The Experts below are selected from a list of 2034 Experts worldwide ranked by ideXlab platform
Veerle Baekelandt - One of the best experts on this subject based on the ideXlab platform.
-
development of an alpha synuclein based rat model for parkinson s disease via Stereotactic Injection of a recombinant adeno associated viral vector
Journal of Visualized Experiments, 2016Co-Authors: Anke Van Der Perren, Rik Gijsbers, Chris Van Den Haute, Cindy Casteels, Koen Van Laere, Veerle BaekelandtAbstract:In order to study the molecular pathways of Parkinson's disease (PD) and to develop novel therapeutic strategies, scientific investigators rely on animal models. The identification of PD-associated genes has led to the development of genetic PD models. Most transgenic α-SYN mouse models develop gradual α-SYN pathology but fail to display clear dopaminergic cell loss and dopamine-dependent behavioral deficits. This hurdle was overcome by direct targeting of the substantia nigra with viral vectors overexpressing PD-associated genes. Local gene delivery using viral vectors provides an attractive way to express transgenes in the central nervous system. Specific brain regions can be targeted (e.g. the substantia nigra), expression can be induced in the adult setting and high expression levels can be achieved. Further, different vector systems based on various viruses can be used. The protocol outlines all crucial steps to perform a viral vector Injection in the substantia nigra of the rat to develop a viral vector-based alpha-synuclein animal model for Parkinson's disease.
-
Noninvasive Monitoring of Long-Term Lentiviral Vector-Mediated Gene Expression in Rodent Brain with Bioluminescence Imaging
Molecular Therapy, 2006Co-Authors: Christophe M. Deroose, Veerle Reumers, Rik Gijsbers, Zeger Debyser, Luc Mortelmans, Guy Bormans, Veerle BaekelandtAbstract:Gene transfer into the central nervous system is an emerging therapeutic strategy for a range of neurological diseases, including neurodegeneration. This approach would benefit from imaging technologies that could determine the extent, magnitude, and duration of transgene expression. We have used bioluminescence imaging (BLI) to image lentiviral vector-mediated gene transfer into the mouse brain. We constructed human immunodeficiency virus type 1 lentiviral vectors that encode firefly luciferase and transduce cells in culture. After Stereotactic Injection of these vectors into the brain, we were able to detect luciferase expression in living mice and rats. We characterized the signal in mouse brain in terms of localization, kinetics, resolution, and reproducibility and demonstrated that it correlates with the level of firefly luciferase expression. Although the signal decreased gradually to about 20% of the initial value in the first month, the signal remained constant thereafter for more than 10 months. We demonstrated that the light signal can be used as a reporter by using a bicistronic vector. This is the first study to document noninvasive monitoring of long-term transgene expression in the adult mouse brain and provides the basis for applying BLI in the study of brain disease and gene therapeutic strategies. © 2006 The American Society of Gene Therapy.
-
lentiviral vector mediated delivery of short hairpin rna results in persistent knockdown of gene expression in mouse brain
Human Gene Therapy, 2003Co-Authors: Chris Van Den Haute, Zeger Debyser, Kristel Eggermont, Bart Nuttin, Veerle BaekelandtAbstract:RNA interference (RNAi) is an evolutionarily conserved mechanism of posttranscriptional gene-specific silencing. For in vivo applications, RNAi has been hampered until recently by inefficient delivery methods and by the transient nature of the gene suppression. Lentiviral vectors (LVs) hold great promise for gene therapeutic applications, pharmaceutical target validation, and functional genomics because stable gene transfer is mediated both in dividing and nondividing cells. We have used a lentiviral vector-based system for RNAi. We produced human immunodeficiency virus type 1-derived LVs encoding a short hairpin RNA specific for enhanced green fluorescent protein (EGFP) mRNA that were capable of inhibiting EGFP expression in mammalian cells. EGFP knockdown persisted after multiple passages of the cells. Of particular interest, our RNAi LVs were equally effective in suppression and prevention of EGFP expression after Stereotactic Injection in adult mouse brain. Therefore, we believe that the use of LVs for stable RNAi in brain will become a powerful aid to probe gene function in vivo and for gene therapy of diseases of the central nervous system.
Ya Ling Tang - One of the best experts on this subject based on the ideXlab platform.
-
treating intracranial abscesses in rats with Stereotactic Injection of biodegradable vancomycin embedded microparticles
Pharmaceutics, 2020Co-Authors: Yuan Yun Tseng, Ya Ling TangAbstract:Brain abscesses are emergent and life-threating despite advances in modern neurosurgical techniques and antibiotics. The present study explores the efficacy of vancomycin embedded to 50:50 poly(lactic-co-glycolide acid) (PLGA) microparticles in the treatment of brain abscess. The vancomycin embedded microparticles (VMPs) were Stereotactically introduced into the cerebral parenchyma in Staphylococcus aureus bacteria- induced brain abscess-bearing rats. Experimental rats were divided into three groups: group A (n = 13; no treatment), group B (n = 14; daily vancomycin Injection (5 mg intraperitoneally), and group C (n = 12; Stereotactic introduction of VMPs into the abscess cavity). Group C exhibited no inflammatory response and significantly increased survival and reduced mean abscess volumes (p <0.001) at the eighth week, compared with other groups. Vancomycin delivery via a biodegradable PLGA vehicle can easily attain Area Under the Curve (AUC)/minimum inhibitory concentration (MIC) ratios of ≥400, and strengthens the therapeutic efficacy of antibiotics without provoking any potential toxicity. Biodegradable VMPs are a safe and sustainable drug delivery vehicle for the treatment of brain abscess.
-
Treating Intracranial Abscesses in Rats with Stereotactic Injection of Biodegradable Vancomycin-Embedded Microparticles.
Pharmaceutics, 2020Co-Authors: Yuan Yun Tseng, Ya Ling TangAbstract:Brain abscesses are emergent and life-threating despite advances in modern neurosurgical techniques and antibiotics. The present study explores the efficacy of vancomycin embedded to 50:50 poly(lactic-co-glycolide acid) (PLGA) microparticles in the treatment of brain abscess. The vancomycin embedded microparticles (VMPs) were Stereotactically introduced into the cerebral parenchyma in Staphylococcus aureus bacteria- induced brain abscess-bearing rats. Experimental rats were divided into three groups: group A (n = 13; no treatment), group B (n = 14; daily vancomycin Injection (5 mg intraperitoneally), and group C (n = 12; Stereotactic introduction of VMPs into the abscess cavity). Group C exhibited no inflammatory response and significantly increased survival and reduced mean abscess volumes (p
Duk L Na - One of the best experts on this subject based on the ideXlab platform.
-
Stereotactic brain Injection of human umbilical cord blood mesenchymal stem cells in patients with alzheimer s disease dementia a phase 1 clinical trial
Alzheimer's & Dementia: Translational Research & Clinical Interventions, 2015Co-Authors: Jong Wook Chang, Juhee Chin, Soo Jin Choi, Hunki Kwon, Yearn Seong Choe, Duk L NaAbstract:Abstract Introduction We conducted a phase 1 clinical trial in nine patients with mild-to-moderate Alzheimer's disease to evaluate the safety and dose-limiting toxicity of Stereotactic brain Injection of human umbilical cord blood–derived mesenchymal stem cells (hUCB-MSCs). Methods The low- (n = 3) and high-dose (n = 6) groups received a total of 3.0 × 10 6 cells/60 μL and 6.0 × 10 6 cells/60 μL, respectively, into the bilateral hippocampi and right precuneus. Results No patient showed serious adverse events including fever during the 24-month follow-up period. During the 12-week follow-up period, the most common acute adverse event was wound pain from the surgical procedure (n = 9), followed by headache (n = 4), dizziness (n = 3), and postoperative delirium (n = 3). There was no dose-limiting toxicity. Discussion Administration of hUCB-MSCs into the hippocampus and precuneus by Stereotactic Injection was feasible, safe, and well tolerated. Further trials are warranted to test the efficacy. Clinical Trial Registration ClinicalTrial.gov identifier NCT01297218 and NCT01696591.
-
featured article Stereotactic brain Injection of human umbilical cord blood mesenchymal stem cells in patients with alzheimer s disease dementia a phase 1 clinical trial
2015Co-Authors: Jong Wook Chang, Juhee Chin, Soo Jin Choi, Hunki Kwon, Yearn Seong Choe, Duk L NaAbstract:Introduction: We conducted a phase 1 clinical trial in nine patients with mild-to-moderate Alzheimer’s disease to evaluate the safety and dose-limiting toxicity of Stereotactic brain Injection of human umbilical cord blood–derived mesenchymal stem cells (hUCB-MSCs). Methods: The low- (n 5 3) and high-dose (n 5 6) groups received a total of 3.0 ! 10 6 cells/60 mL and 6.0 ! 10 6 cells/60 mL, respectively, into the bilateral hippocampi and right precuneus. Results: No patient showed serious adverse events including fever during the 24-month follow-up period. During the 12-week follow-up period, the most common acute adverse event was wound pain from the surgical procedure (n 5 9), followed by headache (n 5 4), dizziness (n 5 3), and postoperative delirium (n 5 3). There was no dose-limiting toxicity. Discussion: Administration of hUCB-MSCs into the hippocampus and precuneus by Stereotactic Injection was feasible, safe, and well tolerated. Further trials are warranted to test the efficacy. Clinical Trial Registration: ClinicalTrial.gov identifier NCT01297218 and NCT01696591.
Yuan Yun Tseng - One of the best experts on this subject based on the ideXlab platform.
-
treating intracranial abscesses in rats with Stereotactic Injection of biodegradable vancomycin embedded microparticles
Pharmaceutics, 2020Co-Authors: Yuan Yun Tseng, Ya Ling TangAbstract:Brain abscesses are emergent and life-threating despite advances in modern neurosurgical techniques and antibiotics. The present study explores the efficacy of vancomycin embedded to 50:50 poly(lactic-co-glycolide acid) (PLGA) microparticles in the treatment of brain abscess. The vancomycin embedded microparticles (VMPs) were Stereotactically introduced into the cerebral parenchyma in Staphylococcus aureus bacteria- induced brain abscess-bearing rats. Experimental rats were divided into three groups: group A (n = 13; no treatment), group B (n = 14; daily vancomycin Injection (5 mg intraperitoneally), and group C (n = 12; Stereotactic introduction of VMPs into the abscess cavity). Group C exhibited no inflammatory response and significantly increased survival and reduced mean abscess volumes (p <0.001) at the eighth week, compared with other groups. Vancomycin delivery via a biodegradable PLGA vehicle can easily attain Area Under the Curve (AUC)/minimum inhibitory concentration (MIC) ratios of ≥400, and strengthens the therapeutic efficacy of antibiotics without provoking any potential toxicity. Biodegradable VMPs are a safe and sustainable drug delivery vehicle for the treatment of brain abscess.
-
Treating Intracranial Abscesses in Rats with Stereotactic Injection of Biodegradable Vancomycin-Embedded Microparticles.
Pharmaceutics, 2020Co-Authors: Yuan Yun Tseng, Ya Ling TangAbstract:Brain abscesses are emergent and life-threating despite advances in modern neurosurgical techniques and antibiotics. The present study explores the efficacy of vancomycin embedded to 50:50 poly(lactic-co-glycolide acid) (PLGA) microparticles in the treatment of brain abscess. The vancomycin embedded microparticles (VMPs) were Stereotactically introduced into the cerebral parenchyma in Staphylococcus aureus bacteria- induced brain abscess-bearing rats. Experimental rats were divided into three groups: group A (n = 13; no treatment), group B (n = 14; daily vancomycin Injection (5 mg intraperitoneally), and group C (n = 12; Stereotactic introduction of VMPs into the abscess cavity). Group C exhibited no inflammatory response and significantly increased survival and reduced mean abscess volumes (p
Diego Clemente - One of the best experts on this subject based on the ideXlab platform.
-
Tissue-type plasminogen activator exerts EGF-like chemokinetic effects on oligodendrocytes in white matter (re)myelination
Molecular Neurodegeneration, 2017Co-Authors: Camille Leonetti, Richard Macrez, Mathilde Pruvost, Yannick Hommet, Jérémie Bronsard, Maxime Perrigault, Isabel Machin, Denis Vivien, A. Fournier, Diego ClementeAbstract:BackgroundThe ability of oligodendrocyte progenitor cells (OPCs) to give raise to myelin forming cells during developmental myelination, normal adult physiology and post-lesion remyelination in white matter depends on factors which govern their proliferation, migration and differentiation. Tissue plasminogen activator (tPA) is a serine protease expressed in the central nervous system (CNS), where it regulates cell fate. In particular, tPA has been reported to protect oligodendrocytes from apoptosis and to facilitate the migration of neurons. Here, we investigated whether tPA can also participate in the migration of OPCs during CNS development and during remyelination after focal white matter lesion.MethodsOPC migration was estimated by immunohistological analysis in spinal cord and corpus callosum during development in mice embryos (E13 to P0) and after white matter lesion induced by the Stereotactic Injection of lysolecithin in adult mice (1 to 21 days post Injection). Migration was compared in these conditions between wild type and tPA knock-out animals. The action of tPA was further investigated in an in vitro chemokinesis assay.ResultsOPC migration along vessels is delayed in tPA knock-out mice during development and during remyelination. tPA enhances OPC migration via an effect dependent on the activation of epidermal growth factor receptor.ConclusionEndogenous tPA facilitates the migration of OPCs during development and during remyelination after white matter lesion by the virtue of its epidermal growth factor-like domain.