Spectral signatures of L-DOPA-induced dyskinesia depend on L-DOPA dose and are suppressed by ketamine
Exp Neurol. 2021 Mar 1:113670. doi: 10.1016/j.expneurol.2021.113670. Online ahead of print.ABSTRACTL-DOPA-induced dyskinesias (LID) are debilitating motor symptoms of dopamine-replacement therapy for Parkinson's disease (PD) that emerge after years of L-DOPA treatment. While there is an abundance of research into the cellular and synaptic origins of LID, less is known about how LID impacts systems-level circuits and neural synchrony, how synchrony is affected by the dose and duration of L-DOPA exposure, or how potential novel treatments for LID, such as sub-anesthetic ketamine, alter this activity. Sub-anesthetic ketamine ...
Source: Experimental Neurology - March 4, 2021 Category: Neurology Authors: Tony Ye Mitchell J Bartlett Scott J Sherman Torsten Falk Stephen L Cowen Source Type: research

Enoxaparin promotes functional recovery after spinal cord injury by antagonizing PTPR σ
In this study, we demonstrated that enoxaparin, a globally approved anticoagulant consisting of heparin oligosaccharides with an average molecular weight of 45 kDa, induced clustering and inactivated PTPRσ in vitro. Enoxaparin induced PTPRσ clustering, and counteracted PTPRσ-mediated dephosphorylation of cortactin, which was shown to be important for inhibition of axonal regeneration. Systemic administration of enoxaparin promoted anatomical recovery after both optic nerve and spinal cord injuries in rats at clinically tolerated doses. Moreover, enoxaparin promoted recovery of motor function without obvio...
Source: Experimental Neurology - March 4, 2021 Category: Neurology Authors: Sadayuki Ito Tomoya Ozaki Masayoshi Morozumi Shiro Imagama Kenji Kadomatsu Kazuma Sakamoto Source Type: research

Prolonged acute intermittent hypoxia improves forelimb reach-to-grasp function in a rat model of chronic cervical spinal cord injury
Exp Neurol. 2021 Feb 27:113672. doi: 10.1016/j.expneurol.2021.113672. Online ahead of print.ABSTRACTRepetitive acute intermittent hypoxia (AIH - brief, episodes of low inspired oxygen) elicits spinal motor plasticity, resulting in sustained improvements of respiratory and non-respiratory motor function in both animal models and humans with chronic spinal cord injury (SCI). We previously demonstrated that 7 days of AIH combined with task-specific training improves performance on a skilled locomotor task for at least 3 weeks post-treatment in rats with incomplete SCI. Here we investigated the effect of repetitive AIH adminis...
Source: Experimental Neurology - March 2, 2021 Category: Neurology Authors: Breanna M Arnold Behzad M Toosi Sally Caine Gordon S Mitchell Gillian D Muir Source Type: research

Prolonged acute intermittent hypoxia improves forelimb reach-to-grasp function in a rat model of chronic cervical spinal cord injury
Exp Neurol. 2021 Feb 27:113672. doi: 10.1016/j.expneurol.2021.113672. Online ahead of print.ABSTRACTRepetitive acute intermittent hypoxia (AIH - brief, episodes of low inspired oxygen) elicits spinal motor plasticity, resulting in sustained improvements of respiratory and non-respiratory motor function in both animal models and humans with chronic spinal cord injury (SCI). We previously demonstrated that 7 days of AIH combined with task-specific training improves performance on a skilled locomotor task for at least 3 weeks post-treatment in rats with incomplete SCI. Here we investigated the effect of repetitive AIH adminis...
Source: Experimental Neurology - March 2, 2021 Category: Neurology Authors: Breanna M Arnold Behzad M Toosi Sally Caine Gordon S Mitchell Gillian D Muir Source Type: research

Prolonged acute intermittent hypoxia improves forelimb reach-to-grasp function in a rat model of chronic cervical spinal cord injury
Exp Neurol. 2021 Feb 27:113672. doi: 10.1016/j.expneurol.2021.113672. Online ahead of print.ABSTRACTRepetitive acute intermittent hypoxia (AIH - brief, episodes of low inspired oxygen) elicits spinal motor plasticity, resulting in sustained improvements of respiratory and non-respiratory motor function in both animal models and humans with chronic spinal cord injury (SCI). We previously demonstrated that 7 days of AIH combined with task-specific training improves performance on a skilled locomotor task for at least 3 weeks post-treatment in rats with incomplete SCI. Here we investigated the effect of repetitive AIH adminis...
Source: Experimental Neurology - March 2, 2021 Category: Neurology Authors: Breanna M Arnold Behzad M Toosi Sally Caine Gordon S Mitchell Gillian D Muir Source Type: research

Delivery of chondroitinase by canine mucosal olfactory ensheathing cells alongside rehabilitation enhances recovery after spinal cord injury
Exp Neurol. 2021 Feb 26:113660. doi: 10.1016/j.expneurol.2021.113660. Online ahead of print.ABSTRACTSpinal cord injury (SCI) can cause chronic paralysis and incontinence and remains a major worldwide healthcare burden, with no regenerative treatment clinically available. Intraspinal transplantation of olfactory ensheathing cells (OECs) and injection of chondroitinase ABC (chABC) are both promising therapies but limited and unpredictable responses are seen, particularly in canine clinical trials. Sustained delivery of chABC presents a challenge due to its thermal instability; we hypothesised that transplantation of canine o...
Source: Experimental Neurology - March 1, 2021 Category: Neurology Authors: Jon Prager Daisuke Ito Darren R Carwardine Prince Jiju Divya M Chari Nicolas Granger Liang-Fong Wong Source Type: research

Daily acute intermittent hypoxia combined with walking practice enhances walking performance but not intralimb motor coordination in persons with chronic incomplete spinal cord injury
CONCLUSIONS: Consistent with prior studies, daily AIH + WALK triggered improvements in walking speed and endurance that persisted for weeks after treatment. Greatest improvements in speed occurred in persons who used bilateral walking aids. No change in EV and ACC may suggest that intralimb motor coordination was not a significant gait training priority during daily AIH + WALK.PMID:33647273 | DOI:10.1016/j.expneurol.2021.113669 (Source: Experimental Neurology)
Source: Experimental Neurology - March 1, 2021 Category: Neurology Authors: Andrew Q Tan Won Joon Sohn Avantika Naidu Randy D Trumbower Source Type: research

Integrin-dependent microgliosis mediates ketamine-induced neuronal apoptosis during postnatal rat retinal development
CONCLUSIONS: The upregulation of integrin β1 receptors in the microglia acts as a signaling molecule, triggering microgliosis to aggravate ketamine-induced neuronal apoptosis via the release of TNF-α and IL-1β in the early developing rat retina.PMID:33640375 | DOI:10.1016/j.expneurol.2021.113659 (Source: Experimental Neurology)
Source: Experimental Neurology - February 28, 2021 Category: Neurology Authors: Kan Zhang Lei Wu Kana Lin Mazhong Zhang Weiguang Li Xiaoping Tong Jijian Zheng Source Type: research

Integrin-dependent microgliosis mediates ketamine-induced neuronal apoptosis during postnatal rat retinal development
CONCLUSIONS: The upregulation of integrin β1 receptors in the microglia acts as a signaling molecule, triggering microgliosis to aggravate ketamine-induced neuronal apoptosis via the release of TNF-α and IL-1β in the early developing rat retina.PMID:33640375 | DOI:10.1016/j.expneurol.2021.113659 (Source: Experimental Neurology)
Source: Experimental Neurology - February 28, 2021 Category: Neurology Authors: Kan Zhang Lei Wu Kana Lin Mazhong Zhang Weiguang Li Xiaoping Tong Jijian Zheng Source Type: research

PPM1F in hippocampal dentate gyrus regulates the depression-related behaviors by modulating neuronal excitability
Exp Neurol. 2021 Feb 24:113657. doi: 10.1016/j.expneurol.2021.113657. Online ahead of print.ABSTRACTMajor depressive disorder (MDD) is a common, serious, debilitating mental illness. Protein phosphatase Mg2+/Mn2+-dependent 1F (PPM1F), a serine/threonine phosphatase, has been reported to have multiple biological and cellular functions. However, the effects of PPM1F and its neuronal substrates on depressive behaviors remain largely unknown. Here, we show that PPM1F is widely distributed in the hippocampus, and chronic unpredictable stress (CUS) can induce increased expression of PPM1F in the hippocampus, which was correlated...
Source: Experimental Neurology - February 27, 2021 Category: Neurology Authors: Liu Jing Fantao Meng Wentao Wang Minghu Cui Min Wu Shujun Jiang Juanjuan Dai Haifeng Lian Qiongyu Li Zhicheng Xu Yameng Wang Jingyan Zhang Chen Li Source Type: research

Restoring both continence and micturition after chronic spinal cord injury by pudendal neuromodulation
This study reports a novel idea to restore both continence and micturition after SCI by an implantable pudendal nerve stimulator (PNS). The PNS was surgically implanted in four cats with complete SCI at T9-T10 spinal level and tested weekly for 13-14 weeks under awake conditions. These chronic SCI cats consistently exhibited large residual bladder volumes (average 40-50 ml) due to their inability to void efficiently, while urine leakage also occurred frequently. The PNS which consisted of stimulating the pudendal nerve at 20-30 Hz to trigger a spinal reflex bladder contraction and at the same time blocking the pudendal ner...
Source: Experimental Neurology - February 27, 2021 Category: Neurology Authors: Wenbin Guo Katherine Shapiro Zhaoxia Wang Kody Armann Bing Shen Jicheng Wang James R Roppolo William C de Groat Changfeng Tai Source Type: research

Dexamethasone-induced activation of heat shock response ameliorates seizure susceptibility and neuroinflammation in mouse models of Lafora disease
Exp Neurol. 2021 Feb 24:113656. doi: 10.1016/j.expneurol.2021.113656. Online ahead of print.ABSTRACTHeat shock response (HSR) is a conserved cytoprotective pathway controlled by the master transcriptional regulator, the heat shock factor 1 (HSF1), that activates the expression of heat shock proteins (HSPs). HSPs, as chaperones, play essential roles in minimizing stress-induced damages and restoring proteostasis. Therefore, compromised HSR is thought to contribute to neurodegenerative disorders. Lafora disease (LD) is a fatal form of neurodegenerative disorder characterized by the accumulation of abnormal glycogen as Lafora...
Source: Experimental Neurology - February 27, 2021 Category: Neurology Authors: Priyanka Sinha Bhupender Verma Subramaniam Ganesh Source Type: research

PPM1F in hippocampal dentate gyrus regulates the depression-related behaviors by modulating neuronal excitability
Exp Neurol. 2021 Feb 24:113657. doi: 10.1016/j.expneurol.2021.113657. Online ahead of print.ABSTRACTMajor depressive disorder (MDD) is a common, serious, debilitating mental illness. Protein phosphatase Mg2+/Mn2+-dependent 1F (PPM1F), a serine/threonine phosphatase, has been reported to have multiple biological and cellular functions. However, the effects of PPM1F and its neuronal substrates on depressive behaviors remain largely unknown. Here, we show that PPM1F is widely distributed in the hippocampus, and chronic unpredictable stress (CUS) can induce increased expression of PPM1F in the hippocampus, which was correlated...
Source: Experimental Neurology - February 27, 2021 Category: Neurology Authors: Liu Jing Fantao Meng Wentao Wang Minghu Cui Min Wu Shujun Jiang Juanjuan Dai Haifeng Lian Qiongyu Li Zhicheng Xu Yameng Wang Jingyan Zhang Chen Li Source Type: research

Restoring both continence and micturition after chronic spinal cord injury by pudendal neuromodulation
This study reports a novel idea to restore both continence and micturition after SCI by an implantable pudendal nerve stimulator (PNS). The PNS was surgically implanted in four cats with complete SCI at T9-T10 spinal level and tested weekly for 13-14 weeks under awake conditions. These chronic SCI cats consistently exhibited large residual bladder volumes (average 40-50 ml) due to their inability to void efficiently, while urine leakage also occurred frequently. The PNS which consisted of stimulating the pudendal nerve at 20-30 Hz to trigger a spinal reflex bladder contraction and at the same time blocking the pudendal ner...
Source: Experimental Neurology - February 27, 2021 Category: Neurology Authors: Wenbin Guo Katherine Shapiro Zhaoxia Wang Kody Armann Bing Shen Jicheng Wang James R Roppolo William C de Groat Changfeng Tai Source Type: research

Dexamethasone-induced activation of heat shock response ameliorates seizure susceptibility and neuroinflammation in mouse models of Lafora disease
Exp Neurol. 2021 Feb 24:113656. doi: 10.1016/j.expneurol.2021.113656. Online ahead of print.ABSTRACTHeat shock response (HSR) is a conserved cytoprotective pathway controlled by the master transcriptional regulator, the heat shock factor 1 (HSF1), that activates the expression of heat shock proteins (HSPs). HSPs, as chaperones, play essential roles in minimizing stress-induced damages and restoring proteostasis. Therefore, compromised HSR is thought to contribute to neurodegenerative disorders. Lafora disease (LD) is a fatal form of neurodegenerative disorder characterized by the accumulation of abnormal glycogen as Lafora...
Source: Experimental Neurology - February 27, 2021 Category: Neurology Authors: Priyanka Sinha Bhupender Verma Subramaniam Ganesh Source Type: research

A systematic review of neurogenesis in animal models of early brain damage: Implications for cerebral palsy
Exp Neurol. 2021 Feb 22:113643. doi: 10.1016/j.expneurol.2021.113643. Online ahead of print.ABSTRACTBrain damage during early life is the main factor in the development of cerebral palsy (CP), which is one of the leading neurodevelopmental disorders in childhood. Few studies, however, have focused on the mechanisms of cell proliferation, migration, and differentiation in the brain of individuals with CP. We thus conducted a systematic review of preclinical evidence of structural neurogenesis in early brain damage and the underlying mechanisms involved in the pathogenesis of CP. Studies were obtained from Embase, Pubmed, Sc...
Source: Experimental Neurology - February 25, 2021 Category: Neurology Authors: Diego Bulc ão Visco Ana Elisa Toscano Pedro Alberto Romero Ju árez Henrique Jos é Cavalcanti Bezerra Gouveia Omar Guzman-Quevedo Luz Torner Raul Manh ães-de-Castro Source Type: research

A systematic review of neurogenesis in animal models of early brain damage: Implications for cerebral palsy
Exp Neurol. 2021 Feb 22:113643. doi: 10.1016/j.expneurol.2021.113643. Online ahead of print.ABSTRACTBrain damage during early life is the main factor in the development of cerebral palsy (CP), which is one of the leading neurodevelopmental disorders in childhood. Few studies, however, have focused on the mechanisms of cell proliferation, migration, and differentiation in the brain of individuals with CP. We thus conducted a systematic review of preclinical evidence of structural neurogenesis in early brain damage and the underlying mechanisms involved in the pathogenesis of CP. Studies were obtained from Embase, Pubmed, Sc...
Source: Experimental Neurology - February 25, 2021 Category: Neurology Authors: Diego Bulc ão Visco Ana Elisa Toscano Pedro Alberto Romero Ju árez Henrique Jos é Cavalcanti Bezerra Gouveia Omar Guzman-Quevedo Luz Torner Raul Manh ães-de-Castro Source Type: research

The role of complement in brain injury following intracerebral hemorrhage: A review
Exp Neurol. 2021 Feb 19:113654. doi: 10.1016/j.expneurol.2021.113654. Online ahead of print.ABSTRACTIntracerebral hemorrhage (ICH) is a significant cause of death and disability and current treatment is limited to supportive measures to reduce brain edema and secondary hematoma expansion. Current evidence suggests that the complement cascade is activated early after hemorrhage and contributes to brain edema/injury in multiple ways. The aim of this review is to summarize the most recent literature about the role of the complement cascade after ICH. Primary literature demonstrating complement mediated brain edema and neurolo...
Source: Experimental Neurology - February 22, 2021 Category: Neurology Authors: Katherine Holste Fan Xia Hugh J L Garton Shu Wan Ya Hua Richard F Keep Guohua Xi Source Type: research

White matter demyelination predates axonal injury after ischemic stroke in cynomolgus monkeys
In this study, adult male cynomolgus monkeys received surgical middle cerebral artery occlusion (MCAO), and serial magnetic resonance scans to non-invasively assess brain damage. Spontaneous movements were recorded to evaluate post-stroke behavior. The axon and myelin loss, as well as immune cell infiltration were examined using immunohistochemistry. Magnetic resonance imaging revealed cerebral infarcts and white matter injury after MCAO in monkeys, which were confirmed by neurological deficits. Immunostaining of white matter fibers showed substantial demyelination whilst retention of axons in the infarcts 8 days post MCAO...
Source: Experimental Neurology - February 22, 2021 Category: Neurology Authors: Shen Li Jun-Hua Rao Xiao-Yan Lan Xu Li Cheng-Yan Chu Yajie Liang Miroslaw Janowski Hong-Tian Zhang Piotr Walczak Source Type: research

The role of complement in brain injury following intracerebral hemorrhage: A review
Exp Neurol. 2021 Feb 19:113654. doi: 10.1016/j.expneurol.2021.113654. Online ahead of print.ABSTRACTIntracerebral hemorrhage (ICH) is a significant cause of death and disability and current treatment is limited to supportive measures to reduce brain edema and secondary hematoma expansion. Current evidence suggests that the complement cascade is activated early after hemorrhage and contributes to brain edema/injury in multiple ways. The aim of this review is to summarize the most recent literature about the role of the complement cascade after ICH. Primary literature demonstrating complement mediated brain edema and neurolo...
Source: Experimental Neurology - February 22, 2021 Category: Neurology Authors: Katherine Holste Fan Xia Hugh J L Garton Shu Wan Ya Hua Richard F Keep Guohua Xi Source Type: research

White matter demyelination predates axonal injury after ischemic stroke in cynomolgus monkeys
In this study, adult male cynomolgus monkeys received surgical middle cerebral artery occlusion (MCAO), and serial magnetic resonance scans to non-invasively assess brain damage. Spontaneous movements were recorded to evaluate post-stroke behavior. The axon and myelin loss, as well as immune cell infiltration were examined using immunohistochemistry. Magnetic resonance imaging revealed cerebral infarcts and white matter injury after MCAO in monkeys, which were confirmed by neurological deficits. Immunostaining of white matter fibers showed substantial demyelination whilst retention of axons in the infarcts 8 days post MCAO...
Source: Experimental Neurology - February 22, 2021 Category: Neurology Authors: Shen Li Jun-Hua Rao Xiao-Yan Lan Xu Li Cheng-Yan Chu Yajie Liang Miroslaw Janowski Hong-Tian Zhang Piotr Walczak Source Type: research

The role of complement in brain injury following intracerebral hemorrhage: A review
Exp Neurol. 2021 Feb 19:113654. doi: 10.1016/j.expneurol.2021.113654. Online ahead of print.ABSTRACTIntracerebral hemorrhage (ICH) is a significant cause of death and disability and current treatment is limited to supportive measures to reduce brain edema and secondary hematoma expansion. Current evidence suggests that the complement cascade is activated early after hemorrhage and contributes to brain edema/injury in multiple ways. The aim of this review is to summarize the most recent literature about the role of the complement cascade after ICH. Primary literature demonstrating complement mediated brain edema and neurolo...
Source: Experimental Neurology - February 22, 2021 Category: Neurology Authors: Katherine Holste Fan Xia Hugh J L Garton Shu Wan Ya Hua Richard F Keep Guohua Xi Source Type: research

White matter demyelination predates axonal injury after ischemic stroke in cynomolgus monkeys
In this study, adult male cynomolgus monkeys received surgical middle cerebral artery occlusion (MCAO), and serial magnetic resonance scans to non-invasively assess brain damage. Spontaneous movements were recorded to evaluate post-stroke behavior. The axon and myelin loss, as well as immune cell infiltration were examined using immunohistochemistry. Magnetic resonance imaging revealed cerebral infarcts and white matter injury after MCAO in monkeys, which were confirmed by neurological deficits. Immunostaining of white matter fibers showed substantial demyelination whilst retention of axons in the infarcts 8 days post MCAO...
Source: Experimental Neurology - February 22, 2021 Category: Neurology Authors: Shen Li Jun-Hua Rao Xiao-Yan Lan Xu Li Cheng-Yan Chu Yajie Liang Miroslaw Janowski Hong-Tian Zhang Piotr Walczak Source Type: research

Acute treatment with TrkB agonist LM22A-4 confers neuroprotection and preserves myelin integrity in a mouse model of pediatric traumatic brain injury
Exp Neurol. 2021 Feb 17:113652. doi: 10.1016/j.expneurol.2021.113652. Online ahead of print.ABSTRACTYoung children have a high risk of sustaining a traumatic brain injury (TBI), which can have debilitating life-long consequences. Importantly, the young brain shows particular vulnerability to injury, likely attributed to ongoing maturation of the myelinating nervous system at the time of insult. Here, we examined the effect of acute treatment with partial tropomyosin receptor kinase B (TrkB) agonist, LM22A-4, on the pathological and neurobehavioral outcomes after pediatric TBI, with the hypothesis that targeting TrkB would ...
Source: Experimental Neurology - February 20, 2021 Category: Neurology Authors: Jessica L Fletcher Larissa K Dill Rhiannon J Wood Sharon Wang Kate Robertson Simon S Murray Akram Zamani Bridgette D Semple Source Type: research

Chronic intermittent hypoxia alters main olfactory bulb activity and olfaction
Exp Neurol. 2021 Feb 16:113653. doi: 10.1016/j.expneurol.2021.113653. Online ahead of print.ABSTRACTOlfactory dysfunction is commonly observed in patients with obstructive sleep apnea (OSA), which is related to chronic intermittent hypoxia (CIH). OSA patients exhibit alterations in discrimination, identification and odor detection threshold. These olfactory functions strongly rely on neuronal processing within the main olfactory bulb (MOB). However, a direct evaluation of the effects of controlled CIH on olfaction and MOB network activity has not been performed. Here, we used electrophysiological field recordings in vivo t...
Source: Experimental Neurology - February 19, 2021 Category: Neurology Authors: Rebeca Hern ández-Soto Benjam ín Villasana-Salazar Laura Pinedo-Vargas Fernando Pe ña-Ortega Source Type: research

Defining the relative contribution of muscle and Schwann cell denervation on functional recovery after delayed nerve repair
Exp Neurol. 2021 Feb 16:113650. doi: 10.1016/j.expneurol.2021.113650. Online ahead of print.ABSTRACTFunctional recovery following peripheral nerve injury worsens with increasing durations of delay prior to repair. From the time of injury until re-innervation occurs, denervated muscle undergoes progressive atrophy that limits the extent to which motor function can be restored. Similarly, Schwann cells (SC) in the distal nerve lacking axonal interaction progressively lose their capacity to proliferate and support regenerating axons. The relative contributions of these processes to decreased functional recovery is unclear. We...
Source: Experimental Neurology - February 19, 2021 Category: Neurology Authors: Karim A Sarhane Benjamin R Slavin Nicholas Hricz Harsha Malapati Yi-Nan Guo Michael Grzelak Irene Aran Chang Heather Shappell Nicholas von Guionneau Alison L Wong Ruifa Mi Ahmet H öke Sami H Tuffaha Source Type: research

Effect of acute intermittent hypoxia on cortico-diaphragmatic conduction in healthy humans
Exp Neurol. 2021 Feb 16:113651. doi: 10.1016/j.expneurol.2021.113651. Online ahead of print.ABSTRACTAcute intermittent hypoxia (AIH) is a strategy to improve motor output in humans with neuromotor impairment. A single AIH session increases the amplitude of motor evoked potentials (MEP) in a finger muscle (first dorsal interosseous), demonstrating enhanced corticospinal neurotransmission. Since AIH elicits phrenic/diaphragm long-term facilitation (LTF) in rodent models, we tested the hypothesis that AIH augments diaphragm MEPs in humans. Eleven healthy adults (7 males, age = 29 ± 6 years) were tested. Transcranial an...
Source: Experimental Neurology - February 19, 2021 Category: Neurology Authors: Joseph F Welch Raphael R Perim Patrick J Argento Tommy W Sutor Alicia K Vose Jayakrishnan Nair Gordon S Mitchell Emily J Fox Source Type: research

Dietary manipulation of vulnerability to traumatic brain injury-induced neuronal plasma membrane permeability
Exp Neurol. 2021 Feb 15:113649. doi: 10.1016/j.expneurol.2021.113649. Online ahead of print.ABSTRACTTraumatic brain injury (TBI) can produce physical disruptions in the plasma membranes of neurons, referred to as mechanoporation, which lead to increased cell permeability. We suspect that such trauma-induced membrane disruptions may be influenced by the physical properties of the plasma membrane, such as elasticity or rigidity. These membrane properties are influenced by lipid composition, which can be modulated via diet, leading to the intriguing possibility of prophylactically altering diet to confer resiliency to this me...
Source: Experimental Neurology - February 18, 2021 Category: Neurology Authors: Carolyn E Keating Kevin D Browne D Kacy Cullen Source Type: research

Maintenance of protein homeostasis in glia extends lifespan in C. elegans
Exp Neurol. 2021 Feb 15;339:113648. doi: 10.1016/j.expneurol.2021.113648. Online ahead of print.ABSTRACTMounting evidence support that glia play a key role in organismal ageing. However, the mechanisms by which glia impact ageing are not understood. One of the processes that has significant impact on the rate of ageing is the unfolded protein response. The more robust the UPR, the more the organism can counteract the effect of environmental and genetic stressors. However, how decline of cellular UPR translates into organismal ageing and eventual death is not fully understood. Here we discuss recent findings highlighting th...
Source: Experimental Neurology - February 18, 2021 Category: Neurology Authors: Lei Wang Laura Bianchi Source Type: research

Automation of training and testing motor and related tasks in pre-clinical behavioural and rehabilitative neuroscience
We describe the use of common locomotor and non-locomotor tasks used for motor training and testing before and after nervous system injury. This includes a discussion of how these tasks help us to understand the underlying mechanisms of neurological repair and the utility of some tasks for the delivery of rehabilitative training to enhance recovery. We propose two general approaches to automation: automating the physical administration of behavioural tasks (i.e., devices used to facilitate task training, rehabilitative training, and motor testing) and leveraging the use of machine learning in behavior analysis to generate ...
Source: Experimental Neurology - February 18, 2021 Category: Neurology Authors: Kar Men Mah Abel Torres-Esp ín Ben W Hallworth John L Bixby Vance P Lemmon Karim Fouad Keith K Fenrich Source Type: research

Lipoxin A4 regulates microglial M1/M2 polarization after cerebral ischemia-reperfusion injury via the Notch signaling pathway
In this study, clinical features of acute ischemic stroke were simulated using a rat model of model of middle cerebral artery occlusion (MCAO) in vivo and the BV2 microglia oxygen-glucose deprivation/reoxygenation model (OGD/R) in vitro. The protective effects of LXA4 on cerebral ischemia-reperfusion injury were determined using TTC staining, HE staining, and TUNEL staining. The expression of targeted genes was assayed using quantitative real-time PCR (qRT-PCR), immunofluorescence, and western blot to investigated the regulation of LXA4 on microglia polarization after acute ischemic stroke. We found that LXA4 exerted prote...
Source: Experimental Neurology - February 18, 2021 Category: Neurology Authors: Qian-Qian Li Dan-Hua Ding Xin-Yu Wang Yu-Ying Sun Jun Wu Source Type: research

Neuroprotective roles of HAX-1 in ischemic neuronal injury
In this study, the expression and roles of HAX-1 after ischemic stress were investigated using in vivo and in vitro models. The effect of oxidative stress on the regulation of HAX-1 was examined using knockout mice lacking nicotinamide-adenine dinucleotide phosphate oxidase 2 (NOX2), which is a major source of reactive oxygen species (ROS) after cerebral ischemia. Male C57BL/6 J mice were subjected to transient forebrain ischemia induced by 22-min occlusion of the bilateral common carotid arteries, and striatum samples were analyzed. For in vitro ischemic experiments, oxygen and glucose deprivation (OGD) in a rat pheochrom...
Source: Experimental Neurology - February 18, 2021 Category: Neurology Authors: Xin Sui Hideyuki Yoshioka Yuichiro Fukumoto Kazuya Kanemaru Hiroyuki Kinouchi Source Type: research

Increasing O-GlcNAcylation is neuroprotective in young and aged brains after ischemic stroke
In this study, using transient ischemic stroke models, we first demonstrated that neuron-specific overexpression of Xbp1s improved outcome, and pharmacologically boosting O-GlcNAcylation with thiamet-G reversed worse outcome observed in neuron-specific Xbp1 knockout mice. We further showed that thiamet-G treatment improved long-term functional recovery in both young and aged animals after transient ischemic stroke. Mechanistically, using an analytic approach developed here, we discovered that availability of UDP-GlcNAc was compromised in the aged brain, which may constitute a novel mechanism responsible for the impaired O-...
Source: Experimental Neurology - February 18, 2021 Category: Neurology Authors: Zhuoran Wang Xuan Li Ivan Spasojevic Liping Lu Yuntian Shen Xingguang Qu Ulrike Hoffmann David S Warner Wulf Paschen Huaxin Sheng Wei Yang Source Type: research

Acute treatment with TrkB agonist LM22A-4 confers neuroprotection and preserves myelin integrity in a mouse model of pediatric traumatic brain injury.
Abstract Young children have a high risk of sustaining a traumatic brain injury (TBI), which can have debilitating life-long consequences. Importantly, the young brain shows particular vulnerability to injury, likely attributed to ongoing maturation of the myelinating nervous system at the time of insult. Here, we examined the effect of acute treatment with partial tropomyosin receptor kinase B (TrkB) agonist, LM22A-4, on the pathological and neurobehavioral outcomes after pediatric TBI, with the hypothesis that targeting TrkB would minimize tissue damage and support functional recovery. We focused on myelinated t...
Source: Experimental Neurology - February 17, 2021 Category: Neurology Authors: Fletcher JL, Dill LK, Wood RJ, Wang S, Robertson K, Murray SS, Zamani A, Semple BD Tags: Exp Neurol Source Type: research

Chronic intermittent hypoxia alters main olfactory bulb activity and olfaction.
;a-Ortega F Abstract Olfactory dysfunction is commonly observed in patients with obstructive sleep apnea (OSA), which is related to chronic intermittent hypoxia (CIH). OSA patients exhibit alterations in discrimination, identification and odor detection threshold. These olfactory functions strongly rely on neuronal processing within the main olfactory bulb (MOB). However, a direct evaluation of the effects of controlled CIH on olfaction and MOB network activity has not been performed. Here, we used electrophysiological field recordings in vivo to evaluate the effects of 21-day-long CIH on MOB network activity and ...
Source: Experimental Neurology - February 16, 2021 Category: Neurology Authors: Hernández-Soto R, Villasana-Salazar B, Pinedo-Vargas L, Peña-Ortega F Tags: Exp Neurol Source Type: research

Defining the relative contribution of muscle and Schwann cell denervation on functional recovery after delayed nerve repair.
SH Abstract Functional recovery following peripheral nerve injury worsens with increasing durations of delay prior to repair. From the time of injury until re-innervation occurs, denervated muscle undergoes progressive atrophy that limits the extent to which motor function can be restored. Similarly, Schwann cells (SC) in the distal nerve lacking axonal interaction progressively lose their capacity to proliferate and support regenerating axons. The relative contributions of these processes to decreased functional recovery is unclear. We developed a novel rat model to isolate the effects of SC vs. muscle denervati...
Source: Experimental Neurology - February 16, 2021 Category: Neurology Authors: Sarhane KA, Slavin BR, Hricz N, Malapati H, Guo YN, Grzelak M, Chang IA, Shappell H, von Guionneau N, Wong AL, Mi R, Höke A, Tuffaha SH Tags: Exp Neurol Source Type: research

Effect of acute intermittent hypoxia on cortico-diaphragmatic conduction in healthy humans.
Abstract Acute intermittent hypoxia (AIH) is a strategy to improve motor output in humans with neuromotor impairment. A single AIH session increases the amplitude of motor evoked potentials (MEP) in a finger muscle (first dorsal interosseous), demonstrating enhanced corticospinal neurotransmission. Since AIH elicits phrenic/diaphragm long-term facilitation (LTF) in rodent models, we tested the hypothesis that AIH augments diaphragm MEPs in humans. Eleven healthy adults (7 males, age = 29 ± 6 years) were tested. Transcranial and cervical magnetic stimulation were used to induce diaphragm MEPs and c...
Source: Experimental Neurology - February 16, 2021 Category: Neurology Authors: Welch JF, Perim RR, Argento PJ, Sutor TW, Vose AK, Nair J, Mitchell GS, Fox EJ Tags: Exp Neurol Source Type: research

Dietary manipulation of vulnerability to traumatic brain injury-induced neuronal plasma membrane permeability.
Abstract Traumatic brain injury (TBI) can produce physical disruptions in the plasma membranes of neurons, referred to as mechanoporation, which lead to increased cell permeability. We suspect that such trauma-induced membrane disruptions may be influenced by the physical properties of the plasma membrane, such as elasticity or rigidity. These membrane properties are influenced by lipid composition, which can be modulated via diet, leading to the intriguing possibility of prophylactically altering diet to confer resiliency to this mechanism of acute neuronal damage in TBI. In this proof-of-concept study, we used t...
Source: Experimental Neurology - February 15, 2021 Category: Neurology Authors: Keating CE, Browne KD, Cullen DK Tags: Exp Neurol Source Type: research

Maintenance of protein homeostasis in glia extends lifespan in C. elegans.
Abstract Mounting evidence support that glia play a key role in organismal ageing. However, the mechanisms by which glia impact ageing are not understood. One of the processes that has significant impact on the rate of ageing is the unfolded protein response. The more robust the UPR, the more the organism can counteract the effect of environmental and genetic stressors. However, how decline of cellular UPR translates into organismal ageing and eventual death is not fully understood. Here we discuss recent findings highlighting that neuropeptides released by glia act long distance to regulate ageing in C. elegans. ...
Source: Experimental Neurology - February 15, 2021 Category: Neurology Authors: Wang L, Bianchi L Tags: Exp Neurol Source Type: research

Automation of training and testing motor and related tasks in pre-clinical behavioural and rehabilitative neuroscience.
We describe the use of common locomotor and non-locomotor tasks used for motor training and testing before and after nervous system injury. This includes a discussion of how these tasks help us to understand the underlying mechanisms of neurological repair and the utility of some tasks for the delivery of rehabilitative training to enhance recovery. We propose two general approaches to automation: automating the physical administration of behavioural tasks (i.e., devices used to facilitate task training, rehabilitative training, and motor testing) and leveraging the use of machine learning in behavior analysis to generate ...
Source: Experimental Neurology - February 15, 2021 Category: Neurology Authors: Mah KM, Torres-Espín A, Hallworth BW, Bixby JL, Lemmon VP, Fouad K, Fenrich KK Tags: Exp Neurol Source Type: research

Lipoxin A4 regulates microglial M1/M2 polarization after cerebral ischemia-reperfusion injury via the Notch signaling pathway.
In this study, clinical features of acute ischemic stroke were simulated using a rat model of model of middle cerebral artery occlusion (MCAO) in vivo and the BV2 microglia oxygen-glucose deprivation/reoxygenation model (OGD/R) in vitro. The protective effects of LXA4 on cerebral ischemia-reperfusion injury were determined using TTC staining, HE staining, and TUNEL staining. The expression of targeted genes was assayed using quantitative real-time PCR (qRT-PCR), immunofluorescence, and western blot to investigated the regulation of LXA4 on microglia polarization after acute ischemic stroke. We found that LXA4 exerted prote...
Source: Experimental Neurology - February 15, 2021 Category: Neurology Authors: Li QQ, Ding DH, Wang XY, Sun YY, Wu J Tags: Exp Neurol Source Type: research

Neuroprotective roles of HAX-1 in ischemic neuronal injury.
In this study, the expression and roles of HAX-1 after ischemic stress were investigated using in vivo and in vitro models. The effect of oxidative stress on the regulation of HAX-1 was examined using knockout mice lacking nicotinamide-adenine dinucleotide phosphate oxidase 2 (NOX2), which is a major source of reactive oxygen species (ROS) after cerebral ischemia. Male C57BL/6 J mice were subjected to transient forebrain ischemia induced by 22-min occlusion of the bilateral common carotid arteries, and striatum samples were analyzed. For in vitro ischemic experiments, oxygen and glucose deprivation (OGD) in a rat pheo...
Source: Experimental Neurology - February 15, 2021 Category: Neurology Authors: Sui X, Yoshioka H, Fukumoto Y, Kanemaru K, Kinouchi H Tags: Exp Neurol Source Type: research

Increasing O-GlcNAcylation is neuroprotective in young and aged brains after ischemic stroke.
In this study, using transient ischemic stroke models, we first demonstrated that neuron-specific overexpression of Xbp1s improved outcome, and pharmacologically boosting O-GlcNAcylation with thiamet-G reversed worse outcome observed in neuron-specific Xbp1 knockout mice. We further showed that thiamet-G treatment improved long-term functional recovery in both young and aged animals after transient ischemic stroke. Mechanistically, using an analytic approach developed here, we discovered that availability of UDP-GlcNAc was compromised in the aged brain, which may constitute a novel mechanism responsible for the impaired O-...
Source: Experimental Neurology - February 15, 2021 Category: Neurology Authors: Wang Z, Li X, Spasojevic I, Lu L, Shen Y, Qu X, Hoffmann U, Warner DS, Paschen W, Sheng H, Yang W Tags: Exp Neurol Source Type: research

Promotion of corticospinal tract growth by KLF6 requires an injury stimulus and occurs within four weeks of treatment.
Abstract Axons in the corticospinal tract (CST) display a limited capacity for compensatory sprouting after partial spinal injuries, potentially limiting functional recovery. Forced expression of a developmentally expressed transcription factor, Krüppel-like factor 6 (KLF6), enhances axon sprouting by adult CST neurons. Here, using a pyramidotomy model of injury in adult mice, we confirm KLF6's pro-sprouting properties in spared corticospinal tract neurons and show that this effect depends on an injury stimulus. In addition, we probed the time course of KLF6-triggered sprouting of CST axons and demonstrate a ...
Source: Experimental Neurology - February 13, 2021 Category: Neurology Authors: Kramer AA, Olson GM, Chakraborty A, Blackmore MG Tags: Exp Neurol Source Type: research

New psychoactive substances (NPS) and serotonin syndrome onset: A systematic review.
Abstract The use of several new psychoactive substances (NPS) has become very popular and is posing global health risks. Chemically and pharmacologically diverse molecules are constantly emerging and are presenting with a wide range of clinical implications. Serotonin toxicity, and specifically Serotonin Syndrome (SS), might develop as a result of an over-activation of the serotoninergic system caused by several mechanisms resulting in a classic triad of altered mental status, neuromuscular effects, and autonomic hyperactivity. In the present systematic review, we have investigated and summarized the available evi...
Source: Experimental Neurology - February 8, 2021 Category: Neurology Authors: Schifano F, Chiappini S, Miuli A, Corkery JM, Scherbaum N, Napoletano F, Arillotta D, Zangani C, Catalani V, Vento A, Pettorruso M, Martinotti G, di Giannantonio M, Guirguis A Tags: Exp Neurol Source Type: research

The convergence of aversion and reward signals in individual neurons of the mice lateral habenula.
This study investigated whether single neurons in the LHb/VTA respond to both aversion and reward stimuli and how these neurons regulate aversion and reward processing. Using optogenetic combined with multi-channel recording of LHb / VTA neuronal discharge, we found that most single neurons in the LHb/ VTA respond to both aversion and reward stimuli. Interestingly, majority of neurons in LHb were aversion-activated and reward-inhibited neurons, consisting mainly of glutamatergic neurons, while most neurons in VTA were reward-activated and aversion-inhibited neurons, which inhibited by glutamatergic neurons in the LHb. Furt...
Source: Experimental Neurology - February 4, 2021 Category: Neurology Authors: Li J, Fan R, Liu X, Shen X, Liu X, Zhao H Tags: Exp Neurol Source Type: research

Differential effects of the Piezo1 agonist Yoda1 in the trigeminovascular system: An electrophysiological and intravital microscopy study in rats.
Abstract Migraine is associated with the activation and sensitisation of the trigeminovascular system and is often accompanied by mechanical hyperalgesia and allodynia. The mechanisms of mechanotransduction during a migraine attack is yet unknown. We have proposed that the ion channel Piezo1 may be involved, since it is expressed in endothelial cells as well as in trigeminal ganglion neurons, and thus, may contribute to the activation of both the vascular and neuronal component of the trigeminovascular system. We took advantage of extracellular recordings from the trigeminocervical complex - a key relay centre in ...
Source: Experimental Neurology - February 4, 2021 Category: Neurology Authors: Dolgorukova A, Isaeva JE, Verbitskaya E, Lyubashina OA, Giniatullin RА, Sokolov AY Tags: Exp Neurol Source Type: research

SARM1 is required in human derived sensory neurons for injury-induced and neurotoxic axon degeneration.
Abstract Axonal degeneration contributes to the pathogenesis of many neurodegenerative disorders, motivating efforts to dissect the mechanism of pathological axon loss in order to develop therapies for axonal preservation. SARM1 is a particularly attractive therapeutic target, as it is an inducible NAD+ cleaving enzyme that is required for axon loss in multiple mouse models of traumatic and degenerative neurological disease. However, it is essential to establish whether SARM1 triggers axon degeneration in human neurons before proceeding with the development of SARM1-directed therapeutics. Here we combine genome en...
Source: Experimental Neurology - February 3, 2021 Category: Neurology Authors: Chen YH, Sasaki Y, DiAntonio A, Milbrandt J Tags: Exp Neurol Source Type: research

Pattern classification as decision support tool in antipsychotic treatment algorithms.
Abstract Pattern classification aims to establish a new approach in personalized treatment. The scope is to tailor treatment on individual characteristics during all phases of care including prevention, diagnosis, treatment, and clinical outcome. In psychotic disorders, this need results from the fact that a third of patients with psychotic symptoms do not respond to antipsychotic treatment and are described as having treatment-resistant disorders. This, in addition to the high variability of treatment responses among patients, enhances the need of applying advanced classification algorithms to identify antipsycho...
Source: Experimental Neurology - February 3, 2021 Category: Neurology Authors: Korda AI, Andreou C, Borgwardt S Tags: Exp Neurol Source Type: research

Pregnancy swimming prevents early brain mitochondrial dysfunction and causes sex-related long-term neuroprotection following neonatal hypoxia-ischemia in rats.
In conclusion, maternal swimming was able to affect the mitochondrial response to HI in the offspring's brains, preserving its function and preventing cognitive damage in a sex-dependent manner, adding relevant information on maternal exercise neuroprotection and highlighting the importance of mitochondria as a therapeutic target for HI neuropathology. PMID: 33529673 [PubMed - as supplied by publisher] (Source: Experimental Neurology)
Source: Experimental Neurology - January 30, 2021 Category: Neurology Authors: Sanches EF, Dos Santos TM, Odorcyk F, Untertriefallner H, Rezena E, Hoeper E, Avila T, Martini AP, Venturin GT, da Costa JC, Greggio S, Netto CA, Wyse AT Tags: Exp Neurol Source Type: research