Pub Date : 2022-03-01DOI: 10.3390/neuroglia3010003
Erin M Purvis, John C O'Donnell, D Kacy Cullen
Neural precursor cells (NPCs) are generated in the subventricular zone (SVZ) and travel through the rostral migratory stream (RMS) to replace olfactory bulb interneurons in the brains of most adult mammals. Following brain injury, SVZ-derived NPCs can divert from the RMS and migrate toward injured brain regions but arrive in numbers too low to promote functional recovery without experimental intervention. Our lab has biofabricated a "living scaffold" that replicates the structural and functional features of the endogenous RMS. This tissue-engineered rostral migratory stream (TE-RMS) is a new regenerative medicine strategy designed to facilitate stable and sustained NPC delivery into neuron-deficient brain regions following brain injury or neurodegenerative disease and an in vitro tool to investigate the mechanisms of neuronal migration and cell-cell communication. We have previously shown that the TE-RMS replicates the basic structure and protein expression of the endogenous RMS and can direct immature neuronal migration in vitro and in vivo. Here, we further describe profound morphological changes that occur following precise physical manipulation and subsequent self-assembly of astrocytes into the TE-RMS, including significant cytoskeletal rearrangement and nuclear elongation. The unique cytoskeletal and nuclear architecture of TE-RMS astrocytes mimics astrocytes in the endogenous rat RMS. Advanced imaging techniques reveal the unique morphology of TE-RMS cells that has yet to be described of astrocytes in vitro. The TE-RMS offers a novel platform to elucidate astrocyte cytoskeletal and nuclear dynamics and their relationship to cell behavior and function.
{"title":"Unique Astrocyte Cytoskeletal and Nuclear Morphology in a Three-Dimensional Tissue-Engineered Rostral Migratory Stream.","authors":"Erin M Purvis, John C O'Donnell, D Kacy Cullen","doi":"10.3390/neuroglia3010003","DOIUrl":"https://doi.org/10.3390/neuroglia3010003","url":null,"abstract":"<p><p>Neural precursor cells (NPCs) are generated in the subventricular zone (SVZ) and travel through the rostral migratory stream (RMS) to replace olfactory bulb interneurons in the brains of most adult mammals. Following brain injury, SVZ-derived NPCs can divert from the RMS and migrate toward injured brain regions but arrive in numbers too low to promote functional recovery without experimental intervention. Our lab has biofabricated a \"living scaffold\" that replicates the structural and functional features of the endogenous RMS. This tissue-engineered rostral migratory stream (TE-RMS) is a new regenerative medicine strategy designed to facilitate stable and sustained NPC delivery into neuron-deficient brain regions following brain injury or neurodegenerative disease and an in vitro tool to investigate the mechanisms of neuronal migration and cell-cell communication. We have previously shown that the TE-RMS replicates the basic structure and protein expression of the endogenous RMS and can direct immature neuronal migration in vitro and in vivo. Here, we further describe profound morphological changes that occur following precise physical manipulation and subsequent self-assembly of astrocytes into the TE-RMS, including significant cytoskeletal rearrangement and nuclear elongation. The unique cytoskeletal and nuclear architecture of TE-RMS astrocytes mimics astrocytes in the endogenous rat RMS. Advanced imaging techniques reveal the unique morphology of TE-RMS cells that has yet to be described of astrocytes in vitro. The TE-RMS offers a novel platform to elucidate astrocyte cytoskeletal and nuclear dynamics and their relationship to cell behavior and function.</p>","PeriodicalId":74275,"journal":{"name":"Neuroglia (Basel, Switzerland)","volume":"3 1","pages":"41-60"},"PeriodicalIF":0.0,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9910099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10716280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-02-28DOI: 10.3390/neuroglia3010002
Shelby McCubbin, D. Harrison, R. Cooper
Glial cells play a role in many important processes, though the mechanisms through which they affect neighboring cells are not fully known. Insights may be gained by selectively activating glial cell populations in intact organisms utilizing the activatable channel proteins channel rhodopsin (ChR2XXL) and TRPA1. Here, the impacts of the glial-specific expression of these channels were examined in both larval and adult Drosophila. The Glia > ChR2XXL adults and larvae became immobile when exposed to blue light and TRPA1-expressed Drosophila upon heat exposure. The chloride pump expression in glia > eNpHR animals showed no observable differences in adults or larvae. In the in situ neural circuit activity of larvae in the Glia > ChR2XXL, the evoked activity first became more intense with concurrent light exposure, and then the activity was silenced and slowly picked back up after light was turned off. This decrease in motor nerve activity was also noted in the intact behaviors for Glia > ChR2XXL and Glia > TRPA1 larvae. As a proof of concept, this study demonstrated that activation of the glia can produce excessive neural activity and it appears with increased excitation of the glia and depressed motor neuron activity.
{"title":"Glia Excitation in the CNS Modulates Intact Behaviors and Sensory-CNS-Motor Circuitry","authors":"Shelby McCubbin, D. Harrison, R. Cooper","doi":"10.3390/neuroglia3010002","DOIUrl":"https://doi.org/10.3390/neuroglia3010002","url":null,"abstract":"Glial cells play a role in many important processes, though the mechanisms through which they affect neighboring cells are not fully known. Insights may be gained by selectively activating glial cell populations in intact organisms utilizing the activatable channel proteins channel rhodopsin (ChR2XXL) and TRPA1. Here, the impacts of the glial-specific expression of these channels were examined in both larval and adult Drosophila. The Glia > ChR2XXL adults and larvae became immobile when exposed to blue light and TRPA1-expressed Drosophila upon heat exposure. The chloride pump expression in glia > eNpHR animals showed no observable differences in adults or larvae. In the in situ neural circuit activity of larvae in the Glia > ChR2XXL, the evoked activity first became more intense with concurrent light exposure, and then the activity was silenced and slowly picked back up after light was turned off. This decrease in motor nerve activity was also noted in the intact behaviors for Glia > ChR2XXL and Glia > TRPA1 larvae. As a proof of concept, this study demonstrated that activation of the glia can produce excessive neural activity and it appears with increased excitation of the glia and depressed motor neuron activity.","PeriodicalId":74275,"journal":{"name":"Neuroglia (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46106267","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}
Pub Date : 2022-01-28DOI: 10.3390/neuroglia3010001
Q. Delarue, N. Guérout
The primary olfactory system (POS) is in permanent renewal, especially the primary olfactory neurons (PON) are renewed with a turnover of around four weeks, even in adulthood. The re-growth of these axons is helped by a specific population of glial cells: the olfactory ensheathing cells (OECs). In the POS, OECs constitute an “open-channel” in which the axons of PON cause regrowth from peripheral nervous system (PNS) to central nervous system (CNS). The remarkable role played by OECs into the POS has led scientists to investigate their properties and potential beneficial effects after transplantation in different lesion models of the CNS and PNS. In this review, we will resume and discuss more than thirty years of research regarding OEC studies. Indeed, after discussing the embryonic origins of OECs, we will describe the in vitro and in vivo properties exert at physiological state by these cells. Thereafter, we will present and talk over the effects of the transplantation of OECs after spinal cord injury, peripheral injury and other CNS injury models such as demyelinating diseases or traumatic brain injury. Finally, the mechanisms exerted by OECs in these different CNS and PNS lesion paradigms will be stated and we will conclude by presenting the innovations and future directions which can be considered to improve OECs properties and allow us to envisage their use in the near future in clinical applications.
{"title":"Transplantation of Olfactory Ensheathing Cells: Properties and Therapeutic Effects after Transplantation into the Lesioned Nervous System","authors":"Q. Delarue, N. Guérout","doi":"10.3390/neuroglia3010001","DOIUrl":"https://doi.org/10.3390/neuroglia3010001","url":null,"abstract":"The primary olfactory system (POS) is in permanent renewal, especially the primary olfactory neurons (PON) are renewed with a turnover of around four weeks, even in adulthood. The re-growth of these axons is helped by a specific population of glial cells: the olfactory ensheathing cells (OECs). In the POS, OECs constitute an “open-channel” in which the axons of PON cause regrowth from peripheral nervous system (PNS) to central nervous system (CNS). The remarkable role played by OECs into the POS has led scientists to investigate their properties and potential beneficial effects after transplantation in different lesion models of the CNS and PNS. In this review, we will resume and discuss more than thirty years of research regarding OEC studies. Indeed, after discussing the embryonic origins of OECs, we will describe the in vitro and in vivo properties exert at physiological state by these cells. Thereafter, we will present and talk over the effects of the transplantation of OECs after spinal cord injury, peripheral injury and other CNS injury models such as demyelinating diseases or traumatic brain injury. Finally, the mechanisms exerted by OECs in these different CNS and PNS lesion paradigms will be stated and we will conclude by presenting the innovations and future directions which can be considered to improve OECs properties and allow us to envisage their use in the near future in clinical applications.","PeriodicalId":74275,"journal":{"name":"Neuroglia (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42830670","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}
Pub Date : 2021-12-16DOI: 10.3390/neuroglia2010009
S. Okuyama, M. Matsuda, Yuna Okusako, Sanae Miyauchi, Toshiki Omasa, Akiho Ozawa, M. Abe, T. Yaeno, T. Araki, A. Sawamoto, M. Nakajima, Y. Furukawa
Inflammation is the cause and/or result of many diseases in peripheral tissues and the central nervous system. Recent findings suggested that inflammation in peripheral tissue induces an inflammatory response in the brain that activates glial cells, which, in turn, induce neuronal cell dysfunction. Therefore, anti-inflammatory compounds are important for the suppression of chronic inflammation and prevention of disease. The present study revealed microglial activation in the hippocampus of the brain two days after the peripheral administration of lipopolysaccharide (LPS). Furthermore, the expression of the synaptic vesicle membrane protein, synaptophysin, in the CA3 stratum lucidum of the hippocampus was down-regulated 7 days after the LPS injection. The administration of tocotrienols, a type of vitamin E, significantly attenuated these changes in the hippocampus. Collectively, the present results demonstrated the spread of peripheral inflammatory responses to the brain, in which glial activation and neuronal dysfunction were induced, while tocotrienols exerted anti-inflammatory effects and protected neurons from damage.
{"title":"Neuroprotective and Anti-Microglial Activation Effects of Tocotrienols in Brains of Lipopolysaccharide-Induced Inflammatory Model Mice","authors":"S. Okuyama, M. Matsuda, Yuna Okusako, Sanae Miyauchi, Toshiki Omasa, Akiho Ozawa, M. Abe, T. Yaeno, T. Araki, A. Sawamoto, M. Nakajima, Y. Furukawa","doi":"10.3390/neuroglia2010009","DOIUrl":"https://doi.org/10.3390/neuroglia2010009","url":null,"abstract":"Inflammation is the cause and/or result of many diseases in peripheral tissues and the central nervous system. Recent findings suggested that inflammation in peripheral tissue induces an inflammatory response in the brain that activates glial cells, which, in turn, induce neuronal cell dysfunction. Therefore, anti-inflammatory compounds are important for the suppression of chronic inflammation and prevention of disease. The present study revealed microglial activation in the hippocampus of the brain two days after the peripheral administration of lipopolysaccharide (LPS). Furthermore, the expression of the synaptic vesicle membrane protein, synaptophysin, in the CA3 stratum lucidum of the hippocampus was down-regulated 7 days after the LPS injection. The administration of tocotrienols, a type of vitamin E, significantly attenuated these changes in the hippocampus. Collectively, the present results demonstrated the spread of peripheral inflammatory responses to the brain, in which glial activation and neuronal dysfunction were induced, while tocotrienols exerted anti-inflammatory effects and protected neurons from damage.","PeriodicalId":74275,"journal":{"name":"Neuroglia (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48401803","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}
Pub Date : 2021-12-08DOI: 10.3390/neuroglia2010008
J. Sandhu, M. Ribecco‐Lutkiewicz, A. Abulrob
Caveolae are plasma membrane invaginations that are enriched in cholesterol-binding proteins called caveolins. The presence of caveolae and caveolins in mixed cultures of human neurons and glia has not been investigated. Here, we sought to determine the presence of caveolae and caveolins in human NTera-2 (NT2/D1) cells, differentiated with retinoic acid into neuron-like (NT2/N) and astrocyte-like (NT2/A) cells. We found that while caveolin-3 mRNA levels remained relatively constant, caveolin-1 and -2 levels were upregulated in NT2/A and downregulated in NT2/N. No caveolin-1 immunoreactivity was detected in NT2/N. Electron microscopy revealed numerous flask-shaped invaginations (~86–102 nm in diameter) in the plasma membrane of NT2/A and NT2/N cells, while only few were detected in NT2/D1 cells. Immunoelectron microscopy localized caveolin-1 gold particles in the flask-shaped structures on plasmalemma and cytoplasmic vesicles of NT2/A cells. Furthermore, NT2/A endocytosed Alexa 488 conjugated-cholera toxin B subunit (CTX-B) through a caveolae- and clathrin-dependent pathway, whereas NT2/N endocytosed CTX-B through a caveolae-independent pathway. We have established that while NT2/A expressed functional caveolae, the molecular identity of the plasma membrane invaginations in NT2/N is unknown. The expression of caveolin proteins was differentially regulated in these cells. Taken together, our findings support the usefulness of the human NT2 model system to study the role of caveolins in neuron–glia communication, and their involvement in brain health and disease.
{"title":"Molecular and Functional Characterization of Caveolae in Mixed Cultures of Human NT-2 Neurons and Astrocytes","authors":"J. Sandhu, M. Ribecco‐Lutkiewicz, A. Abulrob","doi":"10.3390/neuroglia2010008","DOIUrl":"https://doi.org/10.3390/neuroglia2010008","url":null,"abstract":"Caveolae are plasma membrane invaginations that are enriched in cholesterol-binding proteins called caveolins. The presence of caveolae and caveolins in mixed cultures of human neurons and glia has not been investigated. Here, we sought to determine the presence of caveolae and caveolins in human NTera-2 (NT2/D1) cells, differentiated with retinoic acid into neuron-like (NT2/N) and astrocyte-like (NT2/A) cells. We found that while caveolin-3 mRNA levels remained relatively constant, caveolin-1 and -2 levels were upregulated in NT2/A and downregulated in NT2/N. No caveolin-1 immunoreactivity was detected in NT2/N. Electron microscopy revealed numerous flask-shaped invaginations (~86–102 nm in diameter) in the plasma membrane of NT2/A and NT2/N cells, while only few were detected in NT2/D1 cells. Immunoelectron microscopy localized caveolin-1 gold particles in the flask-shaped structures on plasmalemma and cytoplasmic vesicles of NT2/A cells. Furthermore, NT2/A endocytosed Alexa 488 conjugated-cholera toxin B subunit (CTX-B) through a caveolae- and clathrin-dependent pathway, whereas NT2/N endocytosed CTX-B through a caveolae-independent pathway. We have established that while NT2/A expressed functional caveolae, the molecular identity of the plasma membrane invaginations in NT2/N is unknown. The expression of caveolin proteins was differentially regulated in these cells. Taken together, our findings support the usefulness of the human NT2 model system to study the role of caveolins in neuron–glia communication, and their involvement in brain health and disease.","PeriodicalId":74275,"journal":{"name":"Neuroglia (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43843816","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}
Pub Date : 2021-10-22DOI: 10.3390/neuroglia2010007
Cecilia Pankau, Shelby McCubbin, R. Cooper
Glia, or glial cells, are considered a vital component of the nervous system, serving as an electrical insulator and a protective barrier from the interstitial (extracellular) media. Certain glial cells (i.e., astrocytes, microglia, and oligodendrocytes) within the CNS have been shown to directly affect neural functions, but these properties are challenging to study due to the difficulty involved with selectively-activating specific glia. To overcome this hurdle, we selectively expressed light-sensitive ion channels (i.e., channel rhodopsin, ChR2-XXL) in glia of larvae and adult Drosophila melanogaster. Upon activation of ChR2, both adults and larvae showed a rapid contracture of body wall muscles with the animal remaining in contracture even after the light was turned off. During ChR2-XXL activation, electrophysiological recordings of evoked excitatory junction potentials within body wall muscles of the larvae confirmed a train of motor nerve activity. Additionally, when segmental nerves were transected from the CNS and exposed to light, there were no noted differences in quantal or evoked responses. This suggests that there is not enough expression of ChR2-XXL to influence the segmental axons to detect in our paradigm. Activation of the glia within the CNS is sufficient to excite the motor neurons.
{"title":"The Effect of Optogenetically Activating Glia on Neuronal Function","authors":"Cecilia Pankau, Shelby McCubbin, R. Cooper","doi":"10.3390/neuroglia2010007","DOIUrl":"https://doi.org/10.3390/neuroglia2010007","url":null,"abstract":"Glia, or glial cells, are considered a vital component of the nervous system, serving as an electrical insulator and a protective barrier from the interstitial (extracellular) media. Certain glial cells (i.e., astrocytes, microglia, and oligodendrocytes) within the CNS have been shown to directly affect neural functions, but these properties are challenging to study due to the difficulty involved with selectively-activating specific glia. To overcome this hurdle, we selectively expressed light-sensitive ion channels (i.e., channel rhodopsin, ChR2-XXL) in glia of larvae and adult Drosophila melanogaster. Upon activation of ChR2, both adults and larvae showed a rapid contracture of body wall muscles with the animal remaining in contracture even after the light was turned off. During ChR2-XXL activation, electrophysiological recordings of evoked excitatory junction potentials within body wall muscles of the larvae confirmed a train of motor nerve activity. Additionally, when segmental nerves were transected from the CNS and exposed to light, there were no noted differences in quantal or evoked responses. This suggests that there is not enough expression of ChR2-XXL to influence the segmental axons to detect in our paradigm. Activation of the glia within the CNS is sufficient to excite the motor neurons.","PeriodicalId":74275,"journal":{"name":"Neuroglia (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47094473","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}
Pub Date : 2021-10-14DOI: 10.3390/neuroglia2010006
J. Haidey, G. Gordon
Astrocytes elicit bidirectional control of microvascular diameter in acutely isolated brain slices through vasoconstriction and vasodilation pathways that can be differentially recruited via the free Ca2+ concentration in endfeet and/or the metabolic status of the tissue. However, the Ca2+-level hypothesis has not been tested using direct manipulation. To overcome this, we used Ca2+-clamp whole-cell patching of peri-arteriole astrocytes to change astrocyte-free Ca2+ to different concentrations and examined the vascular response. We discovered that clamping Ca2+ at the approximate resting value (100 nM) had no impact on arteriole diameter in a pre-constricted arteriole. However, a moderate elevation to 250 nM elicited sustained vasodilation that was blocked by the COX-1 antagonist SC-560 (500 nM). The vasodilation to 250 nM Ca2+ was sensitive to the metabolic state, as it converted to vasoconstriction when oxygen tension was dramatically elevated. In normal oxygen, clamping astrocyte Ca2+ well above the resting level (750 nM) produced sustained vasoconstriction, which converted to vasodilation in the 20-HETE blocker HET0016 (1 μM). This response was fully blocked by the addition of SC-560 (500 nM), showing that 20-HETE-induced vasoconstriction dominated the dilatory action of COX-1. These data demonstrate that direct changes in astrocyte free Ca2+ can control multiple arteriole tone states through different mediators.
{"title":"Direct Deviations in Astrocyte Free Ca2+ Concentration Control Multiple Arteriole Tone States","authors":"J. Haidey, G. Gordon","doi":"10.3390/neuroglia2010006","DOIUrl":"https://doi.org/10.3390/neuroglia2010006","url":null,"abstract":"Astrocytes elicit bidirectional control of microvascular diameter in acutely isolated brain slices through vasoconstriction and vasodilation pathways that can be differentially recruited via the free Ca2+ concentration in endfeet and/or the metabolic status of the tissue. However, the Ca2+-level hypothesis has not been tested using direct manipulation. To overcome this, we used Ca2+-clamp whole-cell patching of peri-arteriole astrocytes to change astrocyte-free Ca2+ to different concentrations and examined the vascular response. We discovered that clamping Ca2+ at the approximate resting value (100 nM) had no impact on arteriole diameter in a pre-constricted arteriole. However, a moderate elevation to 250 nM elicited sustained vasodilation that was blocked by the COX-1 antagonist SC-560 (500 nM). The vasodilation to 250 nM Ca2+ was sensitive to the metabolic state, as it converted to vasoconstriction when oxygen tension was dramatically elevated. In normal oxygen, clamping astrocyte Ca2+ well above the resting level (750 nM) produced sustained vasoconstriction, which converted to vasodilation in the 20-HETE blocker HET0016 (1 μM). This response was fully blocked by the addition of SC-560 (500 nM), showing that 20-HETE-induced vasoconstriction dominated the dilatory action of COX-1. These data demonstrate that direct changes in astrocyte free Ca2+ can control multiple arteriole tone states through different mediators.","PeriodicalId":74275,"journal":{"name":"Neuroglia (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44330269","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}
Pub Date : 2021-10-11DOI: 10.3390/neuroglia2010005
G. Teskey, C. Tran
Neurovascular coupling is a key control mechanism in cerebral blood flow (CBF) regulation. Importantly, this process was demonstrated to be affected in several neurological disorders, including epilepsy. Neurovascular coupling (NVC) is the basis for functional brain imaging, such as PET, SPECT, fMRI, and fNIRS, to assess and map neuronal activity, thus understanding NVC is critical to properly interpret functional imaging signals. However, hemodynamics, as assessed by these functional imaging techniques, continue to be used as a surrogate to map seizure activity; studies of NVC and cerebral blood flow control during and following seizures are rare. Recent studies have provided conflicting results, with some studies showing focal increases in CBF at the onset of a seizure while others show decreases. In this brief review article, we provide an overview of the current knowledge state of neurovascular coupling and discuss seizure-related alterations in neurovascular coupling and CBF control.
{"title":"Neurovascular Coupling in Seizures","authors":"G. Teskey, C. Tran","doi":"10.3390/neuroglia2010005","DOIUrl":"https://doi.org/10.3390/neuroglia2010005","url":null,"abstract":"Neurovascular coupling is a key control mechanism in cerebral blood flow (CBF) regulation. Importantly, this process was demonstrated to be affected in several neurological disorders, including epilepsy. Neurovascular coupling (NVC) is the basis for functional brain imaging, such as PET, SPECT, fMRI, and fNIRS, to assess and map neuronal activity, thus understanding NVC is critical to properly interpret functional imaging signals. However, hemodynamics, as assessed by these functional imaging techniques, continue to be used as a surrogate to map seizure activity; studies of NVC and cerebral blood flow control during and following seizures are rare. Recent studies have provided conflicting results, with some studies showing focal increases in CBF at the onset of a seizure while others show decreases. In this brief review article, we provide an overview of the current knowledge state of neurovascular coupling and discuss seizure-related alterations in neurovascular coupling and CBF control.","PeriodicalId":74275,"journal":{"name":"Neuroglia (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45601028","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}
Pub Date : 2021-08-30DOI: 10.3390/neuroglia2010004
M. Hayden
The COVID-19 pandemic has paralleled the great Spanish flu pandemic of 1918–1919 in the United States. Previous historical accounts have strongly suggested a post-viral syndrome and, currently, a post-COVID-19 viral syndrome is unquestionable, which shares many of the characteristics of myalgic encephalomyelitis/chronic fatigue syndrome that is present globally. The original term for this post-acute sequela of SARS-CoV-2 (PASC) was termed long haulers by those who were affected with this syndrome and it is now termed long COVID (LC) or PASC. International researchers and clinicians are desperately trying to better understand the pathobiological mechanisms possibly involved in this syndrome. This review aims to summarize many of the cumulated findings associated with LC/PASC and provides supportive and representative illustrations and transmission electron micrographic remodeling changes within brain tissues associated with a stress type of injury as occurs in the classic db/db and novel BTBR ob/ob obesity and diabetes mellitus mice models. These models are utilized to merely provide a response to metabolic stress injury wound healing mechanisms that are also present in humans. This review posits that neuroglial activation and chronic neuroinflammation may be a common denominator for the development of the complex LC/PASC syndrome following acute COVID-19 due to SARS-CoV-2.
{"title":"Hypothesis: Neuroglia Activation Due to Increased Peripheral and CNS Proinflammatory Cytokines/Chemokines with Neuroinflammation May Result in Long COVID","authors":"M. Hayden","doi":"10.3390/neuroglia2010004","DOIUrl":"https://doi.org/10.3390/neuroglia2010004","url":null,"abstract":"The COVID-19 pandemic has paralleled the great Spanish flu pandemic of 1918–1919 in the United States. Previous historical accounts have strongly suggested a post-viral syndrome and, currently, a post-COVID-19 viral syndrome is unquestionable, which shares many of the characteristics of myalgic encephalomyelitis/chronic fatigue syndrome that is present globally. The original term for this post-acute sequela of SARS-CoV-2 (PASC) was termed long haulers by those who were affected with this syndrome and it is now termed long COVID (LC) or PASC. International researchers and clinicians are desperately trying to better understand the pathobiological mechanisms possibly involved in this syndrome. This review aims to summarize many of the cumulated findings associated with LC/PASC and provides supportive and representative illustrations and transmission electron micrographic remodeling changes within brain tissues associated with a stress type of injury as occurs in the classic db/db and novel BTBR ob/ob obesity and diabetes mellitus mice models. These models are utilized to merely provide a response to metabolic stress injury wound healing mechanisms that are also present in humans. This review posits that neuroglial activation and chronic neuroinflammation may be a common denominator for the development of the complex LC/PASC syndrome following acute COVID-19 due to SARS-CoV-2.","PeriodicalId":74275,"journal":{"name":"Neuroglia (Basel, Switzerland)","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42513762","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}
Pub Date : 2018-12-01Epub Date: 2018-10-16DOI: 10.3390/neuroglia1020022
Seantel Hopkins, Manoj K Gottipati, Vedrana Montana, Elena Bekyarova, Robert C Haddon, Vladimir Parpura
The unique properties of single-walled carbon nanotubes (SWCNTs) have made them interesting candidates for applications in biomedicine. There are diverse chemical groups that can be attached to SWCNTs in order for these tiny tubes to gain various functionalities, for example, water solubility. Due to the availability of these "functionalization" approaches, SWCNTs are seen as agents for a potential anti-cancer therapy. In this context, we tested different chemically-functionalized forms of SWCNTs to determine which modifications make them better combatants against glioblastoma (astrocytoma grade IV), the deadliest brain cancer. We investigated the effects that two types of water soluble SWCNTs, functionalized with polyethylene glycol (SWCNT-PEG) or tetrahydrofurfuryl-terminated polyethylene glycol (SWCNT-PEG-THFF), have on the morphology and vitality, that is, cell adhesion, proliferation and death rate, of the D54MG human glioblastoma cells in culture. We found that SWCNT-PEG-THFF solute, when added to culture media, makes D54MG cells less round (measured as a significant decrease, by ~23%, in the form factor). This morphological change was induced by the PEG-THFF functional group, but not the SWCNT backbone itself. We also found that SWCNT-PEG-THFF solute reduces the proliferation rate of D54MG cells while increasing the rate of cell death. The functional groups PEG and PEG-THFF, on the other hand, reduce the cell death rate of D54MG human glioma cells. These data indicate that the process of functionalization of SWCNTs for potential use as glioma therapeutics may affect their biological effects.
{"title":"Effects of Chemically-Functionalized Single-Walled Carbon Nanotubes on the Morphology and Vitality of D54MG Human Glioblastoma Cells.","authors":"Seantel Hopkins, Manoj K Gottipati, Vedrana Montana, Elena Bekyarova, Robert C Haddon, Vladimir Parpura","doi":"10.3390/neuroglia1020022","DOIUrl":"https://doi.org/10.3390/neuroglia1020022","url":null,"abstract":"<p><p>The unique properties of single-walled carbon nanotubes (SWCNTs) have made them interesting candidates for applications in biomedicine. There are diverse chemical groups that can be attached to SWCNTs in order for these tiny tubes to gain various functionalities, for example, water solubility. Due to the availability of these \"functionalization\" approaches, SWCNTs are seen as agents for a potential anti-cancer therapy. In this context, we tested different chemically-functionalized forms of SWCNTs to determine which modifications make them better combatants against glioblastoma (astrocytoma grade IV), the deadliest brain cancer. We investigated the effects that two types of water soluble SWCNTs, functionalized with polyethylene glycol (SWCNT-PEG) or tetrahydrofurfuryl-terminated polyethylene glycol (SWCNT-PEG-THFF), have on the morphology and vitality, that is, cell adhesion, proliferation and death rate, of the D54MG human glioblastoma cells in culture. We found that SWCNT-PEG-THFF solute, when added to culture media, makes D54MG cells less round (measured as a significant decrease, by ~23%, in the form factor). This morphological change was induced by the PEG-THFF functional group, but not the SWCNT backbone itself. We also found that SWCNT-PEG-THFF solute reduces the proliferation rate of D54MG cells while increasing the rate of cell death. The functional groups PEG and PEG-THFF, on the other hand, reduce the cell death rate of D54MG human glioma cells. These data indicate that the process of functionalization of SWCNTs for potential use as glioma therapeutics may affect their biological effects.</p>","PeriodicalId":74275,"journal":{"name":"Neuroglia (Basel, Switzerland)","volume":"1 2","pages":"327-338"},"PeriodicalIF":0.0,"publicationDate":"2018-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3390/neuroglia1020022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37257717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}