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Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics

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https://www.readbyqxmd.com/read/29790082/chronic-administration-of-pimozide-fails-to-attenuate-motor-and-pathological-deficits-in-two-mouse-models-of-amyotrophic-lateral-sclerosis
#1
Silvia Pozzi, Sai Sampath Thammisetty, Jean-Pierre Julien
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease which presently does not have any efficient therapeutic approach. Pimozide, a Food and Drug Administration (FDA)-approved neuroepileptic drug, has been recently proposed as a promising treatment for ALS patients based on apparent stabilization of right hand muscles after a short-time administration. A new clinical trial started at the end of 2017 to recruit patients with a prolonged drug delivery schedule. Here, our aim was to investigate the effects of chronic administration of pimozide on disease progression and pathological events in two mouse models of ALS...
May 22, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/29736859/pigment-epithelium-derived-factor-plays-a-role-in-alzheimer-s-disease-by-negatively-regulating-a%C3%AE-42
#2
Mao Huang, Weiwei Qi, Shuhuan Fang, Ping Jiang, Cong Yang, Yousheng Mo, Chang Dong, Yan Li, Jun Zhong, Weibin Cai, Zhonghan Yang, Ti Zhou, Qi Wang, Xia Yang, Guoquan Gao
Alzheimer's disease (AD) is the most common cause of dementia. Pigment epithelium-derived factor (PEDF), a unique neurotrophic protein, decreases with aging. Previous reports have conflicted regarding whether the PEDF concentration is altered in AD patients. In addition, the effect of PEDF on AD has not been documented. Here, we tested serum samples of 31 AD patients and 271 normal controls. We found that compared to PEDF levels in young and middle-aged control subjects, PEDF levels were reduced in old-aged controls and even more so in AD patients...
May 7, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/29736858/clinical-trials-in-traumatic-spinal-cord-injury
#3
REVIEW
Jayne Donovan, Steven Kirshblum
Traumatic spinal cord injury (SCI) results in impaired neurologic function that for many individuals is permanent and significantly impacts health, function, quality of life, and life expectancy. Many efforts have been taken to develop effective treatments for SCI; nevertheless, proven therapies targeting neurologic regeneration and functional recovery have been limited. Existing therapeutic approaches, including early surgery, strict blood pressure control, and consideration of treatment with steroids, remain debated and largely focus on mitigating secondary injury after the primary trauma has occurred...
May 7, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/29736857/neuropathic-pain-after-spinal-cord-injury-challenges-and-research-perspectives
#4
REVIEW
Rani Shiao, Corinne A Lee-Kubli
Neuropathic pain is a debilitating consequence of spinal cord injury (SCI) that remains difficult to treat because underlying mechanisms are not yet fully understood. In part, this is due to limitations of evaluating neuropathic pain in animal models in general, and SCI rodents in particular. Though pain in patients is primarily spontaneous, with relatively few patients experiencing evoked pains, animal models of SCI pain have primarily relied upon evoked withdrawals. Greater use of operant tasks for evaluation of the affective dimension of pain in rodents is needed, but these tests have their own limitations such that additional studies of the relationship between evoked withdrawals and operant outcomes are recommended...
May 7, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/29728852/glial-cells-shape-pathology-and-repair-after-spinal-cord-injury
#5
REVIEW
Andrew D Gaudet, Laura K Fonken
Glial cell types were classified less than 100 years ago by del Rio-Hortega. For instance, he correctly surmised that microglia in pathologic central nervous system (CNS) were "voracious monsters" that helped clean the tissue. Although these historical predictions were remarkably accurate, innovative technologies have revealed novel molecular, cellular, and dynamic physiologic aspects of CNS glia. In this review, we integrate recent findings regarding the roles of glia and glial interactions in healthy and injured spinal cord...
May 4, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/29728851/mesenchymal-stem-cell-macrophage-choreography-supporting-spinal-cord-repair
#6
REVIEW
Inés Maldonado-Lasunción, Joost Verhaagen, Martin Oudega
Spinal cord injury results in destructive events that lead to tissue loss and functional impairments. A hallmark of spinal cord injury is the robust and persistent presence of inflammatory macrophages. Mesenchymal stem cells (MSCs) are known to benefit repair of the damaged spinal cord often associated with improved functional recovery. Transplanted MSCs immediately encounter the abundance of inflammatory macrophages in the injury site. It is known that MSCs interact closely and reciprocally with macrophages during tissue healing...
May 4, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/29717413/spinal-cord-injury-scarring-and-inflammation-therapies-targeting-glial-and-inflammatory-responses
#7
REVIEW
Michael B Orr, John C Gensel
Deficits in neuronal function are a hallmark of spinal cord injury (SCI) and therapeutic efforts are often focused on central nervous system (CNS) axon regeneration. However, secondary injury responses by astrocytes, microglia, pericytes, endothelial cells, Schwann cells, fibroblasts, meningeal cells, and other glia not only potentiate SCI damage but also facilitate endogenous repair. Due to their profound impact on the progression of SCI, glial cells and modification of the glial scar are focuses of SCI therapeutic research...
May 1, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/29713909/effects-of-rifaximin-on-central-responses-to-social-stress-a-pilot-experiment
#8
Huiying Wang, Christoph Braun, Paul Enck
Probiotics that promote the gut microbiota have been reported to reduce stress responses, and improve memory and mood. Whether and how antibiotics that eliminate or inhibit pathogenic and commensal gut bacteria also affect central nervous system functions in humans is so far unknown. In a double-blinded randomized study, 16 healthy volunteers (27.00 ± 1.60 years; 9 males) received either rifaximin (600 mg/day) (a poorly absorbable antibiotic) or placebo for 7 days. Before and after the drug intervention, brain activities during rest and during a social stressor inducing feelings of exclusion (Cyberball game) were measured using magnetoencephalography...
April 30, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/29675823/impact-of-neurodegenerative-diseases-on-drug-binding-to-brain-tissues-from-animal-models-to-human-samples
#9
Ana Ugarte, David Corbacho, María S Aymerich, Ana García-Osta, Mar Cuadrado-Tejedor, Julen Oyarzabal
Drug efficacy in the central nervous system (CNS) requires an additional step after crossing the blood-brain barrier. Therapeutic agents must reach their targets in the brain to modulate them; thus, the free drug concentration hypothesis is a key parameter for in vivo pharmacology. Here, we report the impact of neurodegeneration (Alzheimer's disease (AD) and Parkinson's disease (PD) compared with healthy controls) on the binding of 10 known drugs to postmortem brain tissues from animal models and humans. Unbound drug fractions, for some drugs, are significantly different between healthy and injured brain tissues (AD or PD)...
April 19, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/29671241/current-prophylactic-medications-for-migraine-and-their-potential-mechanisms-of-action
#10
REVIEW
Till Sprenger, M Viana, C Tassorelli
A relatively high number of different medications is currently used for migraine prevention in clinical practice. Although these compounds were initially developed for other indications and differ in their mechanisms of action, some general themes can be identified from the mechanisms at play. Efficacious preventive drugs seem to either suppress excitatory nervous signaling via sodium and/or calcium receptors, facilitate GABAergic inhibition, reduce neuronal sensitization, block cortical spreading depression and/or reduce circulating levels of CGRP...
April 18, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/29667112/migraine-therapy-current-approaches-and-new-horizons
#11
EDITORIAL
Peter J Goadsby, Philip R Holland
No abstract text is available yet for this article.
April 17, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/29616494/the-biology-of-monoclonal-antibodies-focus-on-calcitonin-gene-related-peptide-for-prophylactic-migraine-therapy
#12
REVIEW
Bianca Raffaelli, Uwe Reuter
Calcitonin gene-related peptide (CGRP) is 37-amino-acid neuropeptide, crucially involved in migraine pathophysiology. Four monoclonal antibodies (mAbs) targeting the CGRP pathway are currently under evaluation for the prevention of episodic and chronic migraine: eptinezumab (ALD403), fremanezumab (TEV-48125), galcanezumab (LY2951742), and erenumab (AMG334). As reviewed in this article, all 4 antibodies have been proven effective, tolerable, and safe as migraine prophylactic treatments in phase II clinical trials...
April 3, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/29616493/non-pharmacological-approaches-for-migraine
#13
REVIEW
Francesca Puledda, Kevin Shields
Migraine is one of the most common and debilitating neurological disorders. However, the efficacy of pharmacological therapies may have unsatisfactory efficacy and can be poorly tolerated. There is a strong need in clinical practice for alternative approaches for both acute and preventive treatment. Occasionally, this need might arise in the context of low-frequency migraneurs who are not keen to use medication or fear the potential side effects. At the opposite end of the spectrum, clinicians might be faced with patients who have proven refractory to numerous medications...
April 3, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/29582402/association-of-herpes-viral-infections-antiherpetic-therapy-and-dementia-real-or-alternative-fact
#14
EDITORIAL
Avindra Nath
No abstract text is available yet for this article.
March 26, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/29500811/efficacy-of-propranolol-bisoprolol-and-pyridostigmine-for-postural-tachycardia-syndrome-a-randomized-clinical-trial
#15
Jangsup Moon, Do-Yong Kim, Woo-Jin Lee, Han Sang Lee, Jung-Ah Lim, Tae-Joon Kim, Jin-Sun Jun, Byeongsu Park, Jung-Ick Byun, Jun-Sang Sunwoo, Soon-Tae Lee, Keun-Hwa Jung, Kyung-Il Park, Ki-Young Jung, Manho Kim, Sang Kun Lee, Kon Chu
Postural tachycardia syndrome (POTS) is a form of dysautonomia which presents with complex symptoms including orthostatic intolerance. Several medications are prescribed for POTS; however, the efficacy of sustained medical treatment has not been well-investigated. Here, we conducted a 2 × 2 factorial design, randomized, clinical trial of a 3-month medical treatment regimen in POTS patients. Patients were randomly allocated to 4 treatment groups (Group 1: propranolol; Group 2: bisoprolol; Group 3: propranolol + pyridostigmine; Group 4: bisoprolol + pyridostigmine)...
March 2, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/29556965/targeted-cgrp-small-molecule-antagonists-for-acute-migraine-therapy
#16
REVIEW
Philip R Holland, Peter J Goadsby
Migraine is a highly prevalent, severe, and disabling neurological condition with a significant unmet need for effective acute therapies. Patients (~50%) are dissatisfied with their currently available therapies. Calcitonin gene-related peptide (CGRP) has emerged as a key neuropeptide involved in the pathophysiology of migraines. As reviewed in this manuscript, a number of small molecule antagonists of the CGRP receptor have been developed for migraine therapy. Incredibly, the majority of the clinical trials conducted have proven positive, demonstrating the importance of this signalling pathway in migraine...
April 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/29549622/targeted-acid-sensing-ion-channel-therapies-for-migraine
#17
REVIEW
Nazia Karsan, Eric B Gonzales, Gregory Dussor
Acid-sensing ion channels (ASICs) are a family of ion channels, consisting of four members; ASIC1 to 4. These channels are sensitive to changes in pH and are expressed throughout the central and peripheral nervous systems-including brain, spinal cord, and sensory ganglia. They have been implicated in a number of neurological conditions such as stroke and cerebral ischemia, traumatic brain injury, and epilepsy, and more recently in migraine. Their expression within areas of interest in the brain in migraine, such as the hypothalamus and PAG, their demonstrated involvement in preclinical models of meningeal afferent signaling, and their role in cortical spreading depression (the electrophysiological correlate of migraine aura), has enhanced research interest into these channels as potential therapeutic targets in migraine...
April 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/29542022/pilot-single-blind-trial-of-abobotulinumtoxina-in-oromandibular-dystonia
#18
Laura M Scorr, Michael R Silver, John Hanfelt, Elaine Sperin, Alan Freeman, H A Jinnah, Stewart A Factor
Oromandibular dystonia (OMD) causes involuntary movements of masticatory and lingual muscles impairing eating, speaking, and swallowing. Treatment options are limited. The objective of this study was to determine the safety and efficacy of abobotulinumtoxinA (aboBoNTA) in OMD. A dose-finding study (phase 1) followed by a single session, prospective, single-blind trial (phase 2) was carried out. OMD subjects were evaluated at baseline, 6 and 12 weeks. Muscles injected were tailored to individual symptoms using EMG guidance, but the aboBoNTA dose for each muscle was pre-specified based on phase 1 results...
April 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/29516437/therapeutic-approaches-for-the-management-of-trigeminal-autonomic-cephalalgias
#19
REVIEW
Diana Y Wei, Rigmor H Jensen
Trigeminal autonomic cephalalgia (TAC) encompasses 4 unique primary headache types: cluster headache, paroxysmal hemicrania, hemicrania continua, and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing and short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms. They are grouped on the basis of their shared clinical features of unilateral headache of varying durations and ipsilateral cranial autonomic symptoms. The shared clinical features reflect the underlying activation of the trigeminal-autonomic reflex...
April 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/29516436/targeted-nitric-oxide-synthase-inhibitors-for-migraine
#20
REVIEW
Amynah A Pradhan, Zachariah Bertels, Simon Akerman
Nitric oxide (NO) is a small gaseous signaling molecule that has important biological effects. It has been heavily implicated in migraine; and the NO donor, nitroglycerin, has been used extensively as a human migraine trigger. Correspondingly, a number of components of the NO signaling cascade have been shown to be upregulated in migraine patients. NO is endogenously produced in the body by NO synthase (NOS), of which there are three isoforms: neuronal NOS (nNOS), endothelial NOS (eNOS), and inducible NOS (iNOS)...
April 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
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