Journal of neurotrauma
-
Journal of neurotrauma · Apr 2007
Magnetic resonance imaging of diffuse axonal injury: quantitative assessment of white matter lesion volume.
Diffuse axonal injury (DAI) is a common mechanism of traumatic brain injury (TBI) for which there is no well-accepted anatomic measures of injury severity. The present study aims to quantitatively assess DAI by measuring white matter lesion volume visible in fluid-attenuated inversion recovery (FLAIR) weighted images and to determine whether higher lesion volumes are associated with unfavorable functional outcome 6 months after injury. Twenty-four patients who experienced moderate to severe TBI without extra-axial or major cortical contusions were included in this study. ⋯ White matter lesion volume resulting from DAI can be quantitatively and reliably assessed from standard FLAIR-weighted MRIs. Patients with greater DAI volume have poorer functional outcomes. These methods may be useful in stratifying injury severity and for the assessment of DAI-directed therapies.
-
Journal of neurotrauma · Apr 2007
Behavioral, histological, and ex vivo magnetic resonance imaging assessment of graded contusion spinal cord injury in mice.
This study characterized the Infinite Horizon (IH) Impactor for use in mouse models of contusion spinal cord injury (SCI), and investigated the feasibility and reliability of using magnetic resonance imaging (MRI) as a method to accurately measure lesion volume after mouse contusion SCI. Eight-week-old female C57Bl/6 mice received a mild (30 kilodyne), moderate (50 kilodyne), or severe (70 kilodyne) contusion injury at the T9 vertebral level. Uninjured control mice received a T9 laminectomy only. ⋯ Lesion volumes were positively correlated with force of impact, and negatively correlated with spared white matter and functional recovery. Additionally, similar lesion volumes were detected using fibronectin staining and MRI analysis, although MRI may be more sensitive for milder injuries. These results give researchers more options in how to analyze spinal cord injuries in animal models.
-
Journal of neurotrauma · Apr 2007
Pretreatment with the cyclosporin derivative, NIM811, improves the function of synaptic mitochondria following spinal cord contusion in rats.
Trauma to the spinal cord causes a cascade of secondary events, such as mitochondrial dysfunction, which disrupts cellular functions and ultimately leads to cell death. Cyclosporin A (CsA) is a potent immunosuppressant that promotes mitochondrial function by inhibiting mitochondrial permeability transition (mPT). Clinical trials examining CsA in traumatic brain injury are currently under-way, but CsA is potentially neurotoxic. ⋯ NIM811 pretreatment significantly improved mitochondrial respiratory control ratios, and the maximal electron transport capacity of complex I and II, as well as their ATP-producing capacity. Consistent with the improvements in mitochondrial function, NIM811 pretreatment significantly decreased free radical production in isolated mitochondria. These studies are the first to demonstrate the therapeutic potential of CsA derivatives in a model of SCI, and support the need for continued investigation of compounds like NIM811 as an acute treatment for human SCI.
-
Journal of neurotrauma · Apr 2007
Impaired percent alpha variability on continuous electroencephalography is associated with thalamic injury and predicts poor long-term outcome after human traumatic brain injury.
Continuous electroencephalography (cEEG) is potentially useful in determining prognosis in patients with traumatic brain injuries (TBI). The objective of this prospective, observational cohort study was to determine if the percent alpha variability (PAV) on cEEG was predictive of outcome following TBI. Injury characteristics were indexed to assess whether lesions in specific cerebral loci were correlated with PAV and patient recovery. ⋯ Inclusion of PAV enhanced the accuracy of prediction models that encompassed a selective combination of clinical and anatomical variables (adjusted R(2) = 0.458, p < 0.001). The two main results of this study are (1) PAV is a sensitive predictor of 6-month clinical outcomes following TBI, and (2) injury to the thalamus is related to impaired PAV. PAV appears best utilized as a functional adjunct to traditional clinical and anatomical predictors.
-
Traumatic brain injury (TBI) initiates a complex genetic response that may include the expression of organelle specific stress genes. We investigated the effects of brain trauma on the expression of a number of stress genes by in situ hybridization and Western blot analysis including the endoplasmic reticulum (ER) stress gene grp78, ER protein processing enzymes calnexin and protein disulphide isomerase (PDI), the mitochondrial stress gene hsp60, and the cytoplasmic stress gene hsp70. Male Sprague-Dawley rats were subjected either to sham-surgery or moderate (1.8-2.2 atm) parasagittal fluid-percussion (F-P) brain injury followed by 30 min of either normoxic or hypoxic (30-40 mm Hg) gas levels. ⋯ In contrast, mRNA of the cytoplasmic hsp70 was strongly induced at 4 h after brain injury in multiple brain regions within the injured hemisphere, and this expression was greatly enhanced by secondary hypoxia. Because subcellular stress gene expression may reflect where unfolded or damaged proteins are abundant, these findings suggest that abnormal proteins are localized mainly in the cytoplasm, and to a lesser degree in the ER lumen and mitochondria after brain trauma. Thus, distinct parts of the cellular machinery respond to traumatic and metabolic stresses in specific ways.