Journal of neurotrauma
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Polyamines spermine and spermidine are highly regulated, ubiquitous aliphatic cations that maintain DNA structure and function as immunomodulators and as antioxidants. Polyamine homeostasis is disrupted after brain injuries, with concomitant generation of toxic metabolites that may contribute to secondary injuries. To test the hypothesis of increased brain polyamine catabolism after traumatic brain injury (TBI), we determined changes in catabolic enzymes and polyamine levels in the rat brain after lateral controlled cortical impact TBI. ⋯ Interestingly, bilateral increases in cortical SSAT-ir neurons occurred at 72 h post-injury, whereas hippocampal changes occurred only ipsilaterally. Prolonged increases in brain polyamine catabolism are the likely cause of loss of homeostasis in this pathway. The potential for simple therapeutic interventions (e.g., polyamine supplementation or inhibition of polyamine oxidation) is an exciting implication of these studies.
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Journal of neurotrauma · Mar 2010
Vascular endothelial growth factor is involved in mediating increased de novo hippocampal neurogenesis in response to traumatic brain injury.
Stimulating the endogenous repair process after traumatic brain injury (TBI) can be an important approach in neuroregenerative medicine. Vascular endothelial growth factor (VEGF) is one of the molecules that can increase de novo hippocampal neurogenesis. Here, we tested whether VEGF signaling through Flk1 (VEGF receptor 2) is involved in the neurogenic process after experimental TBI. ⋯ We found that VEGF infusion significantly increased the number of BrdU+/Prox1+ new neurons, decreased the number of TUNEL+ cells, but did not change the number of BrdU+ newborn cells per se. Infusion with SU5416 caused no significant changes. Our results suggest that (a) VEGF is a part of the molecular signaling network that mediates de novo hippocampal neurogenesis after TBI; (b) VEGF predominantly mediates survival of de novo granule neurons rather than proliferation of neuroblasts in the injured brain; and (c) additional VEGF receptor(s) and/or other molecular mechanism(s) are also involved in mediating increased neurogenesis following injury.
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Journal of neurotrauma · Mar 2010
Metabolic levels in the corpus callosum and their structural and behavioral correlates after moderate to severe pediatric TBI.
Diffuse axonal injury (DAI) secondary to traumatic brain injury (TBI) contributes to long-term functional morbidity. The corpus callosum (CC) is particularly vulnerable to this type of injury. Magnetic resonance spectroscopy (MRS) was used to characterize the metabolic status of two CC regions of interest (ROIs) (anterior and posterior), and their structural (diffusion tensor imaging; DTI) and neurobehavioral (neurocognitive functioning, bimanual coordination, and interhemispheric transfer time [IHTT]) correlates. ⋯ Inverse corerlations were noted between creatine and posterior FA (r = -0.76), neurocognition (r range -0.22 to -0.71), and IHTT (r = 0.76). Multimodal studies at distinct time points in specific brain structures are necessary to delineate the course of the degenerative and reparative processes following TBI, which allows for preliminary hypotheses about the nature and course of the neural mechanisms of subsequent functional morbidity. This will help guide the future development of targeted therapeutic agents.
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Journal of neurotrauma · Mar 2010
Post-traumatic interpeduncular cistern hemorrhage as a marker for brainstem lesions.
We retrospectively reviewed a prospectively collected database of our diffuse axonal injury (DAI) patients to evaluate the accuracy of the evidence of interpeduncular cistern (IPC) blood on computed tomography (CT) scan when diagnosing brainstem lesions (BSL) early after trauma. From December 1989 to December 2008 we prospectively maintained a clinical and radiological database of head injured patients admitted to our neurosurgical intensive care unit (ICU) that met the following criteria: coma (Glasgow Coma Scale [GCS] score < 9) following the traumatic event; neurological derangement not ascribable to hypoxia, hypotension, or long-acting drugs able to alter state of consciousness; absence of lesions accounting for the severity of coma either on the admission CT scan or on subsequent CT scans; and no contraindications to magnetic resonance imaging (MRI; e.g., indwelling metallic implants). ⋯ The evidence of IPC blood on CT scan as an indicator of BSL had a sensitivity of 0.78 (95% CI: 0.70, 0.86), and a specificity of 0.80 (95% CI: 0.72, 0.88), with a 3.90 likelihood ratio for a positive CT scan, and a 0.28 likelihood ratio for a negative CT scan. Our data suggest that the finding of IPC blood on CT scan early after trauma in patients with otherwise unexplained coma is a good marker for possible brainstem lesions.
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The objective of this study was to estimate the independent association of sex with outcome after mild traumatic brain injury (mTBI). We performed an analysis of a subset of an established cohort involving 1425 mTBI patients presenting to an academic emergency department (ED). The associations between sex and three outcomes determined 3 months after the initial ED visit were examined: post-concussive symptom (PCS) score (0, 1-5, 6-16, and >16), the number of days to return of normal activities (0, 1-7, and >7), and the number of days of work missed (0, 1-7,and >7). ⋯ Female sex is associated with significantly higher odds of poor outcome after mTBI, as measured by PCS score, after control for appropriate confounders. The observed pattern of peak disability for females during the child-bearing years suggests disruption of endogenous estrogen or progesterone production. Attempts to better understand how mTBI affects production of these hormones acutely after injury and during the recovery period may shed light on the mechanism behind poorer outcome among females and putative therapeutic interventions.