The Experts below are selected from a list of 26508 Experts worldwide ranked by ideXlab platform
Vivi M. Heine - One of the best experts on this subject based on the ideXlab platform.
-
Stem cell therapy for white matter disorders: don’t forget the microenvironment!
Journal of Inherited Metabolic Disease, 2016Co-Authors: Stephanie Dooves, Marjo S. Knaap, Vivi M. HeineAbstract:White matter disorders (WMDs) are a major source of handicap at all ages. They often lead to progressive neurological dysfunction and early death. Although causes are highly diverse, WMDs share the property that glia (astrocytes and oligodendrocytes) are among the cells primarily affected, and that myelin is either not formed or lost. Many WMDs might benefit from cell replacement therapies. Successful preclinical studies in Rodent models have already led to the first clinical trials in humans using glial or oligodendrocyte progenitor cells aiming at (re)myelination. However, myelin is usually not the only affected structure. Neurons, microglia, and astrocytes are often also affected and are all important partners in creating the right conditions for proper white matter repair. Composition of the extracellular environment is another factor to be considered. Cell transplantation therapies might therefore require inclusion of non-oligodendroglial cell types and target more than only myelin repair. WMD patients would likely benefit from multimodal therapy approaches involving stem cell transplantation and microenvironment-targeting strategies to alter the local environment to a more favorable state for cell replacement. Furthermore most proof-of-concept studies have been performed with human cells in Rodent Disease models. Since human glial cells show a larger regenerative capacity than their mouse counterparts in the host mouse brain, microenvironmental factors affecting white matter recovery might be overlooked in Rodent studies. We would like to stress that cell replacement therapy is a highly promising therapeutic option for WMDs, but a receptive microenvironment is crucial.
-
Stem cell therapy for white matter disorders: don't forget the microenvironment!
Journal of inherited metabolic disease, 2016Co-Authors: Stephanie Dooves, Marjo S. Van Der Knaap, Vivi M. HeineAbstract:White matter disorders (WMDs) are a major source of handicap at all ages. They often lead to progressive neurological dysfunction and early death. Although causes are highly diverse, WMDs share the property that glia (astrocytes and oligodendrocytes) are among the cells primarily affected, and that myelin is either not formed or lost. Many WMDs might benefit from cell replacement therapies. Successful preclinical studies in Rodent models have already led to the first clinical trials in humans using glial or oligodendrocyte progenitor cells aiming at (re)myelination. However, myelin is usually not the only affected structure. Neurons, microglia, and astrocytes are often also affected and are all important partners in creating the right conditions for proper white matter repair. Composition of the extracellular environment is another factor to be considered. Cell transplantation therapies might therefore require inclusion of non-oligodendroglial cell types and target more than only myelin repair. WMD patients would likely benefit from multimodal therapy approaches involving stem cell transplantation and microenvironment-targeting strategies to alter the local environment to a more favorable state for cell replacement. Furthermore most proof-of-concept studies have been performed with human cells in Rodent Disease models. Since human glial cells show a larger regenerative capacity than their mouse counterparts in the host mouse brain, microenvironmental factors affecting white matter recovery might be overlooked in Rodent studies. We would like to stress that cell replacement therapy is a highly promising therapeutic option for WMDs, but a receptive microenvironment is crucial.
Stephanie Dooves - One of the best experts on this subject based on the ideXlab platform.
-
Stem cell therapy for white matter disorders: don’t forget the microenvironment!
Journal of Inherited Metabolic Disease, 2016Co-Authors: Stephanie Dooves, Marjo S. Knaap, Vivi M. HeineAbstract:White matter disorders (WMDs) are a major source of handicap at all ages. They often lead to progressive neurological dysfunction and early death. Although causes are highly diverse, WMDs share the property that glia (astrocytes and oligodendrocytes) are among the cells primarily affected, and that myelin is either not formed or lost. Many WMDs might benefit from cell replacement therapies. Successful preclinical studies in Rodent models have already led to the first clinical trials in humans using glial or oligodendrocyte progenitor cells aiming at (re)myelination. However, myelin is usually not the only affected structure. Neurons, microglia, and astrocytes are often also affected and are all important partners in creating the right conditions for proper white matter repair. Composition of the extracellular environment is another factor to be considered. Cell transplantation therapies might therefore require inclusion of non-oligodendroglial cell types and target more than only myelin repair. WMD patients would likely benefit from multimodal therapy approaches involving stem cell transplantation and microenvironment-targeting strategies to alter the local environment to a more favorable state for cell replacement. Furthermore most proof-of-concept studies have been performed with human cells in Rodent Disease models. Since human glial cells show a larger regenerative capacity than their mouse counterparts in the host mouse brain, microenvironmental factors affecting white matter recovery might be overlooked in Rodent studies. We would like to stress that cell replacement therapy is a highly promising therapeutic option for WMDs, but a receptive microenvironment is crucial.
-
Stem cell therapy for white matter disorders: don't forget the microenvironment!
Journal of inherited metabolic disease, 2016Co-Authors: Stephanie Dooves, Marjo S. Van Der Knaap, Vivi M. HeineAbstract:White matter disorders (WMDs) are a major source of handicap at all ages. They often lead to progressive neurological dysfunction and early death. Although causes are highly diverse, WMDs share the property that glia (astrocytes and oligodendrocytes) are among the cells primarily affected, and that myelin is either not formed or lost. Many WMDs might benefit from cell replacement therapies. Successful preclinical studies in Rodent models have already led to the first clinical trials in humans using glial or oligodendrocyte progenitor cells aiming at (re)myelination. However, myelin is usually not the only affected structure. Neurons, microglia, and astrocytes are often also affected and are all important partners in creating the right conditions for proper white matter repair. Composition of the extracellular environment is another factor to be considered. Cell transplantation therapies might therefore require inclusion of non-oligodendroglial cell types and target more than only myelin repair. WMD patients would likely benefit from multimodal therapy approaches involving stem cell transplantation and microenvironment-targeting strategies to alter the local environment to a more favorable state for cell replacement. Furthermore most proof-of-concept studies have been performed with human cells in Rodent Disease models. Since human glial cells show a larger regenerative capacity than their mouse counterparts in the host mouse brain, microenvironmental factors affecting white matter recovery might be overlooked in Rodent studies. We would like to stress that cell replacement therapy is a highly promising therapeutic option for WMDs, but a receptive microenvironment is crucial.
Nuria Palomar Martin - One of the best experts on this subject based on the ideXlab platform.
-
Generation of light-producing somatic-transgenic mice using adeno-associated virus vectors
Scientific reports, 2020Co-Authors: Rajvinder Karda, Dp Perocheau, Ahad A. Rahim, Andrew Wong, Natalie Suff, Juan Antinao Diaz, Maha Tijani, Julien Baruteau, Nuria Palomar MartinAbstract:We have previously designed a library of lentiviral vectors to generate somatic-transgenic Rodents to monitor signalling pathways in Diseased organs using whole-body bioluminescence imaging, in conscious, freely moving Rodents. We have now expanded this technology to adeno-associated viral vectors. We first explored bio-distribution by assessing GFP expression after neonatal intravenous delivery of AAV8. We observed widespread gene expression in, central and peripheral nervous system, liver, kidney and skeletal muscle. Next, we selected a constitutive SFFV promoter and NFκB binding sequence for bioluminescence and biosensor evaluation. An intravenous injection of AAV8 containing firefly luciferase and eGFP under transcriptional control of either element resulted in strong and persistent widespread luciferase expression. A single dose of LPS-induced a 10-fold increase in luciferase expression in AAV8-NFκB mice and immunohistochemistry revealed GFP expression in cells of astrocytic and neuronal morphology. Importantly, whole-body bioluminescence persisted up to 240 days. We have validated a novel biosensor technology in an AAV system by using an NFκB response element and revealed its potential to monitor signalling pathway in a non-invasive manner in a model of LPS-induced inflammation. This technology complements existing germline-transgenic models and may be applicable to other Rodent Disease models.
-
Generation of light-producing somatic-transgenic mice using adeno-associated virus vectors
2018Co-Authors: Rajvinder Karda, Dp Perocheau, Ahad A. Rahim, Andrew Wong, Natalie Suff, Juan Antinao Diaz, Nuria Palomar Martin, Michael Hughes, Juliette M. K. M. Delhove, John R. CounsellAbstract:We have previously designed a library of lentiviral vectors to generate somatic-transgenic Rodents to monitor signalling pathways in Diseased organs using whole-body bioluminescence imaging, in conscious, freely moving Rodents. We have now expanded this technology to adeno-associated viral vectors. We first explored bio-distribution by assessing GFP expression after neonatal intravenous delivery of AAV8. We observed widespread gene expression in, central and peripheral nervous system, liver, kidney and skeletal muscle. Next, we selected a constitutive SFFV promoter and NFkB binding sequence for bioluminescence and biosensor evaluation. An intravenous injection of AAV8 containing firefly luciferase and eGFP under transcriptional control of either element resulted in strong and persistent widespread luciferase expression. A single dose of LPS-induced a 10-fold increase in luciferase expression in AAV8-NFkB mice and immunohistochemistry revealed GFP expression in cells of astrocytic and neuronal morphology. Importantly, whole-body bioluminescence persisted up to 240 days. To further restrict biosensor activity to the CNS, we performed intracerebroventricular injection of each vector. We observed greater restriction of bioluminescence to the head and spine with both vectors. Immunohistochemistry revealed strongest expression in cells of neuronal morphology. LPS administration stimulated a 4-fold increase over baseline bioluminescence. We have validated a novel biosensor technology in an AAV system by using an NFkB response element and revealed its potential to monitor signalling pathway in a non-invasive manner using a model of LPS-induced inflammation. This technology employs the 3Rs of biomedical animal research, complements existing germline-transgenic models and may be applicable to other Rodent Disease models with the use of different response elements.
Alexander Rotenberg - One of the best experts on this subject based on the ideXlab platform.
-
Novel Use of Theta Burst Cortical Electrical Stimulation for Modulating Motor Plasticity in Rats
Journal of Medical and Biological Engineering, 2015Co-Authors: Tsung-hsun Hsieh, Ying-zu Huang, Alexander Rotenberg, Yung-hsiao Chiang, Wan-shan Chang Chien, Jia-yi Wang, Jia-jin Chen, Vincent H.s. Chang, Chih-wei PengAbstract:Various forms of cortical stimulation are capable of modulating motor cortical excitability through plasticity-like mechanisms and thus might have therapeutic potential for neurological Diseases. To better understand the neural mechanism underlying the cortical neuromodulation effects and to enable translational research in Rodent Disease models, we developed a focused brain stimulation method using cortical electrical stimulation (CES) on the motor cortex in anesthetized rats. A specific stimulation scheme using theta burst stimulation (TBS) was then adopted to observe the facilitatory and inhibitory effects in motor cortical excitability. Adult male Sprague–Dawley rats were used for all experiments. Under urethane anesthesia, two epidural stainless steel screw electrodes were unilaterally implanted over the primary motor cortex targeting the forelimb area. Brachioradialis motor evoked potentials (MEPs) were obtained by single-pulse CES. Acute MEP changes were measured before and after intermittent and continuous TBS (iTBS and cTBS). For sham intervention, electrodes were implanted, but no TBS was delivered. To examine TBS-elicited plasticity responses, MEP amplitude was measured at baseline and for 30 min after iTBS or cTBS. The MEPs were significantly enhanced immediately after iTBS (p = 0.001) and remained enhanced for 30 min (p 0.05). The developed TBS scheme uses the focused CES method to produce consistent, rapid, and controllable electrophysiological changes in the motor cortex. In particular, the cortical plasticity can be modulated in rat models via the CES–TBS protocols. These findings may have translational relevance for establishing new therapeutic CES applications in neurological disorders.
-
Novel Use of Theta Burst Cortical Electrical Stimulation for Modulating Motor Plasticity in Rats
Journal of Medical and Biological Engineering, 2015Co-Authors: Tsung-hsun Hsieh, Ying-zu Huang, Jia-jin J. Chen, Alexander Rotenberg, Yung-hsiao Chiang, Wan-shan Chang Chien, Vincent Chang, Jia-yi Wang, Chih-wei PengAbstract:Various forms of cortical stimulation are capable of modulating motor cortical excitability through plasticity-like mechanisms and thus might have therapeutic potential for neurological Diseases. To better understand the neural mechanism underlying the cortical neuromodulation effects and to enable translational research in Rodent Disease models, we developed a focused brain stimulation method using cortical electrical stimulation (CES) on the motor cortex in anesthetized rats. A specific stimulation scheme using theta burst stimulation (TBS) was then adopted to observe the facilitatory and inhibitory effects in motor cortical excitability. Adult male Sprague–Dawley rats were used for all experiments. Under urethane anesthesia, two epidural stainless steel screw electrodes were unilaterally implanted over the primary motor cortex targeting the forelimb area. Brachioradialis motor evoked potentials (MEPs) were obtained by single-pulse CES. Acute MEP changes were measured before and after intermittent and continuous TBS (iTBS and cTBS). For sham intervention, electrodes were implanted, but no TBS was delivered. To examine TBS-elicited plasticity responses, MEP amplitude was measured at baseline and for 30 min after iTBS or cTBS. The MEPs were significantly enhanced immediately after iTBS ( p = 0.001) and remained enhanced for 30 min ( p
-
Measures of Cortical Inhibition by Paired-Pulse Transcranial Magnetic Stimulation in Anesthetized Rats
Journal of neurophysiology, 2010Co-Authors: Andrew M. Vahabzadeh-hagh, Paul A. Muller, Alvaro Pascual-leone, Frances E. Jensen, Alexander RotenbergAbstract:Paired-pulse transcranial magnetic stimulation (ppTMS) is a noninvasive method to measure cortical inhibition in vivo. Long interpulse interval (50–500 ms) ppTMS (LI-ppTMS) provokes intracortical inhibitory circuits and can reveal pathologically impaired cortical inhibition in disorders such as epilepsy. Adaptation of ppTMS protocols to Rodent Disease models is highly desirable to facilitate basic and translational research. We previously adapted single-pulse TMS (spTMS) methods to rats, but ppTMS has yet to be applied. Specifically, whether ppTMS elicits an inhibitory response in Rodents is unknown. ppTMS in rats also requires anesthesia, a setting under which the preservation of these measures is undetermined. We therefore tested, in anesthetized rats, whether anesthetic choice affects spTMS-motor-evoked potentials (MEPs), LI-ppTMS in rats, as in humans, elicits intracortical inhibition of the MEP, and rat LI-ppTMS inhibition is acutely impaired in a seizure model. Rats were anesthetized with pentobarbital (PB) or ketamine-atropine-xylazine (KAX) and stimulated unilaterally over the motor cortex while recording bilateral brachioradialis MEPs. LI-ppTMS was applied analogous to human long interval intracortical inhibition (LICI) protocols, and acute changes in inhibition were evaluated following injection of the convulsant pentylenetetrazole (PTZ). We find that spTMS-evoked MEPs were reliably present under either anesthetic, and that LI-ppTMS elicits inhibition of the conditioned MEP in rats, similar to human LICI, by as much as 58 ± 12 and 71 ± 11% under PB and KAX anesthesia, respectively. LI-ppTMS inhibition was reduced to as much as 53% of saline controls following PTZ injection, while spTMS-derived measures of corticospinal excitability were unchanged. Our data show that regional inhibition, similar to human LICI, is present in rats, can be elicited under PB or KAX anesthesia, and is reduced following convulsant administration. These results suggest a potential for LI-ppTMS as a biomarker of impaired cortical inhibition in murine Disease models.
Arnaud Nicot - One of the best experts on this subject based on the ideXlab platform.
-
Gender and sex hormones in multiple sclerosis pathology and therapy.
Frontiers in bioscience : a journal and virtual library, 2009Co-Authors: Arnaud NicotAbstract:Several lines of evidence indicate that gender affects the susceptibility and course of multiple sclerosis (MS) with a higher Disease prevalence and overall better prognosis in women than men. This sex dimorphism may be explained by sex chromosome effects and effects of sex steroid hormones on the immune system, blood brain barrier or parenchymal central nervous system (CNS) cells. The well known improvement in Disease during late pregnancy has also been linked to hormonal changes and has stimulated recent clinical studies to determine the efficacy of and tolerance to sex steroid therapeutic approaches. Both clinical and experimental studies indicate that sex steroid supplementation may be beneficial for MS. This could be related to anti-inflammatory actions on the immune system or CNS and to direct neuroprotective properties. Here, clinical and experimental data are reviewed with respect to the effects of sex hormones or gender in the pathology or therapy of MS or its Rodent Disease models. The different cellular targets as well as some molecular mechanisms likely involved are discussed.
-
Gender and sex hormones in multiple sclerosis pathology and therapy
Frontiers in Bioscience, 2009Co-Authors: Arnaud NicotAbstract:International audienceSeveral lines of evidence indicate that gender affects the susceptibility and course of multiple sclerosis (MS) with a higher Disease prevalence and overall better prognosis in women than men. This sex dimorphism may be explained by sex chromosome effects and effects of sex steroid hormones on the immune system, blood brain barrier or parenchymal central nervous system (CNS) cells. The well known improvement in Disease during late pregnancy has also been linked to hormonal changes and has stimulated recent clinical studies to determine the efficacy of and tolerance to sex steroid therapeutic approaches. Both clinical and experimental studies indicate that sex steroid supplementation may be beneficial for MS. This could be related to anti-inflammatory actions on the immune system or CNS and to direct neuroprotective properties. Here, clinical and experimental data are reviewed with respect to the effects of sex hormones or gender in the pathology or therapy of MS or its Rodent Disease models. The different cellular targets as well as some molecular mechanisms likely involved are discussed
