期刊
JOURNAL OF COMPARATIVE NEUROLOGY
卷 449, 期 3, 页码 217-230出版社
WILEY
DOI: 10.1002/cne.10283
关键词
growth factors; spinal injury; synaptic reorganization; retrograde transport; bladder dysfunction; bladder hypertrophy; neurotrophins
资金
- NIDDK NIH HHS [DK 51369] Funding Source: Medline
- NINDS NIH HHS [NS 40796] Funding Source: Medline
Previous studies have demonstrated changes in urinary bladder neurotrophic factors after bladder dysfunction. We have hypothesized that retrograde transport of neurotrophin(s) from the bladder to lumbosacral dorsal root ganglia (DRG) may play a role in bladder reflex reorganization after spinal cord injury (SCI). In this study, we determined whether the expression of tyrosine kinase receptors (TrkA, TrkB) is altered in lumbosacral DRG after SCI through immunofluorescence techniques. Complete transection of the spinal cord (T8-T10) was performed in female Wistar rats (120-150 g), and animals were studied 5-6 weeks after SCI. One week before killing, Fast Blue (FB) was injected into the bladder to label bladder afferent cells in the L1, L2, L6, and S1 DRG. After SCI, a significant increase in the number of TrkA-immunoreactive (IR) positive cells was detected in the L6-S1 DRG (L6: 1.9-fold, P less than or equal to 0.01; S1: 1.7-fold, P less than or equal to 0.05) and in the L1 DRG (3.0-fold; P less than or equal to 0.01) but not in the L4-L5 DRG compared with spinal-intact (control) rats. After SCI, a significant increase in the number of TrkB-IR cells was also detected in the L6-S1 DRG (L6: 2.2-fold, P less than or equal to 0.01; S1: 1.5-fold, P less than or equal to 0.05) and in the L1-L2 DRG (L1: 1.5-fold, P less than or equal to 0.01; L2:1.3-fold, P less than or equal to 0.05) but not in the L4-L5 DRG compared with control rats. After SCI, the percentage of FB-labeled cells expressing TrkA immunoreactivity (similar to68%) or TrkB immunoreactivity (similar to65%) in L1 and L6 DRG significantly (P less than or equal to 0.01) increased compared with control (20-30%) DRG. After SCI, the percentage of TrkA-IR cells expressing phosphorylated (p)-Trk immunoreactivity significantly increased (1.5- to 2.3-fold increase) in the L1, L6, and S1 DRG. The percentage of TrkB-IR cells expressing p-Trk immunoreactivity after SCI also increased (1.3-fold increase) in the L1 and L6 DRG. These results demonstrate that (1) TrkA and TrkB immunoreactivity is increased in bladder afferent cells after SCI and (2) TrkA and TrkB receptors are phosphorylated in DRG after SCI. Neuroplasticity of lower urinary tract reflexes after SCI may be mediated by both nerve growth factor and brain-derived neurotrophic factor. (C) 2002 Wiley-Liss, Inc.
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