Journal of neurotrauma
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Journal of neurotrauma · May 2008
Treadmill training after spinal cord hemisection in mice promotes axonal sprouting and synapse formation and improves motor recovery.
Treadmill training with weight-support is a therapeutic strategy used in human patients after spinal cord injury (SCI). Exercise leads to locomotor improvement in a variety of animal models; however, the effect of exercise on axonal regrowth has not been directly examined. This study used several locomotor tests, including kinematic gait analysis, to analyze the differences between treadmill-trained and untrained mice in the usage of their paretic hindlimb following a low thoracic hemisection. ⋯ Movement of their hip joint started to approximate the pattern of intact mice, with concomitant use of their ankle. Unlike untrained mice, exercised mice showed decreased muscle atrophy, increased axonal regrowth and collateral sprouting proximal to the lesion site, with maintenance of synaptic markers on motor neurons in the ventral horn. However, there was no axonal regeneration into or across the lesion site indicating that the improved behaviour may have been, at least in part, due to enhanced neural activity above the lesion site.
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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
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
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.