title: Combined SCI and TBI: recovery of forelimb function after unilateral cervical spinal cord injury (SCI) is retarded by contralateral traumatic brain injury (TBI), and ipsilateral TBI balances the effects of SCI on paw placement.
abstract: A significant proportion (estimates range from 16 to 74%) of patients with spinal cord injury (SCI) have concomitant traumatic brain injury (TBI), and the combination often produces difficulties in planning and implementing rehabilitation strategies and drug therapies. For example, many of the drugs used to treat SCI may interfere with cognitive rehabilitation, and conversely drugs that are used to control seizures in TBI patients may undermine locomotor recovery after SCI. The current paper presents an experimental animal model for combined SCI and TBI to help drive mechanistic studies of dual diagnosis. Rats received a unilateral SCI (75 kdyn) at C5 vertebral level, a unilateral TBI (2.0 mm depth, 4.0 m/s velocity impact on the forelimb sensori-motor cortex), or both SCI+TBI. TBI was placed either contralateral or ipsilateral to the SCI. Behavioral recovery was examined using paw placement in a cylinder, grooming, open field locomotion, and the IBB cereal eating test. Over 6weeks, in the paw placement test, SCI+contralateral TBI produced a profound deficit that failed to recover, but SCI+ipsilateral TBI increased the relative use of the paw on the SCI side. In the grooming test, SCI+contralateral TBI produced worse recovery than either lesion alone even though contralateral TBI alone produced no observable deficit. In the IBB forelimb test, SCI+contralateral TBI revealed a severe deficit that recovered in 3 weeks. For open field locomotion, SCI alone or in combination with TBI resulted in an initial deficit that recovered in 2 weeks. Thus, TBI and SCI affected forelimb function differently depending upon the test, reflecting different neural substrates underlying, for example, exploratory paw placement and stereotyped grooming. Concurrent SCI and TBI had significantly different effects on outcomes and recovery, depending upon laterality of the two lesions. Recovery of function after cervical SCI was retarded by the addition of a moderate TBI in the contralateral hemisphere in all tests, but forepaw placements were relatively increased by an ipsilateral TBI relative to SCI alone, perhaps due to the dual competing injuries influencing the use of both forelimbs. These findings emphasize the complexity of recovery from combined CNS injuries, and the possible role of plasticity and laterality in rehabilitation, and provide a start towards a useful preclinical model for evaluating effective therapies for combine SCI and TBI.
authors.affiliation: Department of Neurological Surgery, University of California San Francisco, and San Francisco General Hospital, San Francisco, CA, USA; Brain and Spinal Injury Center, University of California San Francisco, San Francisco, CA, USA. Electronic address: inouet@neurosurg.ucsf.edu.
authors.forename: Tomoo
authors.initials: T
authors.lastname: Inoue
authors.forename: Amity
authors.initials: A
authors.lastname: Lin
authors.forename: Xiaokui
authors.initials: X
authors.lastname: Ma
authors.forename: Stephen L
authors.initials: SL
authors.lastname: McKenna
authors.forename: Graham H
authors.initials: GH
authors.lastname: Creasey
authors.forename: Geoffrey T
authors.initials: GT
authors.lastname: Manley
authors.forename: Adam R
authors.initials: AR
authors.lastname: Ferguson
authors.forename: Jacqueline C
authors.initials: JC
authors.lastname: Bresnahan
authors.forename: Michael S
authors.initials: MS
authors.lastname: Beattie
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000150:complications / Q000503:physiopathology*; D002574:Cervical Vertebrae; D005260:Female; D005552:Forelimb / Q000503:physiopathology*; D007839:Functional Laterality / Q000502:physiology*; D006120:Grooming / Q000502:physiology; D009043:Motor Activity / Q000502:physiology*; D009044:Motor Cortex / Q000503:physiopathology; D051381:Rats; D020318:Rats, Long-Evans; D020127:Recovery of Function / Q000502:physiology*; D013116:Spinal Cord / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000150:complications / Q000503:physiopathology*
keywords: ANOVA; BBB; Basso,Beattie,Bresnahan Locomotor Rating Scale; Behavioral analysis; CCI; CT; HD; IBB; IH; Infinite Horizons impactor; Irvine,Beatties,Bresnahan forelimb rating scale; MRI; Neuronal plasticity; PBS; SCI; SEM; Spinal cord injury; TBI; Traumatic brain injury; analysis of variance; computed tomography; controlled cortical impact; high definition; magnetic resonance imaging; phosphate buffered saline; spinal cord injury; standard error of the mean; traumatic brain injury; ‘Dual diagnosis’