title: Effects of acute intrathecal baclofen in an animal model of TBI-induced spasticity, cognitive, and balance disabilities.
abstract: Spasticity is a major health problem for patients with traumatic brain injury (TBI). In addition to spasticity, TBI patients exhibit enduring cognitive, balance, and other motor impairments. Although the use of antispastic medications, particularly ITB, can decrease the severity of TBI-induced spasticity, current guidelines preclude the use of ITB during the first year after TBI. Therefore, the present study was performed to quantitate disability in an animal model of closed-head TBI (cTBI; Mararou's model) after ITB treatment. After cTBI, significant deficits in spasticity and gait, cognitive, balance, and anxiety-like behaviors were detected. ITB (Lioresal(®)) or saline was administered using Alzet pumps (0.8 μg/hour for 4 weeks). Spasticity measures using velocity-dependent ankle torque and ankle extensor muscle electromyography recordings, footprints (gait), balance performance tests, serial learning, and anxiety-like behaviors were performed at multiple post-treatment and -withdrawal of ITB time points. Our data indicated that 1 month of ITB treatment initiated at post-TBI week 1 blocked the early onset of spasticity and significantly attenuated late-onset spasticity and anxiety-like behavior with no significant adverse effects on cognitive and balance performance. This improved spasticity outcome was accompanied by marked up-regulation of gamma-aminobutyric acid (GABA)/GABAb, norepinephrine, and brain-derived neurotrophic factor expression in spinal cord tissue. Early intervention with ITB treatment was safe, feasible, and effective in this cTBI animal model. Collectively, these data provide a strong molecular footprint of enhanced expression of reflex regulation by presynaptic inhibition. The possibility that acute ITB treatment may decrease maladaptive segmental and descending plasticity is discussed. The data provided by the present animal model initiates a pre-clinical platform for safety, feasibility, and efficacy of early ITB intervention after TBI.
authors.affiliation: Brain Rehabilitation Research Center (151), North Florida/South Georgia VA Health System, Gainesville, Florida 32608-1135, USA. prodip.bose@va.gov
authors.forename: Prodip
authors.initials: P
authors.lastname: Bose
authors.forename: Jiamei
authors.initials: J
authors.lastname: Hou
authors.forename: Rachel
authors.initials: R
authors.lastname: Nelson
authors.forename: Nicole
authors.initials: N
authors.lastname: Nissim
authors.forename: Ron
authors.initials: R
authors.lastname: Parmer
authors.forename: Jonathon
authors.initials: J
authors.lastname: Keener
authors.forename: Paul W
authors.initials: PW
authors.lastname: Wacnik
authors.forename: Floyd J
authors.initials: FJ
authors.lastname: Thompson
mesh_terms: D000818:Animals; D001418:Baclofen / Q000008:administration & dosage*; D001522:Behavior, Animal / Q000187:drug effects; D001930:Brain Injuries / Q000150:complications*; D003071:Cognition / Q000187:drug effects*; D004195:Disease Models, Animal; D019054:Evoked Potentials, Motor / Q000187:drug effects; D058786:GABA-B Receptor Agonists / Q000008:administration & dosage*; D007278:Injections, Spinal; D009128:Muscle Spasticity / Q000209:etiology; D004856:Postural Balance / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D058786:GABA-B Receptor Agonists; D001418:Baclofen