title: Extracellular magnesium enhances the damage to locomotor networks produced by metabolic perturbation mimicking spinal injury in the neonatal rat spinal cord in vitro.
abstract: An acute injury to brain or spinal cord produces profound metabolic perturbation that extends and exacerbates tissue damage. Recent clinical interventions to treat this condition with i.v. Mg(2+) to stabilize its extracellular concentration provided disappointing results. The present study used an in vitro spinal cord model from the neonatal rat to investigate the role of extracellular Mg(2+) in the lesion evoked by a pathological medium mimicking the metabolic perturbation (hypoxia, aglycemia, oxidative stress, and acid pH) occurring in vivo. Damage was measured by taking as outcome locomotor network activity for up to 24 h after the primary insult. Pathological medium in 1 mM Mg(2+) solution (1 h) largely depressed spinal reflexes and suppressed fictive locomotion on the same and the following day. Conversely, pathological medium in either Mg(2+)-free or 5 mM Mg(2+) solution evoked temporary network depression and enabled fictive locomotion the day after. While global cell death was similar regardless of extracellular Mg(2+) solution, white matter was particularly affected. In ventral horn the number of surviving neurons was the highest in Mg(2+) free solution and the lowest in 1 mM Mg(2+), while motoneurons were unaffected. Although the excitotoxic damage elicited by kainate was insensitive to extracellular Mg(2+), 1 mM Mg(2+) potentiated the effect of combining pathological medium with kainate at low concentrations. These results indicate that preserving Mg(2+) homeostasis rendered experimental spinal injury more severe. Furthermore, analyzing ventral horn neuron numbers in relation to fictive locomotion expression might provide a first estimate of the minimal size of the functional locomotor network.
authors: Neurobiology Sector, International School for Advanced Studies (SISSA), Via Beirut 2-4, 34151, Trieste, Italy.
authors: G
authors: G
authors: Margaryan
authors: M
authors: M
authors: Mladinic
authors: C
authors: C
authors: Mattioli
authors: A
authors: A
authors: Nistri
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D016923:Cell Death; D015687:Cell Hypoxia / Q000502:physiology; D004525:Efferent Pathways / Q000473:pathology / Q000503:physiopathology; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D005110:Extracellular Space / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007003:Hypoglycemia / Q000473:pathology / Q000503:physiopathology; D007608:Kainic Acid / Q000633:toxicity; D008124:Locomotion / Q000502:physiology; D008274:Magnesium / Q000378:metabolism*; D009413:Nerve Fibers, Myelinated / Q000473:pathology / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012018:Reflex / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D013119:Spinal Cord Injuries / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*
chemical_list: D018690:Excitatory Amino Acid Agonists; D008274:Magnesium; D007608:Kainic Acid