title: BID Mediates Oxygen-Glucose Deprivation-Induced Neuronal Injury in Organotypic Hippocampal Slice Cultures and Modulates Tissue Inflammation in a Transient Focal Cerebral Ischemia Model without Changing Lesion Volume.
abstract: The BH3 interacting-domain death agonist (BID) is a pro-apoptotic protein involved in death receptor-induced and mitochondria-mediated apoptosis. Recently, it has also been suggested that BID is involved in the regulation of inflammatory responses in the central nervous system. We found that BID deficiency protected organotypic hippocampal slice cultures in vitro from neuronal injury induced by oxygen-glucose deprivation. In vivo, BID-knockout (KO) mice and wild type (WT) mice were subjected to 60 min of transient middle cerebral artery occlusion (tMCAO) to induce focal cerebral ischemia, and allowed to recover for 24 h. Infarct volumes and functional outcome were assessed and the inflammatory response was evaluated using immunofluorescence, Western blotting, quantitative PCR (qPCR) and Mesoscale multiplex analysis. We observed no difference in the infarct volume or neurological outcome between BID-KO and WT mice. The inflammatory response was reduced by BID deficiency as indicated by a change in microglial/leukocyte response. In conclusion, our data suggest that BID deficiency is neuroprotective in an in vitro model and modulates the inflammatory response to focal cerebral ischemia in vivo. However, this is not translated into a robust neuroprotection in vivo.
authors: Department of Neurology, Institute of Clinical Research, Odense University HospitalOdense, Denmark; Department of Physiology and Medical Physics, Centre for the Study of Neurological Disorders and 3U-COEN, Royal College of Surgeons in IrelandDublin, Ireland; Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern DenmarkOdense, Denmark.
authors: Nellie Anne
authors: NA
authors: Martin
authors: Department of Physiology and Medical Physics, Centre for the Study of Neurological Disorders and 3U-COEN, Royal College of Surgeons in Ireland Dublin, Ireland.
authors: Helena
authors: H
authors: Bonner
authors: Department of Neurology, Institute of Clinical Research, Odense University HospitalOdense, Denmark; Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern DenmarkOdense, Denmark.
authors: Maria Louise
authors: ML
authors: Elkjær
authors: Department of Physiology and Medical Physics, Centre for the Study of Neurological Disorders and 3U-COEN, Royal College of Surgeons in Ireland Dublin, Ireland.
authors: Beatrice
authors: B
authors: D'Orsi
authors: Department of Physiology and Medical Physics, Centre for the Study of Neurological Disorders and 3U-COEN, Royal College of Surgeons in Ireland Dublin, Ireland.
authors: Gang
authors: G
authors: Chen
authors: Department of Physiology and Medical Physics, Centre for the Study of Neurological Disorders and 3U-COEN, Royal College of Surgeons in Ireland Dublin, Ireland.
authors: Hans Georg
authors: HG
authors: König
authors: Department of Experimental Medical Sciences, Experimental Neuroinflammation Laboratory, Lund University Lund, Sweden.
authors: Martina
authors: M
authors: Svensson
authors: Department of Experimental Medical Sciences, Experimental Neuroinflammation Laboratory, Lund University Lund, Sweden.
authors: Tomas
authors: T
authors: Deierborg
authors: Department of Physiology and Medical Physics, Centre for the Study of Neurological Disorders and 3U-COEN, Royal College of Surgeons in Ireland Dublin, Ireland.
authors: Shona
authors: S
authors: Pfeiffer
authors: Department of Physiology and Medical Physics, Centre for the Study of Neurological Disorders and 3U-COEN, Royal College of Surgeons in Ireland Dublin, Ireland.
authors: Jochen H
authors: JH
authors: Prehn
authors: Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark Odense, Denmark.
authors: Kate Lykke
authors: KL
authors: Lambertsen
keywords: BID; focal cerebral ischemia; inflammation; neuronal injury; organotypic hippocampal slice cultures