Muscle xenografts reproduce key molecular features of facioscapulohumeral muscular dystrophy.
We report that FSHD cells mature into organized and innervated human muscle fibers with minimal contamination of murine myonuclei. They also reconstitute the satellite cell niche within the xenografts. FSHD xenografts express DUX4 and DUX4 downstream targets, retain the 4q35 epigenetic signature of their original donors, and express a novel protein biomarker of FSHD, SLC34A2. Ours is the first scalable, mature in vivo human model of FSHD. It should be useful for studies of the pathogenic mechanism of the disease as well as for testing therapeutic strategies targeting DUX4 expression. PMID: 31306642 [PubMed - as suppli...
Source: Experimental Neurology - July 12, 2019 Category: Neurology Authors: Mueller AL, O'Neill A, Jones TI, Llach A, Rojas LA, Sakellariou P, Stadler G, Wright WE, Eyerman D, Jones PL, Bloch RJ Tags: Exp Neurol Source Type: research
Transcranial focal electrical stimulation via concentric ring electrodes in freely moving cats: Antiepileptogenic and postictal effects.
In conclusion, tripolar TFS applied via a TCRE over the ipsilateral temporal area significantly delayed AK. This taken together with other reports of tripolar TFS aborting seizures in acute seizure models suggests that tripolar TFS is a promising new modality that should be considered for further testing. PMID: 31301285 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - July 10, 2019 Category: Neurology Authors: Valdés-Cruz A, Villasana-Salazar B, Williams B, Martínez-Vargas D, Magdaleno-Madrigal VM, Almazán-Alvarado S, Besio WG Tags: Exp Neurol Source Type: research
The α7 nicotinic receptor silent agonist R-47 prevents and reverses paclitaxel-induced peripheral neuropathy in mice without tolerance or altering nicotine reward and withdrawal.
The α7 nicotinic receptor silent agonist R-47 prevents and reverses paclitaxel-induced peripheral neuropathy in mice without tolerance or altering nicotine reward and withdrawal. Exp Neurol. 2019 Jul 09;:113010 Authors: Toma W, Kyte SL, Bagdas D, Jackson A, Meade JA, Rahman F, Chen ZJ, Del Fabbro E, Cantwell L, Kulkarni A, Thakur GA, Papke RL, Bigbee JW, Gewirtz DA, Damaj MI Abstract Various antitumor drugs, including paclitaxel, frequently cause chemotherapy-induced peripheral neuropathy (CIPN) that can be sustained even after therapy has been completed. The current work was designed to evaluat...
Source: Experimental Neurology - July 9, 2019 Category: Neurology Authors: Toma W, Kyte SL, Bagdas D, Jackson A, Meade JA, Rahman F, Chen ZJ, Del Fabbro E, Cantwell L, Kulkarni A, Thakur GA, Papke RL, Bigbee JW, Gewirtz DA, Damaj MI Tags: Exp Neurol Source Type: research
Gastrointestinal dysfunction after spinal cord injury.
Abstract The gastrointestinal tract of vertebrates is a heterogeneous organ system innervated to varying degrees by a local enteric neural network as well as extrinsic parasympathetic and sympathetic neural circuits located along the brainstem and spinal axis. This diverse organ system serves to regulate the secretory and propulsive reflexes integral to the digestion and absorption of nutrients. The quasi-segmental distribution of the neural circuits innervating the gastrointestinal (GI) tract produces varying degrees of dysfunction depending upon the level of spinal cord injury (SCI). At all levels of SCI, GI dys...
Source: Experimental Neurology - July 9, 2019 Category: Neurology Authors: Holmes GM, Blanke EN Tags: Exp Neurol Source Type: research
Activation of GPR30 with G1 attenuates neuronal apoptosis via src/EGFR/stat3 signaling pathway after subarachnoid hemorrhage in male rats.
CONCLUSION: G1 reduced EBI through attenuating neuronal apoptosis after SAH in male rats, partly via activating src/EGFR/stat3/signaling pathway. G1 may provide a promising therapeutic strategy for SAH patients. PMID: 31295444 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - July 8, 2019 Category: Neurology Authors: Peng J, Zuo Y, Huang L, Okada T, Liu S, Zuo G, Zhang G, Tang J, Xia Y, Zhang JH Tags: Exp Neurol Source Type: research
Delayed recanalization at 3 days after permanent MCAO attenuates neuronal apoptosis through FGF21/FGFR1/PI3K/Caspase-3 pathway in rats.
Abstract Reperfusion exceeded time window may induce ischemia/reperfusion injury, increase hemorrhagic transformation, and deteriorate neurological outcomes in ischemic stroke models. However, the increasing clinical evidences supported that reperfusion even within 6-24 h may salvage ischemic tissue and improve neurological outcomes in selected large vessel occlusion patients, without inducing serious ischemia/reperfusion injury and hemorrhagic transformation. The underlying molecular mechanisms are less clear. In present study, we demonstrated that delayed recanalization at 3 days after permanent middle cereb...
Source: Experimental Neurology - July 8, 2019 Category: Neurology Authors: Zheng W, Matei N, Pang J, Luo X, Song Z, Tang J, Zhang JH Tags: Exp Neurol Source Type: research
Insulin actions in the mesolimbic dopamine system.
Abstract As a major circulating feeding related hormone, insulin crosses the brain blood barrier and acts on the central nervous system to modulate both homeostatic and non-homeostatic feeding behaviours. The mesolimbic dopamine system is implicated in motivation and the reinforcement of food intake, and it can be delicately tuned in response to insulin. Studies have demonstrated differential effects of insulin in the ventral tegmental area (VTA) compared to the nucleus accumbens (NAc). This review summarizes current findings and discusses possible explanations for the discrepancies of insulin effects on the VTA a...
Source: Experimental Neurology - July 4, 2019 Category: Neurology Authors: Liu S, Borgland SL Tags: Exp Neurol Source Type: research
Comorbidities of early-onset temporal epilepsy: Cognitive, social, emotional, and morphologic dimensions.
ron; P, Kubová H Abstract Epilepsy, the most common neurologic disorder in childhood, is associated with a subset of psychiatric dysfunctions, including cognitive deficits, and alterations in emotionality (e.g., anxiety and depression) and social functioning. In the present study, we evaluated an integrative set of behavioral responses, including cognitive/socio-cognitive and emotional dimensions, using a number of behavioral paradigms in the LiCl/pilocarpine model of status epilepticus (SE) in rats. The aims of the study were to examine whether SE affects: 1) non-associative learning (habituation of explor...
Source: Experimental Neurology - July 3, 2019 Category: Neurology Authors: Mikulecká A, Druga R, Stuchlík A, Mareš P, Kubová H Tags: Exp Neurol Source Type: research
Neuroinflammation in the pathogenesis of axonal Charcot-Marie-Tooth disease caused by lack of GDAP1.
lau F Abstract Mutations in the GDAP1 mitochondrial outer membrane gene cause Charcot-Marie-. Tooth (CMT) neuropathy. Reduction or absence of GDAP1 has been associated with abnormal changes in the mitochondrial morphology and dynamics, oxidative stress and changes in calcium homeostasis. Neuroinflammation has been described in rodent models of genetic demyelinating CMT neuropathies but not in CMT primarily associated with axonopathy. Inflammatory processes have also been related to mitochondrial changes and oxidative stress in central neurodegenerative disorders. Here we investigated the presence of neuroinflammat...
Source: Experimental Neurology - July 1, 2019 Category: Neurology Authors: Fernandez-Lizarbe S, Civera-Tregón A, Cantarero L, Herrer I, Juarez P, Hoenicka J, Palau F Tags: Exp Neurol Source Type: research
Astrogliosis inhibition attenuates hydrocephalus by increasing cerebrospinal fluid reabsorption through the glymphatic system after germinal matrix hemorrhage running title: Glymphatic system and hydrocephalus.
Abstract Germinal matrix hemorrhage (GMH) results from the rupture of the immature thin-walled blood vessels and consequent bleeding into the subependymal germinal matrix and possible lateral ventricles. The purpose of this study is to investigate how astrogliosis impacts the glymphatic-meningeal lymphatic system in cerebrospinal fluid (CSF) reabsorption after GMH and how the anti-scarring agent olomoucine attenuates post-hemorrhagic hydrocephalus. GMH was induced by stereotaxic collagenase infusion into P7 Sprague-Dawley rats of both sexes. Western blot and immunofluorescence were used to assess astrogliosis and ...
Source: Experimental Neurology - June 28, 2019 Category: Neurology Authors: Ding Y, Zhang T, Wu G, McBride DW, Xu N, Klebe DW, Zhang Y, Li Q, Tang J, Zhang JH Tags: Exp Neurol Source Type: research
Activation of the spinal neuronal network responsible for visceral control during locomotion.
Abstract It has been established that stepping of the decerebrate cat was accompanied by involvement of the urinary system: external urethral sphincter (EUS) and detrusor muscle activation, as well as the corresponding increase of the intravesical pressure. Detrusor and EUS evoked EMG activity matched the limbs locomotor movements. Immunohistochemical labeling of the immediate early gene c-fos expression was used to reveal the neural mechanisms of such somatovisceral interconnection within the sacral neural pathways. Study showed that two locomotor modes (forward and backward walking) had significantly different k...
Source: Experimental Neurology - June 26, 2019 Category: Neurology Authors: Natalia M, Vsevolod L, Aleksandr V, Elena B, Oleg G, Pavel M Tags: Exp Neurol Source Type: research
Blockade of voltage-gated potassium channels ameliorates diabetes-associated cognitive dysfunction in vivo and in vitro.
Abstract The voltage-gated potassium (Kv) channel blockers tetraethylammonium (TEA) and 4-aminopyridine (4-AP) have shown beneficial effects on some neurological disorders. But their involvements in diabetes-associated cognitive dysfunction are still unknown. The present study aims to investigate whether the blockade of Kv channels by TEA and 4-AP alleviate cognitive decline in diabetes. In vivo, the effects of TEA and 4-AP (5 mg/kg body weight per day, 1 mg/kg body weight per day intraperitoneal injected for 4 weeks, respectively) were investigated in streptozotocin-induced C57BL/6 diabetic mice. In vitro s...
Source: Experimental Neurology - June 26, 2019 Category: Neurology Authors: Yan W, Zhang M, Yu Y, Yi X, Guo T, Hu H, Sun Q, Chen M, Xiong H, Chen L Tags: Exp Neurol Source Type: research
Erythropoietin and caffeine exert similar protective impact against neonatal intermittent hypoxia: Apnea of prematurity and sex dimorphism.
Abstract Apnea of prematurity (AoP) is associated with severe and repeated episodes of arterial oxygen desaturation (intermittent hypoxia - IH), which in turn increases the number of apneas. So far, there is no data addressing whether IH leads to sex-specific respiratory consequences, neither if drugs targeting AoP are more effective in males or females. We used rat pups for investigating whether IH-mediated increase of apneas is sex-specific. We also tested whether caffeine (treatment of choice of AoP), erythropoietin (Epo - a neuroprotective factor and potent respiratory stimulant), and combination of both (caff...
Source: Experimental Neurology - June 26, 2019 Category: Neurology Authors: Laouafa S, Iturri P, Arias C, Marcouiller F, Gonzales M, Joseph V, Bairam A, Soliz J Tags: Exp Neurol Source Type: research
Melatonin alleviates asphyxial cardiac arrest-induced cerebellar Purkinje cell death by attenuation of oxidative stress.
Abstract Although multiple reports using animal models have confirmed that melatonin appears to promote neuroprotective effects following ischemia/reperfusion-induced brain injury, the relationship between its protective effects and activation of autophagy in Purkinje cells following asphyxial cardiac arrest and cardiopulmonary resuscitation (CA/CPR) remains unclear. Rats used in this study were randomly assigned to 6 groups as follows; vehicle-treated sham operated group, vehicle-treated asphyxial CA/CPR operated group, melatonin-treated sham operated group, melatonin-treated asphyxial CA/CPR operated group, PDOT...
Source: Experimental Neurology - June 25, 2019 Category: Neurology Authors: Cho JH, Tae HJ, Kim IS, Song M, Kim H, Lee TK, Kim YM, Ryoo S, Kim DW, Lee CH, Hwang IK, Yan BC, Kang IJ, Won MH, Lee JC Tags: Exp Neurol Source Type: research
Matrix-metalloproteinase expression and gelatinase activity in the avian retina and their influence on M üller glia proliferation.
This study used hydrogels containing a gelatinase-degradable fluorescent peptide to measure gelatinase activity in vitro and dye quenched gelatin to localize enzymatic activity in situ. These data were corroborated by using single cell RNA sequencing (scRNA-seq). Gelatinase mRNA, specifically MMP2, was detected in oligodendrocytes and non-astrocytic inner retinal glia. Total retinal gelatinase activity was reduced following NMDA-treatment, and sustained inhibition of MMP2 prior to damage or growth factor treatment increased the formation of proliferating MGPCs and c-fos signaling. We observed that microglia, Müller gl...
Source: Experimental Neurology - June 25, 2019 Category: Neurology Authors: Campbell WA, Deshmukh A, Blum S, Todd L, Mendonca N, Weist J, Zent J, Hoang TV, Blackshaw S, Leight J, Fischer AJ Tags: Exp Neurol Source Type: research
Docosahexaenoic acid decreased neuroinflammation in rat pups after controlled cortical impact.
CONCLUSIONS: DHA decreased oxidative stress and histologic and mRNA markers of microglial pro-inflammatory activation in rat pup brain acutely after CCI associated with improved short term cognitive function. DHA administration after CCI has neuroprotective effects, which may result in part from modulation of microglial activation toward a less inflammatory profile in the first week after CCI. Future and ongoing studies will focus on phagocytic function and reactive oxygen species production in microglia and macrophages to test functional effects of DHA on neuroinflammation in our model. Given its favorable safety profile ...
Source: Experimental Neurology - June 24, 2019 Category: Neurology Authors: Schober ME, Requena DF, Casper TC, Velhorst AK, Lolofie A, McFarlane KE, Otto TE, Terry C, Gensel JC Tags: Exp Neurol Source Type: research
RvD1binding with FPR2 attenuates inflammation via Rac1/NOX2 pathway after neonatal hypoxic-ischemic injury in rats.
The objective of this study was to explore the protective role of RvD1 through reducing inflammation after HI and to study the contribution of Ras-related C3 botulinum toxin substrate 1 (Rac1)/nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) pathways in RvD1-mediated protection. Rat pups (10-day old) were subjected to HI or sham surgery. RvD1 was administrated by intraperitoneal injection 1 h after HI. FPR2 small interfering ribonucleic acid (siRNA) and Rac1 activation CRISPR were administered prior to RvD1 treatment to elucidate the possible mechanisms. Time course expression of FPR2 by Western blot ...
Source: Experimental Neurology - June 24, 2019 Category: Neurology Authors: Liu W, Huang J, Doycheva D, Gamdzyk M, Tang J, Zhang JH Tags: Exp Neurol Source Type: research
MicroRNA-34a mediates ethanol-induced impairment of neural differentiation of neural crest cells by targeting autophagy-related gene 9a.
The objective of this study is to test whether ethanol exposure can inhibit the neural differentiation of NCCs by inhibiting autophagy and whether miR-34a is involved in ethanol-induced inhibition of autophagy in NCCs. We found that ethanol exposure resulted in the inhibition of neural differentiation of NCCs. Exposure to ethanol also significantly decreased autophagy in NCCs, as indicated by a decreased LC3II/I ratio and an elevated expression of p62 protein. Knockdown of p62 restored the expression of the neurogenesis genes, NF and Mash1, in ethanol-exposed NCCs, suggesting that ethanol exposure can inhibit the neural di...
Source: Experimental Neurology - June 24, 2019 Category: Neurology Authors: Fan H, Yuan F, Yun Y, Wu T, Lu L, Liu J, Feng W, Chen SY Tags: Exp Neurol Source Type: research
Targeting high-mobility group box protein 1 (HMGB1) in pediatric traumatic brain injury: Chronic neuroinflammatory, behavioral, and epileptogenic consequences.
This study therefore examined the chronic consequences of acute HMGB1 inhibition in the same model, to test the hypothesis that HMGB1 is a pivotal mediator of neuropathological, neurobehavioral, and epilepsy outcomes in pediatric TBI. HMGB1 was inhibited by treatment with 50 mg/kg i.p. Glycyrrhizin (Gly), compared to vehicle controls, commencing 1 h prior to moderate TBI or sham surgery in post-natal day 21 mice. We first demonstrated that Gly reduced brain HMGB1 levels and brain edema at an acute time point of 3 days post-injury. Subsequent analysis over a chronic time course found that pediatric TBI resulted in s...
Source: Experimental Neurology - June 20, 2019 Category: Neurology Authors: Webster KM, Shultz SR, Ozturk E, Dill L, Sun M, Casillas-Espinosa P, Jones NC, Crack PJ, O'Brien TJ, Semple BD Tags: Exp Neurol Source Type: research
Physical impacts of PLGA scaffolding on hMSCs: Recovery neurobiology insight for implant design to treat spinal cord injury.
Abstract Our earlier work generated a powerful platform technology of polymeric scaffolding of stem cells to investigate and treat the injured or diseased central nervous system. However, the reciprocal sequelae between biophysical properties of the polymer and responses of the stem cell have not been examined in situ in lesioned spinal cords. We postulated that implantable synthetic scaffolds, acting through physical features, might affect donor cell behavior and host tissue remodeling. To test this hypothesis, poly(d,l-lactic-co-glycolic acid) (PLGA) in either low/soft or high/hard rigidity was fabricated for ca...
Source: Experimental Neurology - June 20, 2019 Category: Neurology Authors: Han IB, Thakor DK, Ropper AE, Yu D, Wang L, Kabatas S, Zeng X, Kim SW, Zafonte RD, Teng YD Tags: Exp Neurol Source Type: research
EPO regulates neuroprotective Transmembrane BAX Inhibitor-1 Motif-containing (TMBIM) family members GRINA and FAIM2 after cerebral ischemia-reperfusion injury.
Abstract BACKGROUND AND PURPOSE: Transmembrane BAX Inhibitor-1 Motif-containing (TMBIM) family members exert inhibitory activities in apoptosis and necroptosis. FAIM2 (TMBIM-2) is neuroprotective against murine focal ischemia and is regulated by erythropoietin (EPO). Similar to FAIM2, GRINA (TMBIM-3) is predominantly expressed in the brain. The role of GRINA in transient brain ischemia, its potential synergistic effects with FAIM2 and its regulation by EPO treatment were assessed. METHODS: We performed transient (30 min) middle cerebral artery occlusion (tMCAo) followed by 72 h of reperfusion in GRINA-def...
Source: Experimental Neurology - June 15, 2019 Category: Neurology Authors: Habib P, Stamm AS, Zeyen T, Noristani R, Slowik A, Beyer C, Wilhelm T, Huber M, Komnig D, Schulz JB, Reich A Tags: Exp Neurol Source Type: research
SCI and depression: Does inflammation commandeer the brain?
Abstract The incidence of depression is almost twice as high in the spinally injured population compared to the general population. While this incidence has long been attributed to the psychological, economic, and social burdens that accompany spinal cord injury (SCI), data from animal studies indicate that the biology of SCI may play an important role in the development of depression. Inflammation has been shown to impact stress response in rodents and humans, and inflammatory cytokines have been associated with depression for decades. The inflammation inherent to SCI may disrupt necessary mechanisms of mental ho...
Source: Experimental Neurology - June 13, 2019 Category: Neurology Authors: Brakel K, Hook M Tags: Exp Neurol Source Type: research
Enhanced descending pain facilitation in acute traumatic brain injury.
Abstract Acute and persistent pain are recognized consequences of TBI that can enhance suffering and significantly impair rehabilitative efforts. Both experimental models and clinical studies suggest that TBI may result in an imbalance between descending pain facilitatory and inhibitory pathways. The aim of this study was to assess the role of enhanced descending serotonin-mediated pain facilitation in a rat TBI model using selective spinal serotonergic fiber depletion with 5, 7-dihydroxytryptamine (DHT). We observed significant hindpaw allodynia in TBI rats that was reduced after DHT but not vehicle treatment. Im...
Source: Experimental Neurology - June 8, 2019 Category: Neurology Authors: Irvine KA, Sahbaie P, Ferguson AR, Clark JD Tags: Exp Neurol Source Type: research
Roles of Reelin/Disabled1 pathway on functional recovery of hemiplegic mice after neural cell transplantation; Reelin promotes migration toward motor cortex and maturation to motoneurons of neural grafts.
We examined involvement of Reelin pathway in functional recovery of hemiplegic mice after neural transplantation. Reelin was expressed 1 day after cryogenic injury of right motor cortex. We transplanted neural stem/progenitor cells (NSPCs) from wild-type mice into ipsilateral striatum of hemiplegic mice. The grafts migrated from the striatum and reached the injured cortex 14 days after transplantation. The transplantation significantly improved their motor functions (P 80%) did not migrate and thus remained at the striatum. The grafts did not express the forebrain motoneuron associated markers nor the cell adhesion m...
Source: Experimental Neurology - June 8, 2019 Category: Neurology Authors: Arimitsu N, Takai K, Fujiwara N, Shimizu J, Ueda Y, Wakisaka S, Hirotsu C, Murayama MA, Suzuki T, Suzuki N Tags: Exp Neurol Source Type: research
Norepinephrine and serotonin are required for vagus nerve stimulation directed cortical plasticity.
Abstract Vagus nerve stimulation (VNS) paired with forelimb training drives robust, specific reorganization of movement representations in the motor cortex. This effect is hypothesized to be mediated by VNS-dependent engagement of neuromodulatory networks. VNS influences activity in the locus coeruleus (LC) and dorsal raphe nucleus (DRN), but the involvement of these neuromodulatory networks in VNS-directed plasticity is unknown. We tested the hypothesis that cortical norepinephrine and serotonin are required for VNS-dependent enhancement of motor cortex plasticity. Rats were trained on a lever pressing task empha...
Source: Experimental Neurology - June 7, 2019 Category: Neurology Authors: Hulsey DR, Shedd CM, Sarker SF, Kilgard MP, Hays SA Tags: Exp Neurol Source Type: research
A missense mutation in SLC6A1 associated with Lennox-Gastaut syndrome impairs GABA transporter 1 protein trafficking and function.
CONCLUSIONS: This mutation caused instability of the mutant transporter protein, which resulted in reduced cell surface and total protein levels. The mutation also caused reduced GABA uptake in addition to reduced protein expression, leading to reduced GABA clearance, and altered GABAergic signaling in the brain. The impaired trafficking and reduced GABA uptake function may explain the epilepsy phenotype in the patient. PMID: 31176687 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - June 6, 2019 Category: Neurology Authors: Cai K, Wang J, Eissman J, Wang J, Nwosu G, Shen W, Liang HC, Li XJ, Zhu HX, Yi YH, Song J, Xu D, Delpire E, Liao WP, Shi YW, Kang JQ Tags: Exp Neurol Source Type: research
Imaging spinal cord activity in behaving animals.
Abstract The spinal cord is the primary neurological link between the brain and peripheral organs. How important it is in everyday life is apparent in patients with spinal cord injury or motoneuron disease, who have dramatically reduced musculoskeletal control or capacity to sense their environment. Despite its crucial role in sensory and motor processing little is known about the cellular and molecular signaling events that underlie spinal cord function under naturalistic conditions. While genetic, electrophysiological, pharmacological, and circuit tracing studies have revealed important roles for different molec...
Source: Experimental Neurology - June 5, 2019 Category: Neurology Authors: Nelson NA, Wang X, Cook D, Carey EM, Nimmerjahn A Tags: Exp Neurol Source Type: research
Depression-like behavior corresponds with cardiac changes in a rodent model of spinal cord injury.
Abstract In previous studies we have shown that approximately 1/3 of male Sprague Dawley rats develop symptoms of depression following a spinal cord injury (SCI). Using established behavioral tests to measure depression in rodents we found that after SCI, subjects characterized as depressed had decreased sucrose preference, open field activity, social exploration, and burrowing behavior. As some of these tests of depression could be affected by the compromised motor function inherent to the SCI condition, the current study examined whether non-subjective, physiological differences in heart rate and heart rate vari...
Source: Experimental Neurology - May 31, 2019 Category: Neurology Authors: Brakel K, Aceves A, Aceves M, Hierholzer A, Nguyen N, Hook M Tags: Exp Neurol Source Type: research
Imaging the execution phase of neuroinflammatory disease models.
Abstract In vivo imaging of the rodent spinal cord has advanced our understanding of how resident cells of the central nervous system (CNS) respond to neuroinflammation. By combining two-photon imaging and experimental autoimmune encephalomyelitis (EAE), the most widely used rodent model of multiple sclerosis (MS), it has been possible, for example, to study how axons degenerate when confronted with inflammatory cells, how oligodendrocytes get damaged in inflammatory lesions, and how immune cells themselves adapt their phenotype and functionality to the changing lesion environment. Similar approaches are now incre...
Source: Experimental Neurology - May 29, 2019 Category: Neurology Authors: Schumacher AM, Misgeld T, Kerschensteiner M, Snaidero N Tags: Exp Neurol Source Type: research
Toll-like receptors and inflammation in metabolic neuropathy; a role in early versus late disease?
Abstract Neuropathy is a common, morbid complication of the metabolic syndrome, prediabetes, and diabetes. Recent studies have indicated a potential role for the immune system in the development of neuropathy. In particular, toll-like receptors (TLR) 2 and 4 have been linked to metabolic dysfunction, and blocking TLR4 is proposed as a treatment for neuropathic pain. In the current study, we investigated the role of the immune system, particularly TLRs 2 and 4, in the pathogenesis and progression of neuropathy. Sural or sciatic nerve gene expression arrays from humans and murine neuropathy models of prediabetes and...
Source: Experimental Neurology - May 27, 2019 Category: Neurology Authors: Elzinga S, Murdock BJ, Guo K, Hayes JM, Tabbey MA, Hur J, Feldman EL Tags: Exp Neurol Source Type: research
Inhibitor of DNA binding 2 promotes axonal growth through upregulation of Neurogenin2.
In this study, we investigated the mechanism of Id2 in promoting axonal growth and revealed that Ngn2 contributed to the growth-activating role of Id2 in neurons. Ngn2 expression was upregulated with increased Id2 activity by assessing RNA and protein levels. Forced expression of Id2 or Ngn2 in cortical neurons significantly promoted axonal growth with little effect on dendrites. Furthermore, knockdown of Ngn2 impaired the axonal growth promoting effect of Id2, implying that the effect of Id2 on axonal growth depends on Ngn2. These findings suggest that elevation of neuronal Ngn2 may be a new therapeutic strategy to stimul...
Source: Experimental Neurology - May 27, 2019 Category: Neurology Authors: Huang Z, Liu J, Jin J, Chen Q, Shields LBE, Zhang YP, Shields CB, Zhou L, Zhou B, Yu P Tags: Exp Neurol Source Type: research
Severe biallelic loss-of-function mutations in nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) in two fetuses with fetal akinesia deformation sequence.
We report here on two stillborn siblings with fetal akinesia deformation sequence (FADS), severely reduced skeletal muscle mass and hydrops fetalis. Clinical exome sequencing identified compound heterozygous NMNAT2 variant alleles in both cases. Both protein variants are incapable of supporting axon survival in mouse primary neuron cultures when overexpressed. In vitro assays demonstrate altered protein stability and/or defects in NAD+ synthesis and chaperone functions. Thus, both patient NMNAT2 alleles are null or severely hypo-morphic. These data indicate a previously unknown role for NMNAT2 in human neurological develop...
Source: Experimental Neurology - May 25, 2019 Category: Neurology Authors: Lukacs M, Gilley J, Zhu Y, Orsomando G, Angeletti C, Liu J, Yang X, Park J, Hopkin RJ, Coleman MP, Zhai RG, Stottmann RW Tags: Exp Neurol Source Type: research
Temporal changes in neuroinflammation and brain glucose metabolism in a rat model of viral vector-induced α-synucleinopathy.
Temporal changes in neuroinflammation and brain glucose metabolism in a rat model of viral vector-induced α-synucleinopathy. Exp Neurol. 2019 May 25;:112964 Authors: Crabbé M, Van der Perren A, Kounelis S, Lavreys T, Bormans G, Baekelandt V, Casteels C, Van Laere K Abstract Rat models based on viral vector-mediated overexpression of α-synuclein are regarded as highly valuable models that closely mimic cardinal features of human Parkinson's disease (PD) such as L-DOPA-dependent motor impairment, dopaminergic neurodegeneration and α-synuclein inclusions. To date, the downstream ...
Source: Experimental Neurology - May 25, 2019 Category: Neurology Authors: Crabbé M, Van der Perren A, Kounelis S, Lavreys T, Bormans G, Baekelandt V, Casteels C, Van Laere K Tags: Exp Neurol Source Type: research
Homozygous NMNAT2 mutation in sisters with polyneuropathy and erythromelalgia.
Coleman MP Abstract We identified a homozygous missense mutation in the gene encoding NAD synthesizing enzyme NMNAT2 in two siblings with childhood onset polyneuropathy with erythromelalgia. No additional homozygotes for this rare allele, which leads to amino acid substitution T94M, were present among the unaffected relatives tested or in the 60,000 exomes of the ExAC database. For axons to survive, axonal NMNAT2 activity has to be maintained above a threshold level but the T94M mutation confers a partial loss of function both in the ability of NMNAT2 to support axon survival and in its enzymatic properties. Elec...
Source: Experimental Neurology - May 24, 2019 Category: Neurology Authors: Huppke P, Wegener E, Gilley J, Angeletti C, Kurth I, Drenth JPH, Stadelmann C, Barrantes-Freer A, Brück W, Thiele H, Nürnberg P, Gärtner J, Orsomando G, Coleman MP Tags: Exp Neurol Source Type: research
LINGO-1 deficiency promotes nerve regeneration through reduction of cell apoptosis, inflammation, and glial scar after spinal cord injury in mice.
Abstract Leucine-rich repeat and immunoglobulin domain-containing protein 1 (LINGO-1) is a transmembrane protein that negatively regulates neural regeneration in the central nervous system. LINGO-1 expression is up-regulated after central nerve injury, and is accompanied by cell death. Both LINGO-1 and cell death in the injury microenvironment are thought to limit neural regeneration, but the relationship between LINGO-1 and cell death has not been characterized. To investigate whether LINGO-1 deletion improves the spinal cord microenvironment after spinal cord injury (SCI) and contributes to cell survival, we gen...
Source: Experimental Neurology - May 24, 2019 Category: Neurology Authors: Huang LJ, Li G, Ding Y, Sun JH, Wu TT, Zhao W, Zeng YS Tags: Exp Neurol Source Type: research
Independent replication of motor cortex and cervical spinal cord electrical stimulation to promote forelimb motor function after spinal cord injury in rats.
Abstract Cervical spinal cord injury (SCI) impairs arm and hand function largely by interrupting descending tracts. Most SCI spare some axons at the lesion, including the corticospinal tract (CST), which is critical for voluntary movement. We targeted descending motor connections with paired electrical stimulation of motor cortex and cervical spinal cord in the rat. We sought to replicate the previously published effects of intermittent theta burst stimulation of forelimb motor cortex combined with trans-spinal direct current stimulation placed on the skin over the neck to target the cervical enlargement. We hypot...
Source: Experimental Neurology - May 21, 2019 Category: Neurology Authors: Yang Q, Ramamurthy A, Lall S, Santos J, Ratnadurai-Giridharan S, Zareen N, Alexander H, Ryan D, Martin JH, Carmel JB Tags: Exp Neurol Source Type: research
Electrical stimulation affects neural stem cell fate and function in vitro.
Abstract Electrical stimulation (ES) has been applied in cell culture system to enhance neural stem cell (NSC) proliferation, neuronal differentiation, migration, and integration. According to the mechanism of its function, ES can be classified into induced electrical (EFs) and electromagnetic fields (EMFs). EFs guide axonal growth and induce directional cell migration, whereas EMFs promote neurogenesis and facilitates NSCs to differentiate into functional neurons. Conductive nanomaterials have been used as functional scaffolds to provide mechanical support and biophysical cues in guiding neural cell growth and di...
Source: Experimental Neurology - May 21, 2019 Category: Neurology Authors: Zhu R, Sun Z, Li C, Ramakrishna S, Chiu K, He L Tags: Exp Neurol Source Type: research
Neuroimmune responses in the developing brain following traumatic brain injury.
Abstract Traumatic brain injury (TBI) is one of the leading causes of both acute and long-term morbidity in the pediatric population, leading to a substantial, long term socioeconomic burden. Despite the increase in the amount of pre-clinical and clinical research, treatment options for TBI rely heavily on supportive care with very limited targeted interventions that improve the acute and chronic sequelae of TBI. Other than injury prevention, not much can be done to limit the primary injury, which consists of tissue damage and cellular destruction. Secondary injury is the result of the ongoing complex inflammatory...
Source: Experimental Neurology - May 17, 2019 Category: Neurology Authors: Nasr IW, Chun Y, Kannan S Tags: Exp Neurol Source Type: research
In vivo glutamate clearance defects in a mouse model of Lafora disease.
In conclusion, the hippocampus of Epm2b-/- mice presents an in vivo impairment in glutamate uptake which could contribute to epileptogenesis. PMID: 31108086 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - May 17, 2019 Category: Neurology Authors: Muñoz-Ballester C, Santana N, Perez-Jimenez E, Viana R, Artigas F, Sanz P Tags: Exp Neurol Source Type: research
Maternal thyroid hormone deficiency and cardiorespiratory disorder in rat pups.
Abstract During gestation, the mother is the main source of thyroid hormones for the foetus. Thus, hypothyroidism during pregnancy and/or preterm birth compromise thyroid hormone supply for the foetus. Maternal hypothyroidism increases risk of preterm birth and both conditions are associated with respiratory distress in infants. Since thyroid hormones are essential for normal brain development, it is plausible that maternal thyroid hormone deficiency plays a role in respiratory disorders related to neurological immaturity in the newborn; however, this hypothesis is yet to be tested. Here, we used methimazole treat...
Source: Experimental Neurology - May 17, 2019 Category: Neurology Authors: Rousseau JP, Buteau-Poulin A, Kinkead R Tags: Exp Neurol Source Type: research
Surgical preparations, labeling strategies, and optical techniques for cell-resolved, in vivo imaging in the mouse spinal cord.
Abstract In vivo optical imaging has enabled detailed studies of cellular dynamics in the brain of rodents in both healthy and diseased states. Such studies were made possible by three advances: surgical preparations that give optical access to the brain; strategies for in vivo labeling of cells with structural and functional fluorescent indicators; and optical imaging techniques that are relatively insensitive to light scattering by tissue. In vivo imaging in the rodent spinal cord has lagged behind than that in the brain, largely due to the anatomy around the spinal cord that complicates the surgical preparation...
Source: Experimental Neurology - May 13, 2019 Category: Neurology Authors: Cheng YT, Lett KM, Schaffer CB Tags: Exp Neurol Source Type: research
GDNF pretreatment overcomes Schwann cell phenotype mismatch to promote motor axon regeneration via sensory graft.
Abstract In the clinic, severe motor nerve injury is commonly repaired by autologous sensory nerve bridging, but the ability of Schwann cells (SCs) in sensory nerves to support motor neuron axon growth is poor due to phenotype mismatch. In vitro experiments have demonstrated that sensory-derived SCs overcome phenotypic mismatch-induced growth inhibition after pretreatment with exogenous glial cell-derived neurotrophic factor (GDNF) and induce motor neuron axonal growth. Thus, we introduced a novel staging surgery: In the first stage of surgery, the denervated sensory nerve was pretreated with sustained-release GDN...
Source: Experimental Neurology - May 13, 2019 Category: Neurology Authors: Fang X, Zhang C, Yu Z, Li W, Huang Z, Zhang W Tags: Exp Neurol Source Type: research
The accumulation of T cells within acellular nerve allografts is length-dependent and critical for nerve regeneration.
Abstract Repair of traumatic nerve injuries can require graft material to bridge the defect. The use of alternatives to bridge the defect, such as acellular nerve allografts (ANAs), is being more common and desired. Although ANAs support axon regeneration across short defects (3 cm) is limited. It is unclear why alternatives, including ANAs, are functionally limited by length. After repairing Lewis rat nerve defects using short (2 cm) or long (4 cm) ANAs, we showed that long ANAs have severely reduced axon regeneration across the grafts and contain Schwann cells with a unique phenotype. But additionally, we ...
Source: Experimental Neurology - May 11, 2019 Category: Neurology Authors: Pan D, Hunter DA, Schellhardt L, Jo S, Santosa KB, Larson EL, Fuchs AG, Snyder-Warwick AK, Mackinnon SE, Wood MD Tags: Exp Neurol Source Type: research
Serotonergic mechanisms in spinal cord injury.
Abstract Spinal cord injury (SCI) is a tragic event causing irreversible losses of sensory, motor, and autonomic functions, that may also be associated with chronic neuropathic pain. Serotonin (5-HT) neurotransmission in the spinal cord is critical for modulating sensory, motor, and autonomic functions. Following SCI, 5-HT axons caudal to the lesion site degenerate, and the degree of axonal degeneration positively correlates with lesion severity. Rostral to the lesion, 5-HT axons sprout, irrespective of the severity of the injury. Unlike callosal fibers and cholinergic projections, 5-HT axons are more resistant to...
Source: Experimental Neurology - May 11, 2019 Category: Neurology Authors: Perrin FE, Noristani HN Tags: Exp Neurol Source Type: research
Time to reconsider extended erythropoietin treatment for infantile traumatic brain injury?
Abstract Pediatric traumatic brain injury (TBI) remains a leading cause of childhood morbidity and mortality worldwide. Most efforts to reduce the chronic impact of pediatric TBI involve prevention and minimization of secondary injury. Currently, no treatments are used in routine clinical care during the acute and subacute phases to actively repair injury to the developing brain. The endogenous pluripotent cytokine erythropoietin (EPO) holds promise as an emerging neuroreparative agent in perinatal brain injury (PBI). EPO signaling in the central nervous system (CNS) is essential for multiple stages of neurodevelo...
Source: Experimental Neurology - May 10, 2019 Category: Neurology Authors: Jantzie L, El Demerdash N, Newville JC, Robinson S Tags: Exp Neurol Source Type: research
Hypoactivity of the lateral habenula contributes to negative symptoms and cognitive dysfunction of schizophrenia in rats.
Abstract Dopaminergic (DAergic) hypofunction in the medial prefrontal cortex (mPFC) has been implicated in the negative and cognitive symptoms of schizophrenia and is regulated by serotonergic (5-HTergic) neurons in the dorsal raphe nucleus (DRN). The lateral habenula (LHb) is a key element in controlling DRN 5-HT neurons. We investigated how the LHb impacts the activity of mPFC neurons and whether it mediates the involvement of DRN on development of symptoms in a pharmacological animal model of schizophrenia. We used immunohisochemistry to assess cytochrome-c oxidase (COX) activity of the LHb in MK-801 model rats...
Source: Experimental Neurology - May 10, 2019 Category: Neurology Authors: Li J, Yang S, Liu X, Han Y, Li Y, Feng J, Zhao H Tags: Exp Neurol Source Type: research
Distal denervation in the SOD1 knockout mouse correlates with loss of mitochondria at the motor nerve terminal.
Abstract Impairment of mitochondrial transport has long been implicated in the pathogenesis of neuropathy and neurodegeneration. However, the role of mitochondria in stabilizing motor nerve terminals at neuromuscular junction (NMJ) remains unclear. We previously demonstrated that mice lacking the antioxidant enzyme, superoxide dismutase-1 (Sod1-/-), develop progressive NMJ denervation. This was rescued by expression of SOD1 exclusively in the mitochondrial intermembrane space (MitoSOD1/Sod1-/-), suggesting that oxidative stress within mitochondria drives denervation in these animals. However, we also observed redu...
Source: Experimental Neurology - May 10, 2019 Category: Neurology Authors: Hayes LR, Asress SA, Li Y, Galkin A, Stepanova A, Kawamata H, Manfredi G, Glass JD Tags: Exp Neurol Source Type: research
Mitochondrial methionine sulfoxide reductase B2 links oxidative stress to Alzheimer's disease-like pathology.
Abstract Methionine sulfoxide reductase B2 (MSRB2) is a mitochondrial protein that protects cell from oxidative stress. The antioxidant activity suggests that MSRB2 may play a role in the pathophysiology of Alzheimer's disease (AD). Here, we report that in APP/PS1 mice, an animal model of AD, MSRB2 protein levels were decreased in the hippocampus at both young (6 mon) and old (18 mon) age, and in the cortex only at an old age, respectively. In HEK293 cells that stably express human full-length β-amyloid precursor protein (APP, HEK/APP), MSRB2 reduced the protein and mRNA levels of APP and β-amyloid conve...
Source: Experimental Neurology - May 9, 2019 Category: Neurology Authors: Xiang XJ, Song L, Deng XJ, Tang Y, Min Z, Luo B, Wen QX, Li KY, Chen J, Ma YL, Zhu BL, Yan Z, Chen GJ Tags: Exp Neurol Source Type: research
Deferoxamine therapy reduces brain hemin accumulation after intracerebral hemorrhage in piglets.
In conclusion, hemin accumulation occurs in and around the hematoma. Increases in Hpx and CD91 may be important in scavenging that hemin. DFX treatment decreased hemin release from the hematoma and reduced the expression of Hpx and CD91. PMID: 31078524 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - May 9, 2019 Category: Neurology Authors: Hu S, Hua Y, Keep RF, Feng H, Xi G Tags: Exp Neurol Source Type: research
Visual discrimination impairment after experimental stroke is associated with disturbances in the polarization of the astrocytic aquaporin-4 and increased accumulation of neurotoxic proteins.
Abstract Numerous clinical studies have documented the high incidence of cognitive impairment after stroke. However, there is only limited knowledge about the underlying mechanisms. Interestingly, there is emerging evidence suggesting that cognitive function after stroke may be affected due to reduced waste clearance and subsequent accumulation of neurotoxic proteins. To further explore this potential association, we utilised a model of experimental stroke in mice. Specifically, a photothrombotic vascular occlusion targeting motor and sensory parts of the cerebral cortex was induced in young adult mice, and change...
Source: Experimental Neurology - May 8, 2019 Category: Neurology Authors: Sanchez-Bezanilla S, TeBay C, Nilsson M, Walker FR, Ong LK Tags: Exp Neurol Source Type: research