Experimental neurology
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Experimental neurology · Feb 2005
Nerve growth factor injection into semispinal neck muscle evokes sustained facilitation of the jaw-opening reflex in anesthetized mice -- possible implications for tension-type headache.
Nociceptive input from neck muscles probably plays a role in the pathophysiology of tension-type headache. In order to elaborate an animal model, the impact of noxious input from neck muscles on orofacial sensorimotor processing was investigated by electrophysiological means in anesthetized mice. Group IV muscle afferents of the semispinal neck muscle were excited by local injection of nerve growth factor (NGF, 0.8 microM, 20 microl). ⋯ After intramuscular injection of isotonic saline into the right semispinal neck muscle (20 microl), the JOR remained unchanged (n = 10). Local NGF injection into neck muscles evoked noxious input to the brainstem that induced a sustained central facilitation of the JOR for more than 1 h. This long-term facilitation of orofacial sensorimotor processing by a singular NGF injection possibly reflects plastic changes of nociceptive synaptic processing that may be involved in the pathophysiology of headache.
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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
Unilateral ischemic sensorimotor cortical damage in female rats: forelimb behavioral effects and dendritic structural plasticity in the contralateral homotopic cortex.
Previous studies in male rats with unilateral sensorimotor cortical (SMC) damage have demonstrated dendritic structural plasticity in the contralateral homotopic cortex and an enhancement of skilled reaching performance in the forelimb ipsilateral to the lesion compared to sham-operated rats. The purpose of this study was to determine if these findings could be replicated in an ischemic lesion model in female rats. Female rats were given sham operations or unilateral ischemic (endothelin-1 induced) damage in the forelimb representation area of the SMC opposite their preferred forelimb. ⋯ Additionally, there were major laminar-dependent increases in the surface density of MAP2 IR dendrites in the cortex opposite lesions and trained limbs. These findings in female rats are consistent with the dendritic and behavioral changes previously found in male rats. They extend these previous findings by indicating that lesion size is an important variable in the enhancement of reaching performance.
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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.