title: Memantine plus vitamin D prevents axonal degeneration caused by lysed blood.
abstract: Intracranial hemorrhage, whether due to traumatic brain injury or ruptured cerebral aneurysm, is characterized by major neurological damage and a high mortality rate. Apart from cerebral vasospasm and mass effect, brain injury results from the release of unclotted blood that contacts neurons causing calcic stress. The combination of memantine with vitamin D, a neurosteroid hormone, may prevent blood neurotoxicity. Our purpose was to examine the potential protective effects of memantine + vitamin D against lysed or clotted blood in cortical neuronal cultures. We provide the first evidence that cortical axons in contact with lysed blood degenerate less after exposure to lysed blood in microfluidic neuronal cultures enriched with both memantine and vitamin D compared to control medium and cultures enriched with only memantine or only vitamin D. The reported synergistic neuroprotective effect of memantine + vitamin D, the combination originating an effect stronger than the sum, strongly encourages using both drugs following intracranial hemorrhage.
authors.affiliation: †Department of Anesthesiology and Intensive Care, University Hospital of Saint-Etienne, 42055 Saint-Etienne Cedex 2, France.
authors.forename: David
authors.initials: D
authors.lastname: Charier
authors.affiliation: ‡Department of Neuroscience, Division of Geriatric Medicine, Angers University Hospital, 49933 Angers Cedex 9, France.|§University Memory Clinic, 49933 Angers Cedex 9, France.|∥UPRES EA 4638, University of Angers, UNAM, 49000 Angers, France.|⊥Biomathics, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Beauchet
authors.affiliation: #CNRS UMR 8256, Biological Adaptation and Ageing, Paris, France.|∇Sorbonne University, UPMC University Paris 6, UMR7102, 75006 Paris, France.
authors.forename: Morgane
authors.initials: M
authors.lastname: Bell
authors.affiliation: #CNRS UMR 8256, Biological Adaptation and Ageing, Paris, France.|∇Sorbonne University, UPMC University Paris 6, UMR7102, 75006 Paris, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Brugg
authors.affiliation: ○Robarts Research Institute, Schulich School of Medicine and Dentistry, the University of Western Ontario, London, Ontario N6A 3K7, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Bartha
authors.affiliation: ‡Department of Neuroscience, Division of Geriatric Medicine, Angers University Hospital, 49933 Angers Cedex 9, France.|§University Memory Clinic, 49933 Angers Cedex 9, France.|∥UPRES EA 4638, University of Angers, UNAM, 49000 Angers, France.|○Robarts Research Institute, Schulich School of Medicine and Dentistry, the University of Western Ontario, London, Ontario N6A 3K7, Canada.
authors.forename: Cedric
authors.initials: C
authors.lastname: Annweiler
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects*; D001773:Blood Cells / Q000166:cytology; D001777:Blood Coagulation; D002458:Cell Fractionation; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004357:Drug Synergism; D004622:Embryo, Mammalian; D056656:Lab-On-A-Chip Devices; D008559:Memantine / Q000494:pharmacology*; D051379:Mice; D009410:Nerve Degeneration / Q000517:prevention & control*; D009474:Neurons / Q000166:cytology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D014807:Vitamin D / Q000494:pharmacology*
chemical_list: D018696:Neuroprotective Agents; D014807:Vitamin D; D008559:Memantine
keywords: Intracranial hemorrhage; blood; memantine; neuroprotection; vitamin D