Extracellular magnesium enhances the damage to locomotor networks produced by metabolic perturbation mimicking spinal injury in the neonatal rat spinal cord in vitro.
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.
Margaryan
G
G
Neurobiology Sector, International School for Advanced Studies (SISSA), Via Beirut 2-4, 34151, Trieste, Italy.
Mladinic
M
M
Mattioli
C
C
Nistri
A
A
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*
D018690:Excitatory Amino Acid Agonists; D008274:Magnesium; D007608:Kainic Acid