title: Reticulospinal plasticity after cervical spinal cord injury in the rat involves withdrawal of projections below the injury.
abstract: Restoring voluntary fine motor control of the arm and hand is one of the main goals following cervical spinal cord injury (SCI). Although the functional improvement achievable with rehabilitative training in rat models is frequently accompanied by corticospinal tract (CST) plasticity, CST rewiring alone seems insufficient to account for the observed recovery. Recent investigations in animal models of SCI have suggested that the reticulospinal tract (RtST) might contribute to mediating improved motor performance of the forelimb. Here we investigate whether the spared RtST can compensate for the loss of CST input and whether RtST projections rearrange in response to cervical SCI. Animals underwent unilateral ablation of the dorsal CST and rubrospinal tract at spinal level C4, while the ventral RtST projections were spared. At the end of the six-week recovery period, injured animals had made significant improvements in single pellet reaching. This was not accompanied by increased sprouting of the injured CST above the injury compared to uninjured control animals. Injury-induced changes in RtST fiber density within the gray matter, as well as in the number of RtST collaterals entering the gray matter or crossing the cord midline were minor above the injury. However, all analyses directly below the injured spinal level consistently point to a significant decrease of RtST projections. The mechanism and the functional relevance behind this new finding warrant further study. Our results also suggest that mechanisms other than anatomical plasticity, such as plastic changes on a cellular level, might be responsible for the observed spontaneous recovery.
authors.affiliation: Centre for Neuroscience, Department of Rehabilitation Medicine, 3-88 Corbett Hall, University of Alberta, Edmonton, AB T6E 2G4, Canada. weishaup@ualberta.ca
authors.forename: N
authors.initials: N
authors.lastname: Weishaupt
authors.forename: C
authors.initials: C
authors.lastname: Hurd
authors.forename: D Z
authors.initials: DZ
authors.lastname: Wei
authors.forename: K
authors.initials: K
authors.lastname: Fouad
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001933:Brain Stem / Q000378:metabolism / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000627:therapeutic use; D002574:Cervical Vertebrae; D004195:Disease Models, Animal; D005260:Female; D005552:Forelimb / Q000503:physiopathology; D007839:Functional Laterality; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D009416:Nerve Regeneration; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D020933:Neurotrophin 3 / Q000096:biosynthesis / Q000627:therapeutic use; D011597:Psychomotor Performance; D011712:Pyramidal Tracts / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D011917:Rats, Inbred Lew; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D013997:Time Factors; D014161:Transduction, Genetic
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D020933:Neurotrophin 3; D049452:Green Fluorescent Proteins
keywords: AAV; Adeno-associated viral vectors; Axon collaterals; BDNF; CST; Corticospinal tract; DAB; Diaminobenzidine; GFP; NT-3; Neurotrophin 3; RST; RtST; SCI; Single pellet reaching; brain-derived neurotrophic factor; corticospinal tract; green-fluorescent protein; p.i; post-injury; reticulospinal tract; rubrospinal tract; spinal cord injury