title: Suppression of excitotoxicity and foreign body response by memantine in chronic cannula implantation into the rat brain.
abstract: Chronic brain implants are accompanied by a tissue response that causes the loss of neurons in the vicinity of the implant and the formation of a glial scar that is also referred to as foreign body response. Despite immense progress in the field of brain-computer interface (BCI) research the biocompatibility of chronic brain implants remains a primary concern in device design. Excitotoxic overstimulation of NMDA-receptors by extrasynaptic glutamate plays a pivotal role in cell death in the acute phase of the tissue reaction. In this study, we examined the effect of the uncompetitive NMDA-receptor antagonist memantine locally applied during cannula implantation in the caudal forelimb area (CFA) of the motor cortex (M1) in Lister Hooded rats on their behavioural performance in a skilled reaching and a rung-ladder task as well as in the open field. Moreover, the distribution of neurons and glial cells in the vicinity of the implant were assessed. Memantine improved the performance in the behavioural paradigms compared to controls and increased the number of surviving neurons in the vicinity of the implant even above basal levels accompanied by a reduction in astrocytic scar formation directly around the implant with no effect on the microglia/macrophage activation two and six weeks after cannula implantation. These findings suggest that memantine is a potential therapeutic agent in the acute phase of chronic foreign body implantation in the motor cortex in terms of increasing the viability of neurons adjacent to the implant and of improving the behavioural outcome after surgery.
authors.affiliation: Department of Neuropharmacology, Brain Research Institute, Centre for Cognitive Sciences, University of Bremen, 28334 Bremen, Germany. Electronic address: linda.hayn@uni-bremen.de.
authors.forename: Linda
authors.initials: L
authors.lastname: Hayn
authors.affiliation: Department of Neuropharmacology, Brain Research Institute, Centre for Cognitive Sciences, University of Bremen, 28334 Bremen, Germany. Electronic address: michael.koch@uni-bremen.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Koch
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D001696:Biomechanical Phenomena; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002408:Catheters, Indwelling / Q000009:adverse effects*; D002470:Cell Survival / Q000187:drug effects; D002921:Cicatrix / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005552:Forelimb / Q000503:physiopathology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D008297:Male; D008559:Memantine / Q000494:pharmacology*; D008840:Microfilament Proteins / Q000378:metabolism; D017628:Microglia / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009044:Motor Cortex / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats
chemical_list: C100745:Aif1 protein, rat; D034961:Antigens, Nuclear; D002135:Calcium-Binding Proteins; D018691:Excitatory Amino Acid Antagonists; D005904:Glial Fibrillary Acidic Protein; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; C546339:Rbfox3 protein, rat; D018698:Glutamic Acid; D008559:Memantine
keywords: Excitotoxicity; Foreign body response; Glutamate; Implant; Memantine; Skilled reaching task