Journal of neurotrauma
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Journal of neurotrauma · Jul 2011
Traumatic axonal injury in the optic nerve: evidence for axonal swelling, disconnection, dieback, and reorganization.
Traumatic axonal injury (TAI) is a major feature of traumatic brain injury (TBI) and is associated with much of its morbidity. To date, significant insight has been gained into the initiating pathogenesis of TAI. However, the nature of TAI within the injured brain precludes the consistent evaluation of its specific anterograde and retrograde sequelae. ⋯ Concomitant with this evolving axonal pathology, focal YFP fluorescence quenching occurred and mapped precisely to immunoreactive loci positive for Texas-Red-conjugated-IgG, indicating that blood-brain barrier disruption and its attendant edema contributed to this phenomenon. This was confirmed through the use of antibodies targeting endogenous YFP, which demonstrated the retention of intact immunoreactive axons despite YFP fluorescence quenching. Collectively, the results of this study within the injured optic nerve provide unprecedented insight into the evolving pathobiology associated with TAI.
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Journal of neurotrauma · Jul 2011
Comparative StudyObjective measures of motor dysfunction after compression spinal cord injury in adult rats: correlations with locomotor rating scores.
Precise assessment of motor deficits after traumatic spinal cord injury (SCI) in rodents is crucial for understanding the mechanisms of functional recovery and testing therapeutic approaches. Here we analyzed the applicability to a rat SCI model of an objective approach, the single-frame motion analysis, created and used for functional analysis in mice. Adult female Wistar rats were subjected to graded compression of the spinal cord. ⋯ FSA co-varied with RHI only in the severely impaired rats, while RHI and CLS were barely correlated. Our findings suggest that the numerical parameters estimate, as intended by design, predominantly different aspects of locomotion. The use of these objective measures combined with BBB rating provides a time- and cost-efficient opportunity for versatile and reliable functional evaluations in both severely and moderately impaired rats, combining clinical assessment with precise numerical measures.
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Journal of neurotrauma · Jul 2011
Cardiovascular responses to static muscle contraction in patients with brachial plexus injury treated with intercostal nerve transfer.
Pressor response is carried in afferent fibers of somatic nerves to increase blood pressure (BP) and heart rate (HR) during static exercise in humans. However, there is no information that peripheral responses restore muscle contraction with nerve transfer operation. In this study, we aimed to assess isometric exercise-induced pressor responses in patients with brachial plexus injury (BPI) after intercostal nerve transfer (ICNT) to restore elbow flexor muscles. ⋯ Isometric static exercise at 35% of MVC did not induce pressor and HR changes on the ICNT side. The difference in the responses between the two sides could have been caused by incomplete recovery of afferent nerve function following nerve repair, despite the restoration of efferent nerve function. Alternatively, the HR and BP responses to static contraction may depend upon the active muscle mass.
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Journal of neurotrauma · Jul 2011
Curcumin attenuates the expression and secretion of RANTES after spinal cord injury in vivo and lipopolysaccharide-induced astrocyte reactivation in vitro.
Curcumin has been proposed for treatment of various neuroinflammatory and neurodegenerative conditions, including post-traumatic inflammation during acute spinal cord injury (SCI). In this study, we examined whether curcumin anti-inflammation involves regulation of astrocyte reactivation, with special focus on the injury-induced RANTES (regulated on expression normal T-cell expressed and secreted) from astrocytes in acute SCI. Male Sprague-Dawley (SD) rats were subjected to impact injury of the spinal cord followed by treatment with curcumin (40 mg/kg i.p.). ⋯ Furthermore, cortical neurons cultured with astrocyte conditioned medium (ACM) conditioned with both LPS and curcumin (LPS-curcumin/ACM), which characteristically exhibited decreased RANTES expression when compared with ACM from astrocytes treated with LPS alone (LPS/ACM), showed higher level of cell viability and lower level of cell death as assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction activity assay and lactate dehydrogenase release assay, respectively. Knockdown of RANTES expression by siRNA (siRANTES) shows reduced RANTES expression and release from LPS-reactivated astrocytes, and ACM obtained from this condition (LPS-siRANTES/ACM) becomes less cytotoxic as compared with the LPS-ACM. Therefore, curcumin reduction of robust RANTES production in reactivated astrocytes both in vitro and in vivo may contribute to its neuroprotection and potential application in SCI.
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Journal of neurotrauma · Jul 2011
Attenuation of astrocyte activation by TAT-mediated delivery of a peptide JNK inhibitor.
Astrocyte activation contributes to the brain's response to disease and injury. Activated astrocytes generate harmful radicals that exacerbate brain damage including nitric oxide, peroxides and superoxides. Furthermore, reactive astrocytes hinder regeneration of damaged neural circuits by secreting neuro-developmental inhibitors and glycosaminoglycans (GAGs), which physically block growth cone extension. ⋯ TAT fused to a peptide JNK inhibitor delivered the peptide inhibitor to activated astrocytes and significantly reduced activation. Our study is the first to report significant and direct modulation of astrocyte activation with a peptide JNK inhibitor. Our promising in vitro results warrant in vivo follow-up, as TAT-mediated protein delivery may have broad therapeutic potential for preventing astrocyte activation with the possibility of limiting off-target, negative side effects.