Monoaminergic regulation of nociceptive circuitry in a Parkinson's disease rat model.
Abstract Pain is a common nonmotor symptom of Parkinson's disease (PD) that remains neglected and misunderstood. Elucidating the nondopaminergic circuitry may be key to better understanding PD and improving current treatments. We investigated the role of monoamines in nociceptive behavior and descending analgesic circuitry in a rat 6-hydroxydopamine (6-OHDA)-induced PD model and explored the resulting motor dysfunctions and inflammatory responses. Rats pretreated with noradrenaline and serotonin reuptake inhibitors were given unilateral striatal 6-OHDA injections and evaluated for mechanical hyperalgesia and motor...
Source: Experimental Neurology - April 24, 2019 Category: Neurology Authors: Campos ACP, Berzuino MB, Hernandes MS, Fonoff ET, Pagano RL Tags: Exp Neurol Source Type: research
Roscovitine, an experimental CDK5 inhibitor, causes delayed suppression of microglial, but not astroglial recruitment around intracerebral dopaminergic grafts.
kkhah G Abstract Inhibitors of cell cycle proteins are known to reduce glial activation and to be neuroprotective in a number of settings. In the context of intracerebral grafting, glial activation is documented to correlate with graft rejection. However, the effects of modification of glial reactivity following grafting in the CNS are poorly understood. Moreover, it is not completely clear if the glial cells themselves trigger the rejection process, or are they secondarily activated. The present study investigated the effect of microglial inhibition by the cyclin-dependant kinase 5 (CDK5) inhibitor roscovitine fo...
Source: Experimental Neurology - April 24, 2019 Category: Neurology Authors: Tomov N, Surchev L, Wiedenmann C, Döbrössy M, Nikkhah G Tags: Exp Neurol Source Type: research
Insulin resistance and hippocampal dysfunction: Disentangling peripheral and brain causes from consequences.
Abstract In the periphery insulin plays a critical role in the regulation of metabolic homeostasis by stimulating glucose uptake into peripheral organs. In the central nervous system (CNS), insulin plays a critical role in the formation of neural circuits and synaptic connections from the earliest stages of development and facilitates and promotes neuroplasticity in the adult brain. Beyond these physiological roles of insulin, a shared feature between the periphery and CNS is that decreases in insulin receptor activity and signaling (i.e. insulin resistance) contributes to the pathological consequences of type 2 d...
Source: Experimental Neurology - April 24, 2019 Category: Neurology Authors: Grillo CA, Woodruff J, Macht VA, Reagan LP Tags: Exp Neurol Source Type: research
Genetic and pharmacological manipulation of glial glutamate transporters does not alter infection-induced seizure activity.
Abstract The contribution of glial transporters to glutamate movement across the membrane has been identified as a potential target for anti-seizure therapies. Two such glutamate transporters, GLT-1 and system xc-, are expressed on glial cells, and modulation of their expression and function have been identified as a means by which seizures, neuronal injury, and gliosis can be reduced in models of brain injury. While GLT-1 is responsible for the majority of glutamate uptake in the brain, system xc- releases glutamate in the extracellular cleft in exchange for cystine and represents as such the major source of hipp...
Source: Experimental Neurology - April 22, 2019 Category: Neurology Authors: Loewen JL, Albertini G, Dahle EJ, Sato H, Smolders IJ, Massie A, Wilcox KS Tags: Exp Neurol Source Type: research
Probing the coding logic of thermosensation using spinal cord calcium imaging.
Abstract The spinal cord dorsal horn is the first relay station of the neural network for processing somatosensory information. High-throughput recording methods facilitate the study of sensory coding in the cortex but have not been successfully applied to study spinal cord circuitry until recently. Here, we review the development of the in vivo two-photon spinal calcium imaging preparation and biological findings from the first systematic characterization of the spinal response to cutaneous thermal stimuli, focusing on the difference between the coding of heat and cold, and the contribution of different periphera...
Source: Experimental Neurology - April 20, 2019 Category: Neurology Authors: Ran C, Chen X Tags: Exp Neurol Source Type: research
Combining molecular intervention with in vivo imaging to untangle mechanisms of axon pathology and outgrowth following spinal cord injury.
Abstract In vivo imaging of the spinal cord has allowed the observation of single axons over relatively long periods in the living mouse. After spinal cord injury, this methodology has helped to differentiate several pathological stages and tissue processes which impact axon morphology. In addition, the combination of in vivo imaging techniques with specific molecular intervention has shown that specific pathological axon changes can respond to distinct treatments. Combining in vivo imaging with molecular interventions is, hence, a powerful approach to extend our knowledge of the pathological processes leading to ...
Source: Experimental Neurology - April 13, 2019 Category: Neurology Authors: Denecke CK, Aljović A, Bareyre FM Tags: Exp Neurol Source Type: research
Understanding the axonal response to injury by in vivo imaging in the mouse spinal cord: A tale of two branches.
This article reviews evidence from in vivo spinal cord imaging that axonal branches markedly impact the degenerative and regenerative responses to injury. At a major bifurcation point, depending on whether one or both axonal branches are injured, neurons may choose either a more self-preservative response or a more dynamic response. The stabilizing effect of the spared branch may underlie a well-known divergence in neuronal responses to injury, and illustrates an example where in vivo spinal cord imaging reveals insights that are difficult to elucidate with conventional histological methods. PMID: 30986398 [PubMed - a...
Source: Experimental Neurology - April 12, 2019 Category: Neurology Authors: Zheng B, Lorenzana AO, Ma L Tags: Exp Neurol Source Type: research
OCT4B-190 protects against ischemic stroke by modulating GSK-3 β/HDAC6.
OCT4B-190 protects against ischemic stroke by modulating GSK-3β/HDAC6. Exp Neurol. 2019 Apr 11;: Authors: Chen Y, Wu Z, Zhu X, Zhang M, Zang X, Li X, Xu Y Abstract OCT4 is a key regulator in maintaining the pluripotency and self-renewal of embryonic stem cells (ESCs). Human OCT4 gene has three mRNA isoforms, termed OCT4A, OCT4B and OCT4B1. The 190-amino-acid protein isoform (OCT4B-190) is one of the major products of OCT4B mRNA, the biological function of which is still not well defined. Recent evidence suggests that OCT4B-190 may function in the cellular stress response. The glycogen synthase ki...
Source: Experimental Neurology - April 11, 2019 Category: Neurology Authors: Chen Y, Wu Z, Zhu X, Zhang M, Zang X, Li X, Xu Y Tags: Exp Neurol Source Type: research
Detection of brain specific cardiolipins in plasma after experimental pediatric head injury.
Abstract Cardiolipin (CL) is a mitochondria-specific phospholipid that is central to maintenance and regulation of mitochondrial bioenergetic and metabolic functions. CL molecular species display great tissue variation with brain exhibiting a distinct, highly diverse CL population. We recently showed that the appearance of unique brain-type CLs in plasma could serve as a brain-specific marker of mitochondrial/tissue injury in patients after cardiac arrest. Mitochondrial dysfunction has been increasingly implicated as a critical mechanism underlying the pathogenesis of traumatic brain injury (TBI). Therefore, we hy...
Source: Experimental Neurology - April 11, 2019 Category: Neurology Authors: Anthonymuthu TS, Kenny EM, Hier ZE, Clark RSB, Kochanek PM, Kagan VE, Bayır H Tags: Exp Neurol Source Type: research
Improved memory and reduced anxiety in δ-catenin transgenic mice.
Improved memory and reduced anxiety in δ-catenin transgenic mice. Exp Neurol. 2019 Apr 11;: Authors: Ryu T, Park HJ, Kim H, Cho YC, Kim BC, Jo J, Seo YW, Choi WS, Kim K Abstract δ-Catenin is abundant in the brain and affects its synaptic plasticity. Furthermore, loss of δ-catenin is related to the deficits of learning and memory, mental retardation (cri-du-chat syndrome), and autism. A few studies about δ-catenin deficiency mice were performed. However, the effect of δ-catenin overexpression in the brain has not been investigated as yet. Therefore we generated a δ-c...
Source: Experimental Neurology - April 11, 2019 Category: Neurology Authors: Ryu T, Park HJ, Kim H, Cho YC, Kim BC, Jo J, Seo YW, Choi WS, Kim K Tags: Exp Neurol Source Type: research
Depletion of microglia immediately following traumatic brain injury in the pediatric rat: Implications for cellular and behavioral pathology.
Abstract The inflammatory response is a significant component of the pathophysiology of pediatric traumatic brain injury. High levels of inflammatory mediators have been found in the cerebrospinal fluid of brain-injured children which have been linked to poor prognosis. Targeting aspects of the inflammatory response in the hopes of finding a viable post-injury therapeutic option has gained attention. Microglia are largely responsible for perpetuating the injury-induced inflammatory response but in the developing brain they play beneficial roles in both normal and disease states. Following closed head injury in the...
Source: Experimental Neurology - April 10, 2019 Category: Neurology Authors: Hanlon LA, Raghupathi R, Huh JW Tags: Exp Neurol Source Type: research
Excess glutamate secreted from astrocytes drives upregulation of P-glycoprotein in endothelial cells in amyotrophic lateral sclerosis.
In this study, we found that glutamate, which is abnormally secreted by mutant SOD1 and sporadic ALS astrocytes, drives upregulation of P-gp expression and activity levels in endothelial cells via activation of N-Methyl-D-Aspartic acid (NMDA) receptors. Surprisingly, astrocyte-secreted glutamate regulation of endothelial P-gp levels is not a mechanism shared by all forms of ALS. C9orf72-ALS astrocytes had no effect on endothelial cell P-gp expression and did not display increased glutamate secretion. Utilizing an optimized in vitro human BBB model consisting of patient-derived induced pluripotent stem cells, we showed that...
Source: Experimental Neurology - April 8, 2019 Category: Neurology Authors: Mohamed LA, Markandaiah S, Bonanno S, Pasinelli P, Trotti D Tags: Exp Neurol Source Type: research
Insulin resistance: Genetic associations with depression and cognition in population based cohorts.
Abstract Insulin resistance, broadly defined as the reduced ability of insulin to exert its biological action, has been associated with depression and cognitive dysfunction in observational studies. However, it is unclear whether these associations are causal and whether they might be underpinned by other shared factors. To address this knowledge gap, we capitalized on the stability of genetic biomarkers through the lifetime, and on their unidirectional relationship with depression and cognition. Specifically, we determined the association between quantitative measures of cognitive function and depression and gene...
Source: Experimental Neurology - April 6, 2019 Category: Neurology Authors: Frangou S, Shirali M, Adams MJ, Howard DM, Gibson J, Hall LS, Smith BH, Padmanabhan S, Murray AD, Porteous DJ, Haley CS, Deary IJ, Clarke TK, McIntosh AM Tags: Exp Neurol Source Type: research
Metabolic perturbations after pediatric TBI: It's not just about glucose.
Abstract Improved patient survival following pediatric traumatic brain injury (TBI) has uncovered a currently limited understanding of both the adaptive and maladaptive metabolic perturbations that occur during the acute and long-term phases of recovery. While much is known about the redundancy of metabolic pathways that provide adequate energy and substrates for normal brain growth and development, the field is only beginning to characterize perturbations in these metabolic pathways after pediatric TBI. To date, the majority of studies have focused on dysregulated oxidative glucose metabolism after injury; howeve...
Source: Experimental Neurology - April 2, 2019 Category: Neurology Authors: Bowman CE, Scafidi J, Scafidi S Tags: Exp Neurol Source Type: research
Understanding the link between insulin resistance and Alzheimer's disease: Insights from animal models.
ce FG Abstract Alzheimer's disease (AD) is a devastating neurodegenerative disease affecting millions of people worldwide. AD is characterized by a profound impairment of higher cognitive functions and still lacks any effective disease-modifying treatment. Defective insulin signaling has been implicated in AD pathophysiology, but the mechanisms underlying this process are not fully understood. Here, we review the molecular mechanisms underlying defective brain insulin signaling in rodent models of AD, and in a non-human primate (NHP) model of the disease that recapitulates features observed in AD brains. We furthe...
Source: Experimental Neurology - March 28, 2019 Category: Neurology Authors: De Silva NML, Gonçalves RA, Boehnke SE, Forny-Germano L, Munoz DP, De Felice FG Tags: Exp Neurol Source Type: research
MicroRNA-132 attenuates cerebral injury by protecting blood-brain-barrier in MCAO mice.
Abstract MicroRNAs (miRNAs) have been widely reported to induce posttranscriptional gene silencing and led to an explosion of new strategies for the treatment of human disease. It has been reported that the expression of MicroRNA-132 (miR-132) are altered both in the blood and brain after stroke. However, the effect of miR-132 on blood-brain barrier (BBB) disruption in ischemia stroke has not been studied. Here we will investigate the effects of miR-132 on the permeability of BBB after ischemic stroke and explore the potential mechanism underlying observed protection. Eight week-old mice were injected intracerebro...
Source: Experimental Neurology - March 28, 2019 Category: Neurology Authors: Zuo X, Lu J, Manaenko A, Qi X, Tang J, Mei Q, Xia Y, Hu Q Tags: Exp Neurol Source Type: research
Translational approach towards determining the role of cerebral autoregulation in outcome after traumatic brain injury.
Abstract Cerebral autoregulation is impaired after traumatic brain injury (TBI), contributing to poor outcome. In the context of the neurovascular unit, cerebral autoregulation contributes to neuronal cell integrity and clinically Glasgow Coma Scale is correlated to intactness of autoregulation after TBI. Cerebral Perfusion Pressure (CPP) is often normalized by use of vasoactive agents to increase mean arterial pressure (MAP) and thereby limit impairment of cerebral autoregulation and neurological deficits. However, current vasoactive agent choice used to elevate MAP to increase CPP after TBI is variable. Vasoacti...
Source: Experimental Neurology - March 27, 2019 Category: Neurology Authors: Armstead WM, Vavilala MS Tags: Exp Neurol Source Type: research
Impairment of pericyte-endothelium crosstalk leads to blood-brain barrier dysfunction following traumatic brain injury.
In conclusion, our data provide an insight that brain trauma causes an early impairment of pericyte-endothelium integrity and results in BBB dysregulation that initiates pathological consequences associated with TBI. PMID: 30926390 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - March 26, 2019 Category: Neurology Authors: Bhowmick S, D'Mello V, Caruso D, Wallerstein A, Abdul-Muneer PM Tags: Exp Neurol Source Type: research
Neuroprotective effects of inter-alpha inhibitor proteins after hypoxic-ischemic brain injury in neonatal rats.
The objective of the current study was to investigate the neuroprotective effects of treatment with IAIPs given immediately or 6 h after HI in both male and female neonatal rats. HI was induced with the Rice-Vannucci method in postnatal (P) day 7 rats. After ligation of the right common carotid artery, P7 rats were exposed to 90 min of hypoxia (8% oxygen). Human plasma-derived IAIPs or placebo (phosphate buffered saline) was given at zero, 24, and 48 h after HI. Brains were perfused, weighed and fixed 72 h after HI at P10. In a second, delayed treatment group, the same procedure was followed except that IAIPs or pl...
Source: Experimental Neurology - March 23, 2019 Category: Neurology Authors: Chen X, Nakada S, Donahue JE, Chen RH, Tucker R, Qiu J, Lim YP, Stopa EG, Stonestreet BS Tags: Exp Neurol Source Type: research
Does pediatric traumatic brain injury cause adult alcohol misuse: Combining preclinical and epidemiological approaches.
Abstract Traumatic brain injury (TBI) is closely interrelated with alcohol use disorders. This is mediated, in part, by the large number of individuals who are intoxicated at the time of their injuries. However, there is also evidence, both preclinically and epidemiologically that TBI, particularly when it occurs early in life can increase the incidence of alcohol use disorders later on. This is extremely important because, drinking after TBI has been associated with much poorer long-term outcomes as compared to individuals who do not drink. However, for a number of reasons including, potential confounders and a r...
Source: Experimental Neurology - March 22, 2019 Category: Neurology Authors: Weil ZM, Karelina K, Corrigan JD Tags: Exp Neurol Source Type: research
HDAC5 promotes optic nerve regeneration by activating the mTOR pathway.
Abstract Neurons in the central nervous system (CNS) regenerate poorly compared to their counterparts in the peripheral nervous system. We previously showed that, in peripheral sensory neurons, nuclear HDAC5 inhibits the expression of regenerative associated genes. After nerve injury, HDAC5 is exported to the cytoplasm to promote axon regeneration. Here we investigated the role of HDAC5 in retinal ganglion cells (RGC), a CNS neuron which fails to survive and regenerate axons after injury. In contrast to PNS neurons, we found that HDAC5 is mostly cytoplasmic in naïve RGCs and its localization is not affected b...
Source: Experimental Neurology - March 22, 2019 Category: Neurology Authors: Pita-Thomas W, Mahar M, Joshi A, Gan D, Cavalli V Tags: Exp Neurol Source Type: research
Chronic spinal cord injury impairs primary CD8 T cell antiviral immunity but does not affect generation or function of memory CD8 T cells.
Abstract Antiviral immunity is severely compromised following trauma to the central nervous system. In mice with chronic spinal cord injury (SCI), primary infection with influenza virus leads to high mortality rates due to impaired expansion of virus-specific CD8 T cells. One strategy to increase resistance to viral infections is to generate memory immune cells that protect from recurrent infections. However, it is unknown if chronic SCI also impairs secondary immune responses to influenza challenge as it does primary responses. Here, we used a mouse model of chronic SCI and a clinically relevant influenza A infec...
Source: Experimental Neurology - March 20, 2019 Category: Neurology Authors: Norden DM, Qatanani A, Bethea JR, Jiang J Tags: Exp Neurol Source Type: research
Muscle ciliary neurotrophic factor receptor α helps maintain choline acetyltransferase levels in denervated motor neurons following peripheral nerve lesion.
Muscle ciliary neurotrophic factor receptor α helps maintain choline acetyltransferase levels in denervated motor neurons following peripheral nerve lesion. Exp Neurol. 2019 Mar 19;: Authors: Lee N, Wanek HA, MacLennan AJ Abstract Systemic ciliary neurotrophic factor (CNTF) administration protects motor neurons from denervating diseases and lesions but produces non-neuromuscular side effects. Therefore, CNTF related therapeutics will need to specifically target motor neuron protective receptor mechanisms. Expression of the essential ligand binding subunit of the CNTF receptor, CNTF receptor &alp...
Source: Experimental Neurology - March 19, 2019 Category: Neurology Authors: Lee N, Wanek HA, MacLennan AJ Tags: Exp Neurol Source Type: research
Deep brain stimulation of the ventroanterior and ventrolateral thalamus improves motor function in a rat model of Parkinson's disease.
Abstract Parkinson's disease (PD) is a neurodegenerative disease with affected individuals exhibiting motor symptoms of bradykinesia, muscle rigidity, tremor, postural instability and gait dysfunction. The current gold standard treatment is pharmacotherapy with levodopa, but long-term use is associated with motor response fluctuations and can cause abnormal movements called dyskinesias. An alternative treatment option is deep brain stimulation (DBS) with the two FDA-approved brain targets for PD situated in the basal ganglia; specifically, in the subthalamic nucleus (STN) and globus pallidus pars interna (GPi). Bo...
Source: Experimental Neurology - March 16, 2019 Category: Neurology Authors: Tucker H, Mahoney E, Chhetri A, Unger K, Mamone G, Kim G, Audil A, Moolick B, Molho ES, Pilitsis JG, Shin DS Tags: Exp Neurol Source Type: research
Outcomes and clinical implications of intranasal insulin administration to the central nervous system.
Abstract Insulin signaling in the brain plays a critical role in metabolic control and cognitive function. Targeting insulinergic pathways in the central nervous system via peripheral insulin administration is feasible, but associated with systemic effects that necessitate tight supervision or countermeasures. The intranasal route of insulin administration, which largely bypasses the circulation and thereby greatly reduces these obstacles, has now been repeatedly tested in proof-of-concept studies in humans as well as animals. It is routinely used in experimental settings to investigate the impact on eating behavi...
Source: Experimental Neurology - March 15, 2019 Category: Neurology Authors: Santiago JCP, Hallschmid M Tags: Exp Neurol Source Type: research
Nociceptor-dependent locomotor dysfunction after clinically-modeled hindlimb muscle stretching in adult rats with spinal cord injury.
Abstract In the course of investigating how common clinical treatments and adaptive technologies affect recovery after spinal cord injury (SCI), we discovered that a clinically-modeled hindlimb stretching protocol dramatically, but transiently, reduces locomotor function. Nociceptive sensory input is capable of altering motor output at the spinal level, and nociceptive neurons are sensitized after SCI. Here we tested the possibility that the stretch-induced motor deficits required the presence of nociceptors using neonatal capsaicin induced depletion of TRPV1+ nociceptive neurons. Following maturation, animals rec...
Source: Experimental Neurology - March 14, 2019 Category: Neurology Authors: Keller AV, Hainline C, Rees K, Krupp S, Prince D, Wood BD, Shum-Siu A, Burke DA, Petruska JC, Magnuson DSK Tags: Exp Neurol Source Type: research
The emerging role of neutrophils as modifiers of recovery after traumatic injury to the developing brain.
Abstract The innate immune response plays a critical role in traumatic brain injury (TBI), contributing to ongoing pathogenesis and worsening long-term outcomes. Here we focus on neutrophils, one of the "first responders" to TBI. These leukocytes are recruited to the injured brain where they release a host of toxic molecules including free radicals, proteases, and pro-inflammatory cytokines, all of which promote secondary tissue damage. There is mounting evidence that the developing brain is more vulnerable to injury that the adult brain. This vulnerability to greater damage from TBI is, in part, attribu...
Source: Experimental Neurology - March 12, 2019 Category: Neurology Authors: von Leden RE, Parker KN, Bates AA, Noble-Haeusslein LJ, Donovan MH Tags: Exp Neurol Source Type: research
Upregulation of interleukin-6 on Cav3.2 T-type calcium channels in dorsal root ganglion neurons contributes to neuropathic pain in rats with spinal nerve ligation.
Abstract The T-type calcium channels Cav3.2, one of the low voltage-activated (LVA) calcium channels, have been found to play important roles in the neuronal excitability. Recently, we and others have demonstrated that accumulation of Cav3.2 channels in the dorsal root ganglion (DRG) neurons and sensory nerves contributes to neuropathic pain after peripheral nerve injury. In the present study, we aimed to further investigate the regulation of Cav3.2 channels by interleukin-6 (IL-6) in DRG neurons in neuropathic pain rats after spinal nerve ligation (SNL). The results showed that Cav3.2 channel protein expression i...
Source: Experimental Neurology - March 11, 2019 Category: Neurology Authors: Liu Q, Chen W, Fan X, Wang J, Fu S, Cui S, Liao F, Cai J, Wang X, Huang Y, Su L, Zhong L, Yi M, Liu F, Wan Y Tags: Exp Neurol Source Type: research
Brain interrupted: Early life traumatic brain injury and addiction vulnerability.
Abstract Recent reports provide evidence for increased risk of substance use disorders (SUD) among patients with a history of early-life traumatic brain injury (TBI). Preclinical research utilizing animal models of TBI have identified injury-induced inflammation, blood-brain barrier permeability, and changes to synapses and neuronal networks within regions of the brain associated with the perception of reward. Importantly, these reward pathway networks are underdeveloped during childhood and adolescence, and early-life TBI pathology may interrupt ongoing maturation. As such, maladaptive changes induced by juvenile...
Source: Experimental Neurology - March 9, 2019 Category: Neurology Authors: Cannella LA, McGary H, Ramirez SH Tags: Exp Neurol Source Type: research
Calcium imaging approaches in investigation of pain mechanism in the spinal cord.
Abstract The continuous advancement of microscopic imaging techniques combined with the discovery and use of more powerful calcium indicators has made calcium imaging technology much more effective and has increased its use in the study of pain circuitry. Using calcium imaging to study spinal pain mechanisms causes less damage to animals compared to electrophysiological techniques and is also able to observe the firing pattern of spinal neurons and the connections between them on a large scale. These advantages allow any changes in spinal cord circuits caused by pain transmission to be observed more effectively. T...
Source: Experimental Neurology - March 7, 2019 Category: Neurology Authors: Xu Q, Dong X Tags: Exp Neurol Source Type: research
Mechanisms underlying vulnerabilities after repeat mild traumatic brain injuries.
Abstract Traumatic brain injury (TBI) has drawn national attention for its high incidence and mechanistic complexity. The majority of TBI cases are "mild" in nature including concussions and mild TBI (mTBI). Concussions are a distinct form of mTBI where diagnosis is difficult, quantification of the incidence is challenging and there is greater risk for subsequent injuries. While concussions occur in the general population, it has become a hallmark injury consistently observed among adolescent and young adult athletes and the risks for repeat TBI (rTBI) is significant. Clinical and experimental evidence s...
Source: Experimental Neurology - March 7, 2019 Category: Neurology Authors: Greco T, Ferguson L, Giza C, Prins ML Tags: Exp Neurol Source Type: research
Ethanol-induced DNA repair in neural stem cells: Is transforming growth factor β1-dependent.
This study tests the hypothesis that ethanol induces a DNA damage response (DDR) in neural stem cells (NSCs) that promotes excision repair (ER) and this repair is influenced by the growth factor environment. Non-immortalized NSCs treated with fibroblast growth factor 2 or transforming growth factor (TGF) β1 were exposed to ethanol. Ethanol increased total DNA damage, reactive oxygen species, and oxidized DNA bases. TGFβ1 potentiated these toxic effects. Transcriptional analyses of cultured NSCs revealed ethanol-induced increases in transcripts related to the DDR (e.g., Hus1 and p53), base ER (e.g., Mutyh and Nthl...
Source: Experimental Neurology - March 7, 2019 Category: Neurology Authors: Hicks SD, Miller MW Tags: Exp Neurol Source Type: research
Efgartigimod improves muscle weakness in a mouse model for muscle-specific kinase myasthenia gravis.
In conclusion, our study shows that efgartigimod has clear therapeutic potential in MuSK myasthenia gravis and forms an exciting candidate drug for many autoantibody-mediated neurological and other disorders. PMID: 30851266 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - March 6, 2019 Category: Neurology Authors: Huijbers MG, Plomp JJ, van Es IE, Fillié-Grijpma YE, Majidi SK, Ulrichts P, de Haard H, Hofman E, van der Maarel SM, Verschuuren JJ Tags: Exp Neurol Source Type: research
Sex differences in pediatric traumatic brain injury.
Abstract The response of the developing brain to traumatic injury is different from the response of the mature, adult brain. There are critical developmental trajectories in the young brain, whereby injury can lead to long term functional abnormalities. Emerging preclinical and clinical literature supports the presence of significant sex differences in both the response to and the recovery from pediatric traumatic brain injury (TBI). These sex differences are seen at all pediatric ages, including neonates/infants, pre-pubertal children, and adolescents. As importantly, the response to neuroprotective therapies or ...
Source: Experimental Neurology - March 1, 2019 Category: Neurology Authors: Arambula SE, Reinl E, El Demerdash N, McCarthy MM, Robertson CL Tags: Exp Neurol Source Type: research
Central neuropeptide-S treatment improves neurofunctions of 6-OHDA-induced Parkinsonian rats.
MA, Ağar A Abstract Parkinson's disease (PD) is characterized by degeneration of the dopaminergic neurons in substantia nigra (SN). The motor symptoms of PD include tremor, rigidity, bradykinesia and postural impairment. In rodents, central administration of neuropeptide-S (NPS) has been shown to induce locomotor activity, dopamine release and neuronal survival by decreasing lipid peroxidation, additionally, the NPS receptor (NPSR) was detected in SN. Accumulating findings suggest that central NPS may ameliorate the parkinsonian symptoms, however, this has been explored incompletely due to the scarcity of experim...
Source: Experimental Neurology - February 27, 2019 Category: Neurology Authors: Bülbül M, Sinen O, Özkan A, Aslan MA, Ağar A Tags: Exp Neurol Source Type: research
Free d-aspartate triggers NMDA receptor-dependent cell death in primary cortical neurons and perturbs JNK activation, Tau phosphorylation, and protein SUMOylation in the cerebral cortex of mice lacking d-aspartate oxidase activity.
Abstract In mammals, free d-aspartate (D-Asp) is abundant in the embryonic brain, while levels remain very low during adulthood as a result of the postnatal expression and activity of the catabolizing enzyme d-aspartate oxidase (DDO). Previous studies have shown that long-lasting exposure to nonphysiological, higher D-Asp concentrations in Ddo knockout (Ddo-/-) mice elicits a precocious decay of synaptic plasticity and cognitive functions, along with a dramatic age-dependent expression of active caspase 3, associated with increased cell death in different brain regions, including hippocampus, prefrontal cortex, an...
Source: Experimental Neurology - February 26, 2019 Category: Neurology Authors: Nuzzo T, Feligioni M, Cristino L, Pagano I, Marcelli S, Iannuzzi F, Imperatore R, D'Angelo L, Petrella C, Carella M, Pollegioni L, Sacchi S, Punzo D, De Girolamo P, Errico F, Canu N, Usiello A Tags: Exp Neurol Source Type: research
Repetitive closed-head impact model of engineered rotational acceleration (CHIMERA) injury in rats increases impulsivity, decreases dopaminergic innervation in the olfactory tubercle and generates white matter inflammation, tau phosphorylation and degeneration.
Abstract Traumatic brain injury (TBI) affects at least 3 M people annually. In humans, repetitive mild TBI (rmTBI) can lead to increased impulsivity and may be associated with chronic traumatic encephalopathy. To better understand the relationship between repetitive TBI (rTBI), impulsivity and neuropathology, we used CHIMERA (Closed-Head Injury Model of Engineered Rotational Acceleration) to deliver five TBIs to rats, which were continuously assessed for trait impulsivity using the delay discounting task and for neuropathology at endpoint. Compared to sham controls, rats with rTBI displayed progressive impairmen...
Source: Experimental Neurology - February 26, 2019 Category: Neurology Authors: Haar CV, Martens KM, Bashir A, McInnes KA, Cheng WH, Cheung H, Stukas S, Barron C, Ladner T, Welch KA, Cripton PA, Winstanley CA, Wellington CL Tags: Exp Neurol Source Type: research
Dim light at night impairs recovery from global cerebral ischemia.
Abstract Nighttime lighting is one of the great conveniences of modernization; however, there is mounting evidence that inopportune light exposure can disrupt physiological and behavioral functions. Hospital patients may be particularly vulnerable to the consequences of light at night due to their compromised physiological state. Cardiac arrest/cardiopulmonary resuscitation (CA) was used to test the hypothesis in mice that exposure to dim light at night impairs central nervous system (CNS) recovery from a major pathological insult. Mice exposed to dim light at night (5 lx) had higher mortality in the week follow...
Source: Experimental Neurology - February 26, 2019 Category: Neurology Authors: Fonken LK, Bedrosian TA, Zhang N, Weil ZM, DeVries AC, Nelson RJ Tags: Exp Neurol Source Type: research
Caffeine inhibits hypoxia-induced nuclear accumulation in HIF-1 α and promotes neonatal neuronal survival.
Caffeine inhibits hypoxia-induced nuclear accumulation in HIF-1α and promotes neonatal neuronal survival. Exp Neurol. 2019 Feb 26;: Authors: Li HL, Zaghloul N, Ahmed I, Omelchenko A, Firestein BL, Huang H, Collins L Abstract Apnea of prematurity (AOP) defined as cessation of breathing for 15-20 s, is commonly seen in preterm infants. Caffeine is widely used to treat AOP due to its safety and effectiveness. Caffeine releases respiratory arrest by competing with adenosine for binding to adenosine A1 and A2A receptors (A1R and A2AR). Long before its use in treating AOP, caffeine has been used as ...
Source: Experimental Neurology - February 26, 2019 Category: Neurology Authors: Li HL, Zaghloul N, Ahmed I, Omelchenko A, Firestein BL, Huang H, Collins L Tags: Exp Neurol Source Type: research
FGF21 promotes functional recovery after hypoxic-ischemic brain injury in neonatal rats by activating the PI3K/Akt signaling pathway via FGFR1/ β-klotho.
FGF21 promotes functional recovery after hypoxic-ischemic brain injury in neonatal rats by activating the PI3K/Akt signaling pathway via FGFR1/β-klotho. Exp Neurol. 2019 Feb 22;: Authors: Ye L, Wang X, Cai C, Zeng S, Bai J, Guo K, Fang M, Hu J, Liu H, Zhu L, Liu F, Wang D, Hu Y, Pan S, Li X, Lin L, Lin Z Abstract Perinatal asphyxia often results in neonatal cerebral hypoxia-ischemia (HI), which is associated with high mortality and severe long-term neurological deficits in newborns. Currently, there are no effective drugs to mitigate the functional impairments post-HI. Previous studies have shown...
Source: Experimental Neurology - February 22, 2019 Category: Neurology Authors: Ye L, Wang X, Cai C, Zeng S, Bai J, Guo K, Fang M, Hu J, Liu H, Zhu L, Liu F, Wang D, Hu Y, Pan S, Li X, Lin L, Lin Z Tags: Exp Neurol Source Type: research
Membrane transporters in traumatic brain injury: Pathological, pharmacotherapeutic, and developmental implications.
Abstract Membrane transporters regulate the trafficking of endogenous and exogenous molecules across biological barriers and within the neurovascular unit. In traumatic brain injury (TBI), they moderate the dynamic movement of therapeutic drugs and injury mediators among neurons, endothelial cells and glial cells, thereby becoming important determinants of pathogenesis and effective pharmacotherapy after TBI. There are three ways transporters may impact outcomes in TBI. First, transporters likely play a key role in the clearance of injury mediators. Second, genetic association studies suggest transporters may be i...
Source: Experimental Neurology - February 21, 2019 Category: Neurology Authors: Hagos FT, Adams SM, Poloyac SM, Kochanek PM, Horvat CM, Clark RSB, Empey PE Tags: Exp Neurol Source Type: research
Imaging in vivo dynamics of sensory axon responses to CNS injury.
Abstract Axons in the adult mammalian brain and spinal cord fail to regenerate upon lesion. In vivo imaging serves as a tool to investigate the immediate response of axons to injury and how the same injured axons behave over time. Here, we describe the dynamic changes that injured sensory axons undergo and methods of imaging them in vivo. First, we explain how sensory axons in the dorsal column of the adult mouse spinal cord respond to axotomy. Then, we highlight practical considerations for implementing two-photon based in vivo imaging of these axons. Finally, we describe future directions for this technique, inc...
Source: Experimental Neurology - February 19, 2019 Category: Neurology Authors: Schaffran B, Hilton BJ, Bradke F Tags: Exp Neurol Source Type: research
Temporal and age-dependent effects of haptoglobin deletion on intracerebral hemorrhage-induced brain damage and neurobehavioral outcomes.
This study reveals that the presence or absence of Hp exerts important time- and age-dependent influences on ICH outcomes. PMID: 30790555 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - February 18, 2019 Category: Neurology Authors: Leclerc JL, Li C, Jean S, Lampert AS, Amador CL, Diller MA, Tolosano E, Doré S Tags: Exp Neurol Source Type: research
Mitoquinone attenuates blood-brain barrier disruption through Nrf2/PHB2/OPA1 pathway after subarachnoid hemorrhage in rats.
CONCLUSIONS: MitoQ attenuates blood-brain barrier disruption via Nrf2/PHB2/OPA1 pathway after SAH in rats. MitoQ may serve as a potential therapeutic strategy for SAH patients. PMID: 30779914 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - February 16, 2019 Category: Neurology Authors: Zhang T, Xu S, Wu P, Zhou K, Wu L, Xie Z, Xu W, Luo X, Li P, Ocak U, Ocak PE, Travis ZD, Tang J, Shi H, Zhang JH Tags: Exp Neurol Source Type: research
Endogenous multidien rhythm of epilepsy in rats.
Abstract Recent trials of chronic EEG in humans showed that epilepsy is a cyclical disorder of the brain with rhythms at multiple time-scales: circadian, multi-day (multidien) or even seasonal. Here, we analyzed chronic EEG data (>30 days) in male epileptic rats and unraveled not only circadian but also, slower, multidien rhythms of interictal epileptiform activity with periodicity of about 2-3 and 5-7 days. Importantly, seizures were not uniformly distributed over time, but rather clustered at preferential phases of these underlying rhythms, delineating critical circadian times and multidien phase of heigh...
Source: Experimental Neurology - February 15, 2019 Category: Neurology Authors: Baud MO, Ghestem A, Benoliel JJ, Becker C, Bernard C Tags: Exp Neurol Source Type: research
Self-propagating, non-synaptic epileptiform activity propagates by endogenous electric fields.
Abstract It is well documented that synapses play a significant role in the transmission of information between neurons. However, in the absence of synaptic transmission, neural activity has been observed to continue to propagate. Previous studies have shown that propagation of epileptiform activity takes place in the absence of synaptic transmission and gap junctions and is outside the range of ionic diffusion and axonal conduction. Computer simulations indicate that electric field coupling could be responsible for the propagation of neural activity under pathological conditions such as epilepsy. Electric fields ...
Source: Experimental Neurology - February 15, 2019 Category: Neurology Authors: Shivacharan RS, Chiang CC, Zhang M, Gonzalez-Reyes LE, Durand DM Tags: Exp Neurol Source Type: research
Parkinson's disease and pain: Modulation of nociceptive circuitry in a rat model of nigrostriatal lesion.
In this study, we evaluated the nociceptive behavior and the descending analgesia circuitry in a rat model of PD. Three independent experiments were performed to investigate: i) thermal nociceptive behavior; ii) mechanical nociceptive behavior and dopaminergic repositioning; and iii) modulation of the pain control circuitry. The rat model of PD, induced by unilateral striatal 6-hydroxydopamine (6-OHDA), did not interfere with thermal nociceptive responses; however, the mechanical nociceptive threshold was decreased bilaterally compared to that of naive or striatal saline-injected rats. This response was reversed by apomorp...
Source: Experimental Neurology - February 14, 2019 Category: Neurology Authors: Domenici RA, Campos ACP, Maciel ST, Berzuino MB, Hernandes MS, Fonoff ET, Pagano RL Tags: Exp Neurol Source Type: research
Methylphenidate administration reverts attentional inflexibility in adolescent rats submitted to a model of neonatal hypoxia-ischemia: Predictive validity for ADHD study.
Abstract Perinatal complications such as birth asphyxia were associated with a higher risk for Attention-Deficit/Hyperactivity Disorder (ADHD) in humans. Data from a rat model of neonatal hypoxia-ischemia (HI) have revealed inattention, impulsive behavior and dopamine (DA) disturbances in the prefrontal cortex (PFC), confirming the face validity and construct validity for ADHD study. However, the predictive validity (similar therapeutic efficacy of the pharmacological treatment available in the clinic) should be considered. Therefore, we aimed to investigate the effects of methylphenidate (MPH) - the treatment of ...
Source: Experimental Neurology - February 13, 2019 Category: Neurology Authors: Miguel PM, Deniz BF, Confortim HD, Bronauth LP, de Oliveira BC, Alves MB, Silveira PP, Pereira LO Tags: Exp Neurol Source Type: research
Treatment of myotonia congenita with retigabine in mice.
In this study, we found that retigabine greatly reduced the duration of myotonia in vitro. Detailed study of its mechanism of action revealed that retigabine had no effect on any of the traditional measures of muscle excitability such as resting potential, input resistance or the properties of single action potentials. Instead it appears to shorten myotonia by activating K+ current during trains of action potentials. Retigabine also greatly reduced the severity of myotonia in vivo, which was measured using a muscle force transducer. Despite its efficacy in vivo, retigabine did not improve motor performance of mice with myo...
Source: Experimental Neurology - February 7, 2019 Category: Neurology Authors: Dupont CX, Denman KS, Hawash AA, Voss AA, Rich MM Tags: Exp Neurol Source Type: research
Conditioning electrical stimulation promotes functional nerve regeneration.
In this study, we found that CES improved nerve regeneration and reinnervation well beyond that of CCL. Specifically, compared to CCL, CES resulted in greater intraepidermal skin and NMJ reinnervation, and greater physiological and functional recovery including mechanosensation, compound muscle action potential on nerve conduction studies, normalization of gait pattern, and motor performance on the horizontal ladder test. These findings have direct clinical relevance as CES could be delivered at the bedside before scheduled nerve surgery. PMID: 30731076 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - February 4, 2019 Category: Neurology Authors: Senger JL, Chan KM, Macandili H, Chan AWM, Verge VMK, Jones KE, Webber CA Tags: Exp Neurol Source Type: research