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 16–74%) 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 6 weeks, 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.

Head injury with concurrent cervical spine injury

“…The combined injuries present a dilemma: 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 (14). A concomitant injury also increases the immune response several-fold with a more profound increase in the spinal cord relative to the brain and, therefore, contributing to the overall long-term morbidity and mortality (15).…”

“…For patients who were discharged, concomitant injury led to increased rehabilitation costs, poor neuropsychological test performances and greater demands on clinician resources than injuries in a single spectrum (18). Recovery of function after cervical SCI is retarded by a moderate TBI in the contra lateral hemisphere (14). A high level of social support is vital to help these patients in their daily lives (19).…”

Studies on long term behavioural changes in group-housed rat models of brain and spinal cord injury using an automated home cage recording system

“…It is important to note that our more detailed observations were carried out in time frames expressing high frequency of activity occurrence, thus we may be missing in grooming activity during more stationary behaviour periods. Alterations in grooming behaviour have been repeatedly studied in rat SCI, but mostly associated to the biomechanical impairments to groom effectively as a behavioural test, mostly in cervical SCI models (28)(29)(30). Grooming is also associated to the animal's self-care routine, and its failure may also be associated with mood impairments, such as depression caused by boredom and lack of social interaction (31).…”

Cognition among community-dwelling individuals with spinal cord injury.

“…Cognitive deficits after SCI are not the topic of many scientific investigations and may be clinically misinterpreted as nonadherence to treatment, inability to learn, poor coping, and/or poor motivation (Bradbury et al, 2008; Inoue et al, 2013; Kushner & Alvarez, 2014). This relative neglect and misunderstanding is unfortunate because cognitive limitations may affect some individuals’ rehabilitation, community reintegration, and/or quality of life (Bradbury et al, 2008; Davidoff et al, 1992).…”

“…However, despite the fact that cognition affects self-care and community reintegration (Bradbury et al, 2008; Davidoff, Roth, & Richards, 1992), relatively little has been published on the cognitive correlates of SCI. Clinically, cognitive limitations may be misinterpreted as nonadherence to treatment, inability to learn, poor coping, and/or poor motivation (Bradbury et al, 2008; Inoue et al, 2013; Kushner & Alvarez, 2014). …”