Activation of NPFFR2 leads to hyperalgesia through the spinal inflammatory mediator CGRP in mice.
Abstract Neuropeptide FF (NPFF) is recognized as an opioid modulating peptide that regulates morphine-induced analgesia. The aim of this study was to delineate the role of NPFFR2 in pain transmission. We found the expression levels of NPFF and NPFFR2 were increased in the lumbar dorsal horn of animals with CFA- and carrageenan-induced inflammation and both NPFFR2 over-expressing transgenic (NPFFR2-Tg) and NPFFR2 agonist-treated mice displayed hyperalgesia. BOLD signals from functional MRI showed that NPFFR2-Tg mice exhibited increased activation of pain-related brain regions after painful stimulation when compared...
Source: Experimental Neurology - February 5, 2017 Category: Neurology Authors: Lin YT, Liu HL, Day YJ, Chang CC, Hsu PH, Chen JC Tags: Exp Neurol Source Type: research

Effects of liposome-based local suppression of nerve growth factor in the bladder on autonomic dysreflexia during urinary bladder distention in rats with spinal cord injury.
CONCLUSIONS: These results indicate that the duration of the post-SCI recovery period affects the severity of AD induced by bladder distention as well as the level of bladder NGF protein, and that local suppression of NGF expression in the bladder reduces SCI-induced AD. Thus, Intravesical application of liposome-NGF antisense conjugates can be a new effective therapy for bladder distention-induced AD after SCI. PMID: 28174025 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - February 4, 2017 Category: Neurology Authors: Kadekawa K, Yoshizawa T, Wada N, Shimizu T, Majima T, Tyagi P, de Groat WC, Sugaya K, Yoshimura N Tags: Exp Neurol Source Type: research

Neuron subset-specific Pten deletion induces abnormal skeletal activity in mice.
In this study, we used NS-Pten conditional knockout mice (a well-studied genetic model of epilepsy). We used microCT analysis to measure BMD, morphology, and mineralization in NS-Pten(+/+) (wildtype) and NS-Pten(-/-) (knockout) mice at 4 and 8weeks, as well as adult Kv4.2(+/+) and Kv4.2(-/-) mice. We measured BMD, bone morphology, and mineralization in adult NS-Pten(+/+) mice that received status epilepticus through kainic acid (20mg/kg intraperitoneal). Further, we measured locomotion for NS-Pten(+/+) and NS-Pten(-/-) mice at 4 and 6weeks. We found that NS-Pten(-/-) mice exhibited low BMD in the tibial metaphysis and mids...
Source: Experimental Neurology - February 2, 2017 Category: Neurology Authors: Lugo JN, Thompson MH, Huber P, Smith G, Kwon RY Tags: Exp Neurol Source Type: research

Mitochondrial ferritin protects SH-SY5Y cells against H2O2-induced oxidative stress and modulates α-synuclein expression.
In this study, we investigated the function of FtMt in α-synuclein regulation and its antioxidant roles in dopaminergic cells using human dopaminergic neuroblastoma cells, SH-SY5Y. In physiological conditions, FtMt knockdown increased α-synuclein expression at the protein level but not at the mRNA level. By contrast, FtMt overexpression reduced α-synuclein expression at the protein level but not at the mRNA level. FtMt enhanced the iron levels in mitochondria but decreased the iron levels in the intracellular labile iron pool. We found that FeCl2 could abolish the effects of FtMt overexpression on α...
Source: Experimental Neurology - February 2, 2017 Category: Neurology Authors: Guan H, Yang H, Yang M, Yanagisawa D, Bellier JP, Mori M, Takahata S, Nonaka T, Zhao S, Tooyama I Tags: Exp Neurol Source Type: research

Transplanted human glial-restricted progenitors can rescue the survival of dysmyelinated mice independent of the production of mature, compact myelin.
Abstract The therapeutic effect of glial progenitor transplantation in diseases of dysmyelination is currently attributed to the formation of new myelin. Using magnetic resonance imaging (MRI), we show that the therapeutic outcome in dysmyelinated shiverer mice is dependent on the extent of cell migration but not presence of mature and compact myelin. Human or mouse glial restricted progenitors (GRPs) were transplanted into rag2(-/)(-)shiverer mouse neonates and followed for over one year. Mouse GRPs produced mature myelin as detected with multi-parametric MRI, but showed limited migration without extended animal ...
Source: Experimental Neurology - February 2, 2017 Category: Neurology Authors: Lyczek A, Arnold A, Zhang J, Campanelli JT, Janowski M, Bulte JW, Walczak P Tags: Exp Neurol Source Type: research

Zebrafish models of autism spectrum disorder.
Abstract Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by motor, social and cognitive deficits that develop during childhood. The pathogenesis of ASD is not well characterized and involves a multifaceted interaction between genetic, neurobiological and environmental factors. Animal (experimental) models possess evolutionarily conserved behaviors and molecular pathways that are highly relevant for studying ASD. The zebrafish (Danio rerio) is a relatively new animal model with promise for understanding the pathogenesis of complex brain disorders and discovering novel treatment...
Source: Experimental Neurology - February 2, 2017 Category: Neurology Authors: Meshalkina DA, Kizlyuk M, Kisel E, Collier AD, Echevarria DJ, Abreu MS, Barcellos LJ, Song C, Warnick JE, Kyzar EJ, Kalueff AV Tags: Exp Neurol Source Type: research

Neurovascular uncoupling in the triple transgenic model of Alzheimer's disease: Impaired cerebral blood flow response to neuronal-derived nitric oxide signaling.
nha J Abstract Nitric oxide (NO)-dependent pathways and cerebrovascular dysfunction have been shown to contribute to the cognitive decline and neurodegeneration observed in Alzheimer's disease (AD) but whether they represent initial factors or later changes of the disease is still a matter of debate. In this work, we aimed at investigating whether and to what extent neuronal-derived NO signaling and related neurovascular coupling are impaired along aging in the hippocampus of the triple transgenic mouse model of Alzheimer's Disease (3xTg-AD). We performed a longitudinal study combining behavior studies, in vivo si...
Source: Experimental Neurology - February 1, 2017 Category: Neurology Authors: Lourenço CF, Ledo A, Barbosa RM, Laranjinha J Tags: Exp Neurol Source Type: research

Insights in spatio-temporal characterization of human fetal neural stem cells.
sser A, Canals JM Abstract Primary human fetal cells have been used in clinical trials of cell replacement therapy for the treatment of neurodegenerative disorders such as Huntington's disease (HD). However, human fetal primary cells are scarce and difficult to work with and so a renewable source of cells is sought. Human fetal neural stem cells (hfNSCs) can be generated from human fetal tissue, but little is known about the differences between hfNSCs obtained from different developmental stages and brain areas. In the present work we characterized hfNSCs, grown as neurospheres, obtained from three developmental s...
Source: Experimental Neurology - January 25, 2017 Category: Neurology Authors: Martín-Ibáñez R, Guardia I, Pardo M, Herranz C, Zietlow R, Vinh NN, Rosser A, Canals JM Tags: Exp Neurol Source Type: research

The 5-alpha reductase inhibitor finasteride reduces dyskinesia in a rat model of Parkinson's disease.
Abstract Levodopa-induced dyskinesia (LID) is a disabling motor complication occurring in Parkinson's disease patients (PD) after long-term l-DOPA treatment. Although its etiology remains unclear, there is accumulating evidence that LID relies on an excessive dopamine receptor transmission, particularly at the downstream signaling of D1 receptors. We previously reported that the pharmacological blockade of 5-alpha reductase (5AR), the rate limiting enzyme in neurosteroids synthesis, rescued a number of behavioral aberrations induced by D1 receptor-selective and non-selective agonists, without inducing extrapyramid...
Source: Experimental Neurology - January 25, 2017 Category: Neurology Authors: Frau R, Savoia P, Fanni S, Fiorentini C, Fidalgo C, Tronci E, Stancampiano R, Meloni M, Cannas A, Marrosu F, Bortolato M, Devoto P, Missale C, Carta M Tags: Exp Neurol Source Type: research

Transplantation site influences the phenotypic differentiation of dopamine neurons in ventral mesencephalic grafts in Parkinsonian rats.
Abstract Foetal midbrain progenitors have been shown to survive, give rise to different classes of dopamine neurons and integrate into the host brain alleviating Parkinsonian symptoms following transplantation in patients and animal models of the disease. Dopamine neuron subpopulations in the midbrain, namely A9 and A10, can be identified anatomically based on cell morphology and ascending axonal projections. G protein-gated inwardly rectifying potassium channel Girk2 and the calcium binding protein Calbindin are the two best available histochemical markers currently used to label (with some overlap) A9- and A10-l...
Source: Experimental Neurology - January 25, 2017 Category: Neurology Authors: Fjodorova M, Torres EM, Dunnett SB Tags: Exp Neurol Source Type: research

Long-Term Protective Effects of AAV9-Mesencephalic Astrocyte-Derived Neurotrophic Factor Gene Transfer in Parkinsonian Rats.
Abstract Intrastriatal injection of mesencephalic astrocyte-derived neurotrophic factor (MANF) protein has been shown to provide neuroprotective and neurorestorative effects in a 6-hydroxydopamine (6-OHDA) - lesioned rat model of Parkinson's disease. Here, we used an adeno-associated virus serotype 9 (AAV9) vector to deliver the human MANF (hMANF) gene into the rat striatum 10 days after a 6-OHDA lesion to examine long-term effects of hMANF on nigral dopaminergic neurons and mechanisms underlying MANF neuroprotection. Intrastriatal injection of AAV9-hMANF vectors led to a robust and widespread expression of the hM...
Source: Experimental Neurology - January 25, 2017 Category: Neurology Authors: Hao F, Yang C, Chen SS, Wang YY, Zhou W, Hao Q, Lu T, Hoffer B, Zhao LR, Duan WM, Xu QY Tags: Exp Neurol Source Type: research

Surgical repair in humans after traumatic nerve injury provides limited functional neural regeneration in adults.
Abstract Traumatic nerve injuries result in devastating loss of neurologic function with unpredictable functional recovery despite optimal medical management. After traumatic nerve injury and denervation, regenerating axons must traverse a complex environment in which they encounter numerous barriers on the way to reinnervation of their target muscle. Outcomes of surgical intervention alone have unfortunately reached a plateau, resulting in often unsatisfactory functional recovery. Over the past few decades, many improvements were developed to supplement and boost the results of surgical repair. Biological optimiz...
Source: Experimental Neurology - January 19, 2017 Category: Neurology Authors: Palispis WA, Gupta R Tags: Exp Neurol Source Type: research

Facilitation of distinct inhibitory synaptic inputs by chemical anoxia in neurons in the oculomotor, facial and hypoglossal motor nuclei of the rat.
Abstract Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the selective loss of motor neurons in the brainstem and spinal cord. Clinical studies have indicated that there is a distinct region-dependent difference in the vulnerability of motor neurons. For example, the motor neurons in the facial and hypoglossal nuclei are more susceptible to neuronal death than those in the oculomotor nucleus. To understand the mechanism underlying the differential susceptibility to cell death of the neurons in different motor nuclei, we compared the effects of chemical anoxia on the membr...
Source: Experimental Neurology - January 18, 2017 Category: Neurology Authors: Takagi S, Kono Y, Nagase M, Mochio S, Kato F Tags: Exp Neurol Source Type: research

Rapid Neuroinflammatory Response Localized to Injured Neurons After Diffuse Traumatic Brain Injury in Swine.
Abstract Despite increasing appreciation of the critical role that neuroinflammatory pathways play in brain injury and neurodegeneration, little is known about acute microglial reactivity following diffuse traumatic brain injury (TBI) - the most common clinical presentation that includes all concussions. Therefore, we investigated acute microglial reactivity using a porcine model of closed-head rotational velocity/acceleration-induced TBI that closely mimics the biomechanical etiology of inertial TBI in humans. We observed rapid microglial reactivity within 15min of both mild and severe TBI. Strikingly, microglial...
Source: Experimental Neurology - January 9, 2017 Category: Neurology Authors: Wofford KL, Harris JP, Browne KD, Brown DP, Grovola MR, Mietus CJ, Wolf JA, Duda JE, Putt ME, Spiller KL, Kacy Cullen D Tags: Exp Neurol Source Type: research

The neuroprotective compound P7C3-A20 promotes neurogenesis and improves cognitive function after ischemic stroke.
Abstract Ischemic stroke is a devastating condition with few therapeutic interventions available. The neuroprotective compound P7C3-A20 inhibits mature neuronal cell death while also increasing the net magnitude of postnatal neurogenesis in models of neurodegeneration and acute injury. P7C3 compounds enhance flux of nicotinamide adenine dinucleotide (NAD) in mammalian cells, a proposed therapeutic approach to treating cerebral ischemia. The effectiveness of P7C3-A20 treatment on chronic histopathological and behavioral outcomes and neurogenesis after ischemic stroke has not previously been established. Here, a tra...
Source: Experimental Neurology - January 8, 2017 Category: Neurology Authors: Loris ZB, Pieper AA, Dalton Dietrich W Tags: Exp Neurol Source Type: research

Omega-3 fatty acids regulate NLRP3 inflammasome activation and prevent behavior deficits after traumatic brain injury.
Abstract Omega-3 fatty acids (ω-3 FAs) attenuate inflammation and improve neurological outcome in response to traumatic brain injury (TBI), but the specific anti-inflammatory mechanisms remain to be elucidated. Here we found that NLRP3 inflammasome and subsequent pro-inflammatory cytokines were activated in human brains after TBI. Rats treated with ω-3 FAs had significantly less TBI-induced caspase-1 cleavage and IL-1β secretion than those with vehicle. G protein-coupled receptor 40 (GPR40) was observed to be involved in this anti-inflammation. GW1100, a GPR40 inhibitor, eliminated the anti-inflam...
Source: Experimental Neurology - January 8, 2017 Category: Neurology Authors: Lin C, Chao H, Li Z, Xu X, Liu Y, Bao Z, Hou L, Liu Y, Wang X, You Y, Liu N, Ji J Tags: Exp Neurol Source Type: research

Ventral medullary control of rapid eye movement sleep and atonia.
Abstract Discrete populations of neurons at multiple levels of the brainstem control rapid eye movement (REM) sleep and the accompanying loss of postural muscle tone, or atonia. The specific contributions of these brainstem cell populations to REM sleep control remains incompletely understood. Here we show in rats that viral vector-based lesions of the ventromedial medulla at a level rostral to the inferior olive (pSOM) produced violent myoclonic twitches and abnormal electromyographic spikes, but not complete loss of tonic atonia, during REM sleep. Motor tone during non-REM (NREM) sleep was unaffected in these sa...
Source: Experimental Neurology - January 7, 2017 Category: Neurology Authors: Chen MC, Vetrivelan R, Guo C, Chang C, Fuller PM, Lu J Tags: Exp Neurol Source Type: research

Glutamine triggers long-lasting increase in striatal network activity in vitro.
Abstract Accumulation of ammonium and glutamine in blood and brain is a key factor in hepatic encephalopathy (HE) - a neuropsychiatric syndrome characterized by various cognitive and motor deficits. MRI imaging identified abnormalities notably in the basal ganglia of HE patients, including its major input station, the striatum. While neurotoxic effects of ammonia have been extensively studied, glutamine is primarily perceived as "detoxified" form of ammonia. We applied ammonium and glutamine to striatal and cortical cells from newborn rats cultured on microelectrode arrays. Glutamine, but not ammonium si...
Source: Experimental Neurology - January 5, 2017 Category: Neurology Authors: Fleischer W, Theiss S, Schnitzler A, Sergeeva O Tags: Exp Neurol Source Type: research

Intranasal C3a treatment ameliorates cognitive impairment in a mouse model of neonatal hypoxic-ischemic brain injury.
In conclusion, our results reveal that brief pharmacological treatment with C3a using a clinically feasible non-invasive mode of administration ameliorates HI-induced cognitive impairment. Intranasal administration is a plausible route to deliver C3a into the brain of asphyxiated infants at high risk of developing hypoxic-ischemic encephalopathy. PMID: 28062175 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - January 3, 2017 Category: Neurology Authors: Morán J, Stokowska A, Walker FR, Mallard C, Hagberg H, Pekna M Tags: Exp Neurol Source Type: research

Editorial of Special Issue: Bio-electronics and prosthetics for neurological diseases.
PMID: 27938804 [PubMed - in process] (Source: Experimental Neurology)
Source: Experimental Neurology - December 14, 2016 Category: Neurology Authors: Ling G, Sanchez J, Pankratz K, Clifford D Tags: Exp Neurol Source Type: research

Evolutionary perspectives: Introduction to the special issue on Axon Regeneration Across Species.
e A PMID: 27912838 [PubMed - in process] (Source: Experimental Neurology)
Source: Experimental Neurology - December 5, 2016 Category: Neurology Authors: He Z, Höke A Tags: Exp Neurol Source Type: research

Special Issue: Respiratory Neuroplasticity.
PMID: 27871363 [PubMed - in process] (Source: Experimental Neurology)
Source: Experimental Neurology - November 24, 2016 Category: Neurology Authors: Fuller DD, Mitchell GS Tags: Exp Neurol Source Type: research

iPS-derived neural progenitor cells from PPMS patients reveal defect in myelin injury response.
Abstract Primary progressive multiple sclerosis (PPMS) is a chronic demyelinating disease of the central nervous system (CNS) currently lacking any effective treatment. Promoting endogenous brain repair offers a potential strategy to halt and possibly restore neurologic function in PPMS. To understand how the microenvironment within white matter lesions plays a role in repair we have focused on neural progenitor cells (NPCs) since these are found in lesions in PPMS and have been found to influence oligodendrocyte progenitor cell maturation (OPCs). To better understand the cellular nature of NPCs in PPMS we develop...
Source: Experimental Neurology - November 16, 2016 Category: Neurology Authors: Nicaise AM, Banda E, Guzzo RM, Russomanno K, Castro-Borrero W, Willis CM, Johnson KM, Lo AC, Crocker SJ Tags: Exp Neurol Source Type: research

Neurotrophic and neuroprotective effects of oxyntomodulin in neuronal cells and a rat model of stroke.
In this study, the neuroprotective effect of OXM was first examined in human neuroblastoma (SH-SY5Y) cells and rat primary cortical neurons. GLP-1R and GCGR antagonists, and inhibitors of various signaling pathways were used in cell culture to characterize the mechanisms of action of OXM. To evaluate translation in vivo, OXM-mediated neuroprotection was assessed in a 60-min, transient middle cerebral artery occlusion (MCAo) rat model of stroke. We found that OXM dose- and time-dependently increased cell viability and protected cells from glutamate toxicity and oxidative stress. These neuroprotective actions of OXM were mai...
Source: Experimental Neurology - November 14, 2016 Category: Neurology Authors: Li Y, Wu KJ, Yu SJ, Tamargo IA, Wang Y, Greig NH Tags: Exp Neurol Source Type: research

NOX4 is an early initiator of neuropathic pain.
Abstract Treatment of neuropathic pain remains challenging as the etiology is heterogeneous and pathomechanisms are incompletely understood. One possible mechanism is oxidative stress due to unphysiological reactive oxygen species (ROS) formation. The only know dedicated enzymatic source of ROS are NADPH oxidases of which the type 4 isoform (NOX4) has been suggested to be involved in the subacute and chronic phase of neuropathic pain. Here, we aim to translate this finding into a treatment strategy by examining the efficacy of the NOX1/4-specific inhibitor GKT136901 using the chronic constriction injury (CCI) mous...
Source: Experimental Neurology - November 14, 2016 Category: Neurology Authors: Geis C, Geuss E, Sommer C, Schmidt HH, Kleinschnitz C Tags: Exp Neurol Source Type: research

The inhibition of spinal synaptic plasticity mediated by activation of AMP-activated protein kinase signaling alleviates the acute pain induced by oxaliplatin.
Abstract Our recent findings demonstrated that oxaliplatin entering CNS may directly induce spinal central sensitization, and contribute to the rapid development of CNS-related side effects including acute pain during chemotherapy. However, the mechanism is largely unclear. In the current study, we found that the amplitude of C-fiber-evoked field potentials was significantly increased and the expression of phosphorylated mammalian AMP-activated protein kinase α (AMPKα) was markedly decreased following high frequency stimulation (HFS) or single intraperitoneal injection of oxaliplatin (4mg/kg). Spinal l...
Source: Experimental Neurology - November 14, 2016 Category: Neurology Authors: Ling YZ, Li ZY, Ou-Yang HD, Ma C, Wu SL, Wei JY, Ding HH, Zhang XL, Liu M, Liu CC, Huang ZZ, Xin WJ Tags: Exp Neurol Source Type: research

Novel GLP-1R/GIPR co-agonist "twincretin" is neuroprotective in cell and rodent models of mild traumatic brain injury.
Novel GLP-1R/GIPR co-agonist "twincretin" is neuroprotective in cell and rodent models of mild traumatic brain injury. Exp Neurol. 2016 Nov 11;: Authors: Tamargo IA, Bader M, Li Y, Yu SJ, Wang Y, Talbot K, DiMarchi RD, Pick CG, Greig NH Abstract Several single incretin receptor agonists that are approved for the treatment of type 2 diabetes mellitus (T2DM) have been shown to be neuroprotective in cell and animal models of neurodegeneration. Recently, a synthetic dual incretin receptor agonist, nicknamed "twincretin," was shown to improve upon the metabolic benefits of single recept...
Source: Experimental Neurology - November 11, 2016 Category: Neurology Authors: Tamargo IA, Bader M, Li Y, Yu SJ, Wang Y, Talbot K, DiMarchi RD, Pick CG, Greig NH Tags: Exp Neurol Source Type: research

Inward rectifier K(+) channel and T-type Ca(2+) channel contribute to enhancement of GABAergic transmission induced by β1-adrenoceptor in the prefrontal cortex.
Inward rectifier K(+) channel and T-type Ca(2+) channel contribute to enhancement of GABAergic transmission induced by β1-adrenoceptor in the prefrontal cortex. Exp Neurol. 2016 Nov 10;: Authors: Luo F, Zheng J, Sun X, Tang H Abstract The functions of prefrontal cortex (PFC) are sensitive to norepinephrine (NE). Endogenously released NE influences synaptic transmission through activation of different subtypes of adrenergic receptors in PFC including α1, α2, β1 or β2-adrenoceptor. Our recent study has revealed that β1-adrenoceptor (β1-AR) activation modulates glutam...
Source: Experimental Neurology - November 10, 2016 Category: Neurology Authors: Luo F, Zheng J, Sun X, Tang H Tags: Exp Neurol Source Type: research

Altered gene expression profile in a mouse model of SCN8A encephalopathy.
Abstract SCN8A encephalopathy is a severe, early-onset epilepsy disorder resulting from de novo gain-of-function mutations in the voltage-gated sodium channel Nav1.6. To identify the effects of this disorder on mRNA expression, RNA-seq was performed on brain tissue from a knock-in mouse expressing the patient mutation p.Asn1768Asp (N1768D). RNA was isolated from forebrain, cerebellum, and brainstem both before and after seizure onset, and from age-matched wildtype littermates. Altered transcript profiles were observed only in forebrain and only after seizures. The abundance of 50 transcripts increased>3-fold an...
Source: Experimental Neurology - November 8, 2016 Category: Neurology Authors: Sprissler RS, Wagnon JL, Bunton-Stasyshyn RK, Meisler MH, Hammer MF Tags: Exp Neurol Source Type: research

Cisplatin-induced neuropathic pain is mediated by upregulation of N-type voltage-gated calcium channels in dorsal root ganglion neurons.
Abstract Cisplatin is important in the treatment of various types of cancer. Although it is highly effective, it also has severe side effects, with neurotoxicity in dorsal root ganglion (DRG) neurons being one of the most common. The key mechanisms of neurotoxicity are still controversially discussed; however, disturbances of the calcium homeostasis in DRG neurons have been suggested to mediate cisplatin neurotoxicity. By using the whole-cell patch-clamp technique, immunostaining and behavioral experiments with Sprague-Dawley rats, we examined the influence of short- and long-term exposure to cisplatin on voltage-...
Source: Experimental Neurology - November 4, 2016 Category: Neurology Authors: Leo M, Schmitt LI, Erkel M, Melnikova M, Thomale J, Hagenacker T Tags: Exp Neurol Source Type: research

Complete spinal cord injury (SCI) transforms how brain derived neurotrophic factor (BDNF) affects nociceptive sensitization.
Abstract Noxious stimulation can induce a lasting increase in neural excitability within the spinal cord (central sensitization) that can promote pain and disrupt adaptive function (maladaptive plasticity). Brain-derived neurotrophic factor (BDNF) is known to regulate the development of plasticity and has been shown to impact the development of spinally-mediated central sensitization. The latter effect has been linked to an alteration in GABA-dependent inhibition. Prior studies have shown that, in spinally transected rats, exposure to regular (fixed spaced) stimulation can counter the development of maladaptive pl...
Source: Experimental Neurology - November 3, 2016 Category: Neurology Authors: Huang YJ, Lee KH, Grau JW Tags: Exp Neurol Source Type: research

Dopamine is produced in the rat spinal cord and regulates micturition reflex after spinal cord injury.
om VJ Abstract Dopamine (DA) neurons in the mammalian central nervous system are thought to be restricted to the brain. DA-mediated regulation of urinary activity is considered to occur through an interaction between midbrain DA neurons and the pontine micturition center. Here we show that DA is produced in the rat spinal cord and modulates the bladder reflex. We observed numerous tyrosine hydroxylase (TH)(+) neurons in the autonomic nuclei and superficial dorsal horn in L6-S3 spinal segments. These neurons are dopamine-β-hydroxylase (DBH)(-) and some contain detectable dopamine decarboxylase (DDC), suggestin...
Source: Experimental Neurology - October 26, 2016 Category: Neurology Authors: Hou S, Carson DM, Wu D, Klaw MC, Houlé JD, Tom VJ Tags: Exp Neurol Source Type: research

Colitis-induced bladder afferent neuronal activation is regulated by BDNF through PLC γ pathway.
Colitis-induced bladder afferent neuronal activation is regulated by BDNF through PLCγ pathway. Exp Neurol. 2016 Nov;285(Pt B):126-135 Authors: Xia C, Shen S, Hashmi F, Qiao LY Abstract Patients with inflammatory bowel disease (IBD) or irritable bowel syndrome (IBS) often experience increased sensory responsiveness in the urinary bladder reflecting neurogenic bladder overactivity. Here we demonstrate that colitis-induced up-regulation of the phospholipase C gamma (PLCγ) pathway downstream of brain-derived neurotrophic factor (BDNF) in bladder afferent neurons in the dorsal root ganglia (DR...
Source: Experimental Neurology - October 26, 2016 Category: Neurology Authors: Xia C, Shen S, Hashmi F, Qiao LY Tags: Exp Neurol Source Type: research

A ventral root avulsion injury model for neurogenic underactive bladder studies.
Abstract Detrusor underactivity (DU) is defined as a contraction of reduced strength and/or duration during bladder emptying and results in incomplete and prolonged bladder emptying. The clinical diagnosis of DU is challenging when present alone or in association with other bladder conditions such as detrusor overactivity, urinary retention, detrusor hyperactivity with impaired contractility, aging, and neurological injuries. Several etiologies may be responsible for DU or the development of an underactive bladder (UAB), but the pathobiology of DU or UAB is not well understood. Therefore, new clinically relevant a...
Source: Experimental Neurology - October 26, 2016 Category: Neurology Authors: Chang HH, Havton LA Tags: Exp Neurol Source Type: research

Phasic activation of the external urethral sphincter increases voiding efficiency in the rat and the cat.
CONCLUSIONS: Artificial phasic EUS bursting restored efficient voiding in rats. Introduction of artificial phasic bursting in cats, which normally exhibit EUS relaxation while voiding, was also effective in promoting efficient voiding. In both species phasic EUS activity increased voiding efficiency via activation of pudendal sensory pathways. These results provide further insight into the function of phasic EUS activity in efficient voiding and highlight a novel approach to increase VE generated by pudendal afferent nerve stimulation. PMID: 27235934 [PubMed - in process] (Source: Experimental Neurology)
Source: Experimental Neurology - October 26, 2016 Category: Neurology Authors: Langdale CL, Grill WM Tags: Exp Neurol Source Type: research

Impairment of sensory afferents by intrathecal administration of botulinum toxin A improves neurogenic detrusor overactivity in chronic spinal cord injured rats.
Abstract Spinal cord injury (SCI) often leads to neurogenic detrusor overactivity (NDO) due to sprouting of sensory afferents on the lumbosacral spinal cord. NDO is characterized by high frequency of voiding contractions and increased intravesical pressure that may lead to urinary incontinence. The latter has been described as one of the consequences of SCI that mostly decreases quality of life. Bladder wall injections of botulinum toxin A (Onabot/A) are an effective option to manage NDO. The toxin strongly impairs parasympathetic and sensory fibres coursing the bladder wall. However the robust parasympathetic inh...
Source: Experimental Neurology - October 26, 2016 Category: Neurology Authors: Coelho A, Oliveira R, Cruz F, Cruz CD Tags: Exp Neurol Source Type: research

Effects of onabotulinumtoxinA on cardiac function following intradetrusor injections.
In conclusion, onabotulinumtoxinA intradetrusor injections do not seem to affect resting state cardiac function. Short-term changes such as total power might rather result from natural cardio-vascular responses to the procedure itself (e.g. discomfort, stress). Further detailed investigations also under physical stress and repeated injections are necessary to fully exclude systemic cardiac side effects of onabotulinumtoxinA intradetrusor injections. PMID: 27342082 [PubMed - in process] (Source: Experimental Neurology)
Source: Experimental Neurology - October 26, 2016 Category: Neurology Authors: Mehnert U, de Kort LM, Wöllner J, Kozomara M, van Koeveringe GA, Kessler TM Tags: Exp Neurol Source Type: research

Accelerated onset of the vesicovesical reflex in postnatal NGF-OE mice and the role of neuropeptides.
Abstract The mechanisms underlying the postnatal maturation of micturition from a somatovesical to a vesicovesical reflex are not known but may involve neuropeptides in the lower urinary tract. A transgenic mouse model with chronic urothelial overexpression (OE) of NGF exhibited increased voiding frequency, increased number of non-voiding contractions, altered morphology and hyperinnervation of the urinary bladder by peptidergic (e.g., Sub P and CGRP) nerve fibers in the adult. In early postnatal and adult NGF-OE mice we have now examined: (1) micturition onset using filter paper void assays and open-outlet, conti...
Source: Experimental Neurology - October 26, 2016 Category: Neurology Authors: Girard B, Peterson A, Malley S, Vizzard MA Tags: Exp Neurol Source Type: research

Neuromodulation of the neural circuits controlling the lower urinary tract.
Abstract The inability to control timely bladder emptying is one of the most serious challenges among the many functional deficits that occur after a spinal cord injury. We previously demonstrated that electrodes placed epidurally on the dorsum of the spinal cord can be used in animals and humans to recover postural and locomotor function after complete paralysis and can be used to enable voiding in spinal rats. In the present study, we examined the neuromodulation of lower urinary tract function associated with acute epidural spinal cord stimulation, locomotion, and peripheral nerve stimulation in adult rats. Her...
Source: Experimental Neurology - October 26, 2016 Category: Neurology Authors: Gad PN, Roy RR, Zhong H, Gerasimenko YP, Taccola G, Edgerton VR Tags: Exp Neurol Source Type: research

Influence of urothelial or suburothelial cholinergic receptors on bladder reflexes in chronic spinal cord injured cats.
Abstract The effects of intravesical administration of a muscarinic receptor agonist (oxotremorine-M, OXO-M) and antagonist (atropine methyl nitrate, AMN) and of a nicotinic receptor agonist (nicotine) and antagonist (hexamethonium, C6) on reflex bladder activity were investigated in conscious female chronic spinal cord injured (SCI) cats using cystometry. OXO-M (50μM) decreased bladder capacity (BC) for triggering micturition contractions, increased maximal micturition pressure (MMP), increased frequency and area under the curve of pre-micturition contractions (PMC-AUC). Nicotine (250μM) decreased BC, incre...
Source: Experimental Neurology - October 26, 2016 Category: Neurology Authors: Ungerer TD, Kim KA, Daugherty SL, Roppolo JR, Tai C, de Groat WC Tags: Exp Neurol Source Type: research

Introduction to Special Issue on Bladder Control in Neurological Diseases.
PMID: 27772666 [PubMed - in process] (Source: Experimental Neurology)
Source: Experimental Neurology - October 26, 2016 Category: Neurology Authors: Havton LA Tags: Exp Neurol Source Type: research

The role of spinal interleukin-1 β and astrocyte connexin 43 in the development of mirror-image pain in an inflammatory pain model.
In this study, we examined the effect of spinal IL-1β on astrocyte gap junctions (GJ) and the development of MIP. Following unilateral carrageenan (CA) injection, mechanical allodynia (MA) was evaluated at various time points. Immunohistochemistry and Western blot analysis were used to determine changes in the expression of GFAP and connexins (Cx) in the spinal cord dorsal horn. Carrageenan rats showed a delayed onset of contralateral MA, which mimicked the temporal expression pattern of spinal Cx43 (an astrocyte gap junctional protein) and GFAP. Intrathecal administration of an interleukin-1 receptor antagonist (IL-1...
Source: Experimental Neurology - October 20, 2016 Category: Neurology Authors: Choi HS, Roh DH, Yoon SY, Kwon SG, Choi SR, Kang SY, Moon JY, Han HJ, Kim HW, J Beitz A, Lee JH Tags: Exp Neurol Source Type: research

Identification of KRT16 as a Target of an Autoantibody Response in Complex Regional Pain Syndrome.
CONCLUSIONS: Pursuing autoimmune contributions to CRPS provides a novel approach to understanding the condition and may allow the development of mechanism-based therapies. The identification of autoantibodies against KRT16 as a biomarker in mice and in humans is a critical step towards these goals, and towards redefining CRPS as having an autoimmune etiology. PMID: 27773721 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - October 20, 2016 Category: Neurology Authors: Tajerian M, Hung V, Khan H, Lahey LJ, Sun Y, Birklein F, Krämer HH, Robinson WH, Kingery WS, Clark JD Tags: Exp Neurol Source Type: research

The role of spinal interleukin-1 β and astrocyte connexin 43 in the development of mirror-image pain in an inflammatory pain model.
In this study, we examined the effect of spinal IL-1β on astrocyte gap junctions (GJ) and the development of MIP. Following unilateral carrageenan (CA) injection, mechanical allodynia (MA) was evaluated at various time points. Immunohistochemistry and Western blot analysis were used to determine changes in the expression of GFAP and connexins (Cx) in the spinal cord dorsal horn. Carrageenan rats showed a delayed onset of contralateral MA, which mimicked the temporal expression pattern of spinal Cx43 (an astrocyte gap junctional protein) and GFAP. Intrathecal administration of an interleukin-1 receptor antagonist (IL-1...
Source: Experimental Neurology - October 20, 2016 Category: Neurology Authors: Choi HS, Roh DH, Yoon SY, Kwon SG, Choi SR, Kang SY, Moon JY, Han HJ, Kim HW, Beitz AJ, Lee JH Tags: Exp Neurol Source Type: research

G-CSF treatment promotes apoptosis of autoreactive T cells to restrict the inflammatory cascade and accelerate recovery in experimental allergic encephalomyelitis.
Abstract G-CSF is a hematopoietic growth factor that regulates the proliferation, differentiation and survival of myeloid lineage cells, which has protective effects in autoimmune neuroinflammatory diseases such as EAE. Here we use EAE model treated by G-CSF to address the hypothesis that G-CSF inhibits the proliferative response of splenic T cells via the enhancement of apoptosis, and this priming effect of G-CSF depends on the cell cycle. Our results show that G-CSF administration reduced EAE frequency and severity of attacks. The inflammatory cells and demyelination areas were decreased in the CNS of G-CSF-trea...
Source: Experimental Neurology - October 19, 2016 Category: Neurology Authors: Peng W Tags: Exp Neurol Source Type: research

Paradoxical lower sensitivity of Locus Coeruleus than Substantia Nigra pars compacta neurons to acute actions of rotenone.
Abstract Parkinson's disease (PD) is not only associated with degeneration of dopaminergic (DAergic) neurons in the Substantia Nigra, but also with profound loss of noradrenergic neurons in the Locus Coeruleus (LC). Remarkably, LC degeneration may exceed, or even precede the loss of nigral DAergic neurons, suggesting that LC neurons may be more susceptible to damage by various insults. Using a combination of electrophysiology, fluorescence imaging and electrochemistry, we directly compared the responses of LC, nigral DAergic and nigral non-dopaminergic (non-DAergic) neurons in rat brain slices to acute application...
Source: Experimental Neurology - October 19, 2016 Category: Neurology Authors: Yee AG, Freestone PS, Bai JZ, Lipski J Tags: Exp Neurol Source Type: research

Progressive neuronal activation accompanies epileptogenesis caused by hippocampal glutamine synthetase inhibition.
Abstract Loss of glutamine synthetase (GS) in hippocampal astrocytes has been implicated in the causation of human mesial temporal lobe epilepsy (MTLE).However, the mechanism by which the deficiency in GS leads to epilepsy is incompletely understood. Here we ask how hippocampal GS inhibition affects seizure phenotype and neuronal activation during epilepsy development (epileptogenesis). Epileptogenesis was induced by infusing the irreversible GS blocker methionine sulfoximine (MSO) unilaterally into the hippocampal formation of rats. We then used continuous video-intracranial electroencephalogram (EEG) monitoring ...
Source: Experimental Neurology - October 18, 2016 Category: Neurology Authors: Albright B, Dhaher R, Wang H, Harb R, Lee TW, Zaveri H, Eid T Tags: Exp Neurol Source Type: research

Complement deposition induced by binding of anti-contactin-1 auto-antibodies is modified by immunoglobulins.
Abstract Inflammatory neuropathies associated with auto-antibodies against paranodal proteins like contactin-1 are reported to respond poorly to treatment with intravenous immunoglobulins (IVIG). A reason might be that IVIG interacts with the complement pathway and these auto-antibodies often belong to the IgG4 subclass that does not activate complement. However, some patients do show a response to IVIG, especially at the beginning of the disease. This corresponds with the finding of coexisting IgG subclasses IgG1, IgG2 and IgG3. We therefore aimed to investigate complement deposition and activation by samples of ...
Source: Experimental Neurology - October 13, 2016 Category: Neurology Authors: Appeltshauser L, Weishaupt A, Sommer C, Doppler K Tags: Exp Neurol Source Type: research

Short- and long-term dopamine depletion causes enhanced beta oscillations in the cortico-basal ganglia loop of parkinsonian rats.
an Riesen C Abstract Abnormally enhanced beta oscillations have been found in deep brain recordings from human Parkinson's disease (PD) patients and in animal models of PD. Recent correlative evidence suggests that beta oscillations are related to disease-specific symptoms such as akinesia and rigidity. However, this hypothesis has also been repeatedly questioned by studies showing no changes in beta power in animal models using an acute pharmacologic dopamine blockade. To further investigate the temporal dynamics of exaggerated beta synchrony in PD, we investigated the reserpine model, which is characterized by a...
Source: Experimental Neurology - October 12, 2016 Category: Neurology Authors: Beck MH, Haumesser JK, Kühn J, Altschüler J, Kühn AA, van Riesen C Tags: Exp Neurol Source Type: research

Increased precursor microRNA-21 following status epilepticus can compete with mature microRNA-21 to alter translation.
Abstract MicroRNA-21 (miR-21) is consistently up-regulated in various neurological disorders, including epilepsy. Here, we show that the biogenesis of miR-21 is altered following pilocarpine status epilepticus (SE) with an increase in precursor miR-21 (pre-miR-21) in rats. We demonstrate that pre-miR-21 has an energetically favorable site overlapping with the miR-21 binding site and competes with mature miR-21 for binding in the 3'UTR of TGFBR2 mRNA, but not NT-3 mRNA in vitro. This binding competition influences miR-21-mediated repression in vitro and correlates with the increase in TGFBR2 and decrease in NT-3 fo...
Source: Experimental Neurology - October 7, 2016 Category: Neurology Authors: Chak K, Roy-Chaudhuri B, Kim HK, Kemp KC, Porter BE, Kay MA Tags: Exp Neurol Source Type: research