronic brain injury in this cohort of veterans.
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Journal of neurotrauma · Mar 2014
Reversal of established traumatic brain injury-induced anxiety-like behavior in rats following delayed, post-injury neuroimmune suppression.
Abstract Traumatic brain injury (TBI) increases the risk of neuropsychiatric disorders, particularly anxiety disorders. Yet, there are presently no therapeutic interventions to prevent the development of post-traumatic anxiety or effective treatments once it has developed. This is because, in large part, of a lack of understanding of the underlying pathophysiology. ⋯ We examined the efficacy of an anti-inflammatory treatment in decreasing anxiety-like behavior and reactive gliosis when introduced at 1 month after injury. Delayed treatment substantially reduced established LFPI-induced freezing behavior and reactive gliosis in brain regions associated with anxiety and continued neuroprotective effects were evidenced 6 months post-treatment. These results support the conclusion that neuroinflammation may be involved in the development and maintenance of anxiety-like behaviors after TBI.