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Reorganization of corticospinal tract fibers after spinal cord injury in adult macaques.

ABSTRACT: Previous studies have shown that sprouting of corticospinal tract (CST) fibers after spinal cord injury (SCI) contributes to recovery of motor functions. However, the neuroanatomical mechanism underlying the functional recovery through sprouting CST fibers remains unclear. Here we investigated the pattern of reorganization of CST fibers below the lesion site after SCI in adult macaques. Unilateral lesions were made at the level between the C7 and the C8 segment. The extent of spontaneous recovery of manual dexterity was assessed with a reaching/grasping task. The impaired dexterous manual movements were gradually recovered after SCI. When anterograde tract tracing with biotinylated dextran amine was performed to identify the intraspinal reinnervation of sprouting CST fibers, it was found that the laminar distribution of CST fibers was changed. The sprouting CST fibers extended preferentially into lamia IX where the spinal motor neuron pool was located, to innervate the motor neurons directly. Instead, few, if any, CST fibers were distributed in the dorsal laminae. The present results indicate that CST fibers below the lesion site after SCI in macaques are reorganized in conjunction with the recovery of dexterous manual movements.

SUBMITTER: Nakagawa H

PROVIDER: S-EPMC4487234 | biostudies-other | 2015

REPOSITORIES: biostudies-other

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Project description:Depending on the severity of a CNS injury, in humans as well as in experimental animal models certain degrees of functional recovery are observed. Rodent studies have provided much evidence for underlying anatomical changes involving neurite outgrowth of both spared and axotomized fiber tracts, also referred to as sprouting. Following a thoracic spinal cord injury (SCI) in adult rats, axotomized fibers of the hindlimb corticospinal tract (CST) were found to sprout into the cervical spinal cord at different rostrocaudal levels. Anterograde tracings showed that these new collaterals of motor cortical hindlimb fibers project into the intermediate laminae of the cervical grey matter, particularly pronounced at the level of cervical segment three (C3). The molecular cues which induce the growth and guide these sprouts of hindlimb CST fibers are unknown. We hypothesize that sectreted factors and guidance and adhesion molecules are specifically expressed in the intermediate laminae of the cervical spinal cord to direct and target the ingrowth of the sprouting hindlimb CST fibers. To test our hypothesis the transcription profile of the target region of sprouts was investigated with RNA sequencing of total RNA extracted from the intermediate laminae (IV-VII) of the spinal gray matter at cervical level C3. Four major comparisons were performed, which were then again compared to each other. The first comparison was between samples of animals with an SCI sacrificed at four different time points after injury (1, 3, 6, 12 weeks after injury). The second and third comparison was between samples of rats with a SCI compared to their sham controls sacrificed at the same time point after surgery (1 week or 12 weeks respectively). The fourth comparison was between samples from animals of the two control groups, rats with a sham surgery which were either sacrificed at one or at twelve weeks after injury. We found that most changes in gene expression ocurred at one week after SCI and least changes occured at twelve weeks after SCI, suggesting that the largest effects on a global level of gene expression occur during early time points after injury. Interestingly, also we also found changes in gene expression when comparing the samples from the two control groups, which suggests that sham surgery consisting of a laminectomy is sufficient to induce transcriptional changes in the spinal cord. This is the first study to provide insight into transcriptional changes in the target region of sprouts investigating the role of the cervical spinal cord (target region) for sprouting of hindlimb CST fibers.

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Reorganization of corticospinal tract fibers after spinal cord injury in adult macaques.

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