Journal of neurotrauma
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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 · May 2008
A time course of contusion-induced oxidative stress and synaptic proteins in cortex in a rat model of TBI.
An imbalance between oxidants and antioxidants has been postulated to lead to oxidative damage in traumatic brain injury (TBI). Oxidative neurodegeneration is a key mediator of exacerbated morphological responses and deficits in behavioral recoveries. The present study was designed to delineate the early temporal sequence of this imbalance in order to enhance possible antioxidant therapy. ⋯ These results indicate that depletion of antioxidant systems following trauma could adversely affect synaptic function and plasticity. Because of the observed differences in the time-course of various markers, it may be necessary to stagger selective types of anti-oxidant therapy to target specific oxidative components. The initial therapeutic window following TBI appears relatively short since oxidative damage occurs as early as 3 h.
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Journal of neurotrauma · May 2008
Extraluminal cooling of bilateral common carotid arteries as a method to achieve selective brain cooling for neuroprotection.
Systemic cooling to achieve brain hypothermia has been investigated as a neuroprotective therapy but can present serious adverse effects. Here we describe a novel method to selectively cool the rat brain and investigate its neuroprotective effects following transient middle cerebral artery occlusion (MCAo). The novelty of our method of selective brain cooling (SBC) was that the extraluminal cooling of the carotid arterial blood was achieved by using a cooling cuff wrapped around each common carotid artery (CCA). ⋯ In subgroup experiments, the incidence of peri-infarct depolarization (PID) was assessed during the MCAo and cooling period. Compared to normothermic but ischemic rats, SBC significantly reduced the number of PID events from 6.2+/-2.5 to 2.0+/-2.5, and reduced infarct volumes from 323+/-79 to 139+/-102 mm3. In conclusion, this extralumimal cooling method of SBC provides a safe and efficient approach to rapidly and safely achieve hypothermic neuroprotection.
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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.