Sympathetic innervation to Moller's smooth muscle in the superior eyelid of the rat normally is derived entirely from the ipsilateral sympathetic chain. Removal of the ipsilateral superior cervical ganglion (SCG) in juvenile and adult rats results in sustained SNS denervation and impairment of Moller's muscle adrenoceptor-mediated contractile response. In contrast, ganglionectomy in neonatal rats results in functional SNS reinnervation from the contralateral SCG. Contralateral reinnervation is beneficial, since contractile responses show less deficit and ptosis is markedly attenuated relative to older preparations in which reinnervation does not occur. The objectives of the present study are to characterize anatomical and physiological aspects of the contralateral projection, determine the cellular mechanisms responsible for enhanced neuroplasticity in neonatal rats and determine if contralkateral reinnervation occurs in other end organs.
The specific aims of the project are to; 1) define the optimal age and time course for smooth muscle reinnervation, 2) determine the structural and functional correlates of contralateral reinnervation (LM histofluorescence and EM cytochemistry to assess density of innervation and neuro-muscular relationships; HRP transport to analyze numbers, size and distribution of ganglion cells; functional analysis of reflex contractile responses to selected stimuli), 3) determine effects on smooth muscle maturation using physiolgical/pharmacological methods to assess function and quantitative LM to analyze muscle volume and cell numbers, 4) determine effects of perturbations which may modify neonatal neuroplasticity, and 5) examine other end organs to determine if contralateral innervation following neonatal denervation is more widespread than realized. This study will attempt to ascertain the mechanism of enhanced neuroplasticity in the neonatal SNS which has not previously been studied. Furthermore, it will provide information of clinical relevance regarding possible amelioration or treatment of cervical SNS lesions (Horner's syndrome) for which adequate therapy does not exist.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
7R01NS023502-02
Application #
3407063
Study Section
Neurology B Subcommittee 1 (NEUB)
Project Start
1987-06-01
Project End
1989-11-30
Budget Start
1987-06-01
Budget End
1987-11-30
Support Year
2
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Kansas
Department
Type
Schools of Medicine
DUNS #
016060860
City
Kansas City
State
KS
Country
United States
Zip Code
66160
Smith, Peter G; Liu, Manxi (2002) Impaired cutaneous wound healing after sensory denervation in developing rats: effects on cell proliferation and apoptosis. Cell Tissue Res 307:281-91
Smith, Peter G; Warn, J Donald; Steinle, Jena J et al. (2002) Modulation of parasympathetic neuron phenotype and function by sympathetic innervation. Auton Neurosci 96:33-42
Hasan, W; Zhang, R; Liu, M et al. (2000) Coordinate expression of NGF and alpha-smooth muscle actin mRNA and protein in cutaneous wound tissue of developing and adult rats. Cell Tissue Res 300:97-109
Smith, P G; Fan, Q; Zhang, R (1999) Divergence of smooth muscle target and sympathetic pathway cell phenotypes in the orbit of the developing rat. J Comp Neurol 408:352-64
Liu, M; Warn, J D; Fan, Q et al. (1999) Relationships between nerves and myofibroblasts during cutaneous wound healing in the developing rat. Cell Tissue Res 297:423-33
Zoubina, E V; Fan, Q; Smith, P G (1998) Variations in uterine innervation during the estrous cycle in rat. J Comp Neurol 397:561-71
Smith, P G; Fan, Q; Zhang, R et al. (1998) Cellular terrain surrounding sympathetic nerve pathways in the rat orbit: comparisons of orbital connective tissue and smooth muscle cell phenotypes. J Comp Neurol 400:529-43
Hiebert, J M; Fan, Q; Smith, P G (1997) Decreased receptivity of pathway connective tissue to sympathetic nerve ingrowth in the developing rat. Brain Res Dev Brain Res 100:35-42
Smith, P G; Fan, Q (1996) Sympathetic nerve trajectories to rat orbital targets: role of connective tissue pathways. J Comp Neurol 365:69-78
Hiebert, J; Smith, P G (1995) Reinnervation of denervated iris by transplanted sympathetic ganglia: effect of neuronal age. Int J Dev Neurosci 13:627-34

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