INTERMITTENT NOXIOUS STIMULATION FOLLOWING SPINAL CORD CONTUSION INJURY IMPAIRS LOCOMOTOR RECOVERY AND REDUCES SPINAL BRAIN-DERIVED NEUROTROPHIC FACTOR-TROPOMYOSIN-RECEPTOR KINASE SIGNALING IN ADULT RATS

被引:42
作者
Garraway, S. M. [1 ]
Turtle, J. D. [1 ]
Huie, J. R. [1 ]
Lee, K. H. [1 ]
Hook, M. A. [1 ]
Woller, S. A. [1 ]
Grau, J. W. [1 ]
机构
[1] Texas A&M Univ, Dept Psychol, College Stn, TX 77843 USA
关键词
BDNF; spinal cord injury; functional recovery; spinal plasticity; nociceptive stimulation; EVOKED FIELD POTENTIALS; INFLAMMATORY PAIN HYPERSENSITIVITY; LONG-TERM POTENTIATION; DORSAL-HORN NEURONS; ERK MAP KINASE; AXONAL REGENERATION; NEUROPATHIC PAIN; UP-REGULATION; PROTEIN-KINASE; TRK RECEPTORS;
D O I
10.1016/j.neuroscience.2011.10.007
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Intermittent nociceptive stimulation following a complete transection or contused spinal cord injury (SCI) has been shown to exert several short- and long-lasting negative consequences. These include maladaptive spinal plasticity, enhanced mechanical allodynia, and impaired functional recovery of locomotor and bladder functions. The neurotrophin, brain-derived neurotrophic factor (BDNF) has been shown to play an important role in adaptive plasticity and also to restore functions following SCI. This suggests that the negative behavioral effects of shock are most likely related to corresponding changes in BDNF spinal levels. In this study, we investigated the cellular effects of nociceptive stimulation in contused adult rats focusing on BDNF, its receptor, tropomyosin-receptor kinase (TrkB), and the subsequent downstream signaling system. The goal was to determine whether the behavioral effect of stimulation is associated with concomitant cellular changes induced during the initial post-injury period. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were used to assess changes in the mRNA and/or protein levels of BDNF, TrkB, and the downstream signaling proteins calcium-calmodulin kinase II (CaMKII) and extracellular related kinase 1/2 (ERK1/2) at 1 h, 24 h, and 7 days following administration of intermittent noxious shock to the tail of contused subjects. In addition, recovery of locomotor function (Basso, Beattie, and Bresnahan [BBB] score) was assessed daily for the first week after injury. The results showed that, although nociceptive stimulation failed to induce any changes in gene expression at 1 h, it significantly reduced the expression of BDNF, TrkB, ERK2, and CaMKII at 24 h. In general, changes in gene expression were spatially localized to the dorsal spinal cord. In addition, locomotor recovery was impaired by shock. Evidence is also provided suggesting that shock engages a neuronal circuitry without having any negative effects on neuronal survival at 24 h. These results suggest that nociceptive activity following SCI decreases BDNF and TrkB levels, which may significantly contribute to diminished functional recovery. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.
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页码:86 / 102
页数:17
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