Astrocytes migrate from human neural stem cell grafts and functionally integrate into the injured rat spinal cord.
Abstract Neural stem cells (NSCs) can differentiate into both neurons and glia after transplantation into spinal cord injury (SCI) sites. The neuronal component of stem cell grafts has the potential to form functional synaptic relays across the lesion site. The glial component may reform a blood-spinal cord barrier, support neuronal function, and contribute to remyelination. We performed a long-term, 1.5-year time course study focused on astrocyte migration, differentiation, integration, and safety following human NSC transplantation into C5 hemisection sites in immunodeficient rats. NSCs that adopted a neuronal f...
Source: Experimental Neurology - January 14, 2019 Category: Neurology Authors: Lien BV, Tuszynski MH, Lu P Tags: Exp Neurol Source Type: research

Bioenergetic dysfunction in a zebrafish model of acute hyperammonemic decompensation.
JG Abstract Acute hyperammonemic encephalopathy is a life-threatening manifestation of individuals with urea cycle disorders, which is associated with high mortality rates and severe neurological sequelae in survivors. Cerebral bioenergetic failure has been proposed as one of the key mechanisms underlying hyperammonemia-induced brain damage, but data supporting this hypothesis remain inconclusive and partially contradictory. Using a previously established zebrafish model of acute hyperammonemic decompensation, we unraveled that acute hyperammonemia leads to a transamination-dependent withdrawal of alpha-ketogluta...
Source: Experimental Neurology - January 14, 2019 Category: Neurology Authors: Zielonka M, Probst J, Carl M, Hoffmann GF, Kölker S, Okun JG Tags: Exp Neurol Source Type: research

Determinants of social behavior deficits and recovery after pediatric traumatic brain injury.
Abstract Traumatic brain injury (TBI) during early childhood is associated with a particularly high risk of developing social behavior impairments, including deficits in social cognition that manifest as reduced social interactions, with profound consequences for the individuals' quality of life. A number of pre-injury, post-injury, and injury-related factors have been identified or hypothesized to determine the extent of social behavior problems after childhood TBI. These include variables associated with the individual themselves (e.g. age, genetics, the injury severity, and extent of white matter damage), proxi...
Source: Experimental Neurology - January 14, 2019 Category: Neurology Authors: Zamani A, Mychasiuk R, Semple BD Tags: Exp Neurol Source Type: research

Eternal sunshine of the neuromodulated mind: Altering fear memories through neuromodulation.
Abstract Anxiety disorders pose one of the greatest threats to mental health. Modern treatment methods exist but are hindered by relapse, toxicity, and low efficacy. The use of neuromodulation to treat anxiety disorders has shown promising results, yet its underpinning mechanisms remain poorly understood. In this review, we make the case for further development of neuromodulation techniques to alter fear memories, with particular regard to future clinical applications in treating anxiety disorders. We start by briefly summarizing the neural circuitry of fear while identifying the pros and cons of possible neuromod...
Source: Experimental Neurology - January 10, 2019 Category: Neurology Authors: Tan SZK, Sheng V, Chan YS, Lim LW Tags: Exp Neurol Source Type: research

Childhood trauma and insulin resistance in patients suffering from depressive disorders.
CONCLUSIONS: Our findings suggest that Fam-HX-DM2 and emotional abuse represent separate risk factors for developing metabolic dysfunction (i.e.: IR) in patients suffering from MDD, and that the effects of emotional abuse on psychiatric illness may depend upon the personal characteristics, including Fam-Hx-DM2. PMID: 30639184 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - January 10, 2019 Category: Neurology Authors: Nasca C, Watson K, Bigio B, Robakis T, Myoraku A, Wroolie T, McEwen BS, Rasgon N Tags: Exp Neurol Source Type: research

EPPS treatment attenuates traumatic brain injury in mice by reducing A β burden and ameliorating neuronal autophagic flux.
EPPS treatment attenuates traumatic brain injury in mice by reducing Aβ burden and ameliorating neuronal autophagic flux. Exp Neurol. 2019 Jan 09;: Authors: Anthony Jalin AMA, Jin R, Wang M, Li G Abstract Beta-amyloid (Aβ) burden and impaired neuronal autophagy contribute to secondary brain injury after traumatic brain injury (TBI). 4-(2-hydroxyethyl)-1-piperazinepropanesulphonic acid (EPPS) treatment has been reported to reduce Aβ aggregation and rescue behavioral deficits in Alzheimer's disease-like mice. Here, we investigated neuroprotective effects of EPPS in a mouse model of TBI. M...
Source: Experimental Neurology - January 9, 2019 Category: Neurology Authors: Anthony Jalin AMA, Jin R, Wang M, Li G Tags: Exp Neurol Source Type: research

Engineering approaches to enhance neural tissue regeneration.
Authors: PMID: 30615850 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - January 4, 2019 Category: Neurology Tags: Exp Neurol Source Type: research

Reproducibility - The key towards clinical implementation of spinal cord injury treatments?
PMID: 30605623 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - December 31, 2018 Category: Neurology Authors: Schaffran B, Bradke F Tags: Exp Neurol Source Type: research

Activation of the hypothalamic paraventricular nucleus by acute intermittent hypoxia: Implications for sympathetic long-term facilitation neuroplasticity.
Abstract Exposure to acute intermittent hypoxia (AIH) induces a progressive increase of sympathetic nerve activity (SNA) that reflects a form of neuroplasticity known as sympathetic long-term facilitation (sLTF). Our recent findings indicate that activity of neurons in the hypothalamic paraventricular nucleus (PVN) contributes to AIH-induced sLTF, but neither the intra-PVN distribution nor the neurochemical identity of AIH responsive neurons has been determined. Here, awake rats were exposed to 10 cycles of AIH and c-Fos immunohistochemistry was performed to identify transcriptionally activated neurons in rostra...
Source: Experimental Neurology - December 31, 2018 Category: Neurology Authors: Maruyama NO, Mitchell NC, Truong TT, Toney GM Tags: Exp Neurol Source Type: research

Chronic stress increases pain sensitivity via activation of the rACC-BLA pathway in rats.
Abstract Exposure to chronic stress can produce maladaptive neurobiological changes in pathways associated with pain processing, which may cause stress-induced hyperalgesia (SIH). However, the underlying mechanisms still remain largely unknown. In previous studies, we have reported that the amygdala is involved in chronic forced swim (FS) stress-induced depressive-like behaviors and the exacerbation of neuropathic pain in rats, of which, the basolateral amygdala (BLA) and the central nucleus of the amygdala (CeA) are shown to play important roles in the integration of affective and sensory information including no...
Source: Experimental Neurology - December 23, 2018 Category: Neurology Authors: Liu LY, Zang RL, Chen L, Zhao HY, Cai J, Wang JK, Guo DQ, Cui YJ, Xing GG Tags: Exp Neurol Source Type: research

Daily acute intermittent hypoxia induced dynamic changes in dendritic mitochondrial ultrastructure and cytochrome oxidase activity in the pre-B ötzinger complex of rats.
Daily acute intermittent hypoxia induced dynamic changes in dendritic mitochondrial ultrastructure and cytochrome oxidase activity in the pre-Bötzinger complex of rats. Exp Neurol. 2018 Dec 23;: Authors: Kang JJ, Guo B, Liang WH, Lam CS, Wu SX, Huang XF, Wong-Riley MTT, Fung ML, Liu YY Abstract Mitochondria, as primary energy generators and Ca2+ biosensor, are dynamically coupled to neuronal activities, and thus play a role in neuroplasticity. Here we report that respiratory neuroplasticity induced by daily acute intermittent hypoxia (dAIH) evoked adaptive changes in the ultrastructure and postsy...
Source: Experimental Neurology - December 23, 2018 Category: Neurology Authors: Kang JJ, Guo B, Liang WH, Lam CS, Wu SX, Huang XF, Wong-Riley MTT, Fung ML, Liu YY Tags: Exp Neurol Source Type: research

Broadening the definition of brain insulin resistance in aging and Alzheimer's disease.
Abstract It has been>20 years since studies first revealed that the brain is insulin sensitive, highlighted by the expression of insulin receptors in neurons and glia, the presence of circulating brain insulin, and even localized insulin production. Following these discoveries, evidence of decreased brain insulin receptor number and function was reported in both clinical samples and animal models of aging and Alzheimer's disease, setting the stage for the hypothesis that neuronal insulin resistance may underlie memory loss in these conditions. The development of therapeutic insulin delivery to the brain using...
Source: Experimental Neurology - December 18, 2018 Category: Neurology Authors: Frazier HN, Ghoweri AO, Anderson KL, Lin RL, Porter NM, Thibault O Tags: Exp Neurol Source Type: research

KU-596 decreases mitochondrial superoxide and improves bioenergetics following downregulation of manganese superoxide dismutase in diabetic sensory neurons.
Abstract Neuronal mitochondrial dysfunction and oxidative stress are key pathophysiologic mechanisms of diabetic peripheral neuropathy (DPN). KU-596 is a small molecule modulator of heat shock protein 90 (Hsp90) that can reverse clinically relevant measures of DPN in diabetic animal models. Mechanistically, drug efficacy requires Hsp70 and correlates with improving mitochondrial maximal respiratory capacity (MRC) and decreasing oxidative stress in diabetic sensory neurons. The goal of this study was to determine if ex vivo treatment of diabetic neurons with KU-596 improves MRC by decreasing glucose-induced oxidati...
Source: Experimental Neurology - December 14, 2018 Category: Neurology Authors: You Z, Zhang Z, Blagg BSJ, Dobrowsky RT Tags: Exp Neurol Source Type: research

Treadmill exercise ameliorates focal cerebral ischemia/reperfusion-induced neurological deficit by promoting dendritic modification and synaptic plasticity via upregulating caveolin-1/VEGF signaling pathways.
Abstract Dendritic and synaptic plasticity in the penumbra are important processes and are considered to be therapeutic targets of ischemic stroke. Treadmill exercise is known to be a beneficial treatment following stroke. However, its effects and potential mechanism in promoting dendritic and synaptic plasticity remain unknown. We have previously demonstrated that the caveolin-1/VEGF signaling pathway plays a positive role in angiogenesis and neurogenesis. Here, we further investigated the effects of treadmill exercise on promoting dendritic and synaptic plasticity in the penumbra and whether they involve the cav...
Source: Experimental Neurology - December 12, 2018 Category: Neurology Authors: Xie Q, Cheng J, Pan G, Wu S, Hu Q, Jiang H, Wang Y, Xiong J, Pang Q, Chen X Tags: Exp Neurol Source Type: research

Mechanisms of decreased cholinergic arousal in focal seizures: In vivo whole-cell recordings from the pedunculopontine tegmental nucleus.
Abstract Focal limbic seizures often impair consciousness/awareness with major negative impact on quality of life. Recent work has shown that limbic seizures depress brainstem arousal systems, including reduced action potential firing in a key node: cholinergic neurons of the pedunculopontine tegmental nucleus (PPT). In vivo whole-cell recordings have not previously been achieved in PPT, but are used here with the goal of elucidating the mechanisms of reduced PPT cholinergic neuronal activity. An established model of focal limbic seizures was used in rats following brief hippocampal stimulation under light anesthe...
Source: Experimental Neurology - December 10, 2018 Category: Neurology Authors: Andrews JP, Yue Z, Ryu JH, Neske G, McCormick DA, Blumenfeld H Tags: Exp Neurol Source Type: research

GCN2 reduces inflammation by p-eIF2 α/ATF4 pathway after intracerebral hemorrhage in mice.
This study aimed to evaluate whether general control non-derepressible-2 (GCN2) stimulation ameliorated neuroinflammation after ICH. Male CD-1 mice were subjected to experimental ICH by infusion of bacterial collagenase. Post-ictus assessment included neurobehavioral tests, brain edema measurement, quantification of neutrophil infiltration and microglia activation, and measurement of TNF-α and IL-1β expression at 24h after ICH. Furthermore, we tested the long-term neurological improvement by GCN2 at 21 days after ICH. Our results showed that GCN2 improved neurological function and reduced brain edema at 24 and...
Source: Experimental Neurology - December 6, 2018 Category: Neurology Authors: Lu Z, Wang Z, Yu L, Ding Y, Xu Y, Xu N, Li R, Tang J, Chen G, Zhang JH Tags: Exp Neurol Source Type: research

Significant changes in circular RNA in the mouse cerebral cortex around an injury site after traumatic brain injury.
Abstract BACKGROUND AND OBJECTIVE: Circular RNA (circRNA) is an important type of non-coding RNA that has not been widely researched in traumatic brain injury (TBI). The present study aimd to detect the altered circRNA expression around an injury site in the mouse cerebral cortex after TBI and explore its potential functions. METHOD: C57BL/6 mice were used to construct a controlled cortical impact (CCI) model to simulate TBI. At 24 h post-TBI, the cortex around the injury site was collected, and the total RNA was extracted to perform RNA sequencing (RNA-seq). The differentially expressed circRNAs were deter...
Source: Experimental Neurology - December 5, 2018 Category: Neurology Authors: Chen Z, Wang H, Zhong J, Yang J, Darwazeh R, Tian X, Huang Z, Jiang L, Cheng C, Wu Y, Guo Z, Sun X Tags: Exp Neurol Source Type: research

Repetitive transcranial magnetic stimulation promotes functional recovery and differentiation of human neural stem cells in rats after ischemic stroke.
Abstract Stem cells hold great promise as a regenerative therapy for ischemic stroke by improving functional outcomes in animal models. However, there are some limitations regarding the cell transplantation, including low rate of survival and differentiation. Repetitive transcranial magnetic stimulation (rTMS) has been widely used in clinical trials as post-stroke rehabilitation in ischemic stroke and has shown to alleviate functional deficits following stroke. The present study was designed to evaluate the therapeutic effects and mechanisms of combined human neural stem cells (hNSCs) with rTMS in a middle cerebra...
Source: Experimental Neurology - December 4, 2018 Category: Neurology Authors: Peng JJ, Sha R, Li MX, Chen LT, Han XH, Guo F, Chen H, Huang XL Tags: Exp Neurol Source Type: research

Comparison of electroencephalogram (EEG) response to MDPV versus the hallucinogenic drugs MK-801 and ketamine in rats.
Abstract Synthetic cathinones, often marketed as 'bath salts', have been reported to induce an excited delirium syndrome with characteristic symptoms such as paranoid, hallucination and even aggression. 3,4-Methylenedioxypyrovalerone (MDPV), a norepinephrine-dopamine reuptake inhibitor (NDRI), is one of the psychoactive ingredients in bath salts. The present study utilized cortical EEG and brain microdialysis in rats to compare the effects of MDPV (0.25, 1 and 2 mg/kg, i.p.) with the hallucinogenic drugs MK-801 (0.05, 0.1 and 0.5 mg/kg, i.p.) and ketamine (5, 15 and 25 mg/kg, i.p.). Results revealed that MDP...
Source: Experimental Neurology - December 3, 2018 Category: Neurology Authors: Shokry IM, Sinha V, Da Silva G, Park SB, Callanan JJ, Tao R Tags: Exp Neurol Source Type: research

CNB-001, a pleiotropic drug is efficacious in embolized agyrencephalic New Zealand white rabbits and ischemic gyrencephalic cynomolgus monkeys.
Abstract Ischemic stroke is an acute neurodegenerative disease that is extremely devastating to patients, their families and society. Stroke is inadequately treated even with endovascular procedures and reperfusion therapy. Using an extensive translational screening process, we have developed a pleiotropic cytoprotective agent with the potential to positively impact a large population of brain ischemia patients and revolutionize the process used for the development of new drugs to treat complex brain disorders. In this unique translational study article, we document that the novel curcumin-based compound, CNB-001,...
Source: Experimental Neurology - December 3, 2018 Category: Neurology Authors: Lapchak PA, Boitano PD, Bombien R, Cook DJ, Doyan S, Lara JM, Schubert DR Tags: Exp Neurol Source Type: research

rhIGF-1 reduces the permeability of the blood-brain barrier following intracerebral hemorrhage in mice.
This study examined insulin-like growth factor-1 (IGF-1) as a treatment and its mechanism of action for protecting the blood-brain barrier after ICH in mice. 171 Male CD-1 mice were subjected to ICH via collagenase or autologous blood. A dose study for recombinant human IGF-1 (rhIGF-1) was performed. Brain water content and behavioral deficits were evaluated at 24 and 72 h after the surgery, and Evans blue extravasation and hemoglobin assay were conducted at 24 h. Western blotting was performed for the mechanism study and interventions were used targeting the IGF-1R/GSK3β/MEKK1 pathway. rhIGF-1 reduced edema and b...
Source: Experimental Neurology - November 29, 2018 Category: Neurology Authors: Nowrangi DS, McBride D, Manaenko A, Dixon B, Tang J, Zhang JH Tags: Exp Neurol Source Type: research

Vitamin D deficiency increases blood-brain barrier dysfunction after ischemic stroke in male rats.
Abstract Because vitamin D hormone deficiency (VDHdef) can worsen severity and outcome for ischemic stroke, we examined the role of VDH in maintaining blood-brain-barrier (BBB integrity) in a rat model of stroke. In most types of stroke, the BBB is markedly compromised, potentially leading to a cascade of injury processes and functional deficits, so we examined a number of biomarkers associated with BBB disruption to determine whether VDH deficiency would further compromise the BBB following a stroke. Male Wistar rats were randomly assigned to one of two diet cohorts, VDH-sufficient (VDHsuf) and VDHdef. The VDHsuf...
Source: Experimental Neurology - November 28, 2018 Category: Neurology Authors: Sayeed I, Turan N, Stein DG, Wali B Tags: Exp Neurol Source Type: research

Routes for the delivery of insulin to the central nervous system: A comparative review.
Abstract Central nervous system (CNS) insulin resistance is a condition in which the cells within the CNS do not respond to insulin appropriately and is often linked to aberrant CNS insulin levels. CNS insulin is primarily derived from the periphery. Aberrant CNS insulin levels can arise due to various factors including i) decreased endogenous insulin transport into the brain, across the blood-brain barrier (BBB), ii) reduced CNS sequestration of insulin, and iii) increased CNS degradation. While the sole route of endogenous insulin transport into the brain is via the BBB, there are multiple therapeutic routes of ...
Source: Experimental Neurology - November 27, 2018 Category: Neurology Authors: Rhea EM, Salameh TS, Banks WA Tags: Exp Neurol Source Type: research

Tacrolimus inhibits Th1 and Th17 responses in MuSK-antibody positive myasthenia gravis patients.
Abstract Muscle specific tyrosine kinase antibody positive myasthenia gravis (MuSK- MG) is characterized by autoantibodies against the MuSK protein of the neuromuscular junction resulting in weakness of bulbar and proximal muscles. We previously demonstrated that patients with MuSK-MG have increased pro-inflammatory Th1 and Th17 responses. Tacrolimus, an immunosuppressant used in AChR-MG and transplantation patients, inhibits T cell responses through interference with IL-2 transcription. The therapeutic efficacy and immunological effect of tacrolimus in MuSK-MG is unclear. In the current study we examined the prol...
Source: Experimental Neurology - November 22, 2018 Category: Neurology Authors: Li Y, Guptill JT, Russo MA, Massey JM, Juel VC, Hobson-Webb LD, Howard JF, Chopra M, Liu W, Yi JS Tags: Exp Neurol Source Type: research

Validation study of neurotrophin-3-releasing chitosan facilitation of neural tissue generation in the severely injured adult rat spinal cord.
Abstract It was previously reported that a tube holding chitosan carriers loaded with neurotrophin-3 (NT-3), after insertion into a 5 mm long transection gap in the adult rat spinal cord, triggered de novo neural tissue generation and functional recovery. Here, we report an effort to validate these findings using stringent blinding methodologies, which are crucial for robustness in reproducing biomedical studies. Radio frequency identification (RFID) chips were utilized to label rats that were randomly assigned into three experimental groups: transection with chitosan-NT-3 implant (C-NT3), transection only (T-co...
Source: Experimental Neurology - November 21, 2018 Category: Neurology Authors: Oudega M, Hao P, Shang J, Haggerty AE, Wang Z, Sun J, Liebl DJ, Shi Y, Cheng L, Duan H, Sun YE, Li X, Lemmon VP Tags: Exp Neurol Source Type: research

Genetic ablation of Gpr37l1 delays tumor occurrence in Ptch1+/- mouse models of medulloblastoma.
This study investigates cerebellar MB phenotypes in newly produced Gpr37l1, Ptch1 double mutant mice. Natural history analysis shows that Gpr37l1 genetic ablation, in Ptch1+/- model animals, results in marked deferment of post-natal tumor occurrence and decreased incidence of more aggressive tumor types. It is also associated with the delayed and diminished presence of more severe types of hyperplastic lesions in Ptch1+/- mice. Consistently, during early post-natal development Gpr37l1-/-;Ptch1+/- pups exhibit reduction in cerebellar GCP proliferation and EGL thickness and a precocious, sustained expression of wingless-type...
Source: Experimental Neurology - November 16, 2018 Category: Neurology Authors: Di Pietro C, La Sala G, Matteoni R, Marazziti D, Tocchini-Valentini GP Tags: Exp Neurol Source Type: research

Vitronectin from brain pericytes promotes adult forebrain neurogenesis by stimulating CNTF.
Abstract Vitronectin (VTN) is a glycoprotein in the blood and affects hemostasis. VTN is also present in the extracellular matrix of various organs but little is known about its function in healthy adult tissues. We show, in adult mice, that VTN is uniquely expressed by approximately half of the pericytes of subventricular zone (SVZ) where neurogenesis continues throughout life. Intracerebral VTN antibody injection or VTN knockout reduced neurogenesis as well as expression of pro-neurogenic CNTF, and anti-neurogenic LIF and IL-6. Conversely, injections of VTN, or plasma from VTN+/+, but not VTN-/- mice, increased ...
Source: Experimental Neurology - November 5, 2018 Category: Neurology Authors: Jia C, Keasey MP, Malone HM, Lovins C, Sante RR, Razskazovskiy V, Hagg T Tags: Exp Neurol Source Type: research

Sonic hedgehog regulation of cavernous nerve regeneration and neurite formation in aged pelvic plexus.
CONCLUSIONS: Reintroduction of SHH protein in an aged prostatectomy model is even more effective in promoting neurite formation/CN regeneration than in the adult. The first 48 h after CN injury are a critical window when growth factors are released, that impact later neurite formation. These studies are significant because most prostatectomy patients are not young and healthy, as with adult rats, so the aged prostatectomy model will more accurately simulate ED patient response. Understanding how neurite formation changes with age is critical for clinical translation of SHH PA to prostatectomy patients. PMID: 3039152...
Source: Experimental Neurology - November 1, 2018 Category: Neurology Authors: Dobbs R, Kalmanek E, Choe S, Harrington DA, Stupp SI, McVary KT, Podlasek CA Tags: Exp Neurol Source Type: research

Parkinsonian GM2 synthase knockout mice lacking mature gangliosides develop urinary dysfunction and neurogenic bladder.
Abstract Parkinson's disease is a neurodegenerative disorder that reduces a patients' quality of life by the relentless progression of motor and non-motor symptoms. Among the non-motor symptoms is a condition called neurogenic bladder that is associated with detrusor muscle underactivity or overactivity occurring from neurologic damage. In Parkinson's disease, Lewy-body-like protein aggregation inside neurons typically contributes to pathology. This is associated with dopaminergic neuron loss in substantia nigra pars compacta (SNc) and in ventral tegmental area (VTA), both of which play a role in micturition. GM1 ...
Source: Experimental Neurology - October 25, 2018 Category: Neurology Authors: Gil-Tommee C, Vidal-Martinez G, Annette Reyes C, Vargas-Medrano J, Herrera GV, Martin SM, Chaparro SA, Perez RG Tags: Exp Neurol Source Type: research

Neurogenesis changes and the fate of progenitor cells after subarachnoid hemorrhage in rats.
CONCLUSION: Neurogenesis in the hippocampus changes overtime after SAH. The neuronal progenitor cells may play an essential role in the neurobehavioral recovery after brain injury induced by SAH, since short-term progenitors helped with the recovery of immature neurons in the hippocampus, whereas long-term progenitors differentiated into mature neurons. PMID: 30359565 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - October 22, 2018 Category: Neurology Authors: Zuo Y, Wang J, Enkhjargal B, Doycheva D, Yan X, Zhang JH, Liu F Tags: Exp Neurol Source Type: research

Impaired chemoreflex correlates with decreased c-Fos in respiratory brainstem centers of the streptozotocin-induced Alzheimer's disease rat model.
In this study we further defined the pathophysiological respiratory response of STZ-AD rats to 10% O2. In addition, we analyzed hypoxia-induced neuronal activation in respiratory and cardiovascular nuclei of the dorsal and ventral brainstem. Two hours of hypoxia induced a transient increase in tidal volume that was followed by a prolonged increase in respiratory rate. Only respiratory rate was significant blunted in the STZ-AD model, which continued over the entire duration of the hypoxic episode. Analysis of c-Fos expression as a marker for neuronal activation showed abundant labeling throughout the nTS, nuclei of the ven...
Source: Experimental Neurology - October 22, 2018 Category: Neurology Authors: Brown AG, Thapa M, Hooker JW, Ostrowski TD Tags: Exp Neurol Source Type: research

Gene expression profiling in a mouse model of Dravet syndrome.
Abstract Dravet syndrome is a severe, early-onset epileptic encephalopathy frequently resulting from de novo mutations of SCN1A. Mice with heterozygous deletion of Scn1a (Scn1a+/-) model many features of Dravet syndrome, including spontaneous seizures and premature lethality. Scn1a+/- mice exhibit variable phenotype penetrance and expressivity dependent upon the strain background. On the 129S6/SvEvTac (129) strain, Scn1a+/- mice do not display an overt phenotype. However Scn1a+/- mice on the [129S6xB6]F1 strain (F1.Scn1a+/-) exhibit juvenile-onset spontaneous seizures and premature lethality. QTL mapping identifie...
Source: Experimental Neurology - October 19, 2018 Category: Neurology Authors: Hawkins NA, Calhoun JD, Huffman AM, Kearney JA Tags: Exp Neurol Source Type: research

Key determinants for morphine withdrawal conditioned context-induced increase in Arc expression in anterior cingulate cortex and withdrawal memory retrieval.
Abstract Addiction memory is subjected to time-dependent shifts toward neocortex in remote period to promote long-term addiction memory storage, which plays an important role in drug relapse. However, how the activity and neuroplasticity of the anterior cingulate cortex (ACC) change after contextual morphine withdrawal conditioning and what factors determine this change remain to be determined. In this paper, using immunohistochemical and single-cell microinjection techniques, combining behavioral assay, we found that (1) contextual withdrawal conditioning increases the expression of c-Fos, but not Arc, in the ACC...
Source: Experimental Neurology - October 18, 2018 Category: Neurology Authors: Chen M, Shao D, Fu Y, Ma Q, Chen M, Cui D, Song J, Sheng H, Yang L, Dong Y, Lai B, Zheng P Tags: Exp Neurol Source Type: research

Neuronal and vascular deficits following chronic adaptation to high altitude.
Abstract We sought to understand the mechanisms underlying cognitive deficits that are reported to affect non-native subjects following their prolonged stay and/or work at high altitude (HA). We found that mice exposed to a simulated environment of 5000 m exhibit deficits in hippocampal learning and memory accompanied by abnormalities in brain MR imaging. Exposure (1-8 months) to HA led to an increase in brain ventricular volume, a reduction in relative cerebral blood flow and changes in diffusion tensor imaging (DTI) derived parameters within the hippocampus and corpus callosum. Furthermore, neuropathological...
Source: Experimental Neurology - October 12, 2018 Category: Neurology Authors: Cramer NP, Korotcov A, Bosomtwi A, Xu X, Holman D, Whiting K, Jones S, Hoy A, Dardzinski BJ, Galdzicki Z Tags: Exp Neurol Source Type: research

Positive modulation of mGluR5 attenuates seizures and reduces TNF- α+ macrophages and microglia in the brain in a murine model of virus-induced temporal lobe epilepsy.
Positive modulation of mGluR5 attenuates seizures and reduces TNF-α+ macrophages and microglia in the brain in a murine model of virus-induced temporal lobe epilepsy. Exp Neurol. 2018 Oct 11;: Authors: Hanak TJ, Libbey JE, Doty DJ, Sim JT, DePaula-Silva AB, Fujinami RS Abstract Viral encephalitis markedly increases the risk for the development of epilepsy. The Theiler's murine encephalomyelitis virus (TMEV)-induced model of seizures/epilepsy is a murine model of both viral-induced seizures/epilepsy and human Temporal Lobe Epilepsy. The inflammatory cytokines interleukin (IL)-6 and tumor necrosis...
Source: Experimental Neurology - October 11, 2018 Category: Neurology Authors: Hanak TJ, Libbey JE, Doty DJ, Sim JT, DePaula-Silva AB, Fujinami RS Tags: Exp Neurol Source Type: research

Expression of pathogenic SCN9A mutations in the zebrafish: A model to study small fiber neuropathy.
Abstract Small fiber neuropathy (SFN) patients experience a spectrum of sensory abnormalities, including attenuated responses to non-noxious temperatures in combination with a decreased density of the small-nerve fibers. Gain-of-function mutations in the voltage-gated sodium channels SCN9A, SCN10A and SCN11A have been identified as an underlying genetic cause in a subpopulation of patients with SFN. Based on clinical-diagnostic tests for SFN, we have set up a panel of two read-outs reflecting SFN in zebrafish, being nerve density and behavioral responses. Nerve density was studied using a transgenic line in which ...
Source: Experimental Neurology - October 11, 2018 Category: Neurology Authors: Eijkenboom I, Sopacua M, Otten ABC, Gerrits MM, Hoeijmakers JGJ, Waxman SG, Lombardi R, Lauria G, Merkies ISJ, Smeets HJM, Faber CG, Vanoevelen JM, PROPANE Study Group Tags: Exp Neurol Source Type: research

Distinct roles of angiotensin receptors in autonomic dysreflexia following high-level spinal cord injury in mice.
In conclusion, we identified a specific role of the Ang-(1-7) receptor Mas in regulating the systemic blood pressure increase in AD in T4-SCI mice. Furthermore, AT1a signaling is not involved in this hemodynamic response, but underlies increased vascular reactivity in mesenteric arteries in response to Ang II, where it may contribute to adaptive changes in regional blood flow. PMID: 30315807 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - October 10, 2018 Category: Neurology Authors: Järve A, Todiras M, Lian X, Filippelli-Silva R, Qadri F, Martin RP, Gollasch M, Bader M Tags: Exp Neurol Source Type: research

Astrocyte-specific deletion of Kir6.1/K-ATP channel aggravates cerebral ischemia/reperfusion injury through endoplasmic reticulum stress in mice.
Abstract ATP-sensitive potassium (K-ATP) channels, coupling cell metabolism to cell membrane potential, are involved in brain diseases including stroke. Emerging evidence shows that astrocytes play important roles in the pathophysiology of cerebral ischemia. Kir6.1, a pore-forming subunit of K-ATP channel, is prominently expressed in astrocytes and participates in regulating its function. However, the exact role of astrocytic Kir6.1-containg K-ATP channel (Kir6.1/K-ATP) in ischemic stroke remains unclear. Here, we found that astrocytic Kir6.1 knockout (KO) mice exhibited larger infarct areas and more severe brain ...
Source: Experimental Neurology - October 10, 2018 Category: Neurology Authors: Zhong CJ, Chen MM, Lu M, Ding JH, Du RH, Hu G Tags: Exp Neurol Source Type: research

Reduced Purkinje cell size is compatible with near normal morphology and function of the cerebellar cortex in a mouse model of spinocerebellar ataxia.
JP Abstract Spinocerebellar ataxia type 14 (SCA14) is a dominantly inherited neurodegenerative disease caused by diverse mutations in the Protein Kinase C gamma (PKCγ) gene which is one of the crucial signaling molecules of Purkinje cells. We have previously created a mouse model of SCA14 by transgenic expression of a mutated PKCγ gene causing SCA14 with a mutation in the catalytic domain. Purkinje cells from the mutated mice have a strong reduction of their dendritic tree in organotypic slice cultures typical for increased PKC activity. There was no overt degeneration of Purkinje cells in vivo and th...
Source: Experimental Neurology - October 9, 2018 Category: Neurology Authors: Trzesniewski J, Altmann S, Jäger L, Kapfhammer JP Tags: Exp Neurol Source Type: research

Rapid plasticity of intact axons following a lesion to the visual pathways during early brain development is triggered by microglial activation.
ty CA Abstract Lesions in the central nervous system (CNS) can often induce structural reorganization within intact circuits of the brain. Several studies show advances in the understanding of mechanisms of brain plasticity and the role of the immune system activation. Microglia, a myeloid derived cell population colonizes the CNS during early phases of embryonic development. In the present study, we evaluated the role of microglial activation in the sprouting of intact axons following lesions of the visual pathways. We evaluated the temporal course of microglial activation in the superior colliculus following a c...
Source: Experimental Neurology - October 9, 2018 Category: Neurology Authors: da Silva Chagas L, Trindade P, Gomes ALT, Mendonça HR, Campello-Costa P, da Cunha Faria Melibeu A, Linden R, Serfaty CA Tags: Exp Neurol Source Type: research

A Mesenchymal stem cell line (B10) increases angiogenesis in a rat MCAO model.
Abstract A human mesenchymal stem cell line (B10) transplantation has been shown to improve ischemia-induced neurological deficits in animal stroke models. To understand the underlying mechanism, we have investigated the effects of B10 transplantation on cerebral angiogenesis in a rat middle cerebral artery occlusion (MCAO) model. B10 cells were transplanted intravenously 24 h after MCAO. Immunofluorescence staining results showed that compared to PBS-groups, vWF positive vessel and endoglin positive new vessels were increased in B10-transplanted MCAO groups in the lesion areas. The mRNA of angiogenesis factors ...
Source: Experimental Neurology - October 3, 2018 Category: Neurology Authors: Sheikh AM, Yano S, Mitaki S, Haque MA, Yamaguchi S, Nagai A Tags: Exp Neurol Source Type: research

Matrices, scaffolds & carriers for cell delivery in nerve regeneration.
Matrices, scaffolds & carriers for cell delivery in nerve regeneration. Exp Neurol. 2018 Oct 03;: Authors: Wang ZZ, Sakiyama-Elbert SE Abstract Nerve injuries can be life-long debilitating traumas that severely impact patients' quality of life. While many acellular neural scaffolds have been developed to aid the process of nerve regeneration, complete functional recovery is still very difficult to achieve, especially for long-gap peripheral nerve injury and most cases of spinal cord injury. Cell-based therapies have shown many promising results for improving nerve regeneration. With recent advance...
Source: Experimental Neurology - October 3, 2018 Category: Neurology Authors: Wang ZZ, Sakiyama-Elbert SE Tags: Exp Neurol Source Type: research

Insulin-like growth factor (IGF)-1 treatment stabilizes the microvascular cytoskeleton under ischemic conditions.
Abstract Our previous studies showed that Insulin-like Growth Factor (IGF)-1 reduced blood brain barrier pemeability and decreased infarct volume caused by middle cerebral artery occlusion (MCAo) in middle aged female rats. Similarly, cultures of primary brain microvessel endothelial cells from middle-aged female rats and exposed to stroke-like conditions (oxygen glucose deprivation; OGD) confirmed that IGF-1 reduced dye transfer across this cell monolayer. Surprisingly, IGF-1 did not attenuate endothelial cell death caused by OGD. To reconcile these findings, the present study tested the hypothesis that, at the e...
Source: Experimental Neurology - October 1, 2018 Category: Neurology Authors: Bake S, Okoreeh A, Khosravian H, Sohrabji F Tags: Exp Neurol Source Type: research

Self-reinforcing effects of mTOR hyperactive neurons on dendritic growth.
Abstract Loss of the mTOR pathway negative regulator PTEN from hippocampal dentate granule cells leads to neuronal hypertrophy, increased dendritic branching and aberrant basal dendrite formation in animal models. Similar changes are evident in humans with mTOR pathway mutations. These genetic conditions are associated with autism, cognitive dysfunction and epilepsy. Interestingly, humans with mTOR pathway mutations often present with mosaic disruptions of gene function, producing lesions that range from focal cortical dysplasia to hemimegalanecephaly. Whether mTOR-mediated neuronal dysmorphogenesis is impacted by...
Source: Experimental Neurology - September 27, 2018 Category: Neurology Authors: Arafa SR, LaSarge CL, Pun RYK, Khademi S, Danzer SC Tags: Exp Neurol Source Type: research

Engaging pain fibers after a spinal cord injury fosters hemorrhage and expands the area of secondary injury.
Abstract In humans, spinal cord injury (SCI) is often accompanied by additional tissue damage (polytrauma) that can engage pain (nociceptive) fibers. Prior work has shown that this nociceptive input can expand the area of tissue damage (secondary injury), undermine behavioral recovery, and enhance the development of chronic pain. Here, it is shown that nociceptive input given a day after a lower thoracic contusion injury in rats enhances the infiltration of red blood cells at the site of injury, producing an area of hemorrhage that expands secondary injury. Peripheral nociceptive fibers were engaged 24 h after i...
Source: Experimental Neurology - September 27, 2018 Category: Neurology Authors: Turtle JD, Henwood MK, Strain MM, Huang YJ, Miranda RC, Grau JW Tags: Exp Neurol Source Type: research

Impact of anaesthesia on circadian rhythms and implications for laboratory experiments.
Abstract General anaesthesia is a widely used tool to enable surgery in animal experimentation. There is now convincing evidence that general anaesthesia can cause profound and strongly time-dependant shifts in circadian rhythms of behaviour (sleep-wake cycles), physiology (core body temperature, blood pressure, heart rate and hormone release) and cognitive parameters (learning and memory) in a range of species. These effects have the potential to confound laboratory experiments, and may lead to misinterpretation of results. Here, we summarise these effects and advise caution to those conducting laboratory experim...
Source: Experimental Neurology - September 27, 2018 Category: Neurology Authors: Orts-Sebastian A, Ludin NM, Pawley MDM, Cheeseman JF, Warman GR Tags: Exp Neurol Source Type: research

Serotonin2B receptors in the rat dorsal raphe nucleus exert a GABA-mediated tonic inhibitory control on serotonin neurons.
Abstract The central serotonin2B receptor (5-HT2BR) is a well-established modulator of dopamine (DA) neuron activity in the rodent brain. Recent studies in rats have shown that the effect of 5-HT2BR antagonists on accumbal and medial prefrontal cortex (mPFC) DA outflow results from a primary action in the dorsal raphe nucleus (DRN), where they activate 5-HT neurons innervating the mPFC. Although the mechanisms underlying this interaction remain largely unknown, data in the literature suggest the involvement of DRN GABAergic interneurons in the control of 5-HT activity. The present study examined this hypothesis us...
Source: Experimental Neurology - September 23, 2018 Category: Neurology Authors: Cathala A, Devroye C, Drutel G, Revest JM, Artigas F, Spampinato U Tags: Exp Neurol Source Type: research

Tat-HA-NR2B9c attenuate oxaliplatin-induced neuropathic pain.
In this study, we studied whether Tat-HA-NR2B9c could be an effective treatment for oxaliplatin-induced neuropathic pain. To conform it, a rat model of oxaliplatin-induced neuropathic was established, and analgesic effect of Tat-HA-NR2B9c was studied. Here, we show that oxaliplatin induces the interaction of NMDARs with PSD-95. Uncoupling the complex by Tat-HA-NR2B9c has potent analgesic effect in oxaliplatin-induced cold hyperalgesia and mechanical allodynia without suppressing general behavioral. Tat-HA-NR2B9c neither inhibits NMDARs function nor impacts antitumor activity of oxaliplatin. Thus, this new drug may serve as...
Source: Experimental Neurology - September 22, 2018 Category: Neurology Authors: Zhou HH, Zhang L, Zhang HX, Xu BR, Zhang JP, Zhou YJ, Qian XP, Ge WH Tags: Exp Neurol Source Type: research

Spinal cord astrocytomas: progresses in experimental and clinical investigations for developing recovery neurobiology-based novel therapies.
Abstract Spinal cord astrocytomas (SCAs) have discernibly unique signatures in regards to epidemiology, clinical oncological features, genetic markers, pathophysiology, and research and therapeutic challenges. Overall, there are presently very limited clinical management options for high grade SCAs despite progresses made in validating key molecular markers and standardizing tumor classification. The endeavors were aimed to improve diagnosis, therapy design and prognosis assessment, as well as to define more effective oncolytic targets. Efficacious treatment for high grade SCAs still remains an unmet medical deman...
Source: Experimental Neurology - September 20, 2018 Category: Neurology Authors: Teng YD, Abd-El-Barr M, Wang L, Hajiali H, Wu L, Zafonte RD Tags: Exp Neurol Source Type: research

Early intrathecal infusion of everolimus restores cognitive function and mood in a murine model of Alzheimer's disease.
Abstract The discovery that mammalian target of rapamycin (mTOR) inhibition increases lifespan in mice and restores/delays many aging phenotypes has led to the identification of a novel potential therapeutic target for the treatment of Alzheimer's disease (AD). Among mTOR inhibitors, everolimus, which has been developed to improve the pharmacokinetic characteristics of rapamycin, has been extensively profiled in preclinical and clinical studies as anticancer and immunosuppressive agent, but no information is available about its potential effects on neurodegenerative disorders. Using a reliable mouse model of AD (3...
Source: Experimental Neurology - September 19, 2018 Category: Neurology Authors: Cassano T, Magini A, Giovagnoli S, Polchi A, Calcagnini S, Pace L, Lavecchia MA, Scuderi C, Bronzuoli MR, Ruggeri L, Gentileschi MP, Romano A, Gaetani S, De Marco F, Emiliani C, Dolcetta D Tags: Exp Neurol Source Type: research