Genetic neutrophil deficiency ameliorates cerebral ischemia-reperfusion injury.
Abstract Neutrophils respond rapidly to cerebral ischemia and are thought to contribute to inflammation-mediated injury during stroke. Using myeloid Mcl1 knockout mice as a model of genetic neutrophil deficiency, we investigated the contribution of neutrophils to stroke pathophysiology. Myeloid Mcl1 knockout mice were subjected to transient middle cerebral artery occlusion and infarct size was assessed by MRI after 24h reperfusion. Immune cell mobilization and infiltration was assessed by flow cytometry. We found that myeloid Mcl1 knockout mice had significantly reduced infarct size when compared to heterozygous a...
Source: Experimental Neurology - August 30, 2017 Category: Neurology Authors: Frieler RA, Chung Y, Ahlers CG, Gheordunescu G, Song J, Vigil TM, Shah YM, Mortensen RM Tags: Exp Neurol Source Type: research

The promise of signal transduction in genetically driven sarcomas of the nerve.
Abstract Neurofibromatosis type 1 (NF1) is an autosomal dominant tumor predisposition syndrome. Malignant peripheral nerve sheath tumors (MPNST) are aggressive soft tissue sarcomas arising from peripheral nerve sheaths, and the most commonly lethal feature associated with NF1. The hallmark of NF1 and NF1-related MPNST is the loss of neurofibromin expression. Loss of neurofibromin is considered a tumor-promoting event, and leads to constitutive activation of RAS and its downstream effectors. However, RAS activation alone is not sufficient for MPNST formation, and additional tumor suppressors and signaling pathways ...
Source: Experimental Neurology - August 28, 2017 Category: Neurology Authors: Kim A, Pratilas CA Tags: Exp Neurol Source Type: research

Intraspinal TLR4 activation promotes iron storage but does not protect neurons or oligodendrocytes from progressive iron-mediated damage.
Abstract Iron is essential for basic cellular functions but in excess is highly toxic. For this reason, free iron and iron storage are controlled in the periphery by elaborate regulatory mechanisms. In contrast, iron regulation in the central nervous system (CNS) is not well defined. Given that excess iron is present after trauma, hemorrhagic stroke and neurodegeneration, understanding normal iron regulation and promoting iron uptake in CNS pathology is crucial. Peripherally, toll-like receptor 4 (TLR4) activation promotes iron sequestration by macrophages. Notably, iron-rich sites of CNS pathology typically conta...
Source: Experimental Neurology - August 26, 2017 Category: Neurology Authors: Goldstein EZ, Church JS, Pukos N, Gottipati M, Popovich PG, McTigue DM Tags: Exp Neurol Source Type: research

AMPK activation: Role in the signaling pathways of neuroinflammation and neurodegeneration.
s AKS Abstract Adenosine monophosphate-activated protein kinase (AMPK) is an evolutionarily conserved sensor of cellular energy status and has been reported to be involved in chronic inflammatory disorders. AMPK is expressed in immune cells, such as dendritic cells, macrophages, lymphocytes and neutrophils, and is an important regulator of inflammatory responses through the regulation of complex signaling networks in part by inhibiting downstream cascade pathways, such as nuclear factor kB, which is a key regulator of innate immunity and inflammation, as well as acting as a negative regulator of toll-like receptor...
Source: Experimental Neurology - August 24, 2017 Category: Neurology Authors: Peixoto CA, de Oliveira WH, da Rocha Araújo SM, Nunes AKS Tags: Exp Neurol Source Type: research

Effects of GABA microinjection into dorsal raphe nucleus on behavior and activity of lateral habenular neurons in mice.
Abstract The dorsal raphe nucleus (DRN) is a key site for 5-hydroxytryptamine (5-HT) synthesis and release. DRN dysfunction has been implicated in several stress-related disorders, including depression and anxiety. The lateral habenular nucleus (LHb) has been shown to inhibit the activity of DRN 5-HT neurons, and thus the LHb-DRN pathway plays an important role in the pathogenesis of depression. Although it is known that the LHb also receives the projection from the 5-HT neuron in the DRN, whether 5-HT neurons in the DRN can influence activity of the LHb in vivo and whether this effect is related to the induced be...
Source: Experimental Neurology - August 24, 2017 Category: Neurology Authors: Xiao J, Song M, Li F, Liu X, Anwar A, Zhao H Tags: Exp Neurol Source Type: research

Microglia and macrophages differ in their inflammatory profile after permanent brain ischemia.
Abstract We studied the expression of pro- and anti-inflammatory molecules in microglia and infiltrating monocyte-derived macrophages after permanent Middle Cerebral Artery Occlusion (pMCAO). LysM-EGFP knock-in mice were used to distinguish between these two cell types, as peripheral myeloid cells are LysM-EGFP(+), while microglia are not. This was confirmed with P2ry12 (a microglial specific marker), Iba-1 and EGFP immunostaining. The peak of LysM-EGFP(+) myeloid cell infiltration was 72h post-ischemia, and were distributed evenly in the lesion core, surrounded by a dense region of microglia. Flow cytometry showe...
Source: Experimental Neurology - August 23, 2017 Category: Neurology Authors: Zarruk JG, Greenhalgh AD, David S Tags: Exp Neurol Source Type: research

Contribution of amygdala CRF neurons to chronic pain.
Abstract We investigated the role of amygdala corticotropin-releasing factor (CRF) neurons in the perturbations of descending pain inhibition caused by neuropathic pain. Forced swim increased the tail-flick response latency in uninjured mice, a phenomenon known as stress-induced analgesia (SIA) but did not change the tail-flick response latency in mice with neuropathic pain caused by sciatic nerve constriction. Neuropathic pain also increased the expression of CRF in the central amygdala (CeAmy) and ΔFosB in the dorsal horn of the spinal cord. Next, we injected the CeAmy of CRF-cre mice with cre activated AA...
Source: Experimental Neurology - August 19, 2017 Category: Neurology Authors: Andreoli M, Marketkar T, Dimitrov E Tags: Exp Neurol Source Type: research

Immunization of mice with LRP4 induces myasthenia similar to MuSK-associated myasthenia gravis.
In this study, we purified antigens corresponding to the extracellular region of human LRP4 stably expressed with chaperones in 293 cells and used these antigens to immunize female A/J mice. Immunization with LRP4 protein caused mice to develop myasthenia having similar electrophysiological and histological features as are observed in MG patients with circulating Abs against muscle-specific kinase (MuSK). Our results clearly demonstrate that active immunization of mice with LRP4 proteins causes myasthenia similar to the MG induced by anti-MuSK Abs. Further experimental and clinical studies are required to prove the pathoge...
Source: Experimental Neurology - August 17, 2017 Category: Neurology Authors: Mori S, Motohashi N, Takashima R, Kishi M, Nishimune H, Shigemoto K Tags: Exp Neurol Source Type: research

Scavenging reactive oxygen species inhibits status epilepticus-induced neuroinflammation.
Abstract Inflammation has been identified as an important mediator of seizures and epileptogenesis. Understanding the mechanisms underlying seizure-induced neuroinflammation could lead to the development of novel therapies for the epilepsies. Reactive oxygen species (ROS) are recognized as mediators of seizure-induced neuronal damage and are known to increase in models of epilepsies. ROS are also known to contribute to inflammation in several disease states. We hypothesized that ROS are key modulators of neuroinflammation i.e. pro-inflammatory cytokine production and microglial activation in acquired epilepsy. The...
Source: Experimental Neurology - August 16, 2017 Category: Neurology Authors: McElroy PB, Liang LP, Day BJ, Patel M Tags: Exp Neurol Source Type: research

Decreased surface expression of the δ subunit of the GABAA receptor contributes to reduced tonic inhibition in dentate granule cells in a mouse model of fragile X syndrome.
Decreased surface expression of the δ subunit of the GABAA receptor contributes to reduced tonic inhibition in dentate granule cells in a mouse model of fragile X syndrome. Exp Neurol. 2017 Aug 16;: Authors: Zhang N, Peng Z, Tong X, Kerstin Lindemeyer A, Cetina Y, Huang CS, Olsen RW, Otis TS, Houser CR Abstract While numerous changes in the GABA system have been identified in models of Fragile X Syndrome (FXS), alterations in subunits of the GABAA receptors (GABAARs) that mediate tonic inhibition are particularly intriguing. Considering the key role of tonic inhibition in controlling neuronal ex...
Source: Experimental Neurology - August 16, 2017 Category: Neurology Authors: Zhang N, Peng Z, Tong X, Kerstin Lindemeyer A, Cetina Y, Huang CS, Olsen RW, Otis TS, Houser CR Tags: Exp Neurol Source Type: research

Urate promotes SNCA/ α-synuclein clearance via regulating mTOR-dependent macroautophagy.
Urate promotes SNCA/α-synuclein clearance via regulating mTOR-dependent macroautophagy. Exp Neurol. 2017 Aug 15;: Authors: Sheng YL, Chen X, Hou XO, Xin-Yuan, Yuan BS, Yuan YQ, Zhang QL, Cao X, Liu CF, Luo WF, Hu LF Abstract Serum urate levels are reported to be significantly lowered in patients with Parkinson's disease (PD) and inversely correlated to the risk and progression of PD. However, the mechanism by which urate affects PD is poorly understood. Here we showed that treatment with uric acid (UA) resulted in an autophagy activity enhancement in PC12 cells in dose- and time-dependent manner...
Source: Experimental Neurology - August 15, 2017 Category: Neurology Authors: Sheng YL, Chen X, Hou XO, Xin-Yuan, Yuan BS, Yuan YQ, Zhang QL, Cao X, Liu CF, Luo WF, Hu LF Tags: Exp Neurol Source Type: research

Motor cortex and spinal cord neuromodulation promote corticospinal tract axonal outgrowth and motor recovery after cervical contusion spinal cord injury.
In this study, we used a neuromodulatory approach to promote skilled movement recovery and repair of the corticospinal tract (CST) after a moderately severe C4 midline contusion in adult rats. We used bilateral epidural intermittent theta burst (iTBS) electrical stimulation of motor cortex to promote CST axonal sprouting and cathodal trans-spinal direct current stimulation (tsDCS) to enhance spinal cord activation to motor cortex stimulation after injury. We used Finite Element Method (FEM) modeling to direct tsDCS to the cervical enlargement. Combined iTBS-tsDCS was delivered for 30min daily for 10days. We compared the ef...
Source: Experimental Neurology - August 10, 2017 Category: Neurology Authors: Zareen N, Shinozaki M, Ryan D, Alexander H, Amer A, Truong D, Khadka N, Sarkar A, Naeem S, Bikson M, Martin J Tags: Exp Neurol Source Type: research

Insulin prevents aberrant mitochondrial phenotype in sensory neurons of type 1 diabetic rats.
Abstract Diabetic neuropathy affects approximately 50% of diabetic patients. Down-regulation of mitochondrial gene expression and function has been reported in both human tissues and in dorsal root ganglia (DRG) from animal models of type 1 and type 2 diabetes. We hypothesized that loss of direct insulin signaling in diabetes contributes to loss of mitochondrial function in DRG neurons and to development of neuropathy. Sensory neurons obtained from age-matched adult control or streptozotocin (STZ)-induced type 1 diabetic rats were cultured with or without insulin before determining mitochondrial respiration and ex...
Source: Experimental Neurology - August 10, 2017 Category: Neurology Authors: Aghanoori MR, Smith DR, Chowdhury SR, Sabbir MG, Calcutt NA, Fernyhough P Tags: Exp Neurol Source Type: research

Traumatic brain injuries during development disrupt dopaminergic signaling.
Abstract Traumatic brain injuries (TBI) sustained during peri-adolescent development produce lasting neuro-behavioral changes that render individuals at an increased risk for developing substance abuse disorders. Experimental and clinical evidence of a prolonged period of hypodopaminergia after TBI have been well documented, but the effect of juvenile TBI on dopaminergic dysfunction and its relationship with substance abuse have not been investigated. In order to determine the effect of juvenile brain injury on dopaminergic signaling, female mice were injured at 21days of age and then beginning seven weeks later w...
Source: Experimental Neurology - August 9, 2017 Category: Neurology Authors: Karelina K, Gaier KR, Weil ZM Tags: Exp Neurol Source Type: research

Corrigendum to "Sealing frequency of B104 cells declines exponentially with decreasing transection distance from the axon hillock" [Exp. Neurol. 279 (2016) 149-158].
Corrigendum to "Sealing frequency of B104 cells declines exponentially with decreasing transection distance from the axon hillock" [Exp. Neurol. 279 (2016) 149-158]. Exp Neurol. 2017 Aug 09;: Authors: McGill CH, Bhupanapadu Sunkesula SR, Poon AD, Mikesh M, Bittner GD PMID: 28802980 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - August 9, 2017 Category: Neurology Authors: McGill CH, Bhupanapadu Sunkesula SR, Poon AD, Mikesh M, Bittner GD Tags: Exp Neurol Source Type: research

HSPB1 mutations causing hereditary neuropathy in humans disrupt non-cell autonomous protection of motor neurons.
In this study, we examined the non-cell autonomous role of wild type and mutant HSPB1 in an astrocyte-motor neuron co-culture model system of ALS. Astrocyte-specific overexpression of wild type HSPB1 was sufficient to attenuate SOD1(G93A) astrocyte-mediated toxicity in motor neurons, whereas, overexpression of mutHSPB1 failed to ameliorate motor neuron toxicity. Expression of a phosphomimetic HSPB1 mutant in SOD1(G93A) astrocytes also reduced toxicity to motor neurons, suggesting that phosphorylation may contribute to HSPB1 mediated-neuroprotection. These data provide evidence that astrocytic HSPB1 expression may play a ce...
Source: Experimental Neurology - August 7, 2017 Category: Neurology Authors: Heilman PL, Song S, Miranda CJ, Meyer K, Srivastava AK, Knapp A, Wier CG, Kaspar BK, Kolb SJ Tags: Exp Neurol Source Type: research

Calcium, mitochondrial dysfunction and slowing the progression of Parkinson's disease.
Abstract Parkinson's disease is characterized by progressively distributed Lewy pathology and neurodegeneration. The motor symptoms of cPD are unequivocally linked to the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc). Several features of these neurons appear to make them selectively vulnerable to factors thought to cause cPD, like aging, genetic mutations and environmental toxins. Among these features, Ca(2+) entry through Cav1 channels is particularly amenable to pharmacotherapy in early stage cPD patients. This review outlines the linkage between these channels, mitochondrial o...
Source: Experimental Neurology - August 2, 2017 Category: Neurology Authors: James Surmeier D, Halliday GM, Simuni T Tags: Exp Neurol Source Type: research

Advances in nonhuman primate models of autism: Integrating neuroscience and behavior.
Abstract Given the prevalence and societal impact of autism spectrum disorders (ASD), there is an urgent need to develop innovative preventative strategies and treatments to reduce the alarming number of cases and improve core symptoms for afflicted individuals. Translational efforts between clinical and preclinical research are needed to (i) identify and evaluate putative causes of ASD, (ii) determine the underlying neurobiological mechanisms, (iii) develop and test novel therapeutic approaches and (iv) ultimately translate basic research into safe and effective clinical practices. However, modeling a uniquely hu...
Source: Experimental Neurology - July 31, 2017 Category: Neurology Authors: Bauman MD, Schumann CS Tags: Exp Neurol Source Type: research

Experimental animal models of Parkinson's disease: A transition from assessing symptomatology to α-synuclein targeted disease modification.
Experimental animal models of Parkinson's disease: A transition from assessing symptomatology to α-synuclein targeted disease modification. Exp Neurol. 2017 Jul 29;: Authors: Ko WKD, Bezard E Abstract With the understanding that α-synuclein plays a major role in the pathogenesis of Parkinson's disease (PD), novel animal models have been developed for conducting preclinical research in screening novel disease modifying therapies. Advancements in research techniques in α-synuclein targeted disease modification have utilised methods such as viral mediated expression of human α-syn...
Source: Experimental Neurology - July 29, 2017 Category: Neurology Authors: Ko WKD, Bezard E Tags: Exp Neurol Source Type: research

Achieving neuroprotection with LRRK2 kinase inhibitors in Parkinson disease.
Abstract In the translation of discoveries from the laboratory to the clinic, the track record in developing disease-modifying therapies in neurodegenerative disease is poor. A carefully designed development pipeline built from discoveries in both pre-clinical models and patient populations is necessary to optimize the chances for success. Genetic variation in the leucine-rich repeat kinase two gene (LRRK2) is linked to Parkinson disease (PD) susceptibility. Pathogenic mutations, particularly those in the LRRK2 GTPase (Roc) and COR domains, increase LRRK2 kinase activities in cells and tissues. In some PD models, ...
Source: Experimental Neurology - July 29, 2017 Category: Neurology Authors: West AB Tags: Exp Neurol Source Type: research

Survival of iPSC-derived grafts within the striatum of immunodeficient mice: Importance of developmental stage of both transplant and host recipient.
This study demonstrated that increased murine transplant-recipient age (adult vs neonate) resulted in decreased graft survival and volume/rostro-caudal spread after six weeks in vivo, regardless of "age" of the cells transplanted. Importantly, this study implicates that the in vivo setting may provide a better neurogenic niche for iPSC-based modeling as compared to the in vitro setting. Together, these results recapitulate findings from fetal striatal progenitor transplantation studies and further demonstrate the influence of the host environment on cellular survival and maturation. PMID: 28760579 [PubMed - ...
Source: Experimental Neurology - July 28, 2017 Category: Neurology Authors: Tom CM, Younesi S, Meer E, Bresee C, Godoy M, Mattis VB Tags: Exp Neurol Source Type: research

BDNF over-expression induces striatal serotonin fiber sprouting and increases the susceptibility to l-DOPA-induced dyskinesia in 6-OHDA-lesioned rats.
This study suggests that BDNF over-expression, by inducing changes in pre-synaptic serotonin axons trophism, is able to exacerbate maladaptive responses to l-DOPA administration. PMID: 28757258 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - July 27, 2017 Category: Neurology Authors: Tronci E, Napolitano F, Muñoz A, Fidalgo C, Rossi F, Björklund A, Usiello A, Carta M Tags: Exp Neurol Source Type: research

Endotoxemia induces lung-brain coupling and multi-organ injury following cerebral ischemia-reperfusion.
Abstract Post-ischemic neurodegeneration remains the principal cause of mortality following cardiac resuscitation. Recent studies have implicated gastrointestinal ischemia in the sepsis-like response associated with the post-cardiac arrest syndrome (PCAS). However, the extent to which the resulting low-grade endotoxemia present in up to 86% of resuscitated patients affects cerebral ischemia-reperfusion injury has not been investigated. Here we report that a single injection of low-dose lipopolysaccharide (50μg/kg, IP) delivered after global cerebral ischemia (GCI) induces blood-brain barrier permeability, micro...
Source: Experimental Neurology - July 27, 2017 Category: Neurology Authors: Mai N, Prifti L, Rininger A, Bazarian H, Halterman MW Tags: Exp Neurol Source Type: research

ErbB4 protects against neuronal apoptosis via activation of YAP/PIK3CB signaling pathway in a rat model of subarachnoid hemorrhage.
In this study, we explored the neuroprotective effects of ErbB4 and its downstream YAP (yes-associated protein)/PIK3CB signaling pathway in early brain injury after SAH in a rat model using the endovascular perforation method. Rats were neurologically evaluated with the Modified Garcia Scale and beam balance test at 24h and 72h after SAH. An ErbB4 activator Neuregulin 1β1 (Nrg 1β1), ErbB4 siRNA and YAP siRNA were used to explore this pathway. The expression of p-ErbB4 and YAP was significantly increased after SAH. Multiple immunofluorescence labeling experiments demonstrated that ErbB4 is mainly expressed in neur...
Source: Experimental Neurology - July 26, 2017 Category: Neurology Authors: Yan F, Tan X, Wan W, Dixon BJ, Fan R, Enkhjargal B, Li Q, Zhang J, Chen G, Zhang JH Tags: Exp Neurol Source Type: research

Multiple mild traumatic brain injury in the rat produces persistent pathological alterations in the brain.
Abstract Multiple mild traumatic brain injury (mmTBI), in certain cases, produces persistent symptoms. However, the molecular mechanisms underlying these symptoms remain unclear. Here, we demonstrate extended pathological changes in the rat brain following mmTBI. Using the lateral fluid percussion (LFP) technique we exposed adult male Wistar rats to a mild TBI (mTBI) once a week for four weeks and compared them to surgical shams. At 90days following the last TBI or sham procedure the animals were cognitively tested in the Morris Water Maze (MWM), euthanized, and the brains removed for immunohistochemistry. At 90da...
Source: Experimental Neurology - July 26, 2017 Category: Neurology Authors: Brooks DM, Patel SA, Wohlgehagen ED, Semmens E, Pearce A, Sorich EA, Rau TF Tags: Exp Neurol Source Type: research

The differentiated networks related to essential tremor onset and its amplitude modulation after alcohol intake.
Abstract The dysregulation of endogenous rhythms within brain networks have been implicated in a broad range of motor and non-motor pathologies. Essential tremor (ET), classically the purview of a single aberrant pacemaker, has recently become associated with network-level dysfunction across multiple brain regions. Specifically, it has been suggested that motor cortex constitutes an important node in a tremor-generating network involving the cerebellum. Yet the mechanisms by which these regions relate to tremor remain a matter of considerable debate. We sought to discriminate the contributions of cerebral and cere...
Source: Experimental Neurology - July 25, 2017 Category: Neurology Authors: Pedrosa DJ, Nelles C, Brown P, Volz LJ, Pelzer EA, Tittgemeyer M, Brittain JS, Timmermann L Tags: Exp Neurol Source Type: research

Monocyte depletion early after stroke promotes neurogenesis from endogenous neural stem cells in adult brain.
Abstract Ischemic stroke, caused by middle cerebral artery occlusion, leads to long-lasting formation of new striatal neurons from neural stem/progenitor cells (NSPCs) in the subventricular zone (SVZ) of adult rodents. Concomitantly with this neurogenic response, SVZ exhibits activation of resident microglia and infiltrating monocytes. Here we show that depletion of circulating monocytes, using the anti-CCR2 antibody MC-21 during the first week after stroke, enhances striatal neurogenesis at one week post-insult, most likely by increasing short-term survival of the newly formed neuroblasts in the SVZ and adjacent ...
Source: Experimental Neurology - July 23, 2017 Category: Neurology Authors: Laterza C, Wattananit S, Uoshima N, Ge R, Tornero D, Monni E, Lindvall O, Kokaia Z Tags: Exp Neurol Source Type: research

Neuropathic pain in experimental autoimmune neuritis is associated with altered electrophysiological properties of nociceptive DRG neurons.
Abstract Guillain-Barré syndrome (GBS) is an acute, immune-mediated polyradiculoneuropathy characterized by rapidly progressive paresis and sensory disturbances. Moderate to severe and often intractable neuropathic pain is a common symptom of GBS, but its underlying mechanisms are unknown. Pathology of GBS is classically attributed to demyelination of large, myelinated peripheral fibers. However, there is increasing evidence that neuropathic pain in GBS is associated with impaired function of small, unmyelinated, nociceptive fibers. We therefore examined the functional properties of small DRG neurons, the s...
Source: Experimental Neurology - July 19, 2017 Category: Neurology Authors: Taha O, Opitz T, Mueller M, Pitsch J, Becker A, Evert BO, Beck H, Jeub M Tags: Exp Neurol Source Type: research

Activation of RAGE/STAT3 pathway by methylglyoxal contributes to spinal central sensitization and persistent pain induced by bortezomib.
Abstract Bortezomib is a first-line chemotherapeutic drug widely used for multiple myeloma and other nonsolid malignancies. Although bortezomib-induced persistent pain is easily diagnosed in clinic, the pathogenic mechanism remains unclear. Here, we studied this issue with use of a rat model of systemic intraperitoneal administration of bortezomib for consecutive 5days. Consisted with our previous study, we found that bortezomib treatment markedly induced mechanical allodynia in rats. Furthermore, we first found that bortezomib treatment significantly induced the upregulation of methylglyoxal in spinal dorsal horn...
Source: Experimental Neurology - July 18, 2017 Category: Neurology Authors: Wei JY, Liu CC, Ouyang HD, Ma C, Xie MX, Liu M, Lei WL, Ding HH, Wu SL, Xin WJ Tags: Exp Neurol Source Type: research

Altered intrinsic functional connectivity in the latent period of epileptogenesis in a temporal lobe epilepsy model.
In this study, we investigated the alterations in intrinsic rsFC during the latent and chronic periods in a pilocarpine-induced TLE mouse model using intrinsic optical signal imaging (IOSI). This technique can monitor the changes in the local hemoglobin concentration according to neuronal activity and can help investigate large-scale brain intrinsic networks. After seeding on the anatomical regions of interest (ROIs) and calculating the correlation coefficients between each ROI, we established and compared functional correlation matrices and functional connectivity maps during the latent and chronic periods of epilepsy. We...
Source: Experimental Neurology - July 17, 2017 Category: Neurology Authors: Lee H, Jung S, Lee P, Jeong Y Tags: Exp Neurol Source Type: research

EMMPRIN overexpression in SVZ neural progenitor cells increases their migration towards ischemic cortex.
Abstract Stimulation of endogenous neurogenesis and recruitment of neural progenitors from the subventricular zone (SVZ) neurogenic site may represent a useful strategy to improve regeneration in the ischemic cortex. Here, we tested whether transgenic overexpression of extracellular matrix metalloproteinase inducer (EMMPRIN), the regulator of matrix metalloproteinases (MMPs) expression, in endogenous neural progenitor cells (NPCs) in the subventricular zone (SVZ) could increase migration towards ischemic injury. For this purpose, we applied a lentivector-mediated gene transfer system. We found that EMMPRIN-transdu...
Source: Experimental Neurology - July 14, 2017 Category: Neurology Authors: Kanemitsu M, Tsupykov O, Potter G, Boitard M, Salmon P, Zgraggen E, Gascon E, Skibo G, Dayer AG, Kiss JZ Tags: Exp Neurol Source Type: research

Optic nerve regeneration in mammals: Regenerated or spared axons?
Abstract Intraorbital optic nerve crush in rodents is widely used as a model to study axon regeneration in the adult mammalian central nervous system. Recent studies using appropriate genetic manipulations have revealed remarkable abilities of mature retinal ganglion cell (RGC) axons to regenerate after optic nerve injury, with some studies demonstrating that axons can then go on to re-innervate a number of central visual targets with partial functional restoration. However, one confounding factor inherent to optic nerve crush injury is the potential incompleteness of the initial lesion, leaving spared axons that ...
Source: Experimental Neurology - July 14, 2017 Category: Neurology Authors: Fischer D, Harvey AR, Pernet V, Lemmon VP, Park KK Tags: Exp Neurol Source Type: research

Sodium selenate activated Wnt/ β-catenin signaling and repressed amyloid-β formation in a triple transgenic mouse model of Alzheimer's disease.
Sodium selenate activated Wnt/β-catenin signaling and repressed amyloid-β formation in a triple transgenic mouse model of Alzheimer's disease. Exp Neurol. 2017 Jul 12;: Authors: Jin N, Zhu H, Liang X, Huang W, Xie Q, Xiao P, Ni J, Liu Q Abstract Accumulating evidences show that selenium dietary intake is inversely associated with the mortality of Alzheimer's disease (AD). Sodium selenate has been reported to reduce neurofibrillary tangles (NFT) in the tauopathic mouse models, but its effects on the Wnt/β-catenin signaling pathway and APP processing remain unknown during AD formation. In...
Source: Experimental Neurology - July 12, 2017 Category: Neurology Authors: Jin N, Zhu H, Liang X, Huang W, Xie Q, Xiao P, Ni J, Liu Q Tags: Exp Neurol Source Type: research

Critical role of EphA4 in early brain injury after subarachnoid hemorrhage in rat.
Abstract Early brain injury (EBI) is reported as a primary cause of mortality in subarachnoid hemorrhage (SAH) patients. Eph receptor A4 (EphA4) has been associated with blood-brain barrier integrity and pro-apoptosis. We aimed to investigate a role of EphA4 in EBI after SAH. One hundred and seventy-nine male adult Sprague-Dawley rats were randomly divided into sham versus endovascular perforation model of SAH groups. SAH grade, neurological score, Evans blue dye extravasation, brain water content, mortality, Fluoro-Jade staining, immunofluorescence staining, and western blot experiments were performed after SAH. ...
Source: Experimental Neurology - July 8, 2017 Category: Neurology Authors: Fan R, Enkhjargal B, Camara R, Yan F, Gong L, ShengtaoYao, Tang J, Chen Y, Zhang JH Tags: Exp Neurol Source Type: research

Myelination of axons emerging from neural progenitor grafts after spinal cord injury.
Abstract Neural progenitor cells (NPCs) grafted to sites of spinal cord injury (SCI) extend numerous axons over long distances and form new synaptic connections with host neurons. In the present study we examined the myelination of axons emerging from NPC grafts. Rat E14 multipotent NPCs constitutively expressing GFP were grafted into adult C5 spinal cord hemisection lesions; 3months later we examined graft-derived axonal diameter and myelination using transmission electron microscopy. 104 graft-derived axons were characterized. Axon diameter ranged from 0.15 to 1.70μm, and 24% of graft-derived axons were myeli...
Source: Experimental Neurology - July 8, 2017 Category: Neurology Authors: Hunt M, Lu P, Tuszynski MH Tags: Exp Neurol Source Type: research

Comparable impediment of cognitive function in female and male rats subsequent to daily administration of haloperidol after traumatic brain injury.
Abstract Antipsychotic drugs, such as haloperidol (HAL), are prescribed in the clinic to manage traumatic brain injury (TBI)-induced agitation. While preclinical studies have consistently shown that once-daily administration of HAL hinders functional recovery after TBI in male rats, its effects in females are unknown. Hence, the objective of this study was to directly compare neurobehavioral and histological outcomes in both sexes to determine whether the reported deleterious effects of HAL extend to females. Anesthetized adult female and male rats received either a controlled cortical impact (CCI) or sham injury ...
Source: Experimental Neurology - July 8, 2017 Category: Neurology Authors: Free KE, Greene AM, Bondi CO, Lajud N, de la Tremblaye PB, Kline AE Tags: Exp Neurol Source Type: research

Beyond infection - Maternal immune activation by environmental factors, microglial development, and relevance for autism spectrum disorders.
Abstract Immune molecules such as cytokines and chemokines and the cells that produce them within the brain, notably microglia, are critical for normal brain development. This recognition has in recent years led to the working hypothesis that inflammatory events during pregnancy, e.g. in response to infection, may disrupt the normal expression of immune molecules during critical stages of neural development and thereby contribute to the risk for neurodevelopmental disorders such as autism spectrum disorder (ASD). This hypothesis has in large part been shepherded by the work of Dr. Paul Patterson and colleagues, wh...
Source: Experimental Neurology - July 8, 2017 Category: Neurology Authors: Bilbo SD, Block CL, Bolton JL, Hanamsagar R, Tran PK Tags: Exp Neurol Source Type: research

Age-related accumulation of phosphorylated mitofusin 2 protein in retinal ganglion cells correlates with glaucoma progression.
We examined the correlation between bioenergetics and axonal transport with mitochondrial mutation frequency and post-translational modifications of mitofusin 2 (Mfn2) in RGCs during glaucoma progression. No increase in the frequency of mtDNA mutations was detected, but we observed significant shifts in mitochondrial protein species. Mfn2 is a fusion protein that functions in mitochondrial biogenesis, maintenance, and mitochondrial transport. We demonstrate that Mfn2 accumulates selectively in RGCs during glaucomatous degeneration, that two novel states of Mfn2 exist in retina and ON, and identify a phosphorylated form tha...
Source: Experimental Neurology - July 3, 2017 Category: Neurology Authors: Nivison MP, Ericson NG, Green VM, Bielas JH, Campbell JS, Horner PJ Tags: Exp Neurol Source Type: research

Macrophage migration inhibitory factor: A multifaceted cytokine implicated in multiple neurological diseases.
Abstract Macrophage migration inhibitory factor (MIF) is a conserved cytokine found as a homotrimer protein. It is found in a wide spectrum of cell types in the body including neuronal and non-neuronal cells. MIF is implicated in several biological processes; chemo-attraction, cytokine activity, and receptor binding, among other functions. More recently, a chaperone-like activity has been added to its repertoire. In this review, we focus on the implication of MIF in the central nervous system and peripheries, its role in neurological disorders, and the mechanisms by which MIF is regulated. Numerous studies have as...
Source: Experimental Neurology - July 2, 2017 Category: Neurology Authors: Leyton-Jaimes MF, Kahn J, Israelson A Tags: Exp Neurol Source Type: research

Evidence that activation of P2X7R does not exacerbate neuronal death after optic nerve transection and focal cerebral ischemia in mice.
Abstract Conflicting data in the literature about the function of P2X7R in survival following ischemia necessitates the conductance of in-depth studies. To investigate the impacts of activation vs inhibition of the receptor on neuronal survival as well as the downstream signaling cascades, in addition to optic nerve transection (ONT), 30min and 90min of middle cerebral artery occlusion (MCAo) models were performed in mice. Intracellular calcium levels were assessed in primary cortical neuron cultures. Here, we show that P2X7R antagonist Brilliant Blue G (BBG) decreased DNA fragmentation, infarct volume, brain swel...
Source: Experimental Neurology - June 29, 2017 Category: Neurology Authors: Caglayan B, Caglayan AB, Beker MC, Yalcin E, Beker M, Kelestemur T, Sertel E, Ozturk G, Kilic U, Sahin F, Kilic E Tags: Exp Neurol Source Type: research

Transient receptor potential melastatin 2 channels (TRPM2) mediate neonatal hypoxic-ischemic brain injury in mice.
We report that the infarct volumes were significantly smaller and behavioral outcomes were improved in both TRPM2(+/-) and TRPM2(-/-) mice compared to that of wildtype mice. Next, we found that TRPM2-null mice showed reduced dephosphorylation of GSK-3β following hypoxic ischemic injury unlike sham mice. TRPM2(+/-) and TRPM2(-/-) mice also had reduced activation of astrocytes and microglia in ipsilateral hemispheres, compared to wildtype mice. These findings suggest that TRPM2 channels play an essential role in mediating hypoxic-ischemic brain injury in neonatal mice. Genetically eliminating TRPM2 channels can provide ...
Source: Experimental Neurology - June 28, 2017 Category: Neurology Authors: Huang S, Turlova E, Li F, Bao MH, Szeto V, Wong R, Abussaud A, Wang H, Zhu S, Gao X, Mori Y, Feng ZP, Sun HS Tags: Exp Neurol Source Type: research

Sociability impairments in Genetic Absence Epilepsy Rats from Strasbourg: Reversal by the T-type calcium channel antagonist Z944.
Abstract Childhood absence epilepsy (CAE) is associated with interictal co-morbid symptoms including abnormalities in social behaviour. Genetic Absence Epilepsy Rats from Strasbourg (GAERS) is a model of CAE that exhibits physiological and behavioural alterations characteristic of the human disorder. However, it is unknown if GAERS display the social deficits often observed in CAE. Sociability in rodents is thought to be mediated by neurological circuits densely populated with T-type calcium channels and GAERS contain a missense mutation in the Cav3.2 T-type calcium channel gene. Thus, the objective of this study ...
Source: Experimental Neurology - June 25, 2017 Category: Neurology Authors: Henbid MT, Marks WN, Collins MJ, Cain SM, Snutch TP, Howland JG Tags: Exp Neurol Source Type: research

Injury-induced gp130 cytokine signaling in peripheral ganglia is reduced in diabetes mellitus.
Abstract Neuropathy is a major diabetic complication. While the mechanism of this neuropathy is not well-understood, it is believed to result in part from deficient nerve regeneration. Work from our laboratory established that gp130 family of cytokines are induced in animals after axonal injury and are involved in the induction of regeneration-associated genes (RAGs) and in the conditioning lesion response. Here, we examine whether a reduction of cytokine signaling occurs in diabetes. Streptozotocin (STZ) was used to destroy pancreatic β cells, leading to chronic hyperglycemia. Mice were injected with either ...
Source: Experimental Neurology - June 20, 2017 Category: Neurology Authors: Niemi JP, Filous AR, DeFrancesco A, Lindborg JA, Malhotra NA, Wilson GN, Zhou B, Crish SD, Zigmond RE Tags: Exp Neurol Source Type: research

Intranasal cotinine improves memory, and reduces depressive-like behavior, and GFAP+ cells loss induced by restraint stress in mice.
Abstract Posttraumatic stress disorder (PTSD), chronic psychological stress, and major depressive disorder have been found to be associated with a significant decrease in glial fibrillary acidic protein (GFAP) immunoreactivity in the hippocampus of rodents. Cotinine is an alkaloid that prevents memory impairment, depressive-like behavior and synaptic loss when co-administered during restraint stress, a model of PTSD and stress-induced depression, in mice. Here, we investigated the effects of post-treatment with intranasal cotinine on depressive- and anxiety-like behaviors, visual recognition memory as well as the ...
Source: Experimental Neurology - June 15, 2017 Category: Neurology Authors: Perez-Urrutia N, Mendoza C, Alvarez-Ricartes N, Oliveros-Matus P, Echeverria F, Grizzell JA, Barreto GE, Iarkov A, Echeverria V Tags: Exp Neurol Source Type: research

Low intensity rTMS has sex-dependent effects on the local response of glia following a penetrating cortical stab injury.
Abstract Repetitive transcranial magnetic stimulation (rTMS), a non-invasive form of brain stimulation, has shown experimental and clinical efficacy in a range of neuromodulatory models, even when delivered at low intensity (i.e. subthreshold for action potential generation). After central nervous system (CNS) injury, studies suggest that reactive astrocytes and microglia can have detrimental but also beneficial effects; thus modulating glial activity, for example through application of rTMS, could potentially be a useful therapeutic tool following neurotrauma. Immunohistochemistry was used to measure the effect o...
Source: Experimental Neurology - June 14, 2017 Category: Neurology Authors: Clarke D, Penrose MA, Harvey AR, Rodger J, Bates KA Tags: Exp Neurol Source Type: research

Clinical approaches to the development of a neuroprotective therapy for PD.
Abstract The development of a neuroprotective or disease-modifying therapy is the major unmet need in the management of Parkinson's Disease (PD) and the goal of much clinical and scientific research. However, despite enormous efforts and expense, no disease-modifying therapy for PD has been approved to date. Historically attempts to define such a therapy have been limited by confounding symptomatic/pharmacologic effects of the study intervention and the lack of a clear and well-defined regulatory and clinical development pathway that leads to a disease-modifying indication. Further, the costs of As a consequence, ...
Source: Experimental Neurology - June 13, 2017 Category: Neurology Authors: Olanow CW, Kieburtz K, Katz R Tags: Exp Neurol Source Type: research

Targeting urate to reduce oxidative stress in Parkinson disease.
Abstract Oxidative stress has been implicated as a core contributor to the initiation and progression of multiple neurological diseases. Genetic and environmental factors can produce oxidative stress through mitochondrial dysfunction leading to the degeneration of dopaminergic and other neurons underlying Parkinson disease (PD). Although clinical trials of antioxidants have thus far failed to demonstrate slowed progression of PD, oxidative stress remains a compelling target. Rather than prompting abandonment of antioxidant strategies, these failures have raised the bar for justifying drug and dosing selections and...
Source: Experimental Neurology - June 13, 2017 Category: Neurology Authors: Crotty GF, Ascherio A, Schwarzschild MA Tags: Exp Neurol Source Type: research

Overexpression of eIF4F components in meningiomas and suppression of meningioma cell growth by inhibiting translation initiation.
Abstract Meningiomas frequently display activation of the PI3K/AKT/mTOR pathway, leading to elevated levels of phospho-4E binding proteins, which enhances protein synthesis; however, it is not known whether inhibition of protein translation is an effective treatment option for meningiomas. We found that human meningiomas expressed high levels of the three components of the eukaryotic initiation factor 4F (eIF4F) translation initiation complex, eIF4A, eIF4E, and eIF4G. The expression of eIF4A and eIF4E was important in sustaining the growth of NF2-deficient benign meningioma Ben-Men-1 cells, as shRNA-mediated knock...
Source: Experimental Neurology - June 10, 2017 Category: Neurology Authors: Oblinger JL, Burns SS, Huang J, Pan L, Ren Y, Shen R, Douglas Kinghorn A, Bradley Welling D, Chang LS Tags: Exp Neurol Source Type: research

CNS disease diminishes the therapeutic functionality of bone marrow mesenchymal stem cells.
Abstract Mesenchymal stem cells (MSCs) have emerged as a potentially powerful cellular therapy for autoimmune diseases including multiple sclerosis (MS). Based on their success in treating animal models of MS like experimental autoimmune encephalomyelitis (EAE), MSCs have moved rapidly into clinical trials for MS. The majority of these trials use autologous MSCs derived from MS patients, although it remains unclear how CNS disease may affect these cells. Here, we report that bone marrow MSCs derived from EAE mice lack therapeutic efficacy compared to naïve MSCs in their ability to ameliorate EAE. Treatment wi...
Source: Experimental Neurology - June 9, 2017 Category: Neurology Authors: Sargent A, Bai L, Shano G, Karl M, Garrison E, Ranasinghe L, Planchon SM, Cohen J, Miller RH Tags: Exp Neurol Source Type: research

The interaction between alpha 7 nicotinic acetylcholine receptor and nuclear peroxisome proliferator-activated receptor- α represents a new antinociceptive signaling pathway in mice.
The interaction between alpha 7 nicotinic acetylcholine receptor and nuclear peroxisome proliferator-activated receptor-α represents a new antinociceptive signaling pathway in mice. Exp Neurol. 2017 Jun 09;: Authors: Donvito G, Bagdas D, Toma W, Rahimpour E, Jackson A, Meade JA, AlSharari S, Kulkarni AR, Ivy Carroll F, Lichtman AH, Papke RL, Thakur GA, Imad Damaj M Abstract Recently, α7 nicotinic acetylcholine receptors (nAChRs), primarily activated by binding of orthosteric agonists, represent a target for anti-inflammatory and analgesic drug development. These receptors may also be modul...
Source: Experimental Neurology - June 9, 2017 Category: Neurology Authors: Donvito G, Bagdas D, Toma W, Rahimpour E, Jackson A, Meade JA, AlSharari S, Kulkarni AR, Ivy Carroll F, Lichtman AH, Papke RL, Thakur GA, Imad Damaj M Tags: Exp Neurol Source Type: research