Journal of neurotrauma
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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
In situ detection of inflammatory mediators in post mortem human brain tissue after traumatic injury.
Little is known about the molecular events following severe traumatic brain injury (TBI) in humans and to date there are no efficient therapies for the treatment of patients. In this study, the first of its kind in human tissue, a total of 21 post mortem trauma brain samples were analyzed. The inflammatory response within the brain tissue was explored by measuring the expression of various inflammatory cytokines at the mRNA and protein levels. ⋯ This study shows for the first time in human brain tissue that 1) pro-inflammatory mediator protein levels are significantly increased in situ following acute brain injury while anti-inflammatory cytokines protein levels remain unchanged; 2) the cerebral inflammatory response begins within minutes of acute TBI, much earlier than previously thought; 3) IL-6, IL-8, TNF-alpha, and IL-1beta mRNA levels are significantly increased following injury; 4) the rise in cytokine protein level coincides with increased levels of their mRNAs suggesting that traumatic injury elicits an immediate cerebral inflammatory response. Altogether these data confirm and extend previous observations on the release of cytokines in the cerebrospinal fluid of severe TBI patients. Finally, this study highlights the need to characterize the cell source of cytokines and elucidate their mode of action.
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Journal of neurotrauma · Mar 2010
Influence of PARP-1 polymorphisms in patients after traumatic brain injury.
Poly(ADP-ribose) polymerase-1 (PARP-1) plays an important role in the cellular response to stress and DNA damage. However, excessive activity of PARP-1 exacerbates brain injury via NAD+ depletion and energy failure. The purpose of this study was to determine if tagging single nucleotide polymorphisms (tSNPs) covering multiple regions of the PARP-1 gene are related to outcome after traumatic brain injury (TBI) in humans. ⋯ This SNP, which did not correlate with outcome, tags a haplotype block spanning the promoter region of the PARP-1 gene. We conclude that after severe TBI in humans, a PARP-1 polymorphism within the automodification-catalytic domain is associated with neurological outcome, while a polymorphism within the promoter region was associated with CSF PAR-modified protein level. These findings must be replicated in a prospective study before the relevance of PARP-1 polymorphisms after TBI can be established.
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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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Journal of neurotrauma · Mar 2010
Neuronal and axonal degeneration in experimental spinal cord injury: in vivo proton magnetic resonance spectroscopy and histology.
Longitudinal in vivo proton magnetic resonance spectroscopy (1H-MRS) and immunohistochemistry were performed to investigate the tissue degeneration in traumatically injured rat spinal cord rostral and caudal to the lesion epicenter. On 1H-MRS significant decreases in N-acetyl aspartate (NAA) and total creatine (Cr) levels in the rostral, epicenter, and caudal segments were observed by 14 days, and levels remained depressed up to 56 days post-injury (PI). In contrast, the total choline (Cho) levels increased significantly in all three segments by 14 days PI, but recovered in the epicenter and caudal, but not the rostral region, at 56 days PI. ⋯ These results suggest delayed tissue degeneration in regions both rostrally and caudally from the epicenter in the injured spinal cord tissue. A rostral-caudal asymmetry in tissue recovery was seen both on MRI-observed hyperintense lesion volume and the Cho, but not NAA and Cr, levels at 56 days PI. These studies suggest that dynamic metabolic changes take place in regions away from the epicenter in injured spinal cord.