Journal of neurotrauma
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Journal of neurotrauma · May 2008
Force-dependent development of neuropathic central pain and time-related CCL2/CCR2 expression after graded spinal cord contusion injuries of the rat.
Spinal cord injury (SCI) often results in intractable chronic central pain syndromes. Recently chemokines such as CCL2 were identified as possible key integrators of neuropathic pain and inflammation after peripheral nerve lesion. The focus of the current study was the investigation of time-dependent CCL2 and CCR2 expression in relation to central neuropathic pain development after spinal cord impact lesions of 100, 150, or 200 kdyn force on spinal cord level T9 in adult rats. ⋯ While in the early post-operative time course, CCL2 and CCR2 were expressed in astroglia and granulocytes only on level T9; there was additional astroglial CCL2 expression in dorsal columns and dorsal horns above and below T9 of severely injured animals 42d after lesion. In dorsal horns (level L3-L5) of animals exhibiting chronic below-level pain CCL2 was co-expressed with transmitters and receptors that are involved in nociceptive processing like calcitonin gene-related peptide (CGRP), Substance-P, vanilloid-receptor-1, and its activated phosphorylated form. These data demonstrate lesion grade dependence of below-level pain development and suggest chemokines as potential candidates for integrating inflammation and central neuropathic pain after SCI.
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Journal of neurotrauma · May 2008
Post-operative expansion of hemorrhagic contusions after unilateral decompressive hemicraniectomy in severe traumatic brain injury.
Decompressive hemicraniectomy is commonly performed in patients with traumatic brain injury (TBI) with diffuse brain swelling or refractory raised intracranial pressure. Expansion of hemorrhagic contusions in TBI patients is common, but its frequency following decompressive hemicraniectomy has not been well established. The aim of this retrospective study was to determine the rate of hemorrhagic contusion expansion following unilateral hemicraniectomy in severe TBI, to identify factors associated with contusion expansion, and to examine whether contusion expansion is associated with worsened clinical outcomes. ⋯ Expansion of hemorrhagic contusions is common after decompressive hemicraniectomy following severe TBI. The volume of hemorrhagic contusion expansion following hemicraniectomy is strongly associated with mortality and poor outcome. Severity of initial CT findings may predict the risk of contusion expansion following hemicraniectomy, thereby identifying a subgroup of patients who might benefit from therapies aimed at augmenting the coagulation system.
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Journal of neurotrauma · May 2008
Androgen regulates neuritin mRNA levels in an in vivo model of steroid-enhanced peripheral nerve regeneration.
Following crush injury to the facial nerve in Syrian hamsters, treatment with androgens enhances axonal regeneration rates and decreases time to recovery. It has been demonstrated in vitro that the ability of androgen to enhance neurite outgrowth in motoneurons is dependent on neuritin-a protein that is involved in the re-establisment of neuronal connectivity following traumatic damage to the central nervous system and that is under the control of several neurotrophic and neuroregenerative factors--and we have hypothesized that neuritin is a mediator of the ability of androgen to increase peripheral nerve regeneration rates in vivo. Testosterone treatment of facial nerve-axotomized hamsters resulted in an approximately 300% increase in neuritin mRNA levels 2 days post-injury. ⋯ In a corroborative in vitro experiment, the androgen dihydrotestosterone induced an approximately 100% increase in neuritin mRNA levels in motoneuron-neuroblastoma cells transfected with androgen receptors, but not in cells without androgen receptors. These data confirm that neuritin is under the control of androgens, and suggest that neuritin is an important effector of androgen in enhancing peripheral nerve regeneration following injury. Given that neuritin has now been shown to be involved in responses to both central and peripheral injuries, and appears to be a common effector molecule for several neurotrophic and neurotherapeutic agents, understanding the neuritin pathway is an important goal for the clinical management of traumatic nervous system injuries.
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Journal of neurotrauma · Apr 2008
Characterizing the dose-response relationship between mannitol and intracranial pressure in traumatic brain injury patients using a high-frequency physiological data collection system.
Despite the widespread use of mannitol to treat elevated intracranial pressure (ICP), there is no consensus regarding the optimal dosage. The objective of this study was to retrospectively characterize the dose-response relationship between mannitol and ICP using data collected with a continuous high-frequency physiological data collection system. To this end, we measured ICP continuously in 28 patients with traumatic brain injury (TBI) who were given at least one dose of mannitol. ⋯ However, at 100 min, ICP had increased in the 50-g group to nearly its initial value but was still lower in the 100-g group (18.6 +/- 7.6 vs. 14.2 +/- 6.7 mm Hg; p = 0.001). Osmotic agents such as mannitol have been used for decades to treat cerebral edema, but there has been no definitive quantitative information regarding the dosing of mannitol. In a large, retrospective study of high-frequency ICP data, we have quantitatively shown that mannitol's effect on ICP is dose-dependent and that higher doses provide a more durable reduction in ICP.
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Journal of neurotrauma · Apr 2008
Effect of inducible nitric oxide synthase on cerebral blood flow after experimental traumatic brain injury in mice.
Inducible nitric oxide synthase (iNOS) has been suggested to play a complex role in the response to central nervous system insults such as traumatic brain injury (TBI) and cerebral ischemia. In the current study, we quantified maps of regional cerebral blood flow (CBF) using an arterial spin-labeling magnetic resonance imaging (MRI) technique, at 24 and 72 h after experimental TBI in iNOS knockout (KO) and wild-type (WT) mice. Our hypothesis was that iNOS would contribute to the level of CBF at 72 h after experimental TBI in mice. ⋯ However, pixel analysis denoted that the contribution of iNOS to CBF at 72 h was not limited to hyperemia flows. In conclusion, iNOS plays a role in the recovery of CBF after CCI in mice. Questions remain if this effect represents a homeostatic component of CBF recovery, pathologic vasodilatation linked to inflammation, or NO-mediated facilitation of angiogenesis.