Journal of neurotrauma
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Journal of neurotrauma · Apr 2005
Traumatic injury activates protein kinase B/Akt in cultured astrocytes: role of extracellular ATP and P2 purinergic receptors.
Protein kinase B/Akt is a key signaling molecule that regulates cell survival, growth, and metabolism, and inhibits apoptosis. Traumatic brain injury (TBI) activates Akt, and Akt has been implicated in neuronal survival after TBI, but little is known about injury-induced Akt activation in astrocytes, cells that exhibit hypertrophic and hyperplastic responses to CNS injury. Here we have investigated the effect of mechanical strain on Akt activation in primary cultures of rat cortical astrocytes growing on deformable Silastic membranes. ⋯ In addition, we found that ATP is rapidly released after mechanical strain and that the P2 purinergic receptor antagonist iso-pyridoxal-5'-phosphate-6-azophenyl-2',5'disulfonate (PPADS) attenuated trauma-induced Akt activation. We conclude that mechanical strain causes activation of Akt in astrocytes via stimulation of P2 receptors. This suggests that P2 receptor/Akt signaling promotes astrocyte survival and growth, and this process may play a role in the generation of reactive gliosis after TBI.
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Journal of neurotrauma · Apr 2005
A significant increase in both basal and maximal calcineurin activity following fluid percussion injury in the rat.
Calcineurin, a neuronally enriched, calcium-stimulated phosphatase, is an important modulator of many neuronal processes, including several that are physiologically related to the pathology of traumatic brain injury. This study examined the effects of moderate, central fluid percussion injury on the activity of this important neuronal enzyme. Animals were sacrificed at several time-points postinjury and cortical, hippocampal, and cerebellar homogenates were assayed for calcineurin activity by dephosphorylation of p-nitrophenol phosphate. ⋯ No brain region tested displayed a significant change in calcineurin enzyme levels as determined by Western blot, demonstrating that increased enzyme synthesis was not responsible for the observed increase in activity. The data support the conclusion that fluid percussion injury results in increased calcineurin activity in the rat forebrain. This increased activity has broad physiological implications, possibly resulting in altered cellular excitability or a greater likelihood of neuronal cell death.
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Journal of neurotrauma · Apr 2005
Whiplash-associated disorders impairment rating: neck disability index score according to severity of MRI findings of ligaments and membranes in the upper cervical spine.
The aim of this study was to explore whether reported pain and functional disability in whiplash-associated disorders (WAD) patients is associated with lesions to specific soft tissue structures in the upper cervical spine, as assessed by MRI. Pre-selected structures for MRI assessment included the alar ligaments, the transverse ligament, the tectorial and the posterior atlanto-occipital membranes. The questionnaire employed was a modification of the Oswestry Low Back Pain Index. ⋯ Lesions to the transverse ligament and to the posterior atlanto-occipital membrane also appeared to be related to the NDI score, although the association was weaker than for the alar ligament. The disability score increased with increasing number of abnormal (grade 2-3) structures. These results indicate that symptoms and complaints among WAD patients can be linked with structural abnormalities in ligaments and membranes in the upper cervical spine, in particular the alar ligaments.