Mechanism and role of the intra-axonal Calreticulin translation in response to axonal injury.
In this study, we addressed the mechanism and role of axotomy-induced intra-axonal translation of the ER chaperone Calreticulin. In vivo peripheral nerve injury increased Calreticulin levels in sensory axons. Using an in vitro model system of sensory neurons amenable to mechanistic dissection we provide evidence that axotomy induces local translation of Calreticulin through PERK (protein kinase RNA-like endoplasmic reticulum kinase) mediated phosphorylation of eIF2α by a mechanism that requires both 5' and 3'UTRs (untranslated regions) elements in Calreticulin mRNA. ShRNA mediated depletion of Calreticulin or inhibit...
Source: Experimental Neurology - October 25, 2019 Category: Neurology Authors: Pacheco A, Merianda T, Twiss JL, Gallo G Tags: Exp Neurol Source Type: research

Deletion of Chitinase-3-like 1 accelerates stroke development through enhancement of Neuroinflammation by STAT6-dependent M2 microglial inactivation in Chitinase-3-like 1 knockout mice.
Abstract Chitinase 3-like 1 (Chi3L1) plays a major role in the pathogenesis of inflammatory diseases. We investigated the effect of Chi3L1 knockout on stroke development. Ischemia/reperfusion was induced by middle cerebral artery occlusion (MCAO) in Chi3L1 knockout and wildtype mice. Significantly increased infarct volume and decreased neurological deficit scores at 24 h after ischemia/reperfusion were found in Chi3L1 knockout mice compared to wildtype mice. Moreover, ischemic neuronal cell death was increased in Chi3L1 knockout mice through increased oxidative stress and release of IL-6 and IL-1β but IL-10...
Source: Experimental Neurology - October 24, 2019 Category: Neurology Authors: Im JH, Yeo IJ, Park PH, Choi DY, Han SB, Yun J, Hong JT Tags: Exp Neurol Source Type: research

Low-intensity contralesional electrical theta burst stimulation modulates ipsilesional excitability and enhances stroke recovery.
Abstract Targeting interhemispheric inhibition using brain stimulation has shown potential for enhancing stroke recovery. Following stroke, increased inhibition originating from the contralesional hemisphere impairs motor activation in ipsilesional areas. We have previously reported that low-intensity electrical theta burst stimulation (TBS) applied to an implanted electrode in the contralesional rat motor cortex reduces interhemispheric inhibition, and improves functional recovery when commenced three days after cortical injury. Here we apply this approach at more clinically relevant later time points and measure...
Source: Experimental Neurology - October 24, 2019 Category: Neurology Authors: Boddington LJ, Gray JP, Schulz JM, Reynolds JNJ Tags: Exp Neurol Source Type: research

A single session of brief electrical stimulation enhances axon regeneration through nerve autografts.
The objectives of this study were to evaluate if ES enhances axon regeneration through nerve grafts and if there is added benefit of a second, delayed session of ES (serial ES) on axon regeneration as compared to a single session only of ES. In female rats, a gap defect was created in the hindlimb common peroneal (CP) nerve and immediately reconstructed with a 10 mm nerve autograft (Experiment 1) or a 20 mm nerve autograft (Experiment 2). In Experiment 1, rats were randomized to 1 h of CP nerve ES or sham stimulation. In Experiment 2, rats were randomized to control (sham ES + sham ES), single ES (ES + sham E...
Source: Experimental Neurology - October 23, 2019 Category: Neurology Authors: Zuo K, Shafa G, Antonyshyn K, Chan K, Gordon T, Borschel GH Tags: Exp Neurol Source Type: research

Oxidative stress contributes differentially to the pathophysiology of Charcot-Marie-Tooth disease type 2K.
Abstract Charcot-Marie-Tooth (CMT) disease is a common inherited peripheral neuropathy. The CMT2K axonal form is associated with GDAP1 dominant mutations, which according to the affected domain cause a gradient of severity. Indeed, the p.C240Y mutation, located within GDAP1 glutathione S-transferase (GST) domain and associated to a mitochondrial complex I defect, is related to a faster disease progression, compared to other mutations, such as the p.R120W located outside the GST domain. Here, we analysed the pathophysiology of six CMT2K fibroblast cell lines, carrying either the p.C240Y or p.R120W mutations. We sho...
Source: Experimental Neurology - October 23, 2019 Category: Neurology Authors: Cassereau J, Chevrollier A, Codron P, Goizet C, Gueguen N, Verny C, Reynier P, Bonneau D, Lenaers G, Procaccio V Tags: Exp Neurol Source Type: research

Loss of PTEN-induced kinase 1 (Pink1) reduces hippocampal tyrosine hydroxylase and impairs learning and memory.
Abstract Phosphatase and tensin homolog (PTEN)-induced kinase 1 (Pink1) is involved in mitochondrial quality control, which is essential for maintaining energy production and minimizing oxidative damage from dysfunctional/depolarized mitochondria. Pink1 mutations are the second most common cause of autosomal recessive Parkinson's disease (PD). In addition to characteristic motor impairments, PD patients also commonly exhibit cognitive impairments. As the hippocampus plays a prominent role in cognition, we tested if loss of Pink1 in mice influences learning and memory. While wild-type mice were able to perform a co...
Source: Experimental Neurology - October 23, 2019 Category: Neurology Authors: Maynard ME, Redell JB, Kobori N, Underwood EL, Fischer TD, Hood KN, LaRoche V, Waxham MN, Moore AN, Dash PK Tags: Exp Neurol Source Type: research

The spinal cord-gut-immune axis as a master regulator of health and neurological function after spinal cord injury.
Abstract Most spinal cord injury (SCI) research programs focus only on the injured spinal cord with the goal of restoring locomotor function by overcoming mechanisms of cell death or axon regeneration failure. Given the importance of the spinal cord as a locomotor control center and the public perception that paralysis is the defining feature of SCI, this "spinal-centric" focus is logical. Unfortunately, such a focus likely will not yield new discoveries that reverse other devastating consequences of SCI including cardiovascular and metabolic disease, bladder/bowel dysfunction and infection. The current ...
Source: Experimental Neurology - October 22, 2019 Category: Neurology Authors: Kigerl KA, Zane K, Adams K, Sullivan MB, Popovich PG Tags: Exp Neurol Source Type: research

Sensory axons inhibit motor axon regeneration in vitro.
Abstract During mammalian embryonic development sensory and motor axons interact as an integral part of the pathfinding process. During regeneration, however, little is known of their interactions with one another. It is thus possible that sensory axons might influence motor axon regeneration in ways not currently appreciated. To explore this possibility we have developed an organotypic model of post-natal nerve regeneration in which sensory and motor axons are color-coded by modality. Motor axons that express yellow fluorescent protein (YFP) and sensory axons that express red fluorescent protein (RFP) are blended...
Source: Experimental Neurology - October 19, 2019 Category: Neurology Authors: Brushart T, Kebaisch F, Wolinsky R, Skolasky R, Li Z, Barker N Tags: Exp Neurol Source Type: research

Stem cell-based therapies for Duchenne muscular dystrophy.
Abstract Muscular dystrophies are a group of genetic muscle disorders that cause progressive muscle weakness and degeneration. Within this group, Duchenne muscular dystrophy (DMD) is the most common and one of the most severe. DMD is an X chromosome linked disease that occurs to 1 in 3500 to 1 in 5000 boys. The cause of DMD is a mutation in the dystrophin gene, whose encoded protein provides both structural support and cell signaling capabilities. So far, there are very limited therapeutic options available and there is no cure for this disease. In this review, we discuss the existing cell therapy research, especi...
Source: Experimental Neurology - October 19, 2019 Category: Neurology Authors: Sun C, Serra C, Lee G, Wagner K Tags: Exp Neurol Source Type: research

Adenosine 2A receptor inhibition protects phrenic motor neurons from cell death induced by protein synthesis inhibition.
Abstract Respiratory motor neuron survival is critical for maintenance of adequate ventilation and airway clearance, preventing dependence to mechanical ventilation and respiratory tract infections. Phrenic motor neurons are highly vulnerable in rodent models of motor neuron disease versus accessory inspiratory motor pools (e.g. intercostals, scalenus). Thus, strategies that promote phrenic motor neuron survival when faced with disease and/or toxic insults are needed to help preserve breathing ability, airway defense and ventilator independence. Adenosine 2A receptors (A2A) are emerging as a potential target to pr...
Source: Experimental Neurology - October 17, 2019 Category: Neurology Authors: Seven YB, Simon AK, Sajjadi E, Zwick A, Satriotomo I, Mitchell GS Tags: Exp Neurol Source Type: research

Acrolein is involved in ischemic stroke-induced neurotoxicity through spermidine/spermine-N1-acetyltransferase activation.
CONCLUSION: Overall, our current results demonstrate that acrolein is a culprit of neuronal damage through GSH depletion in stroke patients. The mechanism underlying the role of acrolein in stroke-related neuronal damage occurs through SSAT-induced polyamine oxidation by NF-kB pathway activation. These results provide a novel mechanism of neurotoxicity in stroke patients, aid in the development of neutralizing or preventive measures, and further our understanding of neural protection. PMID: 31629858 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - October 17, 2019 Category: Neurology Authors: Liu JH, Wang TW, Lin YY, Ho WC, Tsai HC, Chen SP, Lin AM, Liu TY, Wang HT Tags: Exp Neurol Source Type: research

Axonal regeneration and functional recovery driven by endogenous Nogo receptor antagonist LOTUS in a rat model of unilateral pyramidotomy.
Abstract The adult mammalian central nervous system (CNS) rarely recovers from injury. Myelin fragments contain axonal growth inhibitors that limit axonal regeneration, thus playing a major role in determining neural recovery. Nogo receptor-1 (NgR1) and its ligands are among the inhibitors that limit axonal regeneration. It has been previously shown that the endogenous protein, lateral olfactory tract usher substance (LOTUS), antagonizes NgR1-mediated signaling and accelerates neuronal plasticity after spinal cord injury and cerebral ischemia in mice. However, it remained unclear whether LOTUS-mediated reorganizat...
Source: Experimental Neurology - October 17, 2019 Category: Neurology Authors: Ueno R, Takase H, Suenaga J, Kishimoto M, Kurihara Y, Takei K, Kawahara N, Yamamoto T Tags: Exp Neurol Source Type: research

Neural-respiratory inflammasome axis in traumatic brain injury.
Abstract Traumatic brain injury (TBI) is a leading cause of morbidity and mortality. Approximately 20-25% of TBI subjects develop Acute Lung Injury (ALI), but the pathomechanisms of TBI-induced ALI remain poorly defined. Currently, mechanical ventilation is the only therapeutic intervention for TBI-induced lung injury. Our recent studies have shown that the inflammasome plays an important role in the systemic inflammatory response leading to lung injury-post TBI. Here, we outline the role of the extracellular vesicle (EV)-mediated inflammasome signaling in the etiology of TBI-induced ALI. Furthermore, we evaluate ...
Source: Experimental Neurology - October 15, 2019 Category: Neurology Authors: Kerr N, de Rivero Vaccari JP, Dietrich WD, Keane RW Tags: Exp Neurol Source Type: research

GluT4: A central player in hippocampal memory and brain insulin resistance.
Abstract Insulin is now well-established as playing multiple roles within the brain, and specifically as regulating hippocampal cognitive processes and metabolism. Impairments to insulin signaling, such as those seen in type 2 diabetes and Alzheimer's disease, are associated with brain hypometabolism and cognitive impairment, but the mechanisms of insulin's central effects are not determined. Several lines of research converge to suggest that the insulin-responsive glucose transporter GluT4 plays a central role in hippocampal memory processes, and that reduced activation of this transporter may underpin the cognit...
Source: Experimental Neurology - October 12, 2019 Category: Neurology Authors: McNay EC, Pearson-Leary J Tags: Exp Neurol Source Type: research

Neuroimmunological characterization of a mouse model of primary progressive experimental autoimmune encephalomyelitis and effects of immunosuppressive or neuroprotective strategies on disease evolution.
Abstract Progressive multiple sclerosis (PMS) is a devastating disorder sustained by neuroimmune interactions still wait to be identified. Recently, immune-independent, neural bioenergetic derangements have been hypothesized as causative of neurodegeneration in PMS patients. To gather information on the immune and neurodegenerative components during PMS, in the present study we investigated the molecular and cellular events occurring in a Non-obese diabetic (NOD) mouse model of experimental autoimmune encephalomyelitis (EAE). In these mice, we also evaluated the effects of clinically-relevant immunosuppressive (de...
Source: Experimental Neurology - September 16, 2019 Category: Neurology Authors: Buonvicino D, Ranieri G, Pratesi S, Guasti D, Chiarugi A Tags: Exp Neurol Source Type: research

β2-adrenergic receptor-mediated mitochondrial biogenesis improves skeletal muscle recovery following spinal cord injury.
β2-adrenergic receptor-mediated mitochondrial biogenesis improves skeletal muscle recovery following spinal cord injury. Exp Neurol. 2019 Sep 13;:113064 Authors: Scholpa NE, Simmons EC, Tilley DG, Schnellmann RG Abstract In addition to local spinal cord dysfunction, spinal cord injury (SCI) can result in decreased skeletal muscle mitochondrial activity and muscle atrophy. Treatment with the FDA-approved β2-adrenergic receptor (ADRB2) agonist formoterol has been shown to induce mitochondrial biogenesis (MB) in both the spinal cord and skeletal muscle and, therefore, has the potential to addre...
Source: Experimental Neurology - September 13, 2019 Category: Neurology Authors: Scholpa NE, Simmons EC, Tilley DG, Schnellmann RG Tags: Exp Neurol Source Type: research

Amelioration of visual deficits and visual system pathology after mild TBI via the cannabinoid Type-2 receptor inverse agonism of raloxifene.
Abstract Visual deficits after traumatic brain injury (TBI) are common, but interventions that limit the post-trauma impairments have not been identified. We have found that treatment with the cannabinoid type-2 receptor (CB2) inverse agonist SMM-189 for 2 weeks after closed-head blast TBI greatly attenuates the visual deficits and retinal pathology this otherwise produces in mice, by modulating the deleterious role of microglia in the injury process after trauma. SMM-189, however, has not yet been approved for human use. Raloxifene is an FDA-approved estrogen receptor drug that is used to treat osteoporosis, bu...
Source: Experimental Neurology - September 10, 2019 Category: Neurology Authors: Honig MG, Del Mar NA, Henderson DL, Ragsdale TD, Doty JB, Driver JH, Li C, Fortugno AP, Mitchell WM, Perry AM, Moore BM, Reiner A Tags: Exp Neurol Source Type: research

The kainate receptor antagonist UBP310 but not single deletion of GluK1, GluK2, or GluK3 subunits, inhibits MPTP-induced degeneration in the mouse midbrain.
Abstract The excitatory neurotransmitter glutamate is essential in basal ganglia motor circuits and has long been thought to contribute to cell death and degeneration in Parkinson's disease (PD). While previous research has shown a significant role of NMDA and AMPA receptors in both excitotoxicity and PD, the third class of ionotropic glutamate receptors, kainate receptors, have been less well studied. Given the expression of kainate receptor subunits GluK1-GluK3 in key PD-related brain regions, it has been suggested that GluK1-GluK3 may contribute to excitotoxic cell loss. Therefore the neuroprotective potential ...
Source: Experimental Neurology - September 9, 2019 Category: Neurology Authors: Stayte S, Laloli KJ, Rentsch P, Lowth A, Li KM, Pickford R, Vissel B Tags: Exp Neurol Source Type: research

Models of poststroke depression and assessments of core depressive symptoms in rodents: How to choose?
Abstract Our previous studies have indicated that depression and declined cognition have been involved in some neurodegenerative diseases including Stroke, Parkinson's diseases and Vascular Parkinsonism. Post-stroke depression (PSD) is the most common psychiatric disorder following a stroke and has high morbidity and mortality. Studies on PSD are increasingly common, but the specific mechanisms remain unknown. Current research mainly includes clinical and animal aspects. Questionnaires and peripheral blood examination are two of the most common methods used to study clinical PSD. The results of questionnaires are ...
Source: Experimental Neurology - September 7, 2019 Category: Neurology Authors: Tao X, Yang W, Zhu S, Que R, Liu C, Fan T, Wang J, Mo D, Zhang Z, Tan J, Jin K, Yenarih MA, Song T, Wang Q Tags: Exp Neurol Source Type: research

Activation of calcium-impermeable GluR2-containing AMPA receptors in the lateral habenula produces antidepressant-like effects in a rodent model of Parkinson's disease.
In this study, unilateral 6-hydroxydopamine lesions of the substantia nigra pars compacta (SNc) in rats induced depressive-like behaviors and led to hyperactivity of LHb neurons compared to SNc sham-lesioned rats. Interestingly, intra-LHb injection of AMPAR agonist (S)-AMPA produced antidepressant-like effects in the two groups of rats and antagonist NBQX induced depressive-like behaviors, although (S)-AMPA excited LHb neurons and NBQX inhibited these neurons. We further found that intra-LHb injection of (S)-AMPA excited dopaminergic neurons in the anterior ventral tegmental area (aVTA) and serotonergic neurons in the dors...
Source: Experimental Neurology - September 6, 2019 Category: Neurology Authors: Zhang J, Lv S, Tang G, Bian G, Yang Y, Li R, Yang J, Liu J Tags: Exp Neurol Source Type: research

Potential roles of matricellular proteins in stroke.
This article reviews the available information regarding potential roles of matricellular proteins in stroke, and discusses the potential therapeutic approaches against stroke using matricellular proteins. PMID: 31499062 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - September 6, 2019 Category: Neurology Authors: Kawakita F, Kanamaru H, Asada R, Suzuki H Tags: Exp Neurol Source Type: research

Xenon exerts anti-seizure and neuroprotective effects in kainic acid-induced status epilepticus and neonatal hypoxia-induced seizure.
This study aimed to investigate the role of xenon inhalation and explore the role of different xenon ratio gradients and different delayed treatment times in seizure models. Kainic acid (KA)-induced status epilepticus and neonatal hypoxia-induced seizure models were used in our study. Animals were subject to inhalation of xenon mixture for 60 min after the stimulation used to induce seizures. The control group was treated with 70% nitrogen/30% oxygen, as in previous reports. Behavioral changes, electroencephalography, neuronal injury, and learning and memory function were investigated in each group. The results indicate ...
Source: Experimental Neurology - September 6, 2019 Category: Neurology Authors: Zhang Y, Zhang M, Liu S, Zhu W, Yu J, Cui Y, Pan X, Gao X, Wang Q, Sun H Tags: Exp Neurol Source Type: research

Activation of endothelial ras-related C3 botulinum toxin substrate 1 (Rac1) improves post-stroke recovery and angiogenesis via activating Pak1 in mice.
CONCLUSIONS: We conclude that activation of endothelial Rac1 improves functional recovery and angiogenesis after stroke, and this process is mediated by Pak1 signaling. This study provides novel insight for Rac1 in the mechanism of long-term stroke recovery. PMID: 31499064 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - September 6, 2019 Category: Neurology Authors: Bu F, Min JW, Munshi Y, Lai YJ, Qi L, Urayama A, McCullough LD, Li J Tags: Exp Neurol Source Type: research

Synaptic alterations and immune response are sexually dimorphic in a non-pertussis toxin model of experimental autoimmune encephalomyelitis.
Abstract Multiple sclerosis is an autoimmune disorder of the central nervous system (CNS) characterized by locomotor impairments, cognitive deficits, affective disorders, and chronic pain. Females are predominately affected by MS compared to males and develop motor symptoms earlier. However, key symptoms affect all patients regardless of sex. Previous studies have shown that demyelination and axonal damage play key roles in symptom development, but it is unclear why sex differences exist in MS onset, and effective symptom treatment is still lacking. We here used a non-pertussis toxin (nPTX) experimental autoimmune...
Source: Experimental Neurology - September 6, 2019 Category: Neurology Authors: Murphy KL, Fischer R, Swanson KA, Bhatt IJ, Oakley L, Smeyne R, Bracchi-Ricard V, Bethea JR Tags: Exp Neurol Source Type: research

DLK mediates the neuronal intrinsic immune response and regulates glial reaction and neuropathic pain.
Abstract Inflammatory response triggered by nerve injury plays important roles in the development of neurological disorders, such as neuropathic pain. The signaling events leading to inflammation in the nervous system remain poorly understood. Here, by deleting Dlk in sensory neurons driven by Wnt1a-Cre, we show that dual leucine zipper kinase (DLK) is required for the neuronal intrinsic immune response to induce cytokines and chemokines such as Ccl2, Ccl7, and Ccl12 upon nerve injury. The DLK-controlled injury response in sensory neurons could regulate CD11b+ immune cell infiltration in the dorsal root ganglia, a...
Source: Experimental Neurology - September 5, 2019 Category: Neurology Authors: Hu Z, Deng N, Liu K, Zeng W Tags: Exp Neurol Source Type: research

Zfhx3 is required for the differentiation of late born D1-type medium spiny neurons.
Abstract The striatum, the major component of the basal ganglia, consists of the caudate-putamen, nucleus accumbens and olfactory tubercle. The striatal principal projection neurons are comprised of medium spiny neurons (MSNs) with two dopamine receptors: DRD1 (D1 MSNs) and DRD2 (D2 MSNs). In the present study, we demonstrate that Zfhx3 is strongly expressed in the boundary of the subventricular zone (SVZ)/mantle zone (MZ) of the lateral ganglionic eminence (LGE), and its expression in the striatum is downregulated during the first postnatal week. At the cellular level, Zfhx3 is selectively expressed in immature D...
Source: Experimental Neurology - September 3, 2019 Category: Neurology Authors: Zhang Z, Wei S, Du H, Su Z, Wen Y, Shang Z, Song X, Xu Z, You Y, Yang Z Tags: Exp Neurol Source Type: research

Imaging the dynamic interactions between immune cells and the neurovascular interface in the spinal cord.
Abstract Imaging the dynamic interactions between immune cells, glia, neurons and the vasculature in living rodents has revolutionized our understanding of physiological and pathological mechanisms of the CNS. Emerging microscopy and imaging technologies have enabled longitudinal tracking of structural and functional changes in a plethora of different cell types in the brain. The development of novel methods also allowed stable and longitudinal optical access to the spinal cord with minimum tissue perturbation. These important advances facilitated the application of in vivo imaging using two-photon microscopy for ...
Source: Experimental Neurology - August 28, 2019 Category: Neurology Authors: Borjini N, Paouri E, Tognatta R, Akassoglou K, Davalos D Tags: Exp Neurol Source Type: research

Salvinorin A moderates postischemic brain injury by preserving endothelial mitochondrial function via AMPK/Mfn2 activation.
This study aimed to investigate whether KOR activation improves the morphology and function of intracellular mitochondria to protect endothelial cells after cerebral ischemia. A transient ischemic brain damage was generated by establishing middle cerebral artery occlusion (MCAO) model in male Sprague-Dawley rats and oxygen glucose deprivation (OGD) model in human brain microvascular endothelial cells (HBMECs). In vivo findings revealed that SA significantly reduced the infarct size, brain edema and Evans blue effusion after MCAO. In vitro findings revealed that SA improved the cell viability and decreased the apoptotic rat...
Source: Experimental Neurology - August 25, 2019 Category: Neurology Authors: Dong H, Zhou W, Xin J, Shi H, Yao X, He Z, Wang Z Tags: Exp Neurol Source Type: research

Astrocyte-derived fatty acid-binding protein 7 protects blood-brain barrier integrity through a caveolin-1/MMP signaling pathway following traumatic brain injury.
Abstract The astrocyte-endothelial cell interaction is crucial for normal brain homeostasis and blood-brain barrier (BBB) disruption in pathological conditions. However, the mechanism by which astrocytes control BBB integrity, especially after traumatic brain injury (TBI), remains unclear. Here, we present evidence that astrocyte-derived fatty acid-binding protein 7 (FABP7), a differentiation- and migration-associated molecule, may function as a modulator of BBB permeability in a rat weight-drop model of TBI. Immunohistochemical analysis revealed that TBI induced increased expression of FABP7 in astrocytes, accomp...
Source: Experimental Neurology - August 24, 2019 Category: Neurology Authors: Rui Q, Ni H, Lin X, Zhu X, Li D, Liu H, Chen G Tags: Exp Neurol Source Type: research

Physical exercise ameliorates psychiatric disorders and cognitive dysfunctions by hippocampal mitochondrial function and neuroplasticity in post-traumatic stress disorder.
In this study, we investigated the effect of aerobic exercise on mitochondrial function and neuroplasticity in the hippocampus as well as behavioral changes in animal models of PTSD. Exposure to severe stress resulted in mitochondrial dysfunction in the hippocampus, including impaired Ca2+ homeostasis, an increase in reactive oxygen species such as H2O2, a decrease in the O2 respiration rate, and overexpression of membrane permeability transition pore-related proteins, including voltage-dependent anion channel, adenine nucleotide translocase, and cyclophilin-D. Exposure to extreme stress also decreased neuroplasticity by i...
Source: Experimental Neurology - August 22, 2019 Category: Neurology Authors: Seo JH, Park HS, Park SS, Kim CJ, Kim DH, Kim TW Tags: Exp Neurol Source Type: research

Slow-wave activity homeostasis in the somatosensory cortex after spinal cord injury.
fani G, Aguilar J Abstract The cortical reorganization after spinal cord injury (SCI) involves a series of physiological changes that drive the expansion of the intact cortical area to the deafferented cortical area. These changes have always been studied under a stimulus-response paradigm, which demonstrates that the deafferented cortex becomes more responsive to stimulation of body regions above the level of the lesion. However, less is known about how permanent large-scale deafferentation affects spontaneous activity in the somatosensory cortex, an important physiological feature related to the processing of pe...
Source: Experimental Neurology - August 22, 2019 Category: Neurology Authors: Fernández-López E, Alonso-Calviño E, Humanes-Valera D, Foffani G, Aguilar J Tags: Exp Neurol Source Type: research

Sarm1 deletion reduces axon damage, demyelination, and white matter atrophy after experimental traumatic brain injury.
This study demonstrates that Sarm1 inactivation reduces demyelination, and white matter atrophy after TBI, while the post-injury stage impacts when axon protection is effective. PMID: 31445042 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - August 21, 2019 Category: Neurology Authors: Marion CM, McDaniel DP, Armstrong RC Tags: Exp Neurol Source Type: research

CSF transplantation of a specific iPSC-derived neural stem cell subpopulation ameliorates the disease phenotype in a mouse model of spinal muscular atrophy with respiratory distress type 1.
Abstract Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a genetic motor neuron disease affecting infants. This condition is caused by mutations in the IGHMBP2 gene and currently has no cure. Stem cell transplantation is a potential therapeutic strategy for motor neuron diseases such as SMARD1, exerting beneficial effects both by replacing cells and by providing support to endogenous motor neurons. In this work, we demonstrate that human induced pluripotent stem cell (iPSC)-derived neural stem cells (NSCs) selected for the expression of specific markers, namely, Lewis X, CXCR4 and beta 1 integ...
Source: Experimental Neurology - August 21, 2019 Category: Neurology Authors: Forotti G, Nizzardo M, Bucchia M, Ramirez A, Trombetta E, Gatti S, Bresolin N, Comi GP, Corti S Tags: Exp Neurol Source Type: research

Overexpression of α5β1 integrin and angiopoietin-1 co-operatively promote blood-brain barrier integrity and angiogenesis following ischemic stroke.
Overexpression of α5β1 integrin and angiopoietin-1 co-operatively promote blood-brain barrier integrity and angiogenesis following ischemic stroke. Exp Neurol. 2019 Aug 21;:113042 Authors: Wang L, Zhang X, Liu X, Feng G, Fu Y, Milner R, Li L Abstract We previously demonstrated that cross-talk between α5β1 integrin and the angiopoietin-1 (Ang1) / Tie2 receptor plays an important role in regulating brain endothelial angiogenic responses in the ischemic penumbra following cerebral ischemic stroke (CIS). However, a recent study suggested that stimulation of the α5β1 integr...
Source: Experimental Neurology - August 21, 2019 Category: Neurology Authors: Wang L, Zhang X, Liu X, Feng G, Fu Y, Milner R, Li L Tags: Exp Neurol Source Type: research

Early TLR4 inhibition reduces hippocampal injury at puberty in a rat model of neonatal hypoxic-ischemic brain damage via regulation of neuroimmunity and synaptic plasticity.
In conclusion, our findings indicate that early inhibition of TLR4 signalling may improve the long-term prognosis of neonatal HIBD. The mechanisms contributing to this improvement involve reductions in neuronal loss, a decrease in glial cell activation, and an improvement in synaptic plasticity. PMID: 31442443 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - August 20, 2019 Category: Neurology Authors: Tang Z, Cheng S, Sun Y, Zhang Y, Xiang X, Ouyang Z, Zhu X, Wang B, Hei M Tags: Exp Neurol Source Type: research

Acute L-DOPA administration reverses changes in firing pattern and low frequency oscillatory activity in the entopeduncular nucleus from long term L-DOPA treated 6-OHDA-lesioned rats.
Abstract The pathophysiology of Parkinson's disease (PD) and L-DOPA-induced dyskinesia (LID) is associated with aberrant neuronal activity and abnormal high levels of oscillatory activity and synchronization in several basal ganglia nuclei and the cortex. Previously, we have shown that the firing activity of neurons in the substantia nigra pars reticulata (SNr) is relevant in dyskinesia and may be driven by subthalamic nucleus (STN) hyperactivity. Conversely, low frequency oscillatory activity and synchronization in these structures seem to be more important in PD because they are not influenced by prolonged L-DOP...
Source: Experimental Neurology - August 16, 2019 Category: Neurology Authors: Aristieta A, Ruiz-Ortega JA, Morera-Herreras T, Miguelez C, Ugedo L Tags: Exp Neurol Source Type: research

Enhanced regeneration and reinnervation following timed GDNF gene therapy in a cervical ventral root avulsion.
This study is an important step in demonstrating the potential of timed GDNF-gene therapy to enhance axon regeneration after neurosurgical repair of a severe proximal nerve lesion. PMID: 31425689 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - August 16, 2019 Category: Neurology Authors: Eggers R, de Winter F, Arkenaar C, Tannemaat MR, Verhaagen J Tags: Exp Neurol Source Type: research

Demyelination contributes to depression comorbidity in a rat model of chronic epilepsy via dysregulation of Olig2/LINGO-1 and disturbance of calcium homeostasis.
Abstract Depression is the most common comorbidity among patients with epilepsy. Despite prior assumptions that antiepileptic drugs are to blame, more and more pathological studies have shown that latent neurological alterations associated with white matter injury and demyelination may underlie this link. However, whether disturbances in cerebral myelination contribute to the initiation of depression in epilepsy remains unclear. In the present study, we investigated the connection between demyelination disorders and the development of depression comorbidity in epilepsy. We first induced spontaneous recurrent epile...
Source: Experimental Neurology - August 12, 2019 Category: Neurology Authors: Ma T, Li B, Le Y, Xu Y, Wang F, Tian Y, Cai Q, Liu Z, Xiao L, Li H Tags: Exp Neurol Source Type: research

Noninvasive spinal neuromodulation to map and augment lower urinary tract function in rhesus macaques.
Abstract Dysfunction of the lower urinary tract (LUT) is prevalent in neurological disorders, including multiple sclerosis, stroke, spinal cord injury and neurodegenerative conditions. Common symptoms include urgency, incontinence, and urinary retention. Recent advances in neuromodulation have resulted in improved treatments for overactive bladder symptoms of urgency, frequency, and nocturia. However, there are presently no treatments available for the induction of voiding to overcome urinary retention. We demonstrate that transcutaneous spinal cord stimulation (TSCS), a non-invasive intervention, applied over the...
Source: Experimental Neurology - August 7, 2019 Category: Neurology Authors: Havton LA, Christe KL, Edgerton VR, Gad PN Tags: Exp Neurol Source Type: research

Recent advances in the therapeutic uses of chondroitinase ABC.
Abstract Many studies, using pre-clinical models of SCI, have demonstrated the efficacy of chondroitinase ABC as a treatment for spinal cord injury and this has been confirmed in laboratories worldwide and in several animal models. The aim of this review is report the current state of research in the field and to compare the relative efficacies of these new interventions to improve outcomes in both acute and chronic models of SCI. We also report new methods of chondroitinase delivery and the outcomes of two clinical trials using the enzyme to treat spinal cord injury in dogs and disc herniation in human patients. ...
Source: Experimental Neurology - August 6, 2019 Category: Neurology Authors: Muir E, De Winter F, Verhaagen J, Fawcett J Tags: Exp Neurol Source Type: research

A neutral lipid-enriched diet improves myelination and alleviates peripheral nerve pathology in neuropathic mice.
Abstract Charcot-Marie-Tooth (CMT) diseases comprise a genetically heterogeneous group of hereditary peripheral neuropathies. Trembler J (TrJ) mice carry a spontaneous mutation in peripheral myelin protein 22 (PMP22) and model early-onset, severe CMT type 1E disease. Recent studies indicate that phospholipid substitution, or cholesterol-enriched diet, benefit myelinated nerves, however such interventions have not been tested in early-onset dysmyelinating neuropathies. Here, we examined the lipid profile of peripheral nerves from 6-month-old TrJ mice with advanced neuropathy and tested the impact of a 6-week-long n...
Source: Experimental Neurology - August 3, 2019 Category: Neurology Authors: Zhou Y, Bazick H, Miles JR, Fethiere A, Salihi MAI, Fazio S, Tavori H, Notterpek L Tags: Exp Neurol Source Type: research

Reduced serotonin impairs long-term depression in basolateral amygdala complex and causes anxiety-like behaviors in a mouse model of perimenopause.
Abstract Perimenopause is characterized by a gradual depletion of ovarian follicles with increased vulnerability to anxiety. However, the underlying mechanisms remain poorly understood. Herein, we show that chronic exposure to 4-vinylcycloxene diepoxide (VCD) in adult female mice (VCD-mice) caused follicles depletion and decline of serum estradiol (E2) and progesterone levels. Serotonin (5-HT) synthesis in dorsal raphe nucleus (DRN) and serotonergic afferents to basolateral amygdala complex (BLA) were reduced in VCD-mice, which were recovered by the supplement E2. VCD-mice appeared anxiety-like behaviors, which wa...
Source: Experimental Neurology - August 1, 2019 Category: Neurology Authors: Wang Y, Liu Y, Xiong J, Di T, Yuan Z, Wu J, Chen L Tags: Exp Neurol Source Type: research

Impact of mTOR hyperactive neurons on the morphology and physiology of adjacent neurons: Do PTEN KO cells make bad neighbors?
Abstract Hyperactivation of the mechanistic target of rapamycin (mTOR) pathway is associated with epilepsy, autism and brain growth abnormalities in humans. mTOR hyperactivation often results from developmental somatic mutations, producing genetic lesions and associated dysfunction in relatively restricted populations of neurons. Disrupted brain regions, such as those observed in focal cortical dysplasia, can contain a mix of normal and mutant cells. Mutant cells exhibit robust anatomical and physiological changes. Less clear, however, is whether adjacent, initially normal cells are affected by the presence of abn...
Source: Experimental Neurology - August 1, 2019 Category: Neurology Authors: LaSarge CL, Pun RYK, Gu Z, Santos VR, Danzer SC Tags: Exp Neurol Source Type: research

Botch protects neurons from ischemic insult by antagonizing Notch-mediated neuroinflammation.
In conclusion, we found that Botch exerts neuroprotective effects via antagonizing the maturation of Notch1-induced neuronal injury and neuroinflammation, which may provide insights into novel therapeutic targets for the treatment of I/R injury. PMID: 31377404 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - August 1, 2019 Category: Neurology Authors: Li H, Ma J, Fang Q, Li H, Shen H, Li X, Xue Q, Zhu J, Chen G Tags: Exp Neurol Source Type: research

Neuronal activity and microglial activation support corticospinal tract and proprioceptive afferent sprouting in spinal circuits after a corticospinal system lesion.
Abstract Spared corticospinal tract (CST) and proprioceptive afferent (PA) axons sprout after injury and contribute to rewiring spinal circuits, affecting motor recovery. Loss of CST connections post-injury results in corticospinal signal loss and associated spinal activity. We investigated the role of activity loss and injury on CST and PA sprouting. To understand activity-dependence after injury, we compared CST and PA sprouting after motor cortex (MCX) inactivation, produced by chronic MCX muscimol microinfusion, with sprouting after a CST lesion produced by pyramidal tract section (PTx). Activity suppression, ...
Source: Experimental Neurology - July 18, 2019 Category: Neurology Authors: Jiang YQ, Armada K, Martin JH Tags: Exp Neurol Source Type: research

Piriform cortex ictogenicity in vitro.
oli M Abstract The piriform cortex is recognized to play critical roles in focal ictogenesis, both in animal models and in humans. We review here the contribution of in vitro studies performed on rodent brain tissue that were aimed at understanding the ictogenic properties of the piriform cortex and the contiguous olfactory areas. During in vitro experiments, epileptiform events can be easily generated in the piriform area by diverse pro-convulsive drugs (4-aminopyridine, bicuculline, picrotoxin) or by electrical stimulation. Simultaneous intracellular and field potential recordings performed on in vitro preparati...
Source: Experimental Neurology - July 16, 2019 Category: Neurology Authors: de Curtis M, Uva L, Lévesque M, Biella G, Avoli M Tags: Exp Neurol Source Type: research

Anatomical imaging of the piriform cortex in epilepsy.
Abstract The piriform cortex is a distinct brain region that plays a key role in the sense of smell. The piriform cortex is the major part of primary olfactory cortex and has broad connections that extend beyond the olfactory regions into limbic and fronto-temporal cortical networks. Numerous studies have described these anatomical connections via microscopic imaging and tracer studies. More recently, macroscopic anatomical imaging studies have demonstrated changes in the piriform cortex in humans with focal epilepsy as well as in animal models, suggesting this brain region can play a critical role in epileptogene...
Source: Experimental Neurology - July 16, 2019 Category: Neurology Authors: Young JC, Vaughan DN, Nasser HM, Jackson GD Tags: Exp Neurol Source Type: research

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