Outcomes and clinical implications of intranasal insulin administration to the central nervous system.
Abstract Insulin signaling in the brain plays a critical role in metabolic control and cognitive function. Targeting insulinergic pathways in the central nervous system via peripheral insulin administration is feasible, but associated with systemic effects that necessitate tight supervision or countermeasures. The intranasal route of insulin administration, which largely bypasses the circulation and thereby greatly reduces these obstacles, has now been repeatedly tested in proof-of-concept studies in humans as well as animals. It is routinely used in experimental settings to investigate the impact on eating behavi...
Source: Experimental Neurology - March 14, 2019 Category: Neurology Authors: Santiago JCP, Hallschmid M Tags: Exp Neurol Source Type: research

Nociceptor-dependent locomotor dysfunction after clinically-modeled hindlimb muscle stretching in adult rats with spinal cord injury.
Abstract In the course of investigating how common clinical treatments and adaptive technologies affect recovery after spinal cord injury (SCI), we discovered that a clinically-modeled hindlimb stretching protocol dramatically, but transiently, reduces locomotor function. Nociceptive sensory input is capable of altering motor output at the spinal level, and nociceptive neurons are sensitized after SCI. Here we tested the possibility that the stretch-induced motor deficits required the presence of nociceptors using neonatal capsaicin induced depletion of TRPV1+ nociceptive neurons. Following maturation, animals rec...
Source: Experimental Neurology - March 13, 2019 Category: Neurology Authors: Keller AV, Hainline C, Rees K, Krupp S, Prince D, Wood BD, Shum-Siu A, Burke DA, Petruska JC, Magnuson DSK Tags: Exp Neurol Source Type: research

The emerging role of neutrophils as modifiers of recovery after traumatic injury to the developing brain.
Abstract The innate immune response plays a critical role in traumatic brain injury (TBI), contributing to ongoing pathogenesis and worsening long-term outcomes. Here we focus on neutrophils, one of the "first responders" to TBI. These leukocytes are recruited to the injured brain where they release a host of toxic molecules including free radicals, proteases, and pro-inflammatory cytokines, all of which promote secondary tissue damage. There is mounting evidence that the developing brain is more vulnerable to injury that the adult brain. This vulnerability to greater damage from TBI is, in part, attribu...
Source: Experimental Neurology - March 11, 2019 Category: Neurology Authors: von Leden RE, Parker KN, Bates AA, Noble-Haeusslein LJ, Donovan MH Tags: Exp Neurol Source Type: research

Upregulation of interleukin-6 on Cav3.2 T-type calcium channels in dorsal root ganglion neurons contributes to neuropathic pain in rats with spinal nerve ligation.
Abstract The T-type calcium channels Cav3.2, one of the low voltage-activated (LVA) calcium channels, have been found to play important roles in the neuronal excitability. Recently, we and others have demonstrated that accumulation of Cav3.2 channels in the dorsal root ganglion (DRG) neurons and sensory nerves contributes to neuropathic pain after peripheral nerve injury. In the present study, we aimed to further investigate the regulation of Cav3.2 channels by interleukin-6 (IL-6) in DRG neurons in neuropathic pain rats after spinal nerve ligation (SNL). The results showed that Cav3.2 channel protein expression i...
Source: Experimental Neurology - March 10, 2019 Category: Neurology Authors: Liu Q, Chen W, Fan X, Wang J, Fu S, Cui S, Liao F, Cai J, Wang X, Huang Y, Su L, Zhong L, Yi M, Liu F, Wan Y Tags: Exp Neurol Source Type: research

Brain interrupted: Early life traumatic brain injury and addiction vulnerability.
Abstract Recent reports provide evidence for increased risk of substance use disorders (SUD) among patients with a history of early-life traumatic brain injury (TBI). Preclinical research utilizing animal models of TBI have identified injury-induced inflammation, blood-brain barrier permeability, and changes to synapses and neuronal networks within regions of the brain associated with the perception of reward. Importantly, these reward pathway networks are underdeveloped during childhood and adolescence, and early-life TBI pathology may interrupt ongoing maturation. As such, maladaptive changes induced by juvenile...
Source: Experimental Neurology - March 8, 2019 Category: Neurology Authors: Cannella LA, McGary H, Ramirez SH Tags: Exp Neurol Source Type: research

Calcium imaging approaches in investigation of pain mechanism in the spinal cord.
Abstract The continuous advancement of microscopic imaging techniques combined with the discovery and use of more powerful calcium indicators has made calcium imaging technology much more effective and has increased its use in the study of pain circuitry. Using calcium imaging to study spinal pain mechanisms causes less damage to animals compared to electrophysiological techniques and is also able to observe the firing pattern of spinal neurons and the connections between them on a large scale. These advantages allow any changes in spinal cord circuits caused by pain transmission to be observed more effectively. T...
Source: Experimental Neurology - March 6, 2019 Category: Neurology Authors: Xu Q, Dong X Tags: Exp Neurol Source Type: research

Mechanisms underlying vulnerabilities after repeat mild traumatic brain injuries.
Abstract Traumatic brain injury (TBI) has drawn national attention for its high incidence and mechanistic complexity. The majority of TBI cases are "mild" in nature including concussions and mild TBI (mTBI). Concussions are a distinct form of mTBI where diagnosis is difficult, quantification of the incidence is challenging and there is greater risk for subsequent injuries. While concussions occur in the general population, it has become a hallmark injury consistently observed among adolescent and young adult athletes and the risks for repeat TBI (rTBI) is significant. Clinical and experimental evidence s...
Source: Experimental Neurology - March 6, 2019 Category: Neurology Authors: Greco T, Ferguson L, Giza C, Prins ML Tags: Exp Neurol Source Type: research

Ethanol-induced DNA repair in neural stem cells: Is transforming growth factor β1-dependent.
This study tests the hypothesis that ethanol induces a DNA damage response (DDR) in neural stem cells (NSCs) that promotes excision repair (ER) and this repair is influenced by the growth factor environment. Non-immortalized NSCs treated with fibroblast growth factor 2 or transforming growth factor (TGF) β1 were exposed to ethanol. Ethanol increased total DNA damage, reactive oxygen species, and oxidized DNA bases. TGFβ1 potentiated these toxic effects. Transcriptional analyses of cultured NSCs revealed ethanol-induced increases in transcripts related to the DDR (e.g., Hus1 and p53), base ER (e.g., Mutyh and Nthl...
Source: Experimental Neurology - March 6, 2019 Category: Neurology Authors: Hicks SD, Miller MW Tags: Exp Neurol Source Type: research

Efgartigimod improves muscle weakness in a mouse model for muscle-specific kinase myasthenia gravis.
In conclusion, our study shows that efgartigimod has clear therapeutic potential in MuSK myasthenia gravis and forms an exciting candidate drug for many autoantibody-mediated neurological and other disorders. PMID: 30851266 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - March 5, 2019 Category: Neurology Authors: Huijbers MG, Plomp JJ, van Es IE, Fillié-Grijpma YE, Majidi SK, Ulrichts P, de Haard H, Hofman E, van der Maarel SM, Verschuuren JJ Tags: Exp Neurol Source Type: research

Sex differences in pediatric traumatic brain injury.
Abstract The response of the developing brain to traumatic injury is different from the response of the mature, adult brain. There are critical developmental trajectories in the young brain, whereby injury can lead to long term functional abnormalities. Emerging preclinical and clinical literature supports the presence of significant sex differences in both the response to and the recovery from pediatric traumatic brain injury (TBI). These sex differences are seen at all pediatric ages, including neonates/infants, pre-pubertal children, and adolescents. As importantly, the response to neuroprotective therapies or ...
Source: Experimental Neurology - February 28, 2019 Category: Neurology Authors: Arambula SE, Reinl E, El Demerdash N, McCarthy MM, Robertson CL Tags: Exp Neurol Source Type: research

Central neuropeptide-S treatment improves neurofunctions of 6-OHDA-induced Parkinsonian rats.
MA, Ağar A Abstract Parkinson's disease (PD) is characterized by degeneration of the dopaminergic neurons in substantia nigra (SN). The motor symptoms of PD include tremor, rigidity, bradykinesia and postural impairment. In rodents, central administration of neuropeptide-S (NPS) has been shown to induce locomotor activity, dopamine release and neuronal survival by decreasing lipid peroxidation, additionally, the NPS receptor (NPSR) was detected in SN. Accumulating findings suggest that central NPS may ameliorate the parkinsonian symptoms, however, this has been explored incompletely due to the scarcity of experim...
Source: Experimental Neurology - February 26, 2019 Category: Neurology Authors: Bülbül M, Sinen O, Özkan A, Aslan MA, Ağar A Tags: Exp Neurol Source Type: research

Free d-aspartate triggers NMDA receptor-dependent cell death in primary cortical neurons and perturbs JNK activation, Tau phosphorylation, and protein SUMOylation in the cerebral cortex of mice lacking d-aspartate oxidase activity.
Abstract In mammals, free d-aspartate (D-Asp) is abundant in the embryonic brain, while levels remain very low during adulthood as a result of the postnatal expression and activity of the catabolizing enzyme d-aspartate oxidase (DDO). Previous studies have shown that long-lasting exposure to nonphysiological, higher D-Asp concentrations in Ddo knockout (Ddo-/-) mice elicits a precocious decay of synaptic plasticity and cognitive functions, along with a dramatic age-dependent expression of active caspase 3, associated with increased cell death in different brain regions, including hippocampus, prefrontal cortex, an...
Source: Experimental Neurology - February 25, 2019 Category: Neurology Authors: Nuzzo T, Feligioni M, Cristino L, Pagano I, Marcelli S, Iannuzzi F, Imperatore R, D'Angelo L, Petrella C, Carella M, Pollegioni L, Sacchi S, Punzo D, De Girolamo P, Errico F, Canu N, Usiello A Tags: Exp Neurol Source Type: research

Repetitive closed-head impact model of engineered rotational acceleration (CHIMERA) injury in rats increases impulsivity, decreases dopaminergic innervation in the olfactory tubercle and generates white matter inflammation, tau phosphorylation and degeneration.
Abstract Traumatic brain injury (TBI) affects at least 3 M people annually. In humans, repetitive mild TBI (rmTBI) can lead to increased impulsivity and may be associated with chronic traumatic encephalopathy. To better understand the relationship between repetitive TBI (rTBI), impulsivity and neuropathology, we used CHIMERA (Closed-Head Injury Model of Engineered Rotational Acceleration) to deliver five TBIs to rats, which were continuously assessed for trait impulsivity using the delay discounting task and for neuropathology at endpoint. Compared to sham controls, rats with rTBI displayed progressive impairmen...
Source: Experimental Neurology - February 25, 2019 Category: Neurology Authors: Haar CV, Martens KM, Bashir A, McInnes KA, Cheng WH, Cheung H, Stukas S, Barron C, Ladner T, Welch KA, Cripton PA, Winstanley CA, Wellington CL Tags: Exp Neurol Source Type: research

Dim light at night impairs recovery from global cerebral ischemia.
Abstract Nighttime lighting is one of the great conveniences of modernization; however, there is mounting evidence that inopportune light exposure can disrupt physiological and behavioral functions. Hospital patients may be particularly vulnerable to the consequences of light at night due to their compromised physiological state. Cardiac arrest/cardiopulmonary resuscitation (CA) was used to test the hypothesis in mice that exposure to dim light at night impairs central nervous system (CNS) recovery from a major pathological insult. Mice exposed to dim light at night (5 lx) had higher mortality in the week follow...
Source: Experimental Neurology - February 25, 2019 Category: Neurology Authors: Fonken LK, Bedrosian TA, Zhang N, Weil ZM, DeVries AC, Nelson RJ Tags: Exp Neurol Source Type: research

Caffeine inhibits hypoxia-induced nuclear accumulation in HIF-1 α and promotes neonatal neuronal survival.
Caffeine inhibits hypoxia-induced nuclear accumulation in HIF-1α and promotes neonatal neuronal survival. Exp Neurol. 2019 Feb 26;: Authors: Li HL, Zaghloul N, Ahmed I, Omelchenko A, Firestein BL, Huang H, Collins L Abstract Apnea of prematurity (AOP) defined as cessation of breathing for 15-20 s, is commonly seen in preterm infants. Caffeine is widely used to treat AOP due to its safety and effectiveness. Caffeine releases respiratory arrest by competing with adenosine for binding to adenosine A1 and A2A receptors (A1R and A2AR). Long before its use in treating AOP, caffeine has been used as ...
Source: Experimental Neurology - February 25, 2019 Category: Neurology Authors: Li HL, Zaghloul N, Ahmed I, Omelchenko A, Firestein BL, Huang H, Collins L Tags: Exp Neurol Source Type: research

FGF21 promotes functional recovery after hypoxic-ischemic brain injury in neonatal rats by activating the PI3K/Akt signaling pathway via FGFR1/ β-klotho.
FGF21 promotes functional recovery after hypoxic-ischemic brain injury in neonatal rats by activating the PI3K/Akt signaling pathway via FGFR1/β-klotho. Exp Neurol. 2019 Feb 22;: Authors: Ye L, Wang X, Cai C, Zeng S, Bai J, Guo K, Fang M, Hu J, Liu H, Zhu L, Liu F, Wang D, Hu Y, Pan S, Li X, Lin L, Lin Z Abstract Perinatal asphyxia often results in neonatal cerebral hypoxia-ischemia (HI), which is associated with high mortality and severe long-term neurological deficits in newborns. Currently, there are no effective drugs to mitigate the functional impairments post-HI. Previous studies have shown...
Source: Experimental Neurology - February 22, 2019 Category: Neurology Authors: Ye L, Wang X, Cai C, Zeng S, Bai J, Guo K, Fang M, Hu J, Liu H, Zhu L, Liu F, Wang D, Hu Y, Pan S, Li X, Lin L, Lin Z Tags: Exp Neurol Source Type: research

Membrane transporters in traumatic brain injury: Pathological, pharmacotherapeutic, and developmental implications.
Abstract Membrane transporters regulate the trafficking of endogenous and exogenous molecules across biological barriers and within the neurovascular unit. In traumatic brain injury (TBI), they moderate the dynamic movement of therapeutic drugs and injury mediators among neurons, endothelial cells and glial cells, thereby becoming important determinants of pathogenesis and effective pharmacotherapy after TBI. There are three ways transporters may impact outcomes in TBI. First, transporters likely play a key role in the clearance of injury mediators. Second, genetic association studies suggest transporters may be i...
Source: Experimental Neurology - February 21, 2019 Category: Neurology Authors: Hagos FT, Adams SM, Poloyac SM, Kochanek PM, Horvat CM, Clark RSB, Empey PE Tags: Exp Neurol Source Type: research

Imaging in vivo dynamics of sensory axon responses to CNS injury.
Abstract Axons in the adult mammalian brain and spinal cord fail to regenerate upon lesion. In vivo imaging serves as a tool to investigate the immediate response of axons to injury and how the same injured axons behave over time. Here, we describe the dynamic changes that injured sensory axons undergo and methods of imaging them in vivo. First, we explain how sensory axons in the dorsal column of the adult mouse spinal cord respond to axotomy. Then, we highlight practical considerations for implementing two-photon based in vivo imaging of these axons. Finally, we describe future directions for this technique, inc...
Source: Experimental Neurology - February 19, 2019 Category: Neurology Authors: Schaffran B, Hilton BJ, Bradke F Tags: Exp Neurol Source Type: research

Temporal and age-dependent effects of haptoglobin deletion on intracerebral hemorrhage-induced brain damage and neurobehavioral outcomes.
This study reveals that the presence or absence of Hp exerts important time- and age-dependent influences on ICH outcomes. PMID: 30790555 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - February 18, 2019 Category: Neurology Authors: Leclerc JL, Li C, Jean S, Lampert AS, Amador CL, Diller MA, Tolosano E, Doré S Tags: Exp Neurol Source Type: research

Mitoquinone attenuates blood-brain barrier disruption through Nrf2/PHB2/OPA1 pathway after subarachnoid hemorrhage in rats.
CONCLUSIONS: MitoQ attenuates blood-brain barrier disruption via Nrf2/PHB2/OPA1 pathway after SAH in rats. MitoQ may serve as a potential therapeutic strategy for SAH patients. PMID: 30779914 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - February 16, 2019 Category: Neurology Authors: Zhang T, Xu S, Wu P, Zhou K, Wu L, Xie Z, Xu W, Luo X, Li P, Ocak U, Ocak PE, Travis ZD, Tang J, Shi H, Zhang JH Tags: Exp Neurol Source Type: research

Endogenous multidien rhythm of epilepsy in rats.
Abstract Recent trials of chronic EEG in humans showed that epilepsy is a cyclical disorder of the brain with rhythms at multiple time-scales: circadian, multi-day (multidien) or even seasonal. Here, we analyzed chronic EEG data (>30 days) in male epileptic rats and unraveled not only circadian but also, slower, multidien rhythms of interictal epileptiform activity with periodicity of about 2-3 and 5-7 days. Importantly, seizures were not uniformly distributed over time, but rather clustered at preferential phases of these underlying rhythms, delineating critical circadian times and multidien phase of heigh...
Source: Experimental Neurology - February 15, 2019 Category: Neurology Authors: Baud MO, Ghestem A, Benoliel JJ, Becker C, Bernard C Tags: Exp Neurol Source Type: research

Self-propagating, non-synaptic epileptiform activity propagates by endogenous electric fields.
Abstract It is well documented that synapses play a significant role in the transmission of information between neurons. However, in the absence of synaptic transmission, neural activity has been observed to continue to propagate. Previous studies have shown that propagation of epileptiform activity takes place in the absence of synaptic transmission and gap junctions and is outside the range of ionic diffusion and axonal conduction. Computer simulations indicate that electric field coupling could be responsible for the propagation of neural activity under pathological conditions such as epilepsy. Electric fields ...
Source: Experimental Neurology - February 15, 2019 Category: Neurology Authors: Shivacharan RS, Chiang CC, Zhang M, Gonzalez-Reyes LE, Durand DM Tags: Exp Neurol Source Type: research

Parkinson's disease and pain: Modulation of nociceptive circuitry in a rat model of nigrostriatal lesion.
In this study, we evaluated the nociceptive behavior and the descending analgesia circuitry in a rat model of PD. Three independent experiments were performed to investigate: i) thermal nociceptive behavior; ii) mechanical nociceptive behavior and dopaminergic repositioning; and iii) modulation of the pain control circuitry. The rat model of PD, induced by unilateral striatal 6-hydroxydopamine (6-OHDA), did not interfere with thermal nociceptive responses; however, the mechanical nociceptive threshold was decreased bilaterally compared to that of naive or striatal saline-injected rats. This response was reversed by apomorp...
Source: Experimental Neurology - February 14, 2019 Category: Neurology Authors: Domenici RA, Campos ACP, Maciel ST, Berzuino MB, Hernandes MS, Fonoff ET, Pagano RL Tags: Exp Neurol Source Type: research

Methylphenidate administration reverts attentional inflexibility in adolescent rats submitted to a model of neonatal hypoxia-ischemia: Predictive validity for ADHD study.
Abstract Perinatal complications such as birth asphyxia were associated with a higher risk for Attention-Deficit/Hyperactivity Disorder (ADHD) in humans. Data from a rat model of neonatal hypoxia-ischemia (HI) have revealed inattention, impulsive behavior and dopamine (DA) disturbances in the prefrontal cortex (PFC), confirming the face validity and construct validity for ADHD study. However, the predictive validity (similar therapeutic efficacy of the pharmacological treatment available in the clinic) should be considered. Therefore, we aimed to investigate the effects of methylphenidate (MPH) - the treatment of ...
Source: Experimental Neurology - February 13, 2019 Category: Neurology Authors: Miguel PM, Deniz BF, Confortim HD, Bronauth LP, de Oliveira BC, Alves MB, Silveira PP, Pereira LO Tags: Exp Neurol Source Type: research

Treatment of myotonia congenita with retigabine in mice.
In this study, we found that retigabine greatly reduced the duration of myotonia in vitro. Detailed study of its mechanism of action revealed that retigabine had no effect on any of the traditional measures of muscle excitability such as resting potential, input resistance or the properties of single action potentials. Instead it appears to shorten myotonia by activating K+ current during trains of action potentials. Retigabine also greatly reduced the severity of myotonia in vivo, which was measured using a muscle force transducer. Despite its efficacy in vivo, retigabine did not improve motor performance of mice with myo...
Source: Experimental Neurology - February 7, 2019 Category: Neurology Authors: Dupont CX, Denman KS, Hawash AA, Voss AA, Rich MM Tags: Exp Neurol Source Type: research

Conditioning electrical stimulation promotes functional nerve regeneration.
In this study, we found that CES improved nerve regeneration and reinnervation well beyond that of CCL. Specifically, compared to CCL, CES resulted in greater intraepidermal skin and NMJ reinnervation, and greater physiological and functional recovery including mechanosensation, compound muscle action potential on nerve conduction studies, normalization of gait pattern, and motor performance on the horizontal ladder test. These findings have direct clinical relevance as CES could be delivered at the bedside before scheduled nerve surgery. PMID: 30731076 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - February 4, 2019 Category: Neurology Authors: Senger JL, Chan KM, Macandili H, Chan AWM, Verge VMK, Jones KE, Webber CA Tags: Exp Neurol Source Type: research

Mild blast-related TBI in a mouse model alters amygdalar neurostructure and circuitry.
Abstract 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. In our study, we utilized a mouse model of mild blast-related TBI (bTBI) to investig...
Source: Experimental Neurology - January 31, 2019 Category: Neurology Authors: Ratliff WA, Mervis RF, Citron BA, Schwartz B, Rubovitch V, Schreiber S, Pick CG Tags: Exp Neurol Source Type: research

Chronic treatment with galantamine rescues reversal learning in an attentional set-shifting test after experimental brain trauma.
Abstract 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 ana...
Source: Experimental Neurology - January 31, 2019 Category: Neurology Authors: Njoku I, Radabaugh HL, Nicholas MA, Kutash LA, O'Neil DA, Marshall IP, Cheng JP, Kline AE, Bondi CO Tags: Exp Neurol Source Type: research

GATA-4 regulates neuronal apoptosis after intracerebral hemorrhage via the NF- κB/Bax/Caspase-3 pathway both in vivo and in vitro.
In conclusion, the expression of GATA-4 was increased in the brain of rats after ICH. GATA-4 phosphorylation mediates the function of the protein in ICH-induced SBI. Neuronal apoptosis after ICH was mainly induced by NF-κB activation, which was promoted by GATA-4. PMID: 30710529 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - January 30, 2019 Category: Neurology Authors: Xu H, Cao J, Xu J, Li H, Shen H, Li X, Wang Z, Wu J, Chen G Tags: Exp Neurol Source Type: research

Experimental traumatic brain injury results in estrous cycle disruption, neurobehavioral deficits, and impaired GSK3 β/β-catenin signaling in females.
Experimental traumatic brain injury results in estrous cycle disruption, neurobehavioral deficits, and impaired GSK3β/β-catenin signaling in females. Exp Neurol. 2019 Jan 30;: Authors: Fortress AM, Avcu P, Wagner AK, Dixon CE, Pang KCH Abstract 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...
Source: Experimental Neurology - January 30, 2019 Category: Neurology Authors: Fortress AM, Avcu P, Wagner AK, Dixon CE, Pang KCH Tags: Exp Neurol Source Type: research

Retinoid x receptor modulation protects against ER stress response and rescues glaucoma phenotypes in adult mice.
This study investigated changes in RXR expression in the human and mouse retina under glaucomatous stress conditions and investigated the effect of RXR modulation on the RGCs using pharmacological approaches. RXR protein levels in retina were downregulated in both human glaucoma and experimental RGC injury models while RXR agonist, bexarotene treatment resulted in upregulation of RXR expression particularly in the inner retinal layers. Retinal electrophysiological recordings and histological analysis indicated that inner retinal function and retinal laminar structure were preserved upon treatment with bexarotene. These pro...
Source: Experimental Neurology - January 28, 2019 Category: Neurology Authors: Dheer Y, Chitranshi N, Gupta V, Sharma S, Pushpitha K, Abbasi M, Mirzaei M, You Y, Graham SL, Gupta V Tags: Exp Neurol Source Type: research

Long non-coding RNA AK038897 aggravates cerebral ischemia/reperfusion injury via acting as a ceRNA for miR-26a-5p to target DAPK1.
Abstract 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-...
Source: Experimental Neurology - January 28, 2019 Category: Neurology Authors: Wei R, Zhang L, Hu W, Wu J, Zhang W Tags: Exp Neurol Source Type: research

Brain insulin resistance: A treatment target for cognitive impairment and anhedonia in depression.
The objective of this review is to discuss the relationship between brain insulin resistance and depression, as well as possible disease modifying therapeutic agents targeting insulin signalling. PMID: 30695707 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - January 26, 2019 Category: Neurology Authors: Hamer JA, Testani D, Mansur RB, Lee Y, Subramaniapillai M, McIntyre RS Tags: Exp Neurol Source Type: research

Characterization of leptomeningeal inflammation in rodent experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis.
CONCLUSIONS: LMCE peak intensity in the meninges corresponds to the acute inflammatory phase of EAE-MOG disease progression, and is associated with clinical symptoms and higher inflammatory cell density. PMID: 30684521 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - January 23, 2019 Category: Neurology Authors: Pol S, Schweser F, Bertolino N, Preda M, Sveinsson M, Sudyn M, Babek N, Zivadinov R Tags: Exp Neurol Source Type: research

Opioid receptors inhibit the spinal AMPA receptor Ca2+ permeability that mediates latent pain sensitization.
len S Abstract 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. We found that the intraplantar...
Source: Experimental Neurology - January 17, 2019 Category: Neurology Authors: Taylor BK, Sinha GP, Donahue RR, Grachen CM, Morón JA, Doolen S Tags: Exp Neurol Source Type: research

Aripiprazole and environmental enrichment independently improve functional outcome after cortical impact injury in adult male rats, but their combination does not yield additional benefits.
Abstract Typical antipsychotic drugs (APDs) with D2antagonistic 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 D2and 5-HT1Areceptor 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 intr...
Source: Experimental Neurology - January 16, 2019 Category: Neurology Authors: Besagar S, Radabaugh HL, Bleimeister IH, Meyer EA, Niesman PJ, Cheng JP, Bondi CO, Kline AE Tags: Exp Neurol Source Type: research

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