The spinocerebellar projection has an essential role in sensorimotor coordination of limbs and the trunk. Multiple groups of spinocerebellar projections have been identified in retrograde labeling studies. In this study, we aimed at characterizing projection patterns of these groups using a combination of anterograde labeling of the thoracic spinal cord and aldolase C immunostaining of longitudinal stripes of the cerebellar cortex in the mouse. We reconstructed 22 single spinocerebellar axons, wholly in the cerebellum and brain stem and partly, in the spinal cord. They were classified into three groups, (a) non-crossed axons of Clarke's column neurons (NCC, 8 axons), (b) non-crossed axons of marginal Clarke's column neurons (NMCC, 7 axons), and (c) crossed axons of neurons in the medial ventral horn (CMVH, 7 axons), based on previous retrograde labeling studies. While NCC axons projected mainly to multiple bilateral stripes in vermal lobules II-IV and VIII-IX, and the ipsilateral medial cerebellar nucleus, NMCC axons projected mainly to ipsilateral stripes in paravermal lobules II-V and copula pyramidis, and the anterior interposed nucleus. CMVH axons projected bilaterally to multiple stripes in lobules II-V with a small number of terminals but had abundant collaterals in the spinal cord and medullary reticular nuclei as well as in the vestibular and cerebellar nuclei. The results indicate that, while CMVH axons overlap with propriospinal and spinoreticular projections, NCC and NMCC axons are primarily spinocerebellar axons, which seem to be involved in relatively more proximal and distal sensorimotor controls, respectively.
The projection pattern of the olivocerebellar (OC) axons, which terminate mainly as climbing fibers (CFs) in the cerebellar cortex, tightly reflects the compartmental and developmental organization of the cerebellum as revealed by mapping and reconstruction studies in the rat. The avian cerebellum is well lobulated and longitudinally compartmentalized like the mammalian cerebellum. However, the projection pattern of the OC axons has not been studied in detail for most areas of the avian cerebellum. In the present study, we reconstructed labeled chick OC axons resulting from a small focal injection of biotinylated dextran amine into the inferior olive to investigate their morphological characteristics, and to determine their relationship to the general morphology of the chick cerebellum. Labeled CFs were distributed basically in a single longitudinally elongated narrow band-shaped area in lobules I-VIII, but in multiple, transversely widened, band-shaped areas in lobules IX-X. Three of the four reconstructed OC axons terminated in a single longitudinally band-shaped area in lobules IXa-c, whereas the other one terminated in multiple mediolaterally separated areas in lobule IXc, which is part of the flocculus. Single OC axons branched into 14 CFs on average. Two CFs occasionally merged to form a single terminal arbor. Axons also had thin, non-CF collaterals that projected either to a cerebellar nucleus or to the cortex. The results indicate that the morphological characteristics of OC axons, including branching and termination, are basically conserved between the chick and the rat. J. Comp. Neurol. 521:3321-3339, 2013.
Among the spinocerebellar projections vital for sensorimotor coordination of limbs and the trunk, the morphology of spinocerebellar axons originating from the lumbar cord has not been well characterized compared to those from thoracic and sacral cords. We reconstructed 26 single spinocerebellar axons labeled by biotinylated dextran injections into the gray matter of the lumbar spinal cord in mice. Axon terminals were mapped with the zebrin pattern of the cerebellar cortex. Reconstructed axons were primarily classified into ipsilaterally and contralaterally ascending axons, arising mainly from the dorsal and ventral horns, respectively. The majority of ipsilateral and contralateral axons took the dorsal-medullary and ventral-pontine pathways, respectively. The axons of both groups terminated mainly in the vermal and medial paravermal areas of lobules II-V and VIII-IXa, often bilaterally but predominantly ipsilateral to the axonal origin, with a weak preference to particular portions of zebrin stripes. The ipsilateral axons originating from the medial dorsal horn in the upper lumbar cord (n = 3) had abundant (43-147) mossy fiber terminals and no medullary collaterals. The ipsilateral axons originating from the lateral dorsal horn in the lower lumbar cord (n = 9) and the contralateral axons (n = 14) showed remarkable morphology variations. The number of their mossy fiber terminals varied from 2 to 172. Their collaterals, observed in 17 axons out of 23, terminated mainly in the medial cerebellar nucleus, nucleus X, and lateral reticular nucleus in various degrees. The results indicated that the lumbar spinocerebellar projection contains highly heterogeneous axonal populations regarding their pathway, branching, and termination patterns.
This study was aimed at assessing the feasibility and toxicity of using stereotactic body radiation therapy (SBRT) for reirradiation of spinal metastatic tumors. We conducted a retrospective review, from our institutional database, of the data of patients who received reirradiation, with overlap of some prescribed isodose lines to the vertebra from the initial radiation therapy, between 2007 and 2019. We identified 40 patients with spinal metastatic tumors, of whom 2 had 2 metastatic vertebral lesions each, totaling up to 42 target lesions. The median dose to spinal cord at the initial radiation therapy was 30 Gy. SBRT based on the intensity-modulated radiation therapy (IMRT) technique was used for reirradiation to spare the spinal cord. All patients received a prescription dose of 25 Gy in 5 fractions to the planning target volume (PTV). Among the 40 cases who had pain, pain relief was obtained in 24 (60%) after reirradiation. Neurologic improvement was obtained in 8 of 15 cases (53%). The adverse events were evaluated using the Common Terminology Criteria for Adverse Events Version 5.0. Reirradiation was well-tolerated, with only 2 patients experiencing adverse events ≥grade 2 in severity, including 1 patient with grade 3 pain, and another patient with grade 3 spinal fracture. None of the patients developed radiation myelopathy. Our data demonstrated that reirradiation of spinal metastasis using SBRT provided effective pain relief and neurologic improvement, with minimal toxicity.
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