Journal of neurotrauma
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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
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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Journal of neurotrauma · Mar 2010
Diffusion tensor imaging at 3 hours after traumatic spinal cord injury predicts long-term locomotor recovery.
Accurate diagnosis of spinal cord injury (SCI) severity must be achieved before highly aggressive experimental therapies can be tested responsibly in the early phases after trauma. These studies demonstrate for the first time that axial diffusivity (lambda||), derived from diffusion tensor imaging (DTI) within 3 h after SCI, accurately predicts long-term locomotor behavioral recovery in mice. Female C57BL/6 mice underwent sham laminectomy or graded contusive spinal cord injuries at the T9 vertebral level (5 groups, n = 8 for each group). ⋯ The odds of significant locomotor recovery increased by 18% with each 1% increase in normal VLWM measured in the hyperacute phase (odds ratio = 1.18, p = 0.037). The capability of measuring subclinical changes in spinal cord physiology and murine genetic advantages offer an early window into the basic mechanisms of SCI that was not previously possible. Although significant obstacles must still be overcome to derive similar data in human patients, the path to clinical translation is foreseeable and achievable.
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Journal of neurotrauma · Mar 2010
Whole-brain proton MR spectroscopic imaging of mild-to-moderate traumatic brain injury and correlation with neuropsychological deficits.
Changes in the distribution of the magnetic resonance (MR)-observable brain metabolites N-acetyl aspartate (NAA), total choline (Cho), and total creatine (Cre), following mild-to-moderate closed-head traumatic brain injury (mTBI) were evaluated using volumetric proton MR spectroscopic imaging (MRSI). Studies were carried out during the subacute time period following injury, and associations of metabolite indices with neuropsychological test (NPT) results were evaluated. Twenty-nine subjects with mTBI and Glasgow Coma Scale (GCS) scores of 10-15 were included. ⋯ Examination of the association between all of the metabolite measures and the NPT scores found the strongest negative correlations to occur in the frontal lobe and for Cho/NAA. No significant correlations were found between any of the MRSI or NPT measures and the GCS. These results demonstrate that significant and widespread alterations of brain metabolites occur as a result of mild-to-moderate TBI, and that these measures correlate with measures of cognitive performance.
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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.