Superoxide dismutase reduces monosodium glutamate-induced injury in an organotypic whole hemisphere brain slice model of excitotoxicity

• Published in: Journal of biological engineering Vol. 14; no. 1; p. 3
• Main Authors: Liao, Rick, Wood, Thomas R, Nance, Elizabeth
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 04.02.2020; BioMed Central; BMC
• Subjects: 8-hydroxy-2-deoxyguanosine; Antioxidants (Nutrients); Apoptosis; Biochemistry; Brain; Brain injury; Brain slice preparation; Cell death; Cell viability; Cytology; Cytotoxicity; Dehydrogenases; Disease; Enzymes; Excitation; Excitotoxicity; Experiments; Gene expression; Genes; Glutamate; Hyperosmolar stress; Immunoglobulins; Injury prevention; Laboratory animals; Mitochondria; Monosodium glutamate; Morphology; Neuroinflammation; Neurons; Osmotic pressure; Oxidative stress; Penicillin; Peroxynitrite; Scavenging; Sodium glutamate; Superoxide dismutase; Superoxides; Therapeutics; Toxicity; Traumatic brain injury; Tumor necrosis factor-TNF; Canada; Oxidative stress; Mitochondria; Peroxynitrite; Ex vivo; 8-hydroxy-2-deoxyguanosine; Neuroinflammation; Hyperosmolar stress; Antioxidant
• ISSN: 1754-1611; 1754-1611
• DOI: 10.1186/s13036-020-0226-8

Knowledge of glutamate excitotoxicity has increased substantially over the past few decades, with multiple proposed pathways involved in inflicting damage. We sought to develop a monosodium glutamate (MSG) exposed ex vivo organotypic whole hemisphere (OWH) brain slice model of excitotoxicity to study excitotoxic processes and screen the efficacy of superoxide dismutase (SOD). The OWH model is a reproducible platform with high cell viability and retained cellular morphology. OWH slices exposed to MSG induced significant cytotoxicity and downregulation of neuronal excitation-related gene expression. The OWH brain slice model has enabled us to isolate and study components of excitotoxicity, distinguishing the effects of glutamate excitation, hyperosmolar stress, and inflammation. We find that extracellularly administered SOD is significantly protective in inhibiting cell death and restoring healthy mitochondrial morphology. SOD efficacy suggests that superoxide scavenging is a promising therapeutic strategy in excitotoxic injury. Using OWH brain slice models, we can obtain a better understanding of the pathological mechanisms of excitotoxic injury, and more rapidly screen potential therapeutics.