Yusuf Mehkri, Maxwell G Woolridge, Brandon Lucke-Wold
{"title":"Commentary: Calcitonin Gene Related Peptide and Its Clinical Utility for the Treatment of Traumatic Brain Injury, Subarachnoid Hemorrhage and Associated Migraine.","authors":"Yusuf Mehkri, Maxwell G Woolridge, Brandon Lucke-Wold","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":73744,"journal":{"name":"Journal of experimental neurology","volume":"3 3","pages":"71-74"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10583856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Prevention of ischemic stroke is one of the most important issues in patients with atrial fibrillation (AF). Currently, most patients are managed satisfactorily with oral anticoagulant (OAC) therapy. The remaining patients, who cannot tolerate long-term systemic OAC or who have an excess thrombotic burden that cannot be adequately controlled by OAC alone, require local anti-thrombotic therapy such as left atrial appendage (LAA) mechanical exclusion, either by surgical excision or percutaneous closure device implantation. Since the first percutaneous left atrial appendage occlusion (LAAO) device implantation was performed in 2001, there have been numerous unanswered questions, which might be clarified only after additional experience in this field. Although an enormous number of non-valvular atrial fibrillation (NVAF) patients require thrombo-prophylactic management, which can be either systemic or local management, LAAO has not yet been widely adopted as an alternative to anticoagulant therapy because of the extraordinarily diverse anatomical variation within the LAA as well as the complexity of clinical situations (i.e. relative / absolute contraindication to anticoagulant, high bleeding risk with or without prior major bleeding events, recurrent stroke during proper secondary prevention, comorbidities that increase the bleeding risk or thrombotic risk, and are accompanied by a compromised life expectancy, such as malignancy). The preliminary answer to the question regarding the meaningful destination of LAAO has been carefully discussed in this article. Can LAAO replace OAC?
{"title":"Left Atrial Appendage Occlusion: Where are We Going?","authors":"S. Shin, S. Kim, Jai-Wun Park","doi":"10.33696/neurol.2.051","DOIUrl":"https://doi.org/10.33696/neurol.2.051","url":null,"abstract":"Prevention of ischemic stroke is one of the most important issues in patients with atrial fibrillation (AF). Currently, most patients are managed satisfactorily with oral anticoagulant (OAC) therapy. The remaining patients, who cannot tolerate long-term systemic OAC or who have an excess thrombotic burden that cannot be adequately controlled by OAC alone, require local anti-thrombotic therapy such as left atrial appendage (LAA) mechanical exclusion, either by surgical excision or percutaneous closure device implantation. Since the first percutaneous left atrial appendage occlusion (LAAO) device implantation was performed in 2001, there have been numerous unanswered questions, which might be clarified only after additional experience in this field. Although an enormous number of non-valvular atrial fibrillation (NVAF) patients require thrombo-prophylactic management, which can be either systemic or local management, LAAO has not yet been widely adopted as an alternative to anticoagulant therapy because of the extraordinarily diverse anatomical variation within the LAA as well as the complexity of clinical situations (i.e. relative / absolute contraindication to anticoagulant, high bleeding risk with or without prior major bleeding events, recurrent stroke during proper secondary prevention, comorbidities that increase the bleeding risk or thrombotic risk, and are accompanied by a compromised life expectancy, such as malignancy). The preliminary answer to the question regarding the meaningful destination of LAAO has been carefully discussed in this article. Can LAAO replace OAC?","PeriodicalId":73744,"journal":{"name":"Journal of experimental neurology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46971741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stroke is the second largest cause of death worldwide, with a world annual mortality incidence of about 5.5 million people, and it is also the leading cause of disability worldwide with 50% of survivors being chronically disabled [1]. It is estimated that one in four people will experience a stroke in their lifetime [2]. Strokes may be classified into two general types: ischemic and haemorrhagic. Ischemic stroke is caused by a reduction or an interruption of the blood supply to a certain region of the brain due to the obstruction of a blood vessel. In contrast, haemorrhagic stroke occurs due to the rupture of a blood vessel causing bleeding in the brain or in the subarachnoid space [3]. This short communication is centered on ischemic stroke, which is the most prevalent form of stroke worldwide [1].
{"title":"Body Iron Overload is a Determining Factor in Brain Damage in Acute Ischemic Stroke","authors":"J. R. Torrella, R. Rama","doi":"10.33696/neurol.2.047","DOIUrl":"https://doi.org/10.33696/neurol.2.047","url":null,"abstract":"Stroke is the second largest cause of death worldwide, with a world annual mortality incidence of about 5.5 million people, and it is also the leading cause of disability worldwide with 50% of survivors being chronically disabled [1]. It is estimated that one in four people will experience a stroke in their lifetime [2]. Strokes may be classified into two general types: ischemic and haemorrhagic. Ischemic stroke is caused by a reduction or an interruption of the blood supply to a certain region of the brain due to the obstruction of a blood vessel. In contrast, haemorrhagic stroke occurs due to the rupture of a blood vessel causing bleeding in the brain or in the subarachnoid space [3]. This short communication is centered on ischemic stroke, which is the most prevalent form of stroke worldwide [1].","PeriodicalId":73744,"journal":{"name":"Journal of experimental neurology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46466959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Twenty-five percent of small molecules in drug development for CNS indications fail in clinical trials due to complications with neurotoxicity [1]. Unfortunately, this is not discovered earlier. Indeed, it is very infrequent that a drug is flagged for neurotoxic side effects in early drug discovery (1). The consequences are two-fold: 1) loss of time and money in bringing new drugs to market and, 2) the unwitting exposure of patents in clinical trials to the neurotoxic side effects of what otherwise could be a drug candidate that is effectively treating the problem. Known ahead of time, this could have helped guide the chemistry in the early stages of development to modify the molecule to eliminate the neurotoxicity [2].
{"title":"In vivo Neuropathology: Detecting the Neurotoxicity of Candidate Drugs during Early Drug Discovery","authors":"C. Ferris, P. Kulkarni","doi":"10.33696/neurol.2.052","DOIUrl":"https://doi.org/10.33696/neurol.2.052","url":null,"abstract":"Twenty-five percent of small molecules in drug development for CNS indications fail in clinical trials due to complications with neurotoxicity [1]. Unfortunately, this is not discovered earlier. Indeed, it is very infrequent that a drug is flagged for neurotoxic side effects in early drug discovery (1). The consequences are two-fold: 1) loss of time and money in bringing new drugs to market and, 2) the unwitting exposure of patents in clinical trials to the neurotoxic side effects of what otherwise could be a drug candidate that is effectively treating the problem. Known ahead of time, this could have helped guide the chemistry in the early stages of development to modify the molecule to eliminate the neurotoxicity [2].","PeriodicalId":73744,"journal":{"name":"Journal of experimental neurology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45002531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
L. Monti, D. Momi, Tommaso Casseri, Davide Del Roscio, M. Bellini, Alessandro Rossi
Objective: The purpose of the present study was to evaluate, in multiple sclerosis (MS) lesions, the diagnostic performance of two different commercial post-processing MR perfusion software. These two different algorithms for processing Dynamic susceptibility contrast (DSC) perfusion images have been used to differentiate perfusion values among white matter (WM) lesions, normal appearing white matter (NAWM), and grey matter (GM) in MS. The diagnostic performance for diff erentiating among lesions and normal tissue has been measured with respect to the Time to Peak (TTP). Methods and analysis: Analysing DSC perfusion imaging, a retrospective study has been performed on 74 MS patients and 15 normal subjects, by using 1.5 Tesla MRI scanner. TTP maps were generated by using 2 different commercially available algorithms (A;B). Analysis was conducted for the evaluation of diagnostic performance of different algorithms for differentiating between lesions and normal appearing WM and GM. Results: A statistically significant difference between the two algorithms was demonstrated by comparing TTP values among recent, stable lesions and NAWM. TTP values have been used to discriminate among recent, stable lesions and NAWM by using two different software packages. Conclusion: The optimal software should be that which increases the temporal resolution and be not operator dependent. TTP has been able to 1) examine the variability in the quantitative results of DSC MR perfusion imaging generated from identical source data of MS patients, 2) to identify the variables between two commercial post-processing algorithm and 3) to focus on the crucial role of post-processing inter-vendor differences.
{"title":"Comparison of Different Post-Processing Algorithms for Dynamic Susceptibility Contrast Perfusion Imaging of Multiple Sclerosis Lesions: A Time to Peak Analysis","authors":"L. Monti, D. Momi, Tommaso Casseri, Davide Del Roscio, M. Bellini, Alessandro Rossi","doi":"10.33696/neurol.2.049","DOIUrl":"https://doi.org/10.33696/neurol.2.049","url":null,"abstract":"Objective: The purpose of the present study was to evaluate, in multiple sclerosis (MS) lesions, the diagnostic performance of two different commercial post-processing MR perfusion software. These two different algorithms for processing Dynamic susceptibility contrast (DSC) perfusion images have been used to differentiate perfusion values among white matter (WM) lesions, normal appearing white matter (NAWM), and grey matter (GM) in MS. The diagnostic performance for diff erentiating among lesions and normal tissue has been measured with respect to the Time to Peak (TTP). Methods and analysis: Analysing DSC perfusion imaging, a retrospective study has been performed on 74 MS patients and 15 normal subjects, by using 1.5 Tesla MRI scanner. TTP maps were generated by using 2 different commercially available algorithms (A;B). Analysis was conducted for the evaluation of diagnostic performance of different algorithms for differentiating between lesions and normal appearing WM and GM. Results: A statistically significant difference between the two algorithms was demonstrated by comparing TTP values among recent, stable lesions and NAWM. TTP values have been used to discriminate among recent, stable lesions and NAWM by using two different software packages. Conclusion: The optimal software should be that which increases the temporal resolution and be not operator dependent. TTP has been able to 1) examine the variability in the quantitative results of DSC MR perfusion imaging generated from identical source data of MS patients, 2) to identify the variables between two commercial post-processing algorithm and 3) to focus on the crucial role of post-processing inter-vendor differences.","PeriodicalId":73744,"journal":{"name":"Journal of experimental neurology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41528219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
I. Novak, M. Paton, M. Finch-Edmondson, N. Badawi, Michael, Fahey, A. Velde, Ashleigh Hines, Leigha Dark, A. Khamis, Maria Mc Namara, E. Stanton, C. Morgan
Iona Novak1,2*, Madison CB Paton2, Megan Finch-Edmondson2, Nadia Badawi2,3, Michael Fahey4,5, Annate Velde2, Ashleigh Hines2, Leigha Dark6, Amanda Khamis2, Maria Mc Namara2, Emma Stanton2, Cathy Morgan2 1Faculty of Medicine and Health, The University of Sydney, Sydney, Australia 2Cerebral Palsy Alliance Research Institute, Specialty of Child and Adolescent Health, Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia
Iona novak1,2 *， Madison CB Paton2, Megan Finch-Edmondson2, Nadia badawi2,3, Michael fahey4,5, Annate Velde2, Ashleigh Hines2, Leigha Dark6, Amanda Khamis2, Maria Mc namar2, Emma Stanton2, Cathy Morgan2澳大利亚悉尼大学医学与健康学院脑瘫联盟研究所，儿童与青少年健康专业，悉尼医学院，悉尼大学医学与健康学院，澳大利亚悉尼
{"title":"Commentary and Clinical Implications of “State of the Evidence Traffic Lights 2019: Systematic Review of Interventions for Preventing and Treating Children with Cerebral Palsy”","authors":"I. Novak, M. Paton, M. Finch-Edmondson, N. Badawi, Michael, Fahey, A. Velde, Ashleigh Hines, Leigha Dark, A. Khamis, Maria Mc Namara, E. Stanton, C. Morgan","doi":"10.33696/neurol.2.043","DOIUrl":"https://doi.org/10.33696/neurol.2.043","url":null,"abstract":"Iona Novak1,2*, Madison CB Paton2, Megan Finch-Edmondson2, Nadia Badawi2,3, Michael Fahey4,5, Annate Velde2, Ashleigh Hines2, Leigha Dark6, Amanda Khamis2, Maria Mc Namara2, Emma Stanton2, Cathy Morgan2 1Faculty of Medicine and Health, The University of Sydney, Sydney, Australia 2Cerebral Palsy Alliance Research Institute, Specialty of Child and Adolescent Health, Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia","PeriodicalId":73744,"journal":{"name":"Journal of experimental neurology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45543496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
G. Ransmayr, M. Defrancesco, A. Damulina, Philipp Hermann, Thomas, Benke, P. Dal-Bianco, J. Marksteiner, Alexandra Fuchs, F. Fellner, Andreas, Futschik, R. Schmidt
Introduction and background: Care for family members suffering from neurological disorders is often demanding and increases with disease progression. Numerous patientand caregiver-related factors underlying caregiver burden have been identified. Some potential factors need to be clarified. Little is known about the effects of comorbidities and dementia complications on the burden of care for persons living with dementia. Objectives: We hypothesized that burdens of care for family members living with dementia increase with the number and severity of comorbidities and dementia complications. Methods: Multi-center prospective registry study (PRODEM) on caregiver burden in family caregivers (median age 61, 66% female) of 556 persons living with mild to moderate dementia, mainly Alzheimer’s disease (median age 77, 58% female). Results: Caregiver burden (Zarit Burden Interview) did not correlate with arterial hypertension, diabetes, hypercholesterolemia, cardioembolic/thromboembolic diagnoses, heart failure, severe arrhythmia or heart valve disease, but was worse in care recipients with symptoms of anxiety, psychotic episodes, depression and emotional, psychotic, behavioral and somatic symptom clusters (Neuropsychiatric Inventory, Geriatric Depression Scale-15 items). Moreover, caregiver burden correlated with the number of drugs taken daily. MRI evidence of cerebrovascular pathology (total volume of white matter hyperintensities on axial T2w-FLAIR sequences related to intracranial volume, measured in 301 patients) did not correlate with caregiver burden. Gerhard R, Defrancesco M, Damulina A, Hermann P, Benke T, Dal-Bianco P, et al. Much is Known about Caregiver Burden in Dementia What is Next? The Role of Comorbidities and Future Perspectives. J Exp Neurol. 2021;2(3):101-111. J Exp Neurol. 2021 Volume 2, Issue 3 102 Introduction and Background Care for patients with chronic debilitating neurological diseases is often demanding and can result in a variety of negative consequences including mental and physical morbidity. Numerous studies have been published on the burden of care for persons caring for spouses, parents, siblings or children with chronic neurological disorders, particularly for those who live with the care recipient and are directly responsible for care. Most studies address the care for dementia and stroke patients, persons with epilepsy, Parkinson’s disease and atypical parkinsonism, multiple sclerosis, motor neuron disease, Huntington’s disease, brain tumours, chronic pain syndromes, traumatic central nervous system injury, ataxias, and muscular dystrophy [1]. Little is known about caregiver burden in advanced stages of myasthenia gravis, adultonset myopathies, amyloidosis or other debilitating polyneuropathies or other rare neurological diseases. Most studies were performed in highor middle-income countries. The literature from low-income countries on family care for persons with chronic neurological diseases including dementia is spa
{"title":"Much is Known about Caregiver Burden in Dementia - What is Next? The Role of Comorb idities and Future Perspectives","authors":"G. Ransmayr, M. Defrancesco, A. Damulina, Philipp Hermann, Thomas, Benke, P. Dal-Bianco, J. Marksteiner, Alexandra Fuchs, F. Fellner, Andreas, Futschik, R. Schmidt","doi":"10.33696/neurol.2.042","DOIUrl":"https://doi.org/10.33696/neurol.2.042","url":null,"abstract":"Introduction and background: Care for family members suffering from neurological disorders is often demanding and increases with disease progression. Numerous patientand caregiver-related factors underlying caregiver burden have been identified. Some potential factors need to be clarified. Little is known about the effects of comorbidities and dementia complications on the burden of care for persons living with dementia. Objectives: We hypothesized that burdens of care for family members living with dementia increase with the number and severity of comorbidities and dementia complications. Methods: Multi-center prospective registry study (PRODEM) on caregiver burden in family caregivers (median age 61, 66% female) of 556 persons living with mild to moderate dementia, mainly Alzheimer’s disease (median age 77, 58% female). Results: Caregiver burden (Zarit Burden Interview) did not correlate with arterial hypertension, diabetes, hypercholesterolemia, cardioembolic/thromboembolic diagnoses, heart failure, severe arrhythmia or heart valve disease, but was worse in care recipients with symptoms of anxiety, psychotic episodes, depression and emotional, psychotic, behavioral and somatic symptom clusters (Neuropsychiatric Inventory, Geriatric Depression Scale-15 items). Moreover, caregiver burden correlated with the number of drugs taken daily. MRI evidence of cerebrovascular pathology (total volume of white matter hyperintensities on axial T2w-FLAIR sequences related to intracranial volume, measured in 301 patients) did not correlate with caregiver burden. Gerhard R, Defrancesco M, Damulina A, Hermann P, Benke T, Dal-Bianco P, et al. Much is Known about Caregiver Burden in Dementia What is Next? The Role of Comorbidities and Future Perspectives. J Exp Neurol. 2021;2(3):101-111. J Exp Neurol. 2021 Volume 2, Issue 3 102 Introduction and Background Care for patients with chronic debilitating neurological diseases is often demanding and can result in a variety of negative consequences including mental and physical morbidity. Numerous studies have been published on the burden of care for persons caring for spouses, parents, siblings or children with chronic neurological disorders, particularly for those who live with the care recipient and are directly responsible for care. Most studies address the care for dementia and stroke patients, persons with epilepsy, Parkinson’s disease and atypical parkinsonism, multiple sclerosis, motor neuron disease, Huntington’s disease, brain tumours, chronic pain syndromes, traumatic central nervous system injury, ataxias, and muscular dystrophy [1]. Little is known about caregiver burden in advanced stages of myasthenia gravis, adultonset myopathies, amyloidosis or other debilitating polyneuropathies or other rare neurological diseases. Most studies were performed in highor middle-income countries. The literature from low-income countries on family care for persons with chronic neurological diseases including dementia is spa","PeriodicalId":73744,"journal":{"name":"Journal of experimental neurology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46771352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
We recently reviewed the scientific literature that elucidates the impact of cellular senescence on COVID-19 complications [1]. Recent studies have discussed the association of cellular senescence in COVID-19 patients with neurodegenerative diseases [2-5]. Therefore, in the present study, we extend this scientific synopsis to comment on how cellular senescence can promote neurodegenerative diseases and to describe suitable targets for eliminating cellular senescence.
{"title":"Impact of Cellular Senescence on Neurodegenerative Diseases during the COVID-19 Pandemic: Sui table Targets Required to Eliminate Cellular Senescence","authors":"M. Mohiuddin, K. Kasahara","doi":"10.33696/neurol.2.046","DOIUrl":"https://doi.org/10.33696/neurol.2.046","url":null,"abstract":"We recently reviewed the scientific literature that elucidates the impact of cellular senescence on COVID-19 complications [1]. Recent studies have discussed the association of cellular senescence in COVID-19 patients with neurodegenerative diseases [2-5]. Therefore, in the present study, we extend this scientific synopsis to comment on how cellular senescence can promote neurodegenerative diseases and to describe suitable targets for eliminating cellular senescence.","PeriodicalId":73744,"journal":{"name":"Journal of experimental neurology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43169043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Experimental and hereditary defects in the ubiquitous scaffolding proteins of the spectrin gene family cause an array of neuropathologies. Most recognized are ataxias caused by missense, deletions, or truncations in the SPTBN2 gene that encodes beta III spectrin. Such mutations disrupt the organization of post-synaptic receptors, their active transport through the secretory pathway, and the organization and dynamics of the actin-based neuronal skeleton. Similar mutations in SPTAN1 that encodes alpha II spectrin cause severe and usually lethal neurodevelopmental defects including one form of early infantile epileptic encephalopathy type 5 (West syndrome). Defects in these and other spectrins are implicated in degenerative and psychiatric conditions. In recent published work, we describe in mice a novel variant of alpha II spectrin that results in a progressive ataxia with widespread neurodegenerative change. The action of this variant is distinct, in that rather than disrupting a constitutive ligand-binding function of spectrin, the mutation alters its response to calcium and calmodulin-regulated signaling pathways including its response to calpain activation. As such, it represents a novel spectrinopathy that targets a key regulatory pathway where calcium and tyrosine kinase signals converge. Here we briefly discuss the various roles of spectrin in neuronal processes and calcium activated regulatory inputs that control its participation in neuronal growth, organization, and remodeling. We hypothesize that damage to the neuronal spectrin scaffold may be a common final pathway in many neurodegenerative disorders. Targeting the pathways that regulate spectrin function may thus offer novel avenues for therapeutic intervention.
{"title":"The Spread of Spectrin in Ataxia and Neurodegenerative Disease","authors":"J. Morrow, Michael C. Stankewich","doi":"10.33696/neurol.2.045","DOIUrl":"https://doi.org/10.33696/neurol.2.045","url":null,"abstract":"Experimental and hereditary defects in the ubiquitous scaffolding proteins of the spectrin gene family cause an array of neuropathologies. Most recognized are ataxias caused by missense, deletions, or truncations in the SPTBN2 gene that encodes beta III spectrin. Such mutations disrupt the organization of post-synaptic receptors, their active transport through the secretory pathway, and the organization and dynamics of the actin-based neuronal skeleton. Similar mutations in SPTAN1 that encodes alpha II spectrin cause severe and usually lethal neurodevelopmental defects including one form of early infantile epileptic encephalopathy type 5 (West syndrome). Defects in these and other spectrins are implicated in degenerative and psychiatric conditions. In recent published work, we describe in mice a novel variant of alpha II spectrin that results in a progressive ataxia with widespread neurodegenerative change. The action of this variant is distinct, in that rather than disrupting a constitutive ligand-binding function of spectrin, the mutation alters its response to calcium and calmodulin-regulated signaling pathways including its response to calpain activation. As such, it represents a novel spectrinopathy that targets a key regulatory pathway where calcium and tyrosine kinase signals converge. Here we briefly discuss the various roles of spectrin in neuronal processes and calcium activated regulatory inputs that control its participation in neuronal growth, organization, and remodeling. We hypothesize that damage to the neuronal spectrin scaffold may be a common final pathway in many neurodegenerative disorders. Targeting the pathways that regulate spectrin function may thus offer novel avenues for therapeutic intervention.","PeriodicalId":73744,"journal":{"name":"Journal of experimental neurology","volume":"2 1","pages":"131 - 139"},"PeriodicalIF":0.0,"publicationDate":"2021-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48739559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
It has been known for some time that representations in the central nervous system (CNS) are population encoded, that is, encoded as patterns of activity involving very large numbers of highly interconnected neurons in one or more neural networks extending over large expanses of the brain [1-11]. Nonetheless, understanding the computational processes occurring in pools of cortical neurons and the subcortical nuclei with which they interact continues to be one of the major challenges facing systems neuroscience.
{"title":"Neural Population Computing: Parallel Distributed Processing, the Basal Ganglia, and Evolution","authors":"S. Nadeau","doi":"10.33696/neurol.2.038","DOIUrl":"https://doi.org/10.33696/neurol.2.038","url":null,"abstract":"It has been known for some time that representations in the central nervous system (CNS) are population encoded, that is, encoded as patterns of activity involving very large numbers of highly interconnected neurons in one or more neural networks extending over large expanses of the brain [1-11]. Nonetheless, understanding the computational processes occurring in pools of cortical neurons and the subcortical nuclei with which they interact continues to be one of the major challenges facing systems neuroscience.","PeriodicalId":73744,"journal":{"name":"Journal of experimental neurology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45821520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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