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Experimental Neurology

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https://www.readbyqxmd.com/read/28081963/rapid-neuroinflammatory-response-localized-to-injured-neurons-after-diffuse-traumatic-brain-injury-in-swine
#1
Kathryn L Wofford, James P Harris, Kevin D Browne, Daniel P Brown, Michael R Grovola, Constance J Mietus, John A Wolf, John E Duda, Mary E Putt, Kara L Spiller, D Kacy Cullen
Despite increasing appreciation of the critical role that neuroinflammatory pathways play in brain injury and neurodegeneration, little is known about acute microglial reactivity following diffuse traumatic brain injury (TBI) - the most common clinical presentation that includes all concussions. Therefore, we investigated acute microglial reactivity using a porcine model of closed-head rotational velocity/acceleration-induced TBI that closely mimics the biomechanical etiology of inertial TBI in humans. We observed rapid microglial reactivity within 15min of both mild and severe TBI...
January 9, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28077335/omega-3-fatty-acids-regulate-nlrp3-inflammasome-activation-and-prevent-behavior-deficits-after-traumatic-brain-injury
#2
Chao Lin, Honglu Chao, Zheng Li, Xiupeng Xu, Yinlong Liu, Zhongyuan Bao, Lijun Hou, Yan Liu, Xiaoming Wang, Yongping You, Ning Liu, Jing Ji
Omega-3 fatty acids (ω-3 FAs) attenuate inflammation and improve neurological outcome in response to traumatic brain injury (TBI), but the specific anti-inflammatory mechanisms remain to be elucidated. Here we found that NLRP3 inflammasome and subsequent pro-inflammatory cytokines were activated in human brains after TBI. Rats treated with ω-3 FAs had significantly less TBI-induced caspase-1 cleavage and IL-1β secretion than those with vehicle. G protein-coupled receptor 40 (GPR40) was observed to be involved in this anti-inflammation...
January 8, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28077334/the-neuroprotective-compound-p7c3-a20-promotes-neurogenesis-and-improves-cognitive-function-after-ischemic-stroke
#3
Zachary B Loris, Andrew A Pieper, W Dalton Dietrich
Ischemic stroke is a devastating condition with few therapeutic interventions available. The neuroprotective compound P7C3-A20 inhibits mature neuronal cell death while also increasing the net magnitude of postnatal neurogenesis in models of neurodegeneration and acute injury. P7C3 compounds enhance flux of nicotinamide adenine dinucleotide (NAD) in mammalian cells, a proposed therapeutic approach to treating cerebral ischemia. The effectiveness of P7C3-A20 treatment on chronic histopathological and behavioral outcomes and neurogenesis after ischemic stroke has not previously been established...
January 8, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28077261/ventral-medullary-control-of-rapid-eye-movement-sleep-and-atonia
#4
Michael C Chen, Ramalingam Vetrivelan, Chun-Ni Guo, Catie Chang, Patrick M Fuller, Jun Lu
Discrete populations of neurons at multiple levels of the brainstem control rapid eye movement (REM) sleep and the accompanying loss of postural muscle tone, or atonia. The specific contributions of these brainstem cell populations to REM sleep control remains incompletely understood. Here we show in rats that viral vector-based lesions of the ventromedial medulla at a level rostral to the inferior olive (pSOM) produced violent myoclonic twitches and abnormal electromyographic spikes, but not complete loss of tonic atonia, during REM sleep...
January 7, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28065671/glutamine-triggers-long-lasting-increase-in-striatal-network-activity-in-vitro
#5
Wiebke Fleischer, Stephan Theiss, Alfons Schnitzler, Olga Sergeeva
Accumulation of ammonium and glutamine in blood and brain is a key factor in hepatic encephalopathy (HE) - a neuropsychiatric syndrome characterized by various cognitive and motor deficits. MRI imaging identified abnormalities notably in the basal ganglia of HE patients, including its major input station, the striatum. While neurotoxic effects of ammonia have been extensively studied, glutamine is primarily perceived as "detoxified" form of ammonia. We applied ammonium and glutamine to striatal and cortical cells from newborn rats cultured on microelectrode arrays...
January 6, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28062175/intranasal-c3a-treatment-ameliorates-cognitive-impairment-in-a-mouse-model-of-neonatal-hypoxic-ischemic-brain-injury
#6
Javier Morán, Anna Stokowska, Frederik R Walker, Carina Mallard, Henrik Hagberg, Marcela Pekna
Perinatal asphyxia-induced brain injury is often associated with irreversible neurological complications such as intellectual disability and cerebral palsy but available therapies are limited. Novel neuroprotective therapies as well as approaches stimulating neural plasticity mechanism that can compensate for cell death after hypoxia-ischemia (HI) are urgently needed. We previously reported that single i.c.v. injection of complement-derived peptide C3a 1h after HI induction prevented HI-induced cognitive impairment when mice were tested as adults...
January 3, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28041911/disinhibition-of-the-intergeniculate-leaflet-network-in-the-wag-rij-rat-model-of-absence-epilepsy
#7
Lukasz Chrobok, Katarzyna Palus, Jagoda Stanislawa Jeczmien-Lazur, Anna Chrzanowska, Mariusz Kepczynski, Marian Henryk Lewandowski
The intergeniculate leaflet (IGL) of the thalamus is a retinorecipient structure implicated in orchestrating circadian rhythmicity. The IGL network is highly GABAergic and consists mainly of neuropeptide Y-synthesising and enkephalinergic neurons. A high density of GFAP-immunoreactive astrocytes has been observed in the IGL, with a probable function in guarding neuronal inhibition. Interestingly, putatively enkephalinergic IGL neurons generate action potentials with an infra-slow oscillatory (ISO) pattern in vivo in urethane anesthetised Wistar rats, under light-on conditions only...
December 30, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/28038988/serial-in-vivo-imaging-of-transplanted-allogeneic-neural-stem-cell-survival-in-a-mouse-model-of-amyotrophic-lateral-sclerosis
#8
Amit K Srivastava, Sarah K Gross, Akshata A Almad, Camille A Bulte, Nicholas J Maragakis, Jeff W M Bulte
Neural stem cells (NSCs) are being investigated as a possible treatment for amyotrophic lateral sclerosis (ALS) through intraspinal transplantation, but no longitudinal imaging studies exist that describe the survival of engrafted cells over time. Allogeneic firefly luciferase-expressing murine NSCs (Luc(+)-NSCs) were transplanted bilaterally (100,000 cells/2μl) into the cervical spinal cord (C5) parenchyma of pre-symptomatic (63day-old) SOD1(G93A) ALS mice (n=14) and wild-type age-matched littermates (n=14)...
December 28, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/28038987/adaptive-reorganization-of-retinogeniculate-axon-terminals-in-dorsal-lateral-geniculate-nucleus-following-experimental-mild-traumatic-brain-injury
#9
Vishal C Patel, Christopher W D Jurgens, Thomas E Krahe, John T Povlishock
The pathologic process in traumatic brain injury marked by delayed axonal loss, known as diffuse axonal injury (DAI), leads to partial deafferentation of neurons downstream of injured axons. This process is linked to persistent visual dysfunction following mild traumatic brain injury (mTBI), however, examination of deafferentation in humans is impossible with current technology. To investigate potential reorganization in the visual system following mTBI, we utilized the central fluid percussion injury (cFPI) mouse model of mTBI...
December 28, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/28038986/differential-effects-of-minocycline-on-microglial-activation-and-neurodegeneration-following-closed-head-injury-in-the-neonate-rat
#10
L A Hanlon, R Raghupathi, J W Huh
The role of microglia in the pathophysiology of injury to the developing brain has been extensively studied. In children under the age of 4 who have sustained a traumatic brain injury (TBI), markers of microglial/macrophage activation were increased in the cerebrospinal fluid and were associated with worse neurologic outcome. Minocycline is an antibiotic that decreases microglial/macrophage activation following hypoxic-ischemia in neonatal rodents and TBI in adult rodents thereby reducing neurodegeneration and behavioral deficits...
December 27, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/28038985/exploring-the-mechanism-by-which-accumbal-deep-brain-stimulation-attenuates-morphine-induced-reinstatement-through-manganese-enhanced-mri-and-pharmacological-intervention
#11
Lei Zhang, Ying Cui, Ying-Chun Wang, Hong Yin, Jian-Min Zheng, Lu Huang, Zhen-Wei Zhao, Jiang Li
Deep brain stimulation (DBS) of the nucleus accumbens (NAc) has been applied to attenuate drug relapses in animal studies and clinical treatments. However, the mechanisms by which DBS produces its therapeutic effects remain largely unknown. This study is the first to combine manganese-enhanced magnetic resonance imaging (MRI) with DBS to explore the effects of accumbal DBS on the relapse pathway of rats. The images suggested that DBS produced an antidromic activation of the cortico-accumbal afferents. To verify the activating effects of DBS, the expression levels of the protein encoded by the immediate early gene c-Fos following DBS were measured using immunochemical methods...
December 27, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/28024798/zonisamide-attenuates-lactacystin-induced-parkinsonism-in-mice-without-affecting-system-xc
#12
Eduard Bentea, Joeri Van Liefferinge, Lise Verbruggen, Katleen Martens, Sho Kobayashi, Lauren Deneyer, Thomas Demuyser, Giulia Albertini, Katrien Maes, Hideyo Sato, Ilse Smolders, Jan Lewerenz, Ann Massie
Zonisamide (ZNS), an anticonvulsant drug exhibiting symptomatic effects in Parkinson's disease (PD), was recently reported to exert neuroprotection in rodent models. One of the proposed neuroprotective mechanisms involves increased protein expression of xCT, the specific subunit of the cystine/glutamate antiporter system xc(-), inducing glutathione (GSH) synthesis. Here, we investigated the outcome of ZNS treatment in a mouse model of PD based on intranigral proteasome inhibition, and whether the observed effects would be mediated by system xc(-)...
December 24, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/28013000/galanin-contributes-to-monoaminergic-dysfunction-and-to-dependent-neurobehavioral-comorbidities-of-epilepsy
#13
Jesus-Servando Medel-Matus, Don Shin, Raman Sankar, Andrey Mazarati
Status epilepticus (SE) in rats, along with chronic epilepsy, leads to the development of behavioral impairments resembling depressive disorder and/or attention deficit/hyperactivity disorder (ADHD), thus reflecting respective comorbidities in epilepsy patients. Suppressed neurotransmitter tone in the raphe nucleus (RN)-prefrontal cortex (PFC) serotonergic pathway and in the locus coeruleus (LC)-PFC noradrenergic pathway underlies depressive- and impulsive-like behavioral deficits respectively. We examined possible mechanisms leading to the monoamine dysfunction in brainstem efferents, namely modulatory effects of the neuropeptide galanin on serotonin (5-HT) and norepinephrine (NE) signaling...
December 22, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/28011122/lithium-increases-hippocampal-snare-protein-abundance-after-traumatic-brain-injury
#14
Shaun W Carlson, Hong Yan, C Edward Dixon
Rodent models of traumatic brain injury (TBI) reproduce secondary injury sequela and cognitive impairments observed in patients afflicted by a TBI. Impaired neurotransmission has been reported in the weeks following experimental TBI, and may be a contributor to behavioral dysfunction. The soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex, the machinery facilitating vesicular docking and fusion, is a highly-conserved mechanism important for neurotransmission. Following TBI, there is a reduction in both the formation of the SNARE complex and the abundance of multiple SNARE proteins, including the chaperone protein cysteine string protein α (CSPα)...
December 21, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27993509/reggie-1-and-reggie-2-flotillins-participate-in-rab11a-dependent-cargo-trafficking-spine-synapse-formation-and-ltp-related-ampa-receptor-glua1-surface-exposure-in-mouse-hippocampal-neurons
#15
Vsevolod Bodrikov, Aline Pauschert, Gaga Kochlamazashvili, Claudia A O Stuermer
Reggie-1 and -2 (flotillins) reside at recycling vesicles and promote jointly with Rab11a the targeted delivery of cargo. Recycling is essential for synapse formation suggesting that reggies and Rab11a may regulate the development of spine synapses. Recycling vesicles provide cargo for dendritic growth and recycle surface glutamate receptors (AMPAR, GluA) for long-term potentiation (LTP) induced surface exposure. Here, we show reduced number of spine synapses and impairment of an in vitro correlate of LTP in hippocampal neurons from reggie-1 k...
December 16, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27988257/parametric-characterization-of-neural-activity-in-the-locus-coeruleus-in-response-to-vagus-nerve-stimulation
#16
Daniel R Hulsey, Jonathan R Riley, Kristofer W Loerwald, Robert L Rennaker, Michael P Kilgard, Seth A Hays
Vagus nerve stimulation (VNS) has emerged as a therapy to treat a wide range of neurological disorders, including epilepsy, depression, stroke, and tinnitus. Activation of neurons in the locus coeruleus (LC) is believed to mediate many of the effects of VNS in the central nervous system. Despite the importance of the LC, there is a dearth of direct evidence characterizing neural activity in response to VNS. A detailed understanding of the brain activity evoked by VNS across a range of stimulation parameters may guide selection of stimulation regimens for therapeutic use...
December 14, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27956032/alterations-in-hypoglossal-motor-neurons-due-to-gad67-and-vgat-deficiency-in-mice
#17
Matthew J Fogarty, Refik Kanjhan, Yuchio Yanagawa, Peter G Noakes, Mark C Bellingham
There is an emerging body of evidence that glycinergic and GABAergic synaptic inputs onto motor neurons (MNs) help regulate the final number of MNs and axonal muscle innervation patterns. Using mutant glutamate decarboxylase 67 (GAD67) and vesicular inhibitory amino acid transporter (VGAT) deficient mice, we describe the effect that deficiencies of presynaptic GABAergic and/or glycinergic release have on the post-synaptic somato-dendritic structure of motor neurons, and the development of excitatory and inhibitory synaptic inputs to MNs...
December 10, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27940019/the-habenula-as-a-critical-node-in-chronic-stress-related-anxiety
#18
Luis R Jacinto, Rui Mata, Ashley Novais, Fernanda Marques, Nuno Sousa
The habenula is activated in response to stressful and aversive events, resulting in exploratory inhibition. Although possible mechanisms for habenula activation have been proposed, the effects of chronic stress on the habenular structure have never been studied. Herein, we assessed changes in volume, cell density and dendritic structure of habenular cells after chronic stress exposure using stereological and 3D morphological analysis. This study shows for the first time that there is a hemispherical asymmetry in the medial habenula (MHb) of the adult rat, with the right MHb containing more neurons than its left counterpart...
December 7, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27940018/reversible-recovery-of-neuronal-structures-depends-on-the-degree-of-neuronal-damage-after-global-cerebral-ischemia-in-mice
#19
Lirui Zhu, Lei Wang, Furong Ju, Akbar Khan, Xiaofeng Cheng, Shengxiang Zhang
It has been observed by in vivo imaging that damaged neuronal structures can be reversibly restored after ischemic insults with the application of timely therapeutic interventions. However, what degree of neuronal damage can be restored and the time frame for reversible recovery of neuronal structures remain unclear. Here, transcranial two-photon imaging, histological staining and electron microscopy were used to investigate the reversible recovery of neuronal structures from dendrites to soma after different durations of global cerebral ischemia in mice...
December 6, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27923561/neuropathology-and-neurobehavioral-alterations-in-a-rat-model-of-traumatic-brain-injury-to-occupants-of-vehicles-targeted-by-underbody-blasts
#20
Flaubert Tchantchou, William L Fourney, Ulrich H Leiste, Joshua Vaughan, Parisa Rangghran, Adam Puche, Gary Fiskum
Many victims of blast-induced traumatic brain injury are occupants of military vehicles targeted by land mines. Recently improved vehicle designs protect these individuals against blast overpressure, leaving acceleration as the main force potentially responsible for brain injury. We recently developed a unique rat model of under-vehicle blast-induced hyperacceleration where exposure to acceleration as low as 50G force results in histopathological evidence of diffuse axonal injury and astrocyte activation, with no evidence of neuronal cell death...
December 5, 2016: Experimental Neurology
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