title: Motor deficits and recovery in rats with unilateral spinal cord hemisection mimic the Brown-Sequard syndrome.
abstract: Cervical incomplete spinal cord injuries often lead to severe and persistent impairments of sensorimotor functions and are clinically the most frequent type of spinal cord injury. Understanding the motor impairments and the possible functional recovery of upper and lower extremities is of great importance. Animal models investigating motor dysfunction following cervical spinal cord injury are rare. We analysed the differential spontaneous recovery of fore- and hindlimb locomotion by detailed kinematic analysis in adult rats with unilateral C4/C5 hemisection, a lesion that leads to the Brown-Séquard syndrome in humans. The results showed disproportionately better performance of hindlimb compared with forelimb locomotion; hindlimb locomotion showed substantial recovery, whereas the ipsilesional forelimb remained in a very poor functional state. Such a differential motor recovery pattern is also known to occur in monkeys and in humans after similar spinal cord lesions. On the lesioned side, cortico-, rubro-, vestibulo- and reticulospinal tracts and the important modulatory serotonergic, dopaminergic and noradrenergic fibre systems were interrupted by the lesion. In an attempt to facilitate locomotion, different monoaminergic agonists were injected intrathecally. Injections of specific serotonergic and noradrenergic agonists in the chronic phase after the spinal cord lesion revealed remarkable, although mostly functionally negative, modulations of particular parameters of hindlimb locomotion. In contrast, forelimb locomotion was mostly unresponsive to these agonists. These results, therefore, show fundamental differences between fore- and hindlimb spinal motor circuitries and their functional dependence on remaining descending inputs and exogenous spinal excitation. Understanding these differences may help to develop future therapeutic strategies to improve upper and lower limb function in patients with incomplete cervical spinal cord injuries.
authors.affiliation: Brain Research Institute, University and ETH Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland. filli@hifo.uzh.ch
authors.forename: Linard
authors.initials: L
authors.lastname: Filli
authors.forename: Björn
authors.initials: B
authors.lastname: Zörner
authors.forename: Oliver
authors.initials: O
authors.lastname: Weinmann
authors.forename: Martin E
authors.initials: ME
authors.lastname: Schwab
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000627:therapeutic use; D000818:Animals; D001058:Apomorphine / Q000627:therapeutic use; D018437:Brown-Sequard Syndrome / Q000503:physiopathology*; D003000:Clonidine / Q000627:therapeutic use; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000627:therapeutic use; D004347:Drug Interactions; D005260:Female; D007839:Functional Laterality / Q000502:physiology*; D008729:Methoxamine / Q000627:therapeutic use; D009043:Motor Activity / Q000187:drug effects; D009046:Motor Neurons / Q000473:pathology / Q000502:physiology; D009069:Movement Disorders / Q000188:drug therapy / Q000209:etiology*; D011814:Quipazine / Q000627:therapeutic use; D051381:Rats; D011917:Rats, Inbred Lew; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000627:therapeutic use; D013119:Spinal Cord Injuries / Q000150:complications* / Q000188:drug therapy / Q000473:pathology; D013565:Sympatholytics / Q000627:therapeutic use; D013566:Sympathomimetics / Q000627:therapeutic use; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D018491:Dopamine Agonists; D017366:Serotonin Receptor Agonists; D013565:Sympatholytics; D013566:Sympathomimetics; D012701:Serotonin; D011814:Quipazine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D014446:Tyrosine 3-Monooxygenase; D008729:Methoxamine; D003000:Clonidine; D001058:Apomorphine