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Experimental Neurology

Chris X Dupont, Kirsten S Denman, Ahmed A Hawash, Andrew A Voss, Mark M Rich
Patients with myotonia congenita suffer from muscle stiffness caused by muscle hyperexcitability. Although loss-of-function mutations in the ClC-1 muscle chloride channel have been known for 25 years to cause myotonia congenita, this discovery has led to little progress on development of therapy. Currently, treatment is primarily focused on reducing hyperexcitability by blocking Na+ current. However, other approaches such as increasing K+ currents might also be effective. For example, the K+ channel activator retigabine, which opens KCNQ channels, is effective in treating epilepsy because it causes hyperpolarization of the resting membrane potential in neurons...
February 7, 2019: Experimental Neurology
Jenna-Lynn Senger, K Ming Chan, Haecy Macandili, Ashley W M Chan, Valerie M K Verge, Kelvin E Jones, Christine A Webber
Peripheral nerve regeneration following injury is often incomplete, resulting in significant personal and socioeconomic costs. Although a conditioning crush lesion prior to surgical nerve transection and repair greatly promotes nerve regeneration and functional recovery, feasibility and ethical considerations have hindered its clinical applicability. In a recent proof of principle study, we demonstrated that conditioning electrical stimulation (CES) had effects on early nerve regeneration, similar to that seen in conditioning crush lesions (CCL)...
February 4, 2019: Experimental Neurology
Ihuoma Njoku, Hannah L Radabaugh, Melissa A Nicholas, Lindsay A Kutash, Darik A O'Neil, Ian P Marshall, Jeffrey P Cheng, Anthony E Kline, Corina O Bondi
Approximately 10 million new cases of traumatic brain injury (TBI) are reported each year worldwide with many of these injuries resulting in higher order cognitive impairments. Galantamine (GAL), an acetylcholine esterase inhibitor (AChEI) and positive allosteric modulator of nicotinic acetylcholine receptors (nAChRs), has been reported to ameliorate cognitive deficits after clinical TBI. Previously, we demonstrated that controlled cortical impact (CCI) injury to rats resulted in significant executive function impairments as measured by the attentional set-shifting test (AST), a complex cognitive task analogous to the Wisconsin Card Sorting Test (WCST)...
January 31, 2019: Experimental Neurology
Whitney A Ratliff, Ronald F Mervis, Bruce A Citron, Brian Schwartz, Vardit Rubovitch, Shaul Schreiber, Chaim G Pick
Traumatic brain injury (TBI) continues to be a signature injury of our modern conflicts. Due in part to increased use of improvised explosive devices (IEDs), we have seen blast trauma make up a significant portion of TBIs sustained by deployed troops and civilians. In addition to the physical injury, TBI is also a common comorbidity with post-traumatic stress disorder (PTSD). Previous research suggests that PTSD is often associated with increased signaling within the amygdala, leading to feelings of fear and hyperarousal...
January 31, 2019: Experimental Neurology
Ashley M Fortress, Pelin Avcu, Amy K Wagner, C Edward Dixon, Kevin C H Pang
An estimated 2.8 million traumatic brain injuries (TBI) occur within the United States each year. Approximately 40% of new TBI cases are female, however few studies have investigated the effects of TBI on female subjects. In addition to typical neurobehavioral sequelae observed after TBI, such as poor cognition, impaired behavior, and somatic symptoms, women with TBI report amenorrhea or irregular menstrual cycles suggestive of disruptions in the hypothalamic-pituitary-gonadal (HPG) axis. HPG dysfunction following TBI has been linked to poor functional outcome in men and women, but the mechanisms by which this may occur or relate to behavior has not been fully developed or ascertained...
January 30, 2019: Experimental Neurology
Hui Xu, Jie Cao, Jianguo Xu, Haiying Li, Haitao Shen, Xiang Li, Zhong Wang, Jiang Wu, Gang Chen
GATA-binding protein 4 (GATA-4),a member of the GATA family of transcription factors, is expressed in the normal brain and participates in the neural inflammatory response and senescence. However, few studies have investigated whether GATA-4 is involved in the brain damage induced by intracerebral hemorrhage (ICH). The aim of this study was to investigate in vivo and in vitro the role of GATA-4 in ICH-induced secondary brain injury (SBI) and its potential underlying mechanisms. A rat model of ICH was established by autologous blood injection in vivo...
January 30, 2019: Experimental Neurology
Rui Wei, Lin Zhang, Wei Hu, Jie Wu, Wei Zhang
Emerging evidence has suggested a significant role of long non-coding RNAs (lncRNAs) in ischemic stroke by acting as competing endogenous RNAs (ceRNAs) for microRNAs (miRNAs) to regulate certain RNA transcripts. AK038897 is an lncRNA that was reported to be upregulated in rat brains in response to transient focal ischemia. We aimed to investigate the possible regulatory role of AK038897 in ischemic stroke. We detected increased AK038897 and decreased miR-26a-5p levels in mouse brains following middle cerebral artery occlusion/reperfusion (MCAO/R) and in neuro-2A (N2a) neuroblastoma cells following oxygen-glucose deprivation and reoxygenation (OGD/R)...
January 28, 2019: Experimental Neurology
Yogita Dheer, Nitin Chitranshi, Veer Gupta, Samridhi Sharma, Kanishka Pushpitha, Mojdeh Abbasi, Mehdi Mirzaei, Yuyi You, Stuart L Graham, Vivek Gupta
Retinoid X receptors (RXRs) play an important role in transcription, are involved in numerous cellular networks from cell proliferation to lipid metabolism and are essential for normal eye development. RXRs form homo or heterodimers with other nuclear receptors, bind to DNA response elements and regulate several biological processes including neurogenesis. Mounting evidence suggests that RXR activation by selective RXR modulators (sRXRms) may be neuroprotective in the central nervous system. However, their potential neuroprotective role in the retina and specifically in glaucoma remains unexplored...
January 28, 2019: Experimental Neurology
Julia A Hamer, Daniela Testani, Rodrigo B Mansur, Yena Lee, Mehala Subramaniapillai, Roger S McIntyre
Type 2 Diabetes Mellitus (T2DM) and Major Depressive Disorder (MDD) are leading causes of disability worldwide. Indeed, both are costly and burdensome diseases at both individual and socio-economic levels. Notably, there are similar pathophysiological elements, which might explain the overlap in phenotypic symptoms and the high rate of comorbidity. Brain insulin resistance is a shared metabolic abnormality amongst many individuals with T2DM and MDD. Patients with either or both diseases often exhibit disturbances in cognition and mood, as well as the presence of anhedonia-like symptoms...
January 26, 2019: Experimental Neurology
Suyog Pol, Ferdinand Schweser, Nicola Bertolino, Marilena Preda, Michele Sveinsson, Michelle Sudyn, Natan Babek, Robert Zivadinov
BACKGROUND: Leptomeningeal inflammation, as evidenced by leptomeningeal contrast enhancement (LMCE), is associated to cortical pathology in multiple sclerosis. The temporal pattern of LMCE in experimental autoimmune encephalomyelitis (EAE) myelin oligodendrocyte glycoprotein (MOG) is unknown. OBJECTIVE: To investigate LMCE using serial MRI in the EAE model of MS, and its association with clinical disease progression. To characterize the relationship between LMCE and underlying histological correlates...
January 23, 2019: Experimental Neurology
Bradley K Taylor, Ghanshyam P Sinha, Renee R Donahue, Carolyn M Grachen, Jose A Morón, Suzanne Doolen
Acute inflammation induces sensitization of nociceptive neurons and triggers the accumulation of calcium permeable (CP) α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) in the dorsal horn of the spinal cord. This coincides with behavioral signs of acute inflammatory pain, but whether CP-AMPARs contribute to chronic pain remains unclear. To evaluate this question, we first constructed current-voltage (IV) curves of C-fiber stimulus-evoked, AMPAR-mediated EPSCs in lamina II to test for inward rectification, a key characteristic of CP-AMPARs...
January 17, 2019: Experimental Neurology
Sonya Besagar, Hannah L Radabaugh, Isabel H Bleimeister, Elizabeth A Meyer, Peter J Niesman, Jeffrey P Cheng, Corina O Bondi, Anthony E Kline
Typical antipsychotic drugs (APDs) with D2 antagonistic properties impede functional outcome after experimental traumatic brain injury (TBI) and reduce the effectiveness of environmental enrichment (EE). Here we test the hypothesis that aripiprazole (ARIP), an atypical APD with partial D2 and 5-HT1A receptor agonist activities will improve recovery after TBI and when combined with EE will further enhance the benefits. Anesthetized adult male rats received either a controlled cortical impact of moderate severity or sham injury and then were randomly assigned to EE or standard (STD) housing and once daily intraperitoneal injections of ARIP (0...
January 16, 2019: Experimental Neurology
Akram Zamani, Richelle Mychasiuk, Bridgette D Semple
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...
January 14, 2019: Experimental Neurology
Matthias Zielonka, Joris Probst, Matthias Carl, Georg Friedrich Hoffmann, Stefan Kölker, Jürgen Günther Okun
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-ketoglutarate from the tricarboxylic acid (TCA) cycle with consecutive TCA cycle dysfunction, ultimately causing impaired oxidative phosphorylation with ATP shortage, decreased ATP/ADP-ratio and elevated lactate concentrations...
January 14, 2019: Experimental Neurology
Brian V Lien, Mark H Tuszynski, Paul Lu
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...
January 14, 2019: Experimental Neurology
Carla Nasca, Kathleen Watson, Betty Bigio, Thalia Robakis, Alison Myoraku, Tonita Wroolie, Bruce S McEwen, Natalie Rasgon
OBJECTIVE: Insulin resistance (IR) is a metabolic dysfunction often co-morbid with major depressive disorder (MDD). The paths to development of MDD remain largely unspecified, highlighting a need for identification of risk factors. Here, we tested whether specific subscales of childhood trauma as well as family history of type-2 diabetes (Fam-Hx-Dm2) contribute to the development of metabolic dysfunction and severity of depressive symptoms. RESEARCH DESIGN AND METHODS: We used a sample of 45 adults suffering from MDD that was well-characterized for insulin resistance and sensitivity as assessed by measures of fasting plasma glucose (FPG) plasma insulin (FPI) levels, body mass index (BMI), weight, homeostasis model assessment of insulin sensitivity (HOMA), Matsuda index as well as both glucose and insulin responses to oral glucose challenges...
January 10, 2019: Experimental Neurology
Shawn Zheng Kai Tan, Victoria Sheng, Ying-Shing Chan, Lee Wei Lim
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 neuromodulation targets...
January 10, 2019: Experimental Neurology
Angela Melinda A Anthony Jalin, Rong Jin, Min Wang, Guohong Li
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. Mice subjected to controlled cortical impact (CCI) were treated with EPPS (120 mg/kg, orally) immediately after CCI and thereafter once daily for 3 or 7 days...
January 9, 2019: Experimental Neurology
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January 4, 2019: Experimental Neurology
Nadia Oliveira Maruyama, Nathan C Mitchell, Tamara T Truong, Glenn M Toney
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 rostral, middle and caudal planes of the PVN...
December 31, 2018: Experimental Neurology
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