Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology
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J Neuroimmune Pharmacol · Mar 2014
The novel tetramethylpyrazine bis-nitrone (TN-2) protects against MPTP/MPP+-induced neurotoxicity via inhibition of mitochondrial-dependent apoptosis.
Mitochondrial-dependent apoptosis plays an important role in the degeneration of dopaminergic neurons in Parkinson's disease (PD). Methyl-4-phenyl-1,2,3,6-tetra- hydropyridine (MPTP), the most widely used neurotoxin to simulate PD, is converted to 1-methyl-4-phenylpyridinium (MPP(+)) in vivo. MPP(+) induces excessive intracellular reactive oxygen species (ROS), leading to mitochondrial-dependent apoptosis via sequentially opening mitochondria permeability transition pore (mPTP) to release cytochrome c from mitochondria into cytoplasm and activate pro-apoptotic caspase proteins. ⋯ TN-2 decreased excessive intracellular ROS, prevented the loss of mitochondrial membrane potential, blocked the release of mitochondrial cytochrome c and inhibited the activation of caspase-3 and caspase-9. Moreover, TN-2 treatment increased the mRNA expression of mitochondrial biogenesis factors peroxisome proliferator-activated receptor (PPAR)-γ coactivator-1 (PGC- 1α and β) and mitochondrial transcription factor A (Tfam) in SH-SY5Y cells and CGNs. These results suggest that TN-2 protects dopaminergic neurons against MPTP/MPP(+)-induced neurotoxicity via the inhibition of mitochondrial-dependent apoptosis and possibly via the activation of mitochondrial biogenesis, indicating that TN-2 is a potential new treatment for PD.
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J Neuroimmune Pharmacol · Dec 2013
Observational StudyAnti-JCV antibodies detection and JCV DNA levels in PBMC, serum and urine in a cohort of Spanish Multiple Sclerosis patients treated with natalizumab.
One of the most effective multiple sclerosis (MS) treatment is natalizumab. Nevertheless, it has been associated with an increased risk of progressive multifocal leukoencephalopathy (PML) caused by the JC virus (JCV). Our main objective was to assess the utility of testing JCV-DNA, apart from anti-JCV antibodies, to determine which natalizumab-treated MS patients has been previously in contact with the virus. ⋯ Nearly all patients with detectable JCV-DNA levels in PBMC excreted the virus intermittently in urine; while our PML case, positive in PBMC and serum samples 2 month before the PML, excreted JCV permanently. In conclusion, the determination of JCV DNA levels in urine could be complementary to anti-JCV antibodies for identifying MS patients who has been infected by the JCV. Further research would be necessary to understand the different JCV excretion profiles in urine.
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J Neuroimmune Pharmacol · Sep 2013
ReviewCommentary on special issue: CNS diseases and the immune system.
In an increasing number of central nervous system (CNS) diseases a pathogenic contribution of the immune system is proposed. However, the exact underlying mechanisms are often poorly understood. The collection of articles in this special issue presents a state-of-the-art review of adaptive and innate immune mechanisms and their main players in number CNS disorders. The aim of these articles is to stimulate discussion on the question whether the immune system may be a feasible target of therapy for diseases where currently no effective treatment exists.
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J Neuroimmune Pharmacol · Jun 2013
ReviewNeuroinflammation, neuroautoimmunity, and the co-morbidities of complex regional pain syndrome.
Complex Regional Pain Syndrome (CRPS) is associated with non-dermatomal patterns of pain, unusual movement disorders, and somatovisceral dysfunctions. These symptoms are viewed by some neurologists and psychiatrists as being psychogenic in origin. ⋯ From both animal and human studies, evidence is accumulating that neuroinflammation can spread, either anterograde or retrograde, via axonal projections in the CNS, thereby establishing neuroinflammatory tracks and secondary neuroinflammatory foci within the neuraxis. These findings suggest that neuroinflammatory lesions, as well as their associated functional consequences, should be evaluated during the differential diagnosis of non-dermatomal pain presentations, atypical movement disorders, as well as other "medically unexplained symptoms", which are often attributed to psychogenic illness.
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J Neuroimmune Pharmacol · Jun 2013
ReviewMeasuring GABAergic inhibitory activity with TMS-EEG and its potential clinical application for chronic pain.
Chronic pain is debilitating disorder in which the underlying pathophysiology is still unknown. Impaired cortical inhibition is one mechanism that is associated with chronic pain. Cortical inhibition refers to a neurophysiological process in which gamma-aminobutyric acid (GABA) inhibitory interneurons selectively attenuate the activity of pyramidal neurons in the cortex. ⋯ We then demonstrate TMS-EEG as a reliable method in which to record cortical inhibition directly from the prefrontal cortex to examine the modulatory effect of GABAB receptor inhibition on cortical oscillations. Finally, the modulation of GABA and gamma oscillations with repetitive TMS will be suggested as the possible mechanism through which rTMS exerts its therapeutic effects in the treatment of pain. The aim of this paper, therefore, is to present the TMS-EEG as a potential method through which to better classify, diagnose and treat chronic pain.