Journal of neurotrauma
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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 · 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
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.