title: The volatile anesthetic methoxyflurane protects motoneurons against excitotoxicity in an in vitro model of rat spinal cord injury.
abstract: Neuroprotection of the spinal cord during the early phase of injury is an important goal to determine a favorable outcome by prevention of delayed pathological events, including excitotoxicity, which otherwise extend the primary damage and amplify the often irreversible loss of motor function. While intensive care and neurosurgical intervention are important treatments, effective neuroprotection requires further experimental studies focused to target vulnerable neurons, particularly motoneurons. The present investigation examined whether the volatile general anesthetic methoxyflurane might protect spinal locomotor networks from kainate-evoked excitotoxicity using an in vitro rat spinal cord preparation as a model. The protocols involved 1h excitotoxic stimulation on day 1 followed by electrophysiological and immunohistochemical testing on day 2. A single administration of methoxyflurane applied together with kainate (1h), or 30 or even 60 min later prevented any depression of spinal reflexes, loss of motoneuron excitability, and histological damage. Methoxyflurane per se temporarily decreased synaptic transmission and motoneuron excitability, effects readily reversible on washout. Spinal locomotor activity recorded as alternating electrical discharges from lumbar motor pools was fully preserved on the second day after application of methoxyflurane together with (or after) kainate. These data suggest that a volatile general anesthetic could provide strong electrophysiological and histological neuroprotection that enabled expression of locomotor network activity 1 day after the excitotoxic challenge. It is hypothesized that the benefits of early neurosurgery for acute spinal cord injury (SCI) might be enhanced if, in addition to injury decompression and stabilization, the protective role of general anesthesia is exploited.
authors.affiliation: Neuroscience Department, Scuola Internazionale Superiore di Studi Avanzati (SISSA), Trieste, Italy. Electronic address: ashabbir@sissa.it.
authors.forename: A
authors.initials: A
authors.lastname: Shabbir
authors.affiliation: Neuroscience Department, Scuola Internazionale Superiore di Studi Avanzati (SISSA), Trieste, Italy. Electronic address: eb2985@columbia.edu.
authors.forename: E
authors.initials: E
authors.lastname: Bianchetti
authors.affiliation: Neuroscience Department, Scuola Internazionale Superiore di Studi Avanzati (SISSA), Trieste, Italy. Electronic address: nistri@sissa.it.
authors.forename: A
authors.initials: A
authors.lastname: Nistri
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000208:Acute Disease; D018685:Anesthetics, Inhalation / Q000494:pharmacology; D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D007608:Kainic Acid / Q000633:toxicity; D008124:Locomotion / Q000187:drug effects* / Q000502:physiology; D008733:Methoxyflurane / Q000494:pharmacology*; D009046:Motor Neurons / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017208:Rats, Wistar; D012018:Reflex / Q000187:drug effects / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D046509:Tissue Culture Techniques; D016896:Treatment Outcome
chemical_list: D018685:Anesthetics, Inhalation; D018690:Excitatory Amino Acid Agonists; D018696:Neuroprotective Agents; D008733:Methoxyflurane; D007608:Kainic Acid
keywords: fictive locomotion; motoneurons; spinal locomotor network; spinal reflex