It has been reported that rubrospinal axons will not grow around or through spinal lesions in neonatal kittens although corticospinal axons do so readily. In fact, immature rubral neurons, perhaps unlike cortical ones, die in response to axotomy. It is possible, however, that rubrospinal plasticity can be demonstrated at earlier stages of development, particularly when rubral axons are still growing into the spinal cord. This hypothesis would be difficult to test in commonly used placental mammals since lesions would have to be made prenatally, but should be testable in the North American opossum, since the entire development of its rubrospinal tract occurs postnatally. We propose to use retrograde and orthograde transport techniques to determine whether rubrospinal plasticity can be demonstrated during early stages of development. If, as suggested by pilot studies, rubrospinal plasticity can be documented, we will employ fluorescent markers in single and double-labeling paradigms to determine whether it is a result of axonal regeneration or rerouting of late growing axons. We will also attempt to determine if loss of plasticity correlates with the development of a reactive glial response to injury using immunocytochemical techniques to identify glial fibrillary acidic protein and vimentin. It has been shown that axons from brainstem areas other than the red nucleus also fail to grow around or through spinal lesions in neonatal kittens. It may be, however, that such axons, like those from the red nucleus, are capable of plasticity during earlier stages of development. Indeed it is our guiding hypothesis that all descending spinal pathways are capable of plasticity at some stage of development, but that the critical period for each is different. It is likely that differences in critical period reflect differences in developmental history. We plan to eventually test that hypothesis using several brainstem-spinal pathways, but have proposed to begin with the rubrospinal tract because we know its anatomy and developmental history in the most detail.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS025095-07
Application #
2265457
Study Section
Neurology A Study Section (NEUA)
Project Start
1987-07-01
Project End
1995-06-30
Budget Start
1993-07-01
Budget End
1995-06-30
Support Year
7
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Ohio State University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
098987217
City
Columbus
State
OH
Country
United States
Zip Code
43210
Terman, J R; Wang, X M; Martin, G F (2000) Repair of the transected spinal cord at different stages of development in the North American opossum, Didelphis virginiana. Brain Res Bull 53:845-55
Basso, D M (2000) Neuroanatomical substrates of functional recovery after experimental spinal cord injury: implications of basic science research for human spinal cord injury. Phys Ther 80:808-17
Martin, G F; Terman, J R; Wang, X M (2000) Regeneration of descending spinal axons after transection of the thoracic spinal cord during early development in the North American opossum, Didelphis virginiana. Brain Res Bull 53:677-87
Wang, X M; Terman, J R; Martin, G F (1999) Rescue of axotomized rubrospinal neurons by brain-derived neurotrophic factor (BDNF) in the developing opossum, Didelphis virginiana. Brain Res Dev Brain Res 118:177-84
Terman, J R; Wang, X M; Martin, G F (1999) Developmental plasticity of ascending spinal axons studies using the North American opossum, Didelphis virginiana. Brain Res Dev Brain Res 112:65-77
Terman, J R; Wang, X M; Martin, G F (1998) Origin, course, and laterality of spinocerebellar axons in the North American opossum, Didelphis virginiana. Anat Rec 251:528-47
Wang, X M; Basso, D M; Terman, J R et al. (1998) Adult opossums (Didelphis virginiana) demonstrate near normal locomotion after spinal cord transection as neonates. Exp Neurol 151:50-69
Wang, X M; Terman, J R; Martin, G F (1998) Regeneration of supraspinal axons after transection of the thoracic spinal cord in the developing opossum, Didelphis virginiana. J Comp Neurol 398:83-97
Wang, X M; Qin, Y Q; Terman, J R et al. (1997) Early development and developmental plasticity of the fasciculus gracilis in the North American opossum (Didelphis virginiana). Brain Res Dev Brain Res 98:151-63
Terman, J R; Wang, X M; Martin, G F (1997) Developmental plasticity of selected spinocerebellar axons. Studies using the North American opossum, Didelphis virginiana. Brain Res Dev Brain Res 102:309-14

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