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Neuroprotective Eff...
Neuroprotective Effects of Cyclosporine in a Porcine Pre-Clinical Trial of Focal Traumatic Brain Injury
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- Karlsson, Michael (författare)
- Lund University,Lunds universitet,Mitokondriell Medicin,Forskargrupper vid Lunds universitet,Mitochondrial Medicine,Lund University Research Groups,University of Pennsylvania,NeuroVive Pharmaceutical AB,Copenhagen University Hospital
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- Pukenas, Bryan (författare)
- University of Pennsylvania,Hospital of the University of Pennsylvania
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- Chawla, Sanjeev (författare)
- University of Pennsylvania,Hospital of the University of Pennsylvania
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- Ehinger, Johannes K. (författare)
- Lund University,Lunds universitet,Mitokondriell Medicin,Forskargrupper vid Lunds universitet,Mitochondrial Medicine,Lund University Research Groups,University of Pennsylvania,NeuroVive Pharmaceutical AB,The Children's Hospital of Philadelphia
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- Plyler, Ross (författare)
- University of Pennsylvania
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- Stolow, Madeline (författare)
- University of Pennsylvania
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- Gabello, Melissa (författare)
- University of Pennsylvania,The Children's Hospital of Philadelphia
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- Hugerth, Matilda (författare)
- NeuroVive Pharmaceutical AB
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- Elmér, Eskil (författare)
- Lund University,Lunds universitet,Mitokondriell Medicin,Forskargrupper vid Lunds universitet,Mitochondrial Medicine,Lund University Research Groups,NeuroVive Pharmaceutical AB
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- Hansson, Magnus J. (författare)
- Lund University,Lunds universitet,Mitokondriell Medicin,Forskargrupper vid Lunds universitet,Mitochondrial Medicine,Lund University Research Groups,NeuroVive Pharmaceutical AB
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- Margulies, Susan (författare)
- University of Pennsylvania
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- Kilbaugh, Todd (författare)
- University of Pennsylvania,The Children's Hospital of Philadelphia
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(creator_code:org_t)
- Mary Ann Liebert Inc, 2019
- 2019
- Engelska 11 s.
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert Inc. - 0897-7151 .- 1557-9042. ; 36:1, s. 14-24
- Relaterad länk:
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http://dx.doi.org/10...
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https://www.liebertp...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Mitochondrial dysfunction is thought to be a hallmark of traumatic brain injury (TBI) and plays a pivotal role in the resulting cellular injury. Cyclophilin D-mediated activation of the mitochondrial permeability transition pore has been suggested to contribute to this secondary injury cascade. Cyclosporine possesses neuroprotective properties that have been attributed to the desensitization of mitochondrial permeability transition pore activation. In vivo animal experiments have demonstrated neuroprotective effects of cyclosporine in more than 20 independent experimental studies in a multitude of different experimental models. However, the majority of these studies have been carried out in rodents. The aim of the present study was to evaluate the efficacy of a novel and cremophor/kolliphor EL-free lipid emulsion formulation of cyclosporine in a translational large animal model of TBI. A mild-to-moderate focal contusion injury was induced in piglets using a controlled cortical impact device. After initial step-wise analyses of pharmacokinetics and comparing with exposure of cyclosporine in clinical TBI trials, a 5-day dosing regimen with continuous intravenous cyclosporine infusion (20 mg/kg/day) was evaluated in a randomized and blinded placebo-controlled setting. Cyclosporine reduced the volume of parenchymal injury by 35%, as well as improved markers of neuronal injury, as measured with magnetic resonance spectroscopic imaging. Further, a consistent trend toward positive improvements in brain metabolism and mitochondrial function was observed in the pericontusional tissue. In this study, we have demonstrated efficacy using a novel cyclosporine formulation in clinically relevant and translatable outcome metrics in a large animal model of focal TBI.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
Nyckelord
- magnetic resonance imaging
- magnetic resonance spectroscopy imaging
- mitochondria, traumatic brain injury
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- art (ämneskategori)
- ref (ämneskategori)
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Karlsson, Michae ...
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Pukenas, Bryan
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Chawla, Sanjeev
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Ehinger, Johanne ...
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Plyler, Ross
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Stolow, Madeline
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visa fler...
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Gabello, Melissa
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Hugerth, Matilda
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Elmér, Eskil
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Hansson, Magnus ...
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Margulies, Susan
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Kilbaugh, Todd
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visa färre...
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