Journal of neurotrauma
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Journal of neurotrauma · Oct 2010
Docosahexaenoic acid prevents white matter damage after spinal cord injury.
We have previously shown that the omega-3 fatty acid docosahexaenoic acid (DHA) significantly improves several histological and behavioral measures after spinal cord injury (SCI). White matter damage plays a key role in neurological outcome following SCI. Therefore, we examined the effects of the acute intravenous (IV) administration of DHA (250 nmol/kg) 30 min after thoracic compression SCI in rats, alone or in combination with a DHA-enriched diet (400 mg/kg/d, administered for 6 weeks post-injury), on white matter pathology. ⋯ By 6 weeks, damage to myelin and serotonergic fibers was also reduced. For some of the parameters measured, the combination of DHA injection and DHA-enriched diet led to greater neuroprotection than DHA injection alone. These findings demonstrate the therapeutic potential of DHA in SCI, and clearly indicate that this fatty acid confers significant protection to the white matter.
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Vascular endothelial growth factor (VEGF)-A mRNA was previously identified as one of the significantly upregulated transcripts in spinal cord injured tissue from adult rats that developed allodynia. To characterize the role of VEGF-A in the development of pain in spinal cord injury (SCI), we analyzed mechanical allodynia in SCI rats that were treated with either vehicle, VEGF-A isoform 165 (VEGF(165)), or neutralizing VEGF(165)-specific antibody. We have observed that exogenous administration of VEGF(165) increased both the number of SCI rats that develop persistent mechanical allodynia, and the level of hypersensitivity to mechanical stimuli. ⋯ It is possible that another endogenous VEGF isoform activates the same signaling pathway as the exogenously-administered 165 isoform and contributes to SCI pain. Our transcriptional analysis revealed that endogenous VEGF(188) is likely to be the isoform involved in the development of allodynia after SCI. To the best of our knowledge, this is the first study to suggest a possible link between VEGF, nonspecific sprouting of myelinated axons, and mechanical allodynia following SCI.
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Journal of neurotrauma · Oct 2010
Randomized Controlled TrialEndothelin-1 is increased in cerebrospinal fluid and associated with unfavorable outcomes in children after severe traumatic brain injury.
Severe pediatric traumatic brain injury (TBI) is associated with unfavorable outcomes secondary to injury from activation of the inflammatory cascade, the release of excitotoxic neurotransmitters, and changes in the reactivity of cerebral vessels, causing ischemia. Hypoperfusion of injured brain tissues after TBI is also associated with unfavorable outcomes. Therapeutic hypothermia is an investigational treatment strategy for use in patients with severe TBI that has shown differential effects on various cerebrospinal fluid (CSF) mediators in pediatric patients. ⋯ ET-1 is increased in children with severe TBI and is associated with unfavorable outcomes. This increase in ET-1 may mediate the hypoperfusion or cerebrovascular dysfunction accompanying severe TBI in children. Importantly, hypothermia does not affect the brain's ET-1 response as measured in the CSF.
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Journal of neurotrauma · Oct 2010
Development of autonomic dysreflexia after spinal cord injury is associated with a lack of serotonergic axons in the intermediolateral cell column.
Autonomic dysreflexia consistently develops in patients and in rats after severe upper thoracic spinal cord injury (SCI) as a result of exaggerated spinal sympathetic excitation. In this study we induced episodic hypertension in rats after varying degrees of SCI severity to investigate the contribution of serotonergic bulbospinal axons to the development of autonomic dysreflexia after SCI. Female Wistar rats (250-300 g) were used in all experiments in the following groups: (1) uninjured, (2) clip compression at T4 of 20, 35, or 50 g, (3) spinal cord transection at T4, and (4) intrathecal 5,7-dihydroxytryptamine creatinine sulfate (5,7-DHT). ⋯ Intrathecal administration of the 5-HT(2A) agonist dimethoxy-4-iodamphetamine increased resting MAP and blocked colon distension-induced hypertension, whereas the 5-HT(2A) antagonist ketanserin decreased resting MAP and was permissive to the colon distension-induced pressor response in SCI rats. These results suggest that the SCI-induced loss of serotonergic inputs into the spinal cord IMLC is proportional to the pathogenesis of autonomic dysreflexia and hypotension seen after SCI. We thus conclude that sparing of serotonergic axons beyond a critical threshold preserves cardiovascular regulation and prevents the development of autonomic dysreflexia.
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Journal of neurotrauma · Oct 2010
Longitudinal characterization of motor and cognitive deficits in a model of penetrating ballistic-like brain injury.
Traumatic brain injury (TBI) produces a wide range of motor and cognitive changes. While some neurological symptoms may respond to therapeutic intervention during the initial recovery period, others may persist for many years after the initial insult, and often have a devastating impact on quality of life for the TBI victim. ⋯ The results showed that PBBI produced consistent and significant (1) neurological deficits (neuroscore examination: 30 min to 10 weeks post-PBBI), (2) sensorimotor dysfunction in the contralateral forelimb (forelimb asymmetry task: 7 and 21 days), (3) motor dysfunction (balance beam task: 3-7 days; and fixed-speed rotarod task: 3-28 days), and (4) spatial learning deficits in the Morris water maze (MWM) task out to 10 weeks post-injury. Overall, the results of this study demonstrate that PBBI produces enduring motor and cognitive deficits, and identifies the optimal task and testing parameters for facilitating longitudinal screening of promising therapeutic interventions in this brain injury model.