Journal of neurotrauma
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Journal of neurotrauma · Sep 2006
Neuronal response to high rate shear deformation depends on heterogeneity of the local strain field.
Many cellular models of traumatic brain injury (TBI) deform cells in a planar (2-D) configuration, a contrast from the three-dimensional (3-D) architecture of the brain, resulting in strain fields that may fail to represent the complex deformation patterns seen in vivo. Cells cultured in 3-D may more accurately represent in vivo cellular behavior than planar models due to differences in cytostructure, cell-cell/cell-matrix interactions and access to trophic factors; however, the effects of culture configuration on the response to high rate deformation have not been evaluated. We examined cell viability following a defined mechanical insult to primary cortical neurons distributed throughout a bioactive matrix (3-D) or in a monolayer sandwiched between layers of a bioactive matrix (2-D). ⋯ Computer simulations of bulk loading predicted local cellular strains, revealing that neurons in 3-D were subjected to a heterogeneous strain field simultaneously consisting of tensile, compressive and shear strains; conversely, neurons in 2-D experienced a less complex deformation regime varying mainly based on shear strains. These results show differential susceptibility to mechanical loading between neurons cultured in 2-D and 3-D that may be due to differences in cellular strain manifestation. Models of TBI that accurately represent the related cellular biomechanics and pathophysiology are important for the elucidation of cellular tolerances and the development of mechanistically driven intervention strategies.
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Journal of neurotrauma · Aug 2006
Differential behavioral and histopathological responses to graded cortical impact injury in mice.
Controlled cortical impact (CCI) injury, a model of contusive brain injury in humans, is being used with increasing frequency in mice to investigate post-traumatic cell damage and death and to evaluate treatment strategies. Because cellular injury mechanisms and therapeutic approaches may depend on the severity of the initial insult, it is important to utilize a model in which outcomes are sensitive to injury severity. Adult male C57Bl/6 mice were anesthetized and subjected to sham injury (n = 23) or CCI injury at either 0.5 mm (n = 22) or 1.0 mm (n = 22) depth of impact at a velocity of 5 m/sec. ⋯ Regional patterns of IgG extravasation and reactive astrocytosis were similar in the two injured groups, but changes were more persistent in the 1.0 mm group. Both levels of injury resulted in acute loss of neuronal MAP-2 immunoreactivity in the cortex and sub-region specific changes in the hippocampus. Thus, increasing the depth of impact led to similar structural alterations in neurons, astrocytes and the vasculature, but resulted in greater behavioral deficits and cortical and hippocampal cell death.
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Journal of neurotrauma · Aug 2006
Review Meta AnalysisSerum biochemical markers for post-concussion syndrome in patients with mild traumatic brain injury.
Mild traumatic brain injury (MTBI) is a major public health problem in the United States. A significant subset of MTBI patients develop persistent and distressing neurological, cognitive, and behavioral symptoms, known as the post-concussion syndrome (PCS). To date, multiple studies have assessed the relationship between brain-related proteins found in the serum at the time of injury, and the development of PCS. ⋯ Of these markers, S100 appeared to be the best researched. We conclude that no biomarker has consistently demonstrated the ability to predict PCS after MTBI. A combination of clinical factors in conjunction with biochemical markers may be necessary to develop a comprehensive decision rule that more accurately predicts PCS after MTBI.
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Journal of neurotrauma · Aug 2006
Delayed, post-injury treatment with aniracetam improves cognitive performance after traumatic brain injury in rats.
Chronic cognitive impairment is an enduring aspect of traumatic brain injury (TBI) in both humans and animals. Treating cognitive impairment in the post-traumatic stages of injury often involves the delivery of pharmacologic agents aimed at specific neurotransmitter systems. The current investigation examined the effects of the nootropoic drug aniracetam on cognitive recovery following TBI in rats. ⋯ Drug treatment was terminated during MWM testing on postinjury days 16-20. In this experiment, aniracetam-treated rats did not perform better than vehicle-treated rats. The results of these experiments indicate that aniracetam is an effective treatment for cognitive impairment induced by TBI, even when treatment is delayed for a period of days following injury.
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Journal of neurotrauma · Jul 2006
Comparative StudyActivation of spinal GABA receptors attenuates chronic central neuropathic pain after spinal cord injury.
In this study, we investigated the role of the spinal GABAergic system in central neuropathic painlike outcomes following spinal cord injury (SCI) produced by a spinal hemitransection at T13 of the rat. After SCI, mechanical allodynia develops bilaterally in both hind paws of the rat, lasting longer than 40 days, as evidenced by an increase in paw withdrawal frequency in response to a weak von Frey filament. In naive rats, intrathecal (i.t.) administration in the lumbar spinal cord of GABAA and GABAB receptor antagonists, bicuculline (1-5 microg) and phaclofen (0.1-5 microg), respectively, causes a dose-dependent increase in the magnitude of mechanical allodynia. ⋯ The topical application of muscimol (1 microg) or baclofen (0.5 microg) onto the lumbar cord surface reduce the SCIinduced increased responsiveness of WDR neurons. Inhibitory effects of muscimol and baclofen on both the behavioral mechanical allodynia and the hyperexcitability in WDR neuron with SCI compared to controls, were antagonized by pre-treatment of bicuculline (10 microg) and phaclofen (5 microg), respectively. This study provides behavioral and electrophysiological evidence for the important role of the loss of spinal inhibitory tone, mediated by activation of both GABAA and GABAB receptors, in the development of central neuropathic pain following SCI.