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Howard I. Maibach - One of the best experts on this subject based on the ideXlab platform.

Gad A. Simon - One of the best experts on this subject based on the ideXlab platform.

Exuperio Dieztejedor - One of the best experts on this subject based on the ideXlab platform.

  • exosomes promote restoration after an Experimental Animal model of intracerebral hemorrhage
    Journal of Cerebral Blood Flow and Metabolism, 2017
    Co-Authors: Laura Oteroortega, Berta Rodriguezfrutos, Exuperio Dieztejedor, Fernando Lasogarcia, Mari Carmen Gomezde Frutos, Esperanza Medinagutierrez, Juan Antonio Lopez, Jesus Vazquez, Maria Gutierrezfernandez
    Abstract:

    Exosomes are gaining importance because they show great promise in therapeutic applications for several diseases. Particularly in stroke, exosomes derived from mesenchymal stem cell (MSC) therapy work as paracrine effectors responsible for promoting neurovascular remodeling and functional recovery. Adult male rats were subjected to intracerebral hemorrhage (ICH) by intrastriatal injection of collagenase type IV; 24 h after surgery, MSC-derived exosomes were administered through the tail vein. The rats were euthanized at 7 or 28 days after treatment. Functional evaluation, lesion size, fiber tract integrity, axonal sprouting and white matter repair markers, biodistribution of exosomes and secretome proteomics were analyzed. DiI-labeled exosomes were found in the brains of the ICH-treated group and in the liver, lung and spleen. Animals receiving treatment with exosomes showed significantly better results in terms of functional recovery, lesion size, fiber tract integrity, axonal sprouting and white matter repair markers compared with the control group 28 days after stroke. Proteomics analysis of the exosomes identified more than 2000 proteins that could be implicated in brain repair function. In conclusion, white matter integrity was partly restored by exosome administration mediated by molecular repair factors. Exosomes as a treatment could be a heterogeneous process by nature and presents many factors that can influence brain plasticity in an adaptable and versatile manner.

  • white matter repair after extracellular vesicles administration in an Experimental Animal model of subcortical stroke
    Scientific Reports, 2017
    Co-Authors: Laura Oteroortega, Berta Rodriguezfrutos, Blanca Fuentes, Exuperio Dieztejedor, Fernando Lasogarcia, Maria Del Carmen Gomezde Frutos, Jorge Pascualguerra, Maria Gutierrezfernandez
    Abstract:

    Mesenchymal stem cells have previously been shown to mediate brain repair after stroke; they secrete 50–100 nm complexes called extracellular vesicles (EVs), which could be responsible for provoking neurovascular repair and functional recovery. EVs have been observed by electron microscopy and NanoSight, and they contain associated proteins such as CD81 and Alix. This purified, homogeneous population of EVs was administered intravenously after subcortical stroke in rats. To evaluate the EVs effects, we studied the biodistribution, proteomics analysis, functional evaluation, lesion size, fiber tract integrity, axonal sprouting and white matter repair markers. We found that a single administration of EVs improved functional recovery, fiber tract integrity, axonal sprouting and white matter repair markers in an Experimental Animal model of subcortical stroke. EVs were found in the Animals’ brain and peripheral organs after euthanasia. White matter integrity was in part restored by EVs administration mediated by molecular repair factors implicated in axonal sprouting, tract connectivity, remyelination and oligodendrogenesis. These findings are associated with improved functional recovery. This novel role for EVs presents a new perspective in the development of biologics for brain repair.

  • adipose tissue derived mesenchymal stem cells as a strategy to improve recovery after stroke
    Expert Opinion on Biological Therapy, 2015
    Co-Authors: Maria Gutierrezfernandez, Berta Rodriguezfrutos, Blanca Fuentes, Laura Oteroortega, Jaime Ramoscejudo, Exuperio Dieztejedor
    Abstract:

    Introduction: Based on the positive results observed in Experimental Animal models, adipose tissue-derived mesenchymal stem cells (AD-MSCs) constitute a promising therapy for stroke treatment. However, several aspects need to be clarified to identify the optimal conditions for successful clinical translation.Areas covered: This review focuses on AD-MSC treatment for ischemic and hemorrhagic stroke in Experimental Animal models. In addition, we will explore the optimization of treatment conditions including AD-MSC production, administration routes and therapeutic windows for their appropriate use in patients. Finally we will provide an update on clinical trials on this therapy.Expert opinion: Compared with other cell types, AD-MSCs have been less investigated in stroke studies. Currently, Experimental Animal models have shown safety and efficacy with this treatment after stroke. Due to several advantages of AD-MSCs, such as their abundance and accessibility, they can be considered a promising strategy for ...

  • cdp choline treatment induces brain plasticity markers expression in Experimental Animal stroke
    Neurochemistry International, 2012
    Co-Authors: Maria Gutierrezfernandez, Berta Rodriguezfrutos, Blanca Fuentes, Maria Teresa Vallejocremades, Julia Alvarezgrech, Mercedes Expositoalcaide, Exuperio Dieztejedor
    Abstract:

    Abstract We investigated the effect of CDP-choline on brain plasticity markers expression in the acute phase of cerebral infarct in an Experimental Animal model. Male Sprague–Dawley rats were subjected to permanent middle cerebral artery occlusion (pMCAO) and treated or not with CDP-choline (500 mg/kg) daily for 14 days starting 30 min after pMCAO. Functional status was evaluated with Roger’s test; lesion volume with magnetic resonance imaging (MRI) and hematoxylin and eosin staining (HE cell death with TUNEL; cellular proliferation with BrdU immunohistochemistry; vascular endothelial growth factor (VEGF), synaptophysin, glial fibrillary acidic protein (GFAP) and low-density lipoprotein receptor-related protein (LRP) by immunofluorescence and Western-blot techniques. CDP-choline significantly improved functional recovery and decreased lesion volume on MRI, TUNEL-positive cell number and LRP levels at 14 days. In addition, CDP-choline significantly increased BrdU, VEGF and synaptophysin values and decreased GFAP levels in the peri-infarct zone compared with the infarct group. In conclusion, our data indicate that CDP-choline improved functional recovery after permanent middle cerebral artery occlusion in association with reductions in lesion volume, cell death and LRP expression. In fact, CDP-choline increased cell proliferation, vasculogenesis and synaptophysin levels and reduced GFAP levels in the peri-infarct area of the ischemic stroke.

Maria Gutierrezfernandez - One of the best experts on this subject based on the ideXlab platform.

  • exosomes promote restoration after an Experimental Animal model of intracerebral hemorrhage
    Journal of Cerebral Blood Flow and Metabolism, 2017
    Co-Authors: Laura Oteroortega, Berta Rodriguezfrutos, Exuperio Dieztejedor, Fernando Lasogarcia, Mari Carmen Gomezde Frutos, Esperanza Medinagutierrez, Juan Antonio Lopez, Jesus Vazquez, Maria Gutierrezfernandez
    Abstract:

    Exosomes are gaining importance because they show great promise in therapeutic applications for several diseases. Particularly in stroke, exosomes derived from mesenchymal stem cell (MSC) therapy work as paracrine effectors responsible for promoting neurovascular remodeling and functional recovery. Adult male rats were subjected to intracerebral hemorrhage (ICH) by intrastriatal injection of collagenase type IV; 24 h after surgery, MSC-derived exosomes were administered through the tail vein. The rats were euthanized at 7 or 28 days after treatment. Functional evaluation, lesion size, fiber tract integrity, axonal sprouting and white matter repair markers, biodistribution of exosomes and secretome proteomics were analyzed. DiI-labeled exosomes were found in the brains of the ICH-treated group and in the liver, lung and spleen. Animals receiving treatment with exosomes showed significantly better results in terms of functional recovery, lesion size, fiber tract integrity, axonal sprouting and white matter repair markers compared with the control group 28 days after stroke. Proteomics analysis of the exosomes identified more than 2000 proteins that could be implicated in brain repair function. In conclusion, white matter integrity was partly restored by exosome administration mediated by molecular repair factors. Exosomes as a treatment could be a heterogeneous process by nature and presents many factors that can influence brain plasticity in an adaptable and versatile manner.

  • white matter repair after extracellular vesicles administration in an Experimental Animal model of subcortical stroke
    Scientific Reports, 2017
    Co-Authors: Laura Oteroortega, Berta Rodriguezfrutos, Blanca Fuentes, Exuperio Dieztejedor, Fernando Lasogarcia, Maria Del Carmen Gomezde Frutos, Jorge Pascualguerra, Maria Gutierrezfernandez
    Abstract:

    Mesenchymal stem cells have previously been shown to mediate brain repair after stroke; they secrete 50–100 nm complexes called extracellular vesicles (EVs), which could be responsible for provoking neurovascular repair and functional recovery. EVs have been observed by electron microscopy and NanoSight, and they contain associated proteins such as CD81 and Alix. This purified, homogeneous population of EVs was administered intravenously after subcortical stroke in rats. To evaluate the EVs effects, we studied the biodistribution, proteomics analysis, functional evaluation, lesion size, fiber tract integrity, axonal sprouting and white matter repair markers. We found that a single administration of EVs improved functional recovery, fiber tract integrity, axonal sprouting and white matter repair markers in an Experimental Animal model of subcortical stroke. EVs were found in the Animals’ brain and peripheral organs after euthanasia. White matter integrity was in part restored by EVs administration mediated by molecular repair factors implicated in axonal sprouting, tract connectivity, remyelination and oligodendrogenesis. These findings are associated with improved functional recovery. This novel role for EVs presents a new perspective in the development of biologics for brain repair.

  • adipose tissue derived mesenchymal stem cells as a strategy to improve recovery after stroke
    Expert Opinion on Biological Therapy, 2015
    Co-Authors: Maria Gutierrezfernandez, Berta Rodriguezfrutos, Blanca Fuentes, Laura Oteroortega, Jaime Ramoscejudo, Exuperio Dieztejedor
    Abstract:

    Introduction: Based on the positive results observed in Experimental Animal models, adipose tissue-derived mesenchymal stem cells (AD-MSCs) constitute a promising therapy for stroke treatment. However, several aspects need to be clarified to identify the optimal conditions for successful clinical translation.Areas covered: This review focuses on AD-MSC treatment for ischemic and hemorrhagic stroke in Experimental Animal models. In addition, we will explore the optimization of treatment conditions including AD-MSC production, administration routes and therapeutic windows for their appropriate use in patients. Finally we will provide an update on clinical trials on this therapy.Expert opinion: Compared with other cell types, AD-MSCs have been less investigated in stroke studies. Currently, Experimental Animal models have shown safety and efficacy with this treatment after stroke. Due to several advantages of AD-MSCs, such as their abundance and accessibility, they can be considered a promising strategy for ...

  • cdp choline treatment induces brain plasticity markers expression in Experimental Animal stroke
    Neurochemistry International, 2012
    Co-Authors: Maria Gutierrezfernandez, Berta Rodriguezfrutos, Blanca Fuentes, Maria Teresa Vallejocremades, Julia Alvarezgrech, Mercedes Expositoalcaide, Exuperio Dieztejedor
    Abstract:

    Abstract We investigated the effect of CDP-choline on brain plasticity markers expression in the acute phase of cerebral infarct in an Experimental Animal model. Male Sprague–Dawley rats were subjected to permanent middle cerebral artery occlusion (pMCAO) and treated or not with CDP-choline (500 mg/kg) daily for 14 days starting 30 min after pMCAO. Functional status was evaluated with Roger’s test; lesion volume with magnetic resonance imaging (MRI) and hematoxylin and eosin staining (HE cell death with TUNEL; cellular proliferation with BrdU immunohistochemistry; vascular endothelial growth factor (VEGF), synaptophysin, glial fibrillary acidic protein (GFAP) and low-density lipoprotein receptor-related protein (LRP) by immunofluorescence and Western-blot techniques. CDP-choline significantly improved functional recovery and decreased lesion volume on MRI, TUNEL-positive cell number and LRP levels at 14 days. In addition, CDP-choline significantly increased BrdU, VEGF and synaptophysin values and decreased GFAP levels in the peri-infarct zone compared with the infarct group. In conclusion, our data indicate that CDP-choline improved functional recovery after permanent middle cerebral artery occlusion in association with reductions in lesion volume, cell death and LRP expression. In fact, CDP-choline increased cell proliferation, vasculogenesis and synaptophysin levels and reduced GFAP levels in the peri-infarct area of the ischemic stroke.

Sang-ha Oh - One of the best experts on this subject based on the ideXlab platform.

  • Proper Choice of Vessels for Supermicrosurgery Training: An Experimental Animal study.
    Journal of reconstructive microsurgery, 2018
    Co-Authors: Yooseok Ha, Seung Han Song, Nak Heon Kang, Sang-ha Oh
    Abstract:

     Reconstruction using supermicrosurgery, a technique of microneurovascular anastomosis for smaller vessels (< 0.8 mm), has become popular. Experimental Animal studies for supermicrosurgery training have been reported; however, there have been few studies performed according to vessel diameter and pedicle length. In this study, the external diameters of four vessels (femoral, superficial epigastric, axillary, and common thoracic) and pedicle length of two flaps (superficial epigastric and common thoracic-long thoracic) were measured.  The inguinal and pectoral regions of Sprague-Dawley rats (n = 19) were dissected anatomically, and the external diameters of the four vessels were measured (right and left, artery and vein measured separately). After elevating the superficial epigastric and common thoracic-long thoracic flaps, the pedicle length of the flaps was also measured.  Among the 16 vessels examined, the external diameters of 11 and 5 vessels were above and below 0.8 mm, respectively. The external diameters of the superficial epigastric vessel and common thoracic vessel (both arteries and veins) were below 0.8 mm. The external diameters of the femoral and axillary vessels (veins) were above 0.8 mm. The length of the common thoracic-long thoracic pedicle was approximately10 mm longer than that of the superficial epigastric pedicle.  The external diameters of the superficial epigastric vessel and common thoracic vessel are small enough for supermicrosurgery training. The pedicle lengths of both the superficial epigastric and common thoracic-long thoracic flaps are sufficient to perform free flap experiments. Supermicrosurgical free flaps using these two vessels and a study of the physiology and pharmacology of the flaps will likely be possible in the future. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  • Proper Choice of Vessels for Supermicrosurgery Training: An Experimental Animal study.
    Journal of Reconstructive Microsurgery, 2018
    Co-Authors: Yooseok Ha, Seung Han Song, Nak Heon Kang, Sang-ha Oh
    Abstract:

    Background  Reconstruction using supermicrosurgery, a technique of microneurovascular anastomosis for smaller vessels ( Methods  The inguinal and pectoral regions of Sprague-Dawley rats ( n  = 19) were dissected anatomically, and the external diameters of the four vessels were measured (right and left, artery and vein measured separately). After elevating the superficial epigastric and common thoracic–long thoracic flaps, the pedicle length of the flaps was also measured. Results  Among the 16 vessels examined, the external diameters of 11 and 5 vessels were above and below 0.8 mm, respectively. The external diameters of the superficial epigastric vessel and common thoracic vessel (both arteries and veins) were below 0.8 mm. The external diameters of the femoral and axillary vessels (veins) were above 0.8 mm. The length of the common thoracic–long thoracic pedicle was approximately10 mm longer than that of the superficial epigastric pedicle. Conclusions  The external diameters of the superficial epigastric vessel and common thoracic vessel are small enough for supermicrosurgery training. The pedicle lengths of both the superficial epigastric and common thoracic–long thoracic flaps are sufficient to perform free flap experiments. Supermicrosurgical free flaps using these two vessels and a study of the physiology and pharmacology of the flaps will likely be possible in the future.