Motoneuron Loss Associated with Chronic Locomotion Impairments after Spinal Cord Contusion in the Rat

Abstract

Information on the nature of deficits and adaptive mechanisms occurring after spinal cord injury is essential to the design of strategies for promoting functional recovery. Motor impairments and compensations were quantified by three-dimensional kinematic analysis in freely walking rats, 6 months after mild cervical (C7) or moderate lumbar (L2) spinal cord contusion. After C7 contusion, the animals showed reduced elbow extension and wrist movement, whereas reduced knee extension was the main impairment after L2 contusion. In both cases, the duration of the walking cycle increased and forward velocity was reduced due to a longer stance phase. Histology revealed reproducible lesions extending approximately to one spinal cord segment. In the transverse plane, the lesion involved the central gray matter and adjacent axons, including the dorsal corticospinal tract, but partially spared the ventrolateral tracts. Retrograde motoneuron tracing by nerve exposure to HRP or intramuscular injection of aminostilbamidine demonstrated that C7 contusion caused the loss of approximately 40% of triceps brachii motoneurons, whereas approximately 30% of quadriceps femoris motoneurons were lost after L2 contusion. These results demonstrate permanent deficits after incomplete lesions at the spinal cord enlargements and suggest that motoneuron loss contributes to their production.

Dynamic Motor Compensations with Permanent, Focal Loss of Forelimb Force after Cervical Spinal Cord Injury

“…1 Cervical SCI produces segmental neuronal death that contributes to chronic upper limb motor deficits in humans 2,3 or forelimb in rats. 4 Nevertheless, white matter destruction has greater clinical importance because it interrupts the synaptic inputs from brain centers to all the spinal cord segments caudal to the lesion site. Accordingly, thoracic SCI leads to chronic locomotor impairments that correlate with the extent of axonal damage and disconnection of the lumbar spinal cord from supraspinal nuclei.…”

“…This may explain why human stepping-like movements are easier to induce aftercervical than thoracic SCI, 9 and also the chronic weakness detected in human arm muscles that receive innervation from spinal levels just caudal to the lesion site. 10 The loss and recovery of forelimb motor function has been studied in several models of cervical SCI in rats, 4,[11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] cats, [28][29][30] and primates. [31][32][33][34][35] All those studies demonstrated some extent of spontaneous motor function recovery, albeit with persisting deficits as a consequence of interruption of descending axonal tracts or segmental neuronal death.…”

“…Despite these advances, there is still a need of cervical SCI models in which motor performance is comprehensively assessed in the long term to determine the motor components that show recovery and to link the chronic deficits with the neuroanatomical damage. Moreover, motor compensations always coexist with associated impairments in limb synergies, 4,5,8,16,21,36 complicating the interpretation and quantification of spontaneous and treatment-induced functional recovery and demanding the combined use of kinetic, kinematical, electrophysiological, and anatomical techniques for appropriate assessment.…”

“…The topographical organization of MNs in the cervical enlargement 37 offers the possibility of developing lesion paradigms that cause death of selective MN pools, 4,11 which are of interest for investigating strategies for MN protection and/or replacement. [38][39][40][41][42] It is likewise possible to produce segmental motor deficits by performing restricted white matter lesions just rostral to specific groups of MNs and INs, which would become denervated as a consequence of the interruption of axonal tracts originating in brain and cervical propriospinal nuclei.…”

“…In this context, the present work addresses the functional and anatomical consequences of C6 spinal cord hemisection using kinetic and kinematic analysis of locomotion, immunohistochemistry, and retrograde neural tracing. The lesion was aimed at interrupting the axons that originate in brain nuclei and C3/C4 propriospinal premotor neurons to innervate the segments C7/C8, 44 which contain the spinal motor nuclei controlling the triceps brachii (TB) and some forepaw muscles 4,37 and their segmental INs. This would cause major deficits for elbow extension and wrist joint movements in the ipsilateral forelimb that could be detected during locomotion.…”