Experimental neurology
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Experimental neurology · Jan 2010
Schwann cells engineered to express the cell adhesion molecule L1 accelerate myelination and motor recovery after spinal cord injury.
Functional recovery after spinal cord lesion remains an important goal. A combination of inhibitory molecules and lack of appropriate permissive factors in the lesioned spinal cord results in failure of fiber tract reconnection and function. Experimental transplantation in rodent and primate models of CNS injuries has led to the idea that Schwann cells (SCs) are promising candidates for autologous transplantation to assist myelination of lesions and to deliver therapeutic agents in the CNS. ⋯ Morphological analysis indicated that the accelerated functional recovery correlated with earlier and enhanced myelination by both grafted and host SCs. Moreover, increased sprouting of serotonergic fibers into and across the lesion site was observed in the L1/L1-Fc group as compared with controls. Our results suggest that transplantation of L1-overexpressing SCs enhances early events in spinal cord repair after injury and may be considered in combinatorial strategies together with other regeneration-promoting molecules.
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Experimental neurology · Jan 2010
Chronic treatment with agonists of beta(2)-adrenergic receptors in neuropathic pain.
Expression of beta(2)-adrenoceptors (beta(2)-ARs) within the nociceptive system suggested their potential implication in nociception and pain. Recently, we demonstrated that these receptors are essential for neuropathic pain treatment by antidepressant drugs. The aim of the present study was to investigate whether the stimulation of beta(2)-ARs could in fact be adequate to alleviate neuropathic allodynia. ⋯ This action of beta(2)-AR agonists might implicate the endogenous opioid system; indeed chronic clenbuterol effect can be acutely blocked by the delta-opioid receptor antagonist naltrindole. Present results show that beta(2)-ARs are not only essential for the antiallodynic action of antidepressant drugs on sustained neuropathic pain, but also that the stimulation of these receptors is sufficient to relieve neuropathic allodynia in a murine model. Our data suggest that beta(2)-AR agonists may potentially offer an alternative therapy to antidepressant drugs for the chronic treatment of neuropathic pain.
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Complex regional pain syndrome (CRPS) is a pain disorder involving the somatosensory, the somatomotor and the sympathetic nervous systems. Based on experiments conducted by Bove (2009), it is suggested that changes in impulse activity in small-diameter afferents and postganglionic axons generated by neuritis can contribute to signs of early CRPS. The potential mechanisms involved are discussed. These mechanisms include the possibility that CRPS, a disorder of the central nervous system, may be caused by a nerve inflammation.
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Experimental neurology · Jan 2010
Clinical TrialBilateral symmetry and coherence of subthalamic nuclei beta band activity in Parkinson's disease.
Abnormal synchronization of neuronal activity in the basal ganglia has been associated with the dysfunction of sensorimotor circuits in Parkinson's disease (PD). In particular, oscillations at frequencies within the beta range (13-35 Hz) are specifically modulated by dopaminergic medication and are correlated with the clinical state of the subjects. ⋯ Here we demonstrate for the first time that the beta band oscillations recorded in the local field potential of the subthalamic nuclei (STN), while appearing different across subjects, are occurring at the same frequencies bilaterally (p<0.001) and are coherent between the two STNs of individual PD subjects (11/12 cases, p<0.05). These findings suggest the existence of a bilateral network controlling the beta band activity in the basal ganglia in PD.
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Experimental neurology · Dec 2009
Treatments (12 and 48 h) with systemic and brain-selective hypothermia techniques after permanent focal cerebral ischemia in rat.
Mild hypothermia lessens brain injury when initiated after the onset of global or focal ischemia. The present study sought to determine whether cooling to approximately 33 degrees C provides enduring benefit when initiated 1 h after permanent middle cerebral artery occlusion (pMCAO, via electrocautery) in adult rats and whether protection depends upon treatment duration and cooling technique. In the first experiment, systemic cooling was induced in non-anesthetized rats through a whole-body exposure technique that used fans and water mist. ⋯ A direct and uncomplicated comparison between methods is problematic, however, due to unknown gradients in brain temperature and the use of two separate experiments. In summary, prolonged cooling, even when delayed after onset of pMCAO, provides enduring behavioral and histological protection sufficient to suggest that it will be clinically effective. Nonetheless, further pre-clinical work is needed to improve treatment protocols, such as identifying the optimal depth of cooling, and how these factors interact with cooling method.