title: Thoracic 9 Spinal Transection-Induced Model of Muscle Spasticity in the Rat: A Systematic Electrophysiological and Histopathological Characterization.
abstract: The development of spinal hyper-reflexia as part of the spasticity syndrome represents one of the major complications associated with chronic spinal traumatic injury (SCI). The primary mechanism leading to progressive appearance of muscle spasticity is multimodal and may include loss of descending inhibitory tone, alteration of segmental interneuron-mediated inhibition and/or increased reflex activity to sensory input. Here, we characterized a chronic thoracic (Th 9) complete transection model of muscle spasticity in Sprague-Dawley (SD) rats. Isoflurane-anesthetized rats received a Th9 laminectomy and the spinal cord was transected using a scalpel blade. After the transection the presence of muscle spasticity quantified as stretch and cutaneous hyper-reflexia was identified and quantified as time-dependent changes in: i) ankle-rotation-evoked peripheral muscle resistance (PMR) and corresponding electromyography (EMG) activity, ii) Hoffmann reflex, and iii) EMG responses in gastrocnemius muscle after paw tactile stimulation for up to 8 months after injury. To validate the clinical relevance of this model, the treatment potency after systemic treatment with the clinically established anti-spastic agents baclofen (GABAB receptor agonist), tizanidine (α2-adrenergic agonist) and NGX424 (AMPA receptor antagonist) was also tested. During the first 3 months post spinal transection, a progressive increase in ankle rotation-evoked muscle resistance, Hoffmann reflex amplitude and increased EMG responses to peripherally applied tactile stimuli were consistently measured. These changes, indicative of the spasticity syndrome, then remained relatively stable for up to 8 months post injury. Systemic treatment with baclofen, tizanidine and NGX424 led to a significant but transient suppression of spinal hyper-reflexia. These data demonstrate that a chronic Th9 spinal transection model in adult SD rat represents a reliable experimental platform to be used in studying the pathophysiology of chronic spinal injury-induced spasticity. In addition a consistent anti-spastic effect measured after treatment with clinically effective anti-spastic agents indicate that this model can effectively be used in screening new anti-spasticity compounds or procedures aimed at modulating chronic spinal trauma-associated muscle spasticity.
authors.affiliation: Neuroregeneration Laboratory, Department of Anesthesiology, University of California - San Diego, La Jolla, California, United States of America.|Biomedical Sciences Graduate Program University of California San Diego, La Jolla, California, United States of America.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Corleto
authors.affiliation: Neuroregeneration Laboratory, Department of Anesthesiology, University of California - San Diego, La Jolla, California, United States of America.|Department of Pharmacobiology, Centro de Investigacion y de Estudios Avanzados Cinvestav) Sede Sur, Mexico D.F., Mexico.
authors.forename: Mariana
authors.initials: M
authors.lastname: Bravo-Hernández
authors.affiliation: Neuroregeneration Laboratory, Department of Anesthesiology, University of California - San Diego, La Jolla, California, United States of America.
authors.forename: Kota
authors.initials: K
authors.lastname: Kamizato
authors.affiliation: Neuroregeneration Laboratory, Department of Anesthesiology, University of California - San Diego, La Jolla, California, United States of America.
authors.forename: Osamu
authors.initials: O
authors.lastname: Kakinohana
authors.affiliation: Neuroregeneration Laboratory, Department of Anesthesiology, University of California - San Diego, La Jolla, California, United States of America.
authors.forename: Camila
authors.initials: C
authors.lastname: Santucci
authors.affiliation: Neuroregeneration Laboratory, Department of Anesthesiology, University of California - San Diego, La Jolla, California, United States of America.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Navarro
authors.affiliation: Neuroregeneration Laboratory, Department of Anesthesiology, University of California - San Diego, La Jolla, California, United States of America.
authors.forename: Oleksandr
authors.initials: O
authors.lastname: Platoshyn
authors.affiliation: Institute of Neurobiology, Slovak Academy of Sciences, Soltesovej 6, Kosice, Slovakia.
authors.forename: Dasa
authors.initials: D
authors.lastname: Cizkova
authors.affiliation: Institute of Neurobiology, Slovak Academy of Sciences, Soltesovej 6, Kosice, Slovakia.
authors.forename: Nadezda
authors.initials: N
authors.lastname: Lukacova
authors.affiliation: Hospital Nacional de Paraplejicos, SESCAM, Toledo, Spain.
authors.forename: Julian
authors.initials: J
authors.lastname: Taylor
authors.affiliation: Neuroregeneration Laboratory, Department of Anesthesiology, University of California - San Diego, La Jolla, California, United States of America.|Institute of Neurobiology, Slovak Academy of Sciences, Soltesovej 6, Kosice, Slovakia.
authors.forename: Martin
authors.initials: M
authors.lastname: Marsala
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004576:Electromyography; D005260:Female; D006614:Hindlimb / Q000503:physiopathology; D008161:Lumbosacral Region / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009128:Muscle Spasticity / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D018482:Muscle, Skeletal / Q000473:pathology / Q000503:physiopathology; D017207:Rats, Sprague-Dawley; D012021:Reflex, Abnormal; D013116:Spinal Cord / Q000473:pathology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D013904:Thoracic Vertebrae / Q000473:pathology; D055698:Touch Perception