Experimental neurology
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Experimental neurology · Feb 2011
Comparative StudyTNF-α enhances the currents of voltage gated sodium channels in uninjured dorsal root ganglion neurons following motor nerve injury.
The ectopic discharges observed in uninjured dorsal root ganglion (DRG) neurons following various lesions of spinal nerves have been attributed to functional alterations of voltage-gated sodium channels (VGSCs). Such mechanisms may be important for the development of neuropathic pain. However, the pathophysiology underlying the functional modulation of VGSCs following nerve injury is largely unknown. ⋯ Indeed, recombinant rat TNF (rrTNF) enhanced the current densities of TTX-S and Nav1.8 in cultured DRG neurons dose-dependently. Furthermore, genetic deletion of TNF receptor 1 (TNFR-1) in mice attenuated the mechanical allodynia and prevented the increase in sodium currents in DRG neurons induced by L5-VRT. These data suggest that the increase in sodium currents in uninjured DRG neurons following nerve injury might be mediated by over-production of TNF-α.
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Experimental neurology · Feb 2011
Comparative StudyEffects of aging and hypertension on cerebral ischemic susceptibility: evidenced by MR diffusion-perfusion study in rat.
Aging is the most significant non-modifiable risk factor and hypertension is the most significant modifiable risk factor for ischemic stroke. We used magnetic resonance imaging (MRI) to investigate the evidence of ischemic susceptibility after aging and hypertension. Four groups of rat were studied: young normotensive Wistar-Kyoto (WKY) rat, aged normotensive WKY rat, young spontaneously hypertensive rat (SHR) and aged SHR. ⋯ After bilateral common carotid artery occlusion, there was significantly larger damage in the parietal cortex of aged SHR when compared with young WKY rat, young SHR and aged WKY rat (all P<0.05), but not in the hippocampus and thalamus (P>0.05). Our study demonstrated a significantly increased ADC value and reduced CBF in the ischemia-vulnerable cortical area. This cerebral diffusion-perfusion disparity is seen mainly in aged rat and can be more evident if associated with hypertension indicating an increased susceptibility of brain tissue to ischemic injury.
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Experimental neurology · Jan 2011
Utilizing natural activity to dissect the pathophysiology of acute oxaliplatin-induced neuropathy.
Oxaliplatin is first-line chemotherapy for colorectal cancer, but produces dose-limiting neurotoxicity. Acute neurotoxicity following infusion produces symptoms including cold-triggered fasciculations and cramps, with subsequent chronic neuropathy developing at higher cumulative doses. Axonal excitability studies were undertaken in 15 oxaliplatin-treated patients before and immediately after oxaliplatin infusion to determine whether the mechanisms underlying acute neurotoxicity altered resting membrane potential or Na(+)/K(+) pump function. ⋯ Patients with the most abnormal change in the recovery cycle after infusion demonstrated the greatest changes post-contraction. Prominent abnormalities developed in Na(+) channel-associated parameters in response to natural activity, without significant alteration in axonal membrane potential or Na(+)/K(+) pump function. Findings from the present series suggest that oxaliplatin affects nerve excitability through voltage-dependent mechanisms, with specific effects mediated through axonal Na(+) channel inactivation.
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Experimental neurology · Jan 2011
Physiological and histopathological responses following closed rotational head injury depend on direction of head motion.
Rotational inertial forces are thought to be the underlying mechanism for most severe brain injuries. However, little is known about the effect of head rotation direction on injury outcomes, particularly in the pediatric population. Neonatal piglets were subjected to a single non-impact head rotation in the horizontal, coronal, or sagittal direction, and physiological and histopathological responses were observed. ⋯ Significant axonal injury occurred following both horizontal and sagittal rotations. For both groups, the distribution of injury was greater in the frontal and parietotemporal lobes than in the occipital lobes, frequently occurred in the absence of ischemia, and did not correlate with regional cerebral blood flow reductions. We postulate that these direction-dependent differences in injury outcomes are due to differences in tissue mechanical loading produced during head rotation.