Therapeutic acute intermittent hypoxia: A translational roadmap for spinal cord injury and neuromuscular disease
Exp Neurol. 2021 Oct 9:113891. doi: 10.1016/j.expneurol.2021.113891. Online ahead of print.ABSTRACTWe review progress towards greater mechanistic understanding and clinical translation of a strategy to improve respiratory and non-respiratory motor function in people with neuromuscular disorders, therapeutic acute intermittent hypoxia (tAIH). In 2016 and 2020, workshops to create and update a "road map to clinical translation" were held to help guide future research and development of tAIH to restore movement in people living with chronic, incomplete spinal cord injuries. After briefly discussing the pioneering, n...
Source: Experimental Neurology - October 12, 2021 Category: Neurology Authors: Alicia K Vose Joseph F Welch Jayakrishnan Nair Erica A Dale Emily J Fox Gillian D Muir Randy D Trumbower Gordon S Mitchell Source Type: research

Therapeutic acute intermittent hypoxia: A translational roadmap for spinal cord injury and neuromuscular disease
Exp Neurol. 2021 Oct 9:113891. doi: 10.1016/j.expneurol.2021.113891. Online ahead of print.ABSTRACTWe review progress towards greater mechanistic understanding and clinical translation of a strategy to improve respiratory and non-respiratory motor function in people with neuromuscular disorders, therapeutic acute intermittent hypoxia (tAIH). In 2016 and 2020, workshops to create and update a "road map to clinical translation" were held to help guide future research and development of tAIH to restore movement in people living with chronic, incomplete spinal cord injuries. After briefly discussing the pioneering, n...
Source: Experimental Neurology - October 12, 2021 Category: Neurology Authors: Alicia K Vose Joseph F Welch Jayakrishnan Nair Erica A Dale Emily J Fox Gillian D Muir Randy D Trumbower Gordon S Mitchell Source Type: research

Nonsteroidal anti-inflammatory drug (ketoprofen) delivery differentially impacts phrenic long-term facilitation in rats with motor neuron death induced by intrapleural CTB-SAP injections
Exp Neurol. 2021 Oct 8:113892. doi: 10.1016/j.expneurol.2021.113892. Online ahead of print.ABSTRACTIntrapleural injections of cholera toxin B conjugated to saporin (CTB-SAP) selectively eliminates respiratory (e.g., phrenic) motor neurons, and mimics motor neuron death and respiratory deficits observed in rat models of neuromuscular diseases. Additionally, microglial density increases in the phrenic motor nucleus following CTB-SAP. This CTB-SAP rodent model allows us to study the impact of motor neuron death on the output of surviving phrenic motor neurons, and the underlying mechanisms that contribute to enhancing or cons...
Source: Experimental Neurology - October 11, 2021 Category: Neurology Authors: Lauren F Borkowski Amy N Keilholz Catherine L Smith Kaylie A Canda Nicole L Nichols Source Type: research

Altered trajectory of neurodevelopment associated with fetal growth restriction
Exp Neurol. 2021 Oct 7:113885. doi: 10.1016/j.expneurol.2021.113885. Online ahead of print.ABSTRACTFetal growth restriction (FGR) is principally caused by suboptimal placental function. Poor placental function causes an under supply of nutrients and oxygen to the developing fetus, restricting development of individual organs and overall growth. Estimated fetal weight below the 10th or 3rd percentile with uteroplacental dysfunction, and knowledge regarding the onset of growth restriction (early or late), provide diagnostic criteria for fetuses at greatest risk for adverse outcome. Brain development and function is altered w...
Source: Experimental Neurology - October 10, 2021 Category: Neurology Authors: Ingrid Dudink Petra S H üppi St éphane V Sizonenko Margie Castillo-Melendez Amy E Sutherland Beth J Allison Suzanne L Miller Source Type: research

Altered trajectory of neurodevelopment associated with fetal growth restriction
Exp Neurol. 2021 Oct 7:113885. doi: 10.1016/j.expneurol.2021.113885. Online ahead of print.ABSTRACTFetal growth restriction (FGR) is principally caused by suboptimal placental function. Poor placental function causes an under supply of nutrients and oxygen to the developing fetus, restricting development of individual organs and overall growth. Estimated fetal weight below the 10th or 3rd percentile with uteroplacental dysfunction, and knowledge regarding the onset of growth restriction (early or late), provide diagnostic criteria for fetuses at greatest risk for adverse outcome. Brain development and function is altered w...
Source: Experimental Neurology - October 10, 2021 Category: Neurology Authors: Ingrid Dudink Petra S H üppi St éphane V Sizonenko Margie Castillo-Melendez Amy E Sutherland Beth J Allison Suzanne L Miller Source Type: research

Changes of cerebral network activity after invasive stimulation of the mesencephalic locomotor region in a rat stroke model
Exp Neurol. 2021 Oct 5:113884. doi: 10.1016/j.expneurol.2021.113884. Online ahead of print.ABSTRACTMotor deficits after stroke reflect both, focal lesion and network alterations in brain regions distant from infarction. This remote network dysfunction may be caused by aberrant signals from cortical motor regions travelling via mesencephalic locomotor region (MLR) to other locomotor circuits. A method for modulating disturbed network activity is deep brain stimulation. Recently, we have shown that high frequency stimulation (HFS) of the MLR in rats has restored gait impairment after photothrombotic stroke (PTS). However, it...
Source: Experimental Neurology - October 8, 2021 Category: Neurology Authors: Stefanie D Kr ämer Michael K Schuhmann Fabian Schadt Ina Israel Samuel Samnick Jens Volkmann Felix Fluri Source Type: research

Early movement restriction deteriorates motor function and soleus muscle physiology
Exp Neurol. 2021 Oct 5:113886. doi: 10.1016/j.expneurol.2021.113886. Online ahead of print.ABSTRACTChildren with low physical activity and interactions with environment experience atypical sensorimotor development and maturation leading to anatomical and functional disorganization of the sensorimotor circuitry and also to enduring altered motor function. Previous data have shown that postnatal movement restriction in rats results in locomotor disturbances, functional disorganization and hyperexcitability of the hind limb representations in the somatosensory and motor cortices, without apparent brain damage. Due to the reci...
Source: Experimental Neurology - October 8, 2021 Category: Neurology Authors: Canu Marie-H élène Montel Val érie Dereumetz Julie Marqueste Tanguy Decherchi Patrick Coq Jacques-Olivier Dupont Erwan Bastide Bruno Source Type: research

Acute intermittent hypoxia and respiratory muscle recruitment in people with amyotrophic lateral sclerosis: A preliminary study
Exp Neurol. 2021 Oct 5:113890. doi: 10.1016/j.expneurol.2021.113890. Online ahead of print.ABSTRACTRespiratory failure is the main cause of death in amyotrophic lateral sclerosis (ALS). Since no effective treatments to preserve independent breathing are available, there is a critical need for new therapies to preserve or restore breathing ability. Since acute intermittent hypoxia (AIH) elicits spinal respiratory motor plasticity in rodent ALS models, and may restore breathing ability in people with ALS, we performed a proof-of-principle study to investigate this possibility in ALS patients. Quiet breathing, sniff nasal ins...
Source: Experimental Neurology - October 8, 2021 Category: Neurology Authors: Elaheh Sajjadi Yasin B Seven Jessica G Ehrbar James P Wymer Gordon S Mitchell Barbara K Smith Source Type: research

Potential roles of vagus nerve stimulation on traumatic brain injury: Evidence from in vivo and clinical studies
Exp Neurol. 2021 Oct 5;347:113887. doi: 10.1016/j.expneurol.2021.113887. Online ahead of print.ABSTRACTTraumatic Brain Injury (TBI) is a one of the leading causes of death and disability worldwide. The consequences of TBI can be divided into two stages: 1) the immediate neuronal destruction during the initial trauma, resulting in the primary brain injury and pathophysiologic sequelae, and 2) the secondary brain injury, encompassing mitochondrial dysfunction, inflammation, cellular excitotoxicity, oxidative stress, and cortical edema, resulting in increased intracranial pressure (ICP) with exacerbated brain damage. Although...
Source: Experimental Neurology - October 8, 2021 Category: Neurology Authors: Chanon Srihagulang Jirapong Vongsfak Tanat Vaniyapong Nipon Chattipakorn Siriporn C Chattipakorn Source Type: research

Inhibition of the NLRP3 inflammasome by OLT1177 induces functional protection and myelin preservation after spinal cord injury
Exp Neurol. 2021 Oct 5:113889. doi: 10.1016/j.expneurol.2021.113889. Online ahead of print.ABSTRACTSpinal cord injury (SCI) leads to irreversible functional deficits due to the disruption of axons and the death of neurons and glial cells. The inflammatory response that occurs in the injured spinal cord results in tissue degeneration; thus, targeting inflammation after acute SCI is expected to ameliorate histopathological evidence indicative of damage and, consequently, reduce functional disabilities. Interleukin 1 beta (IL-1β) and interleukin 18 (IL-18) are pro-inflammatory cytokines members of the IL-1 family that in...
Source: Experimental Neurology - October 8, 2021 Category: Neurology Authors: Jesus Amo-Aparicio Joana Garcia-Garcia Maria Puigdomenech Isaac Francos-Quijorna Damaris B Skouras Charles A Dinarello Ruben Lopez-Vales Source Type: research

Neurological and cognitive alterations induced by MDMA in humans
Exp Neurol. 2021 Oct 5:113888. doi: 10.1016/j.expneurol.2021.113888. Online ahead of print.ABSTRACT3,4 Methylenedioxymethamphetamine generally referred to as MDMA or 'ecstasy' is a ring-substituted phenethylamine stimulant which produces powerful empathogenic effects. Use of MDMA remains popular despite prohibition, and potential long-term negative consequences of repeated use. MDMA produces its acute subjective effects primarily by stimulating the release of serotonin via action at the serotonin transporter (SERT). There is evidence that MDMA administration may lead to long lasting neurotoxic effects on serotonin neurons ...
Source: Experimental Neurology - October 8, 2021 Category: Neurology Authors: Catharine Montgomery Carl A Roberts Source Type: research

Changes of cerebral network activity after invasive stimulation of the mesencephalic locomotor region in a rat stroke model
Exp Neurol. 2021 Oct 5:113884. doi: 10.1016/j.expneurol.2021.113884. Online ahead of print.ABSTRACTMotor deficits after stroke reflect both, focal lesion and network alterations in brain regions distant from infarction. This remote network dysfunction may be caused by aberrant signals from cortical motor regions travelling via mesencephalic locomotor region (MLR) to other locomotor circuits. A method for modulating disturbed network activity is deep brain stimulation. Recently, we have shown that high frequency stimulation (HFS) of the MLR in rats has restored gait impairment after photothrombotic stroke (PTS). However, it...
Source: Experimental Neurology - October 8, 2021 Category: Neurology Authors: Stefanie D Kr ämer Michael K Schuhmann Fabian Schadt Ina Israel Samuel Samnick Jens Volkmann Felix Fluri Source Type: research

Early movement restriction deteriorates motor function and soleus muscle physiology
Exp Neurol. 2021 Oct 5:113886. doi: 10.1016/j.expneurol.2021.113886. Online ahead of print.ABSTRACTChildren with low physical activity and interactions with environment experience atypical sensorimotor development and maturation leading to anatomical and functional disorganization of the sensorimotor circuitry and also to enduring altered motor function. Previous data have shown that postnatal movement restriction in rats results in locomotor disturbances, functional disorganization and hyperexcitability of the hind limb representations in the somatosensory and motor cortices, without apparent brain damage. Due to the reci...
Source: Experimental Neurology - October 8, 2021 Category: Neurology Authors: Canu Marie-H élène Montel Val érie Dereumetz Julie Marqueste Tanguy Decherchi Patrick Coq Jacques-Olivier Dupont Erwan Bastide Bruno Source Type: research

Acute intermittent hypoxia and respiratory muscle recruitment in people with amyotrophic lateral sclerosis: A preliminary study
Exp Neurol. 2021 Oct 5:113890. doi: 10.1016/j.expneurol.2021.113890. Online ahead of print.ABSTRACTRespiratory failure is the main cause of death in amyotrophic lateral sclerosis (ALS). Since no effective treatments to preserve independent breathing are available, there is a critical need for new therapies to preserve or restore breathing ability. Since acute intermittent hypoxia (AIH) elicits spinal respiratory motor plasticity in rodent ALS models, and may restore breathing ability in people with ALS, we performed a proof-of-principle study to investigate this possibility in ALS patients. Quiet breathing, sniff nasal ins...
Source: Experimental Neurology - October 8, 2021 Category: Neurology Authors: Elaheh Sajjadi Yasin B Seven Jessica G Ehrbar James P Wymer Gordon S Mitchell Barbara K Smith Source Type: research

Potential roles of vagus nerve stimulation on traumatic brain injury: Evidence from in vivo and clinical studies
Exp Neurol. 2021 Oct 5:113887. doi: 10.1016/j.expneurol.2021.113887. Online ahead of print.ABSTRACTTraumatic Brain Injury (TBI) is a one of the leading causes of death and disability worldwide. The consequences of TBI can be divided into two stages: 1) the immediate neuronal destruction during the initial trauma, resulting in the primary brain injury and pathophysiologic sequelae, and 2) the secondary brain injury, encompassing mitochondrial dysfunction, inflammation, cellular excitotoxicity, oxidative stress, and cortical edema, resulting in increased intracranial pressure (ICP) with exacerbated brain damage. Although the...
Source: Experimental Neurology - October 8, 2021 Category: Neurology Authors: Chanon Srihagulang Jirapong Vongsfak Tanat Vaniyapong Nipon Chattipakorn Siriporn C Chattipakorn Source Type: research

Inhibition of the NLRP3 inflammasome by OLT1177 induces functional protection and myelin preservation after spinal cord injury
Exp Neurol. 2021 Oct 5:113889. doi: 10.1016/j.expneurol.2021.113889. Online ahead of print.ABSTRACTSpinal cord injury (SCI) leads to irreversible functional deficits due to the disruption of axons and the death of neurons and glial cells. The inflammatory response that occurs in the injured spinal cord results in tissue degeneration; thus, targeting inflammation after acute SCI is expected to ameliorate histopathological evidence indicative of damage and, consequently, reduce functional disabilities. Interleukin 1 beta (IL-1β) and interleukin 18 (IL-18) are pro-inflammatory cytokines members of the IL-1 family that in...
Source: Experimental Neurology - October 8, 2021 Category: Neurology Authors: Jesus Amo-Aparicio Joana Garcia-Garcia Maria Puigdomenech Isaac Francos-Quijorna Damaris B Skouras Charles A Dinarello Ruben Lopez-Vales Source Type: research

Neurological and cognitive alterations induced by MDMA in humans
Exp Neurol. 2021 Oct 5:113888. doi: 10.1016/j.expneurol.2021.113888. Online ahead of print.ABSTRACT3,4 Methylenedioxymethamphetamine generally referred to as MDMA or 'ecstasy' is a ring-substituted phenethylamine stimulant which produces powerful empathogenic effects. Use of MDMA remains popular despite prohibition, and potential long-term negative consequences of repeated use. MDMA produces its acute subjective effects primarily by stimulating the release of serotonin via action at the serotonin transporter (SERT). There is evidence that MDMA administration may lead to long lasting neurotoxic effects on serotonin neurons ...
Source: Experimental Neurology - October 8, 2021 Category: Neurology Authors: Catharine Montgomery Carl A Roberts Source Type: research

Post-acute delivery of α5-GABAA antagonist, S 44819, improves functional recovery in juvenile rats following stroke
Exp Neurol. 2021 Sep 28:113881. doi: 10.1016/j.expneurol.2021.113881. Online ahead of print.ABSTRACTHypo-excitability was reported in the peri-infarct tissue following stroke, an effect counteracted by a blockage of α5-GABAA receptors in adult rodents. Our present study aims to evaluate the effect of a selective α5-GABAA receptor antagonist, S 44819, in stroke in juvenile animals. We have set up and characterized an original model of transient ischemic stroke in 28 day-old Sprague-Dawley rats (45-min occlusion of the middle cerebral artery by intraluminal suture). In this model, S 44819 (1, 3 and 10 mg/kg, b.i....
Source: Experimental Neurology - October 1, 2021 Category: Neurology Authors: Florent Lebrun Nicolas Violle Annelise Letourneur Christophe Muller Nicolas Fischer Anthony Levilly Cyrille Orset Aurore Sors Denis Vivien Source Type: research

Intersectional genetic tools to study skilled reaching in mice
Exp Neurol. 2021 Sep 28:113879. doi: 10.1016/j.expneurol.2021.113879. Online ahead of print.ABSTRACTReaching to grasp is an evolutionarily conserved behavior and a crucial part of the motor repertoire in mammals. As it is studied in the laboratory, reaching has become the prototypical example of dexterous forelimb movements, illuminating key principles of motor control throughout the spinal cord, brain, and peripheral nervous system. Here, we (1) review the motor elements or phases that comprise the reach, grasp, and retract movements of reaching behavior, (2) highlight the role of intersectional genetic tools in linking t...
Source: Experimental Neurology - October 1, 2021 Category: Neurology Authors: Fabricio do Couto Nicola Isabelle Hua Ariel Levine Source Type: research

Mutation of the murine Prickle1 (R104Q) causes phenotypes analogous to human symptoms of epilepsy and autism
Exp Neurol. 2021 Sep 28:113880. doi: 10.1016/j.expneurol.2021.113880. Online ahead of print.ABSTRACTEpilepsy and autism spectrum disorders (ASD) frequently show comorbidity, suggesting shared or overlapping neurobiological basis underlying these conditions. R104Q is the first mutation in the PRICKLE 1 gene that was discovered in human patients with progressive myoclonus epilepsy (PME). Subsequently, a number of mutations in the PRICKLE 1 gene were shown to be associated with either epilepsy, autism, or both, as well as other developmental disorders. Using CRISPR-Cas9-mediated gene editing, we generated a Prickle1R104Q mous...
Source: Experimental Neurology - October 1, 2021 Category: Neurology Authors: Yue Ban Ting Yu Jingyi Wang Xiaojia Wang Can Liu Clayton Baker Yimin Zou Source Type: research

Post-acute delivery of α5-GABAA antagonist, S 44819, improves functional recovery in juvenile rats following stroke
Exp Neurol. 2021 Sep 28:113881. doi: 10.1016/j.expneurol.2021.113881. Online ahead of print.ABSTRACTHypo-excitability was reported in the peri-infarct tissue following stroke, an effect counteracted by a blockage of α5-GABAA receptors in adult rodents. Our present study aims to evaluate the effect of a selective α5-GABAA receptor antagonist, S 44819, in stroke in juvenile animals. We have set up and characterized an original model of transient ischemic stroke in 28 day-old Sprague-Dawley rats (45-min occlusion of the middle cerebral artery by intraluminal suture). In this model, S 44819 (1, 3 and 10 mg/kg, b.i....
Source: Experimental Neurology - October 1, 2021 Category: Neurology Authors: Florent Lebrun Nicolas Violle Annelise Letourneur Christophe Muller Nicolas Fischer Anthony Levilly Cyrille Orset Aurore Sors Denis Vivien Source Type: research

Intersectional genetic tools to study skilled reaching in mice
Exp Neurol. 2021 Sep 28:113879. doi: 10.1016/j.expneurol.2021.113879. Online ahead of print.ABSTRACTReaching to grasp is an evolutionarily conserved behavior and a crucial part of the motor repertoire in mammals. As it is studied in the laboratory, reaching has become the prototypical example of dexterous forelimb movements, illuminating key principles of motor control throughout the spinal cord, brain, and peripheral nervous system. Here, we (1) review the motor elements or phases that comprise the reach, grasp, and retract movements of reaching behavior, (2) highlight the role of intersectional genetic tools in linking t...
Source: Experimental Neurology - October 1, 2021 Category: Neurology Authors: Fabricio do Couto Nicola Isabelle Hua Ariel Levine Source Type: research

Mutation of the murine Prickle1 (R104Q) causes phenotypes analogous to human symptoms of epilepsy and autism
Exp Neurol. 2021 Sep 28:113880. doi: 10.1016/j.expneurol.2021.113880. Online ahead of print.ABSTRACTEpilepsy and autism spectrum disorders (ASD) frequently show comorbidity, suggesting shared or overlapping neurobiological basis underlying these conditions. R104Q is the first mutation in the PRICKLE 1 gene that was discovered in human patients with progressive myoclonus epilepsy (PME). Subsequently, a number of mutations in the PRICKLE 1 gene were shown to be associated with either epilepsy, autism, or both, as well as other developmental disorders. Using CRISPR-Cas9-mediated gene editing, we generated a Prickle1R104Q mous...
Source: Experimental Neurology - October 1, 2021 Category: Neurology Authors: Yue Ban Ting Yu Jingyi Wang Xiaojia Wang Can Liu Clayton Baker Yimin Zou Source Type: research

Post-acute delivery of α5-GABAA antagonist, S 44819, improves functional recovery in juvenile rats following stroke
Exp Neurol. 2021 Sep 28:113881. doi: 10.1016/j.expneurol.2021.113881. Online ahead of print.ABSTRACTHypo-excitability was reported in the peri-infarct tissue following stroke, an effect counteracted by a blockage of α5-GABAA receptors in adult rodents. Our present study aims to evaluate the effect of a selective α5-GABAA receptor antagonist, S 44819, in stroke in juvenile animals. We have set up and characterized an original model of transient ischemic stroke in 28 day-old Sprague-Dawley rats (45-min occlusion of the middle cerebral artery by intraluminal suture). In this model, S 44819 (1, 3 and 10 mg/kg, b.i....
Source: Experimental Neurology - October 1, 2021 Category: Neurology Authors: Florent Lebrun Nicolas Violle Annelise Letourneur Christophe Muller Nicolas Fischer Anthony Levilly Cyrille Orset Aurore Sors Denis Vivien Source Type: research

Intersectional genetic tools to study skilled reaching in mice
Exp Neurol. 2021 Sep 28:113879. doi: 10.1016/j.expneurol.2021.113879. Online ahead of print.ABSTRACTReaching to grasp is an evolutionarily conserved behavior and a crucial part of the motor repertoire in mammals. As it is studied in the laboratory, reaching has become the prototypical example of dexterous forelimb movements, illuminating key principles of motor control throughout the spinal cord, brain, and peripheral nervous system. Here, we (1) review the motor elements or phases that comprise the reach, grasp, and retract movements of reaching behavior, (2) highlight the role of intersectional genetic tools in linking t...
Source: Experimental Neurology - October 1, 2021 Category: Neurology Authors: Fabricio do Couto Nicola Isabelle Hua Ariel Levine Source Type: research

Mutation of the murine Prickle1 (R104Q) causes phenotypes analogous to human symptoms of epilepsy and autism
Exp Neurol. 2021 Sep 28:113880. doi: 10.1016/j.expneurol.2021.113880. Online ahead of print.ABSTRACTEpilepsy and autism spectrum disorders (ASD) frequently show comorbidity, suggesting shared or overlapping neurobiological basis underlying these conditions. R104Q is the first mutation in the PRICKLE 1 gene that was discovered in human patients with progressive myoclonus epilepsy (PME). Subsequently, a number of mutations in the PRICKLE 1 gene were shown to be associated with either epilepsy, autism, or both, as well as other developmental disorders. Using CRISPR-Cas9-mediated gene editing, we generated a Prickle1R104Q mous...
Source: Experimental Neurology - October 1, 2021 Category: Neurology Authors: Yue Ban Ting Yu Jingyi Wang Xiaojia Wang Can Liu Clayton Baker Yimin Zou Source Type: research

Post-acute delivery of α5-GABAA antagonist, S 44819, improves functional recovery in juvenile rats following stroke
Exp Neurol. 2021 Sep 28:113881. doi: 10.1016/j.expneurol.2021.113881. Online ahead of print.ABSTRACTHypo-excitability was reported in the peri-infarct tissue following stroke, an effect counteracted by a blockage of α5-GABAA receptors in adult rodents. Our present study aims to evaluate the effect of a selective α5-GABAA receptor antagonist, S 44819, in stroke in juvenile animals. We have set up and characterized an original model of transient ischemic stroke in 28 day-old Sprague-Dawley rats (45-min occlusion of the middle cerebral artery by intraluminal suture). In this model, S 44819 (1, 3 and 10 mg/kg, b.i....
Source: Experimental Neurology - October 1, 2021 Category: Neurology Authors: Florent Lebrun Nicolas Violle Annelise Letourneur Christophe Muller Nicolas Fischer Anthony Levilly Cyrille Orset Aurore Sors Denis Vivien Source Type: research

Intersectional genetic tools to study skilled reaching in mice
Exp Neurol. 2021 Sep 28:113879. doi: 10.1016/j.expneurol.2021.113879. Online ahead of print.ABSTRACTReaching to grasp is an evolutionarily conserved behavior and a crucial part of the motor repertoire in mammals. As it is studied in the laboratory, reaching has become the prototypical example of dexterous forelimb movements, illuminating key principles of motor control throughout the spinal cord, brain, and peripheral nervous system. Here, we (1) review the motor elements or phases that comprise the reach, grasp, and retract movements of reaching behavior, (2) highlight the role of intersectional genetic tools in linking t...
Source: Experimental Neurology - October 1, 2021 Category: Neurology Authors: Fabricio do Couto Nicola Isabelle Hua Ariel Levine Source Type: research

Mutation of the murine Prickle1 (R104Q) causes phenotypes analogous to human symptoms of epilepsy and autism
Exp Neurol. 2021 Sep 28:113880. doi: 10.1016/j.expneurol.2021.113880. Online ahead of print.ABSTRACTEpilepsy and autism spectrum disorders (ASD) frequently show comorbidity, suggesting shared or overlapping neurobiological basis underlying these conditions. R104Q is the first mutation in the PRICKLE 1 gene that was discovered in human patients with progressive myoclonus epilepsy (PME). Subsequently, a number of mutations in the PRICKLE 1 gene were shown to be associated with either epilepsy, autism, or both, as well as other developmental disorders. Using CRISPR-Cas9-mediated gene editing, we generated a Prickle1R104Q mous...
Source: Experimental Neurology - October 1, 2021 Category: Neurology Authors: Yue Ban Ting Yu Jingyi Wang Xiaojia Wang Can Liu Clayton Baker Yimin Zou Source Type: research

Post-acute delivery of α5-GABAA antagonist, S 44819, improves functional recovery in juvenile rats following stroke
Exp Neurol. 2021 Sep 28:113881. doi: 10.1016/j.expneurol.2021.113881. Online ahead of print.ABSTRACTHypo-excitability was reported in the peri-infarct tissue following stroke, an effect counteracted by a blockage of α5-GABAA receptors in adult rodents. Our present study aims to evaluate the effect of a selective α5-GABAA receptor antagonist, S 44819, in stroke in juvenile animals. We have set up and characterized an original model of transient ischemic stroke in 28 day-old Sprague-Dawley rats (45-min occlusion of the middle cerebral artery by intraluminal suture). In this model, S 44819 (1, 3 and 10 mg/kg, b.i....
Source: Experimental Neurology - October 1, 2021 Category: Neurology Authors: Florent Lebrun Nicolas Violle Annelise Letourneur Christophe Muller Nicolas Fischer Anthony Levilly Cyrille Orset Aurore Sors Denis Vivien Source Type: research

Intersectional genetic tools to study skilled reaching in mice
Exp Neurol. 2021 Sep 28:113879. doi: 10.1016/j.expneurol.2021.113879. Online ahead of print.ABSTRACTReaching to grasp is an evolutionarily conserved behavior and a crucial part of the motor repertoire in mammals. As it is studied in the laboratory, reaching has become the prototypical example of dexterous forelimb movements, illuminating key principles of motor control throughout the spinal cord, brain, and peripheral nervous system. Here, we (1) review the motor elements or phases that comprise the reach, grasp, and retract movements of reaching behavior, (2) highlight the role of intersectional genetic tools in linking t...
Source: Experimental Neurology - October 1, 2021 Category: Neurology Authors: Fabricio do Couto Nicola Isabelle Hua Ariel Levine Source Type: research

Mutation of the murine Prickle1 (R104Q) causes phenotypes analogous to human symptoms of epilepsy and autism
Exp Neurol. 2021 Sep 28:113880. doi: 10.1016/j.expneurol.2021.113880. Online ahead of print.ABSTRACTEpilepsy and autism spectrum disorders (ASD) frequently show comorbidity, suggesting shared or overlapping neurobiological basis underlying these conditions. R104Q is the first mutation in the PRICKLE 1 gene that was discovered in human patients with progressive myoclonus epilepsy (PME). Subsequently, a number of mutations in the PRICKLE 1 gene were shown to be associated with either epilepsy, autism, or both, as well as other developmental disorders. Using CRISPR-Cas9-mediated gene editing, we generated a Prickle1R104Q mous...
Source: Experimental Neurology - October 1, 2021 Category: Neurology Authors: Yue Ban Ting Yu Jingyi Wang Xiaojia Wang Can Liu Clayton Baker Yimin Zou Source Type: research

Post-acute delivery of α5-GABAA antagonist, S 44819, improves functional recovery in juvenile rats following stroke
Exp Neurol. 2021 Sep 28:113881. doi: 10.1016/j.expneurol.2021.113881. Online ahead of print.ABSTRACTHypo-excitability was reported in the peri-infarct tissue following stroke, an effect counteracted by a blockage of α5-GABAA receptors in adult rodents. Our present study aims to evaluate the effect of a selective α5-GABAA receptor antagonist, S 44819, in stroke in juvenile animals. We have set up and characterized an original model of transient ischemic stroke in 28 day-old Sprague-Dawley rats (45-min occlusion of the middle cerebral artery by intraluminal suture). In this model, S 44819 (1, 3 and 10 mg/kg, b.i....
Source: Experimental Neurology - October 1, 2021 Category: Neurology Authors: Florent Lebrun Nicolas Violle Annelise Letourneur Christophe Muller Nicolas Fischer Anthony Levilly Cyrille Orset Aurore Sors Denis Vivien Source Type: research

Intersectional genetic tools to study skilled reaching in mice
Exp Neurol. 2021 Sep 28:113879. doi: 10.1016/j.expneurol.2021.113879. Online ahead of print.ABSTRACTReaching to grasp is an evolutionarily conserved behavior and a crucial part of the motor repertoire in mammals. As it is studied in the laboratory, reaching has become the prototypical example of dexterous forelimb movements, illuminating key principles of motor control throughout the spinal cord, brain, and peripheral nervous system. Here, we (1) review the motor elements or phases that comprise the reach, grasp, and retract movements of reaching behavior, (2) highlight the role of intersectional genetic tools in linking t...
Source: Experimental Neurology - October 1, 2021 Category: Neurology Authors: Fabricio do Couto Nicola Isabelle Hua Ariel Levine Source Type: research

Mutation of the murine Prickle1 (R104Q) causes phenotypes analogous to human symptoms of epilepsy and autism
Exp Neurol. 2021 Sep 28:113880. doi: 10.1016/j.expneurol.2021.113880. Online ahead of print.ABSTRACTEpilepsy and autism spectrum disorders (ASD) frequently show comorbidity, suggesting shared or overlapping neurobiological basis underlying these conditions. R104Q is the first mutation in the PRICKLE 1 gene that was discovered in human patients with progressive myoclonus epilepsy (PME). Subsequently, a number of mutations in the PRICKLE 1 gene were shown to be associated with either epilepsy, autism, or both, as well as other developmental disorders. Using CRISPR-Cas9-mediated gene editing, we generated a Prickle1R104Q mous...
Source: Experimental Neurology - October 1, 2021 Category: Neurology Authors: Yue Ban Ting Yu Jingyi Wang Xiaojia Wang Can Liu Clayton Baker Yimin Zou Source Type: research

Sigma-1 receptor activation alleviates blood-brain barrier disruption post cerebral ischemia stroke by stimulating the GDNF-GFR α1-RET pathway
In this study, we investigated Sig-1R activation as a BBB integrity promoter via many post ischemic stroke pathways. Sig-1R activation in BBB-associated astrocytes can increase glia-derived neurotrophic factor (GDNF) secretion in bilateral common carotid artery occlusion (BCCAO) mice. Upregulated GDNF activates its receptors in CMECs to promote BBB integrity, and activated Sig-1R in CMECs facilitates this process. In vitro experiments have found that Sig-1R activation in CMECs promotes the interaction between the GDNF α1 receptor and transduction rearrangement gene, increasing PI3K-AKT-junction protein signaling path...
Source: Experimental Neurology - September 28, 2021 Category: Neurology Authors: Danyang Liu Luxi Yang Peng Liu Xuefei Ji Xiaoxiao Qi Ziqi Wang Tianyang Chi Libo Zou Source Type: research

Sigma-1 receptor activation alleviates blood-brain barrier disruption post cerebral ischemia stroke by stimulating the GDNF-GFR α1-RET pathway
In this study, we investigated Sig-1R activation as a BBB integrity promoter via many post ischemic stroke pathways. Sig-1R activation in BBB-associated astrocytes can increase glia-derived neurotrophic factor (GDNF) secretion in bilateral common carotid artery occlusion (BCCAO) mice. Upregulated GDNF activates its receptors in CMECs to promote BBB integrity, and activated Sig-1R in CMECs facilitates this process. In vitro experiments have found that Sig-1R activation in CMECs promotes the interaction between the GDNF α1 receptor and transduction rearrangement gene, increasing PI3K-AKT-junction protein signaling path...
Source: Experimental Neurology - September 28, 2021 Category: Neurology Authors: Danyang Liu Luxi Yang Peng Liu Xuefei Ji Xiaoxiao Qi Ziqi Wang Tianyang Chi Libo Zou Source Type: research

Sigma-1 receptor activation alleviates blood-brain barrier disruption post cerebral ischemia stroke by stimulating the GDNF-GFR α1-RET pathway
In this study, we investigated Sig-1R activation as a BBB integrity promoter via many post ischemic stroke pathways. Sig-1R activation in BBB-associated astrocytes can increase glia-derived neurotrophic factor (GDNF) secretion in bilateral common carotid artery occlusion (BCCAO) mice. Upregulated GDNF activates its receptors in CMECs to promote BBB integrity, and activated Sig-1R in CMECs facilitates this process. In vitro experiments have found that Sig-1R activation in CMECs promotes the interaction between the GDNF α1 receptor and transduction rearrangement gene, increasing PI3K-AKT-junction protein signaling path...
Source: Experimental Neurology - September 28, 2021 Category: Neurology Authors: Danyang Liu Luxi Yang Peng Liu Xuefei Ji Xiaoxiao Qi Ziqi Wang Tianyang Chi Libo Zou Source Type: research

Sigma-1 receptor activation alleviates blood-brain barrier disruption post cerebral ischemia stroke by stimulating the GDNF-GFR α1-RET pathway
In this study, we investigated Sig-1R activation as a BBB integrity promoter via many post ischemic stroke pathways. Sig-1R activation in BBB-associated astrocytes can increase glia-derived neurotrophic factor (GDNF) secretion in bilateral common carotid artery occlusion (BCCAO) mice. Upregulated GDNF activates its receptors in CMECs to promote BBB integrity, and activated Sig-1R in CMECs facilitates this process. In vitro experiments have found that Sig-1R activation in CMECs promotes the interaction between the GDNF α1 receptor and transduction rearrangement gene, increasing PI3K-AKT-junction protein signaling path...
Source: Experimental Neurology - September 28, 2021 Category: Neurology Authors: Danyang Liu Luxi Yang Peng Liu Xuefei Ji Xiaoxiao Qi Ziqi Wang Tianyang Chi Libo Zou Source Type: research

Hypoxic postconditioning promotes neurogenesis by modulating the metabolism of neural stem cells after cerebral ischemia
In conclusion, cerebral ischemia modulated the FAO and glycolysis of neural stem cells. HPC promoted the proliferation and migration of neural stem cells after MCAO, and these effects may be related to the regulation of metabolism, including FAO and glycolysis.PMID:34563509 | DOI:10.1016/j.expneurol.2021.113871 (Source: Experimental Neurology)
Source: Experimental Neurology - September 26, 2021 Category: Neurology Authors: Haiyan Li Sijie Li Changhong Ren Chen Gao Ning Li Chunxiu Wang Lin Wang Wenbo Zhao Xunming Ji Kunlin Jin Source Type: research

Real-time phase and amplitude estimation of neurophysiological signals exploiting a non-resonant oscillator
Exp Neurol. 2021 Sep 23;347:113869. doi: 10.1016/j.expneurol.2021.113869. Online ahead of print.ABSTRACTA recent advancement in the field of neuromodulation is to adapt stimulation parameters according to pre-specified biomarkers tracked in real-time. These markers comprise short and transient signal features, such as bursts of elevated band power. To capture these features, instantaneous measures of phase and/or amplitude are employed, which inform stimulation adjustment with high temporal specificity. For adaptive neuromodulation it is therefore necessary to precisely estimate a signal's phase and amplitude with minimum ...
Source: Experimental Neurology - September 26, 2021 Category: Neurology Authors: Johannes L Busch Lucia K Feldmann Andrea A K ühn Michael Rosenblum Source Type: research

Thioperamide attenuates neuroinflammation and cognitive impairments in Alzheimer's disease via inhibiting gliosis
This study uncovered a novel mechanism involving inflammatory regulating behind the therapeutic effect of thioperamide in AD.PMID:34563511 | DOI:10.1016/j.expneurol.2021.113870 (Source: Experimental Neurology)
Source: Experimental Neurology - September 26, 2021 Category: Neurology Authors: Jiangong Wang Bin Liu Yong Xu Haiyun Luan Chaoyun Wang Meizi Yang Runming Zhao Mengmeng Song Jing Liu Linshan Sun Jingjing You Wentao Wang Fengjiao Sun Haijing Yan Source Type: research

Hypoxic postconditioning promotes neurogenesis by modulating the metabolism of neural stem cells after cerebral ischemia
In conclusion, cerebral ischemia modulated the FAO and glycolysis of neural stem cells. HPC promoted the proliferation and migration of neural stem cells after MCAO, and these effects may be related to the regulation of metabolism, including FAO and glycolysis.PMID:34563509 | DOI:10.1016/j.expneurol.2021.113871 (Source: Experimental Neurology)
Source: Experimental Neurology - September 26, 2021 Category: Neurology Authors: Haiyan Li Sijie Li Changhong Ren Chen Gao Ning Li Chunxiu Wang Lin Wang Wenbo Zhao Xunming Ji Kunlin Jin Source Type: research

Real-time phase and amplitude estimation of neurophysiological signals exploiting a non-resonant oscillator
Exp Neurol. 2021 Sep 23:113869. doi: 10.1016/j.expneurol.2021.113869. Online ahead of print.ABSTRACTA recent advancement in the field of neuromodulation is to adapt stimulation parameters according to pre-specified biomarkers tracked in real-time. These markers comprise short and transient signal features, such as bursts of elevated band power. To capture these features, instantaneous measures of phase and/or amplitude are employed, which inform stimulation adjustment with high temporal specificity. For adaptive neuromodulation it is therefore necessary to precisely estimate a signal's phase and amplitude with minimum dela...
Source: Experimental Neurology - September 26, 2021 Category: Neurology Authors: Johannes L Busch Lucia K Feldmann Andrea A K ühn Michael Rosenblum Source Type: research

Thioperamide attenuates neuroinflammation and cognitive impairments in Alzheimer's disease via inhibiting gliosis
This study uncovered a novel mechanism involving inflammatory regulating behind the therapeutic effect of thioperamide in AD.PMID:34563511 | DOI:10.1016/j.expneurol.2021.113870 (Source: Experimental Neurology)
Source: Experimental Neurology - September 26, 2021 Category: Neurology Authors: Jiangong Wang Bin Liu Yong Xu Haiyun Luan Chaoyun Wang Meizi Yang Runming Zhao Mengmeng Song Jing Liu Linshan Sun Jingjing You Wentao Wang Fengjiao Sun Haijing Yan Source Type: research

Emerging placental biomarkers of health and disease through advanced magnetic resonance imaging (MRI)
Exp Neurol. 2021 Sep 22:113868. doi: 10.1016/j.expneurol.2021.113868. Online ahead of print.ABSTRACTPlacental dysfunction is a major cause of fetal demise, fetal growth restriction, and preterm birth, as well as significant maternal morbidity and mortality. Infant survivors of placental dysfunction are at elevated increased risk for lifelong neuropsychiatric morbidity. However, despite the significant consequences of placental disease, there are no clinical tools to directly and non-invasively assess and measure placental function in pregnancy. In this work, we will review advanced MRI techniques applied to the study of th...
Source: Experimental Neurology - September 25, 2021 Category: Neurology Authors: Nickie Andescavage Catherine Limperopoulos Source Type: research

Emerging placental biomarkers of health and disease through advanced magnetic resonance imaging (MRI)
Exp Neurol. 2021 Sep 22:113868. doi: 10.1016/j.expneurol.2021.113868. Online ahead of print.ABSTRACTPlacental dysfunction is a major cause of fetal demise, fetal growth restriction, and preterm birth, as well as significant maternal morbidity and mortality. Infant survivors of placental dysfunction are at elevated increased risk for lifelong neuropsychiatric morbidity. However, despite the significant consequences of placental disease, there are no clinical tools to directly and non-invasively assess and measure placental function in pregnancy. In this work, we will review advanced MRI techniques applied to the study of th...
Source: Experimental Neurology - September 25, 2021 Category: Neurology Authors: Nickie Andescavage Catherine Limperopoulos Source Type: research

Mannose-binding lectin promotes blood-brain barrier breakdown and exacerbates axonal damage after traumatic brain injury in mice
Exp Neurol. 2021 Sep 20;346:113865. doi: 10.1016/j.expneurol.2021.113865. Online ahead of print.ABSTRACTLeukocyte infiltration and blood-brain barrier breakdown contribute to secondary brain damage after traumatic brain injury (TBI). TBI induces neuroimmune responses triggering pathogenic complement activation through different pathways, including the lectin pathway. We investigated mechanisms underlying mannose-binding lectin (MBL)-mediated brain damage focusing on neutrophil infiltration and blood-brain barrier breakdown in a TBI mouse model. Wild type mice and MBL-/- null mice were subjected to controlled cortical impac...
Source: Experimental Neurology - September 21, 2021 Category: Neurology Authors: Jordi Pedragosa Domenico Mercurio Marco Oggioni Leonardo Marquez-Kisinousky Maria-Grazia de Simoni Anna M Planas Source Type: research

Mannose-binding lectin promotes blood-brain barrier breakdown and exacerbates axonal damage after traumatic brain injury in mice
Exp Neurol. 2021 Sep 18:113865. doi: 10.1016/j.expneurol.2021.113865. Online ahead of print.ABSTRACTLeukocyte infiltration and blood-brain barrier breakdown contribute to secondary brain damage after traumatic brain injury (TBI). TBI induces neuroimmune responses triggering pathogenic complement activation through different pathways, including the lectin pathway. We investigated mechanisms underlying mannose-binding lectin (MBL)-mediated brain damage focusing on neutrophil infiltration and blood-brain barrier breakdown in a TBI mouse model. Wild type mice and MBL-/- null mice were subjected to controlled cortical impact. W...
Source: Experimental Neurology - September 21, 2021 Category: Neurology Authors: Jordi Pedragosa Domenico Mercurio Marco Oggioni Leonardo Marquez-Kisinousky Maria-Grazia de Simoni Anna M Planas Source Type: research

Mannose-binding lectin promotes blood-brain barrier breakdown and exacerbates axonal damage after traumatic brain injury in mice
Exp Neurol. 2021 Sep 18:113865. doi: 10.1016/j.expneurol.2021.113865. Online ahead of print.ABSTRACTLeukocyte infiltration and blood-brain barrier breakdown contribute to secondary brain damage after traumatic brain injury (TBI). TBI induces neuroimmune responses triggering pathogenic complement activation through different pathways, including the lectin pathway. We investigated mechanisms underlying mannose-binding lectin (MBL)-mediated brain damage focusing on neutrophil infiltration and blood-brain barrier breakdown in a TBI mouse model. Wild type mice and MBL-/- null mice were subjected to controlled cortical impact. W...
Source: Experimental Neurology - September 21, 2021 Category: Neurology Authors: Jordi Pedragosa Domenico Mercurio Marco Oggioni Leonardo Marquez-Kisinousky Maria-Grazia de Simoni Anna M Planas Source Type: research