Experimental neurology
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Experimental neurology · Feb 2005
Stepwise motor and all-or-none sensory recovery is associated with nonlinear sparing after incremental spinal cord injury in rats.
Spinal cord injury (SCI) causes motor and sensory deficits that impair functional performance. While more functional recovery occurs with greater white matter sparing (WMS), it is unclear which locomotor features are more vulnerable to SCI than others, if recovery of certain features depends on specific amounts of WMS, and whether motor recovery patterns differ from sensory recovery. Locomotor and sensory recovery after graded contusive SCI with cord displacements of 0.3, 0.5, 0.7, 0.9, 1.1, 1.25, and 1.3 mm was examined for 6 weeks in 80 female Sprague-Dawley rats. ⋯ Mechanical allodynia developed only after injuries resulting in < or =10% WMS. Nonlinear motor and sensory recovery patterns suggest that small reparative changes may substantially improve function in individuals with SCI. A hierarchical locomotor recovery based on simple segmental versus complex supraspinal motor control is proposed.
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Experimental neurology · Jan 2005
Comparative StudyA novel azulenyl nitrone antioxidant protects against MPTP and 3-nitropropionic acid neurotoxicities.
Oxidative stress plays an important role in neuronal death in neurodegenerative disorders such as Parkinson's disease (PD) and Huntington's disease (HD). Animal models of PD or HD, produced by administration of the mitochondrial toxins 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 3-nitropropionic acid (3NP), respectively, show increased free radical generation. Free radicals generated in biological systems can react with spin-trapping compounds, such as nitrones, to form stable adducts. ⋯ The lipid peroxidation marker, malondialdehyde(MDA), was significantly increased in the striatum, cortex, and cerebellum of rats after administration of 3NP. These increases were blocked by co-injection of STAZN. Our data provide further evidence that STAZN is a neuroprotective free radical spin trap, and suggest that the development of new antioxidants will broaden our therapeutic strategies for neurodegenerative diseases.
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Experimental neurology · Jan 2005
Comparative StudyMK801 and amantadine exert different effects on subthalamic neuronal activity in a rodent model of Parkinson's disease.
Efforts to develop adjuvant therapies for the treatment of Parkinson's disease (PD) have led to interest in drugs that could mimic the therapeutic effects of lesion or deep brain stimulation of the subthalamic nucleus (STN). Extracellular single unit recordings were conducted to determine whether noncompetitive NMDA receptor blockade, suggested to have potential as an adjuvant treatment in PD, attenuates rate increases and firing pattern changes observed in the STN in a rodent model of PD. Systemic administration of the noncompetitive NMDA antagonist MK801 to rats with unilateral dopamine cell lesions did not significantly alter burstiness or interspike interval coefficient of variation, although mean firing rate decreased by a modest 20% with 50% of neurons showing decreases in rate >15% and spike train power in the 3-8-Hz (theta) range was reduced. ⋯ In both intact and lesioned animals, amantadine significantly increased STN firing rates and total spike train power in the 8-50-Hz range and did not alter spike power in the 3-8-Hz range or multisecond oscillatory activity. These observations show that an effective noncompetitive NMDA antagonist such as MK801 induces modest change in STN activity in 6-hydroxydopamine (6-OHDA)-lesioned rats, with the most notable effect on multisecond periodicities in firing rate and theta frequency total spike power. Amantadine's effects differed from MK801's, raising questions about its primary mechanism of action and the role in PD pharmacotherapy of the STN rate increases induced by this drug.
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Experimental neurology · Dec 2004
The effect of brain-derived neurotrophic factor on sensory and autonomic function after lingual nerve repair.
Brain-derived neurotrophic factor (BDNF) is important in the response to peripheral nerve injury and may enhance regeneration. We have assessed its role in the functional recovery of sensory afferents and autonomic efferents after repair of the chorda tympani and lingual nerves in the cat. Six months after entubulation repair, with or without the incorporation of BDNF at the repair site, the recovery of secretomotor and vasomotor efferents was determined by recording salivary flow from the submandibular gland and temperature changes on the tongue surface, each evoked by stimulation of the repaired nerve. ⋯ The conduction velocity of afferents in the lingual nerve was also lower, but the mechanoreceptive field size was higher. Thus, despite its known trophic role in the gustatory system, BDNF had not enhanced recovery of these or other fibre populations. We conclude that the application of BDNF to a site of lingual nerve repair has a negative effect on the long-term outcome.
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Experimental neurology · Dec 2004
Comparative StudyModification of the brain-derived neurotrophic factor gene: a portal to transform mesenchymal stem cells into advantageous engineering cells for neuroregeneration and neuroprotection.
Multipotential mesenchymal stem cells (MSCs) are ideal seed cells for recruiting the loss of neural cells due to their strong proliferative capacity, easy acquisition, and considerable tolerance of genetic modifications. After transduction of brain-derived neurotrophic factor (BDNF) gene via recombinant retroviral vectors into the human MSCs, nearly 100% of cells expressed BDNF (which were therefore transformed into BNDF-MSCs) as detected by immunocytochemistry, and the quantity of BDNF in the culture medium was increased by approximately 20,000-fold. In spite of the genomic integration of an exogenous gene, BDNF-MSCs did not present any structural aberration in the chromosomes. ⋯ Compared with the MSCs induced by both RA and BDNF, BDNF-MSCs survived in significantly greater number in the induction medium, and also more cells were induced into neuron-like cells (NeuN, P < 0.01) and oligodendrocyte-like cells (O4, P < 0.05). We suppose that, once engrafted into human central nervous system, the BDNF-MSCs would not only recruit the neuronal losses, but also provide, by way of paracrine, large quantities of BDNF that effectively perform the functions of neuroprotection and neuroregeneration, promoting the activation of endogenous neural stem/progenitor cells and their chemotactic migration. On the other hand, the BDNF-MSCs that can survive in the host environment and differentiate subsequently into functional mature cells may also serve as specifically targeting vectors for ex vivo gene therapy.