Abstract
Autonomic regulation of the urogenital organs is impaired by injuries sustained during pelvic surgery or compression of lumbosacral spinal nerves (e.g., cauda equina syndrome). To understand the impact of injury on both sympathetic and parasympathetic components of this nerve supply, we performed an experimental surgical and immunohistochemical study on adult male rats, where the structure of this complex part of the nervous system has been well defined. We performed unilateral transection of pelvic or hypogastric nerves and analyzed relevant regions of lumbar and sacral spinal cord, up to 4 weeks after injury. Expression of c-Jun, the neuronal injury marker activating transcription factor-3 (ATF-3), and choline acetyltransferase (ChAT) were examined. We found little evidence for chemical or structural changes in substantial numbers of functionally related but uninjured spinal neurons (e.g., in sacral preganglionic neurons after hypogastric nerve injury), failing to support the concept of compensatory events. The effects of injury were greatest in sacral cord, ipsilateral to pelvic nerve transection. Here, around half of all preganglionic neurons expressed c-Jun within 1 week of injury, and substantial ATF-3 expression also occurred, especially in neurons with complete loss of ChAT-immunoreactivity. There did not appear to be any death of retrogradely labeled neurons, in contrast to axotomy studies performed on other regions of spinal cord or sacral ventral root avulsion models. Each of the effects we observed occurred in only a subpopulation of preganglionic neurons at that spinal level, raising the possibility that distinct functional subgroups have different susceptibility to trauma-induced degeneration and potentially different regenerative abilities. Identification of the cellular basis of these differences may provide insights into organ-specific strategies for attenuating degeneration or promoting regeneration of these circuits after trauma.
Highlights
Parasympathetic preganglionic neurons in the sacral spinal cord are essential for urogenital reflexes, including voiding, penile erection, and stimulation of secretions from the internal reproductive tract
Functional data suggests that following pelvic nerve transection, uninjured lumbar preganglionic axons grow collaterals to restore central innervation to parasympathetic pelvic ganglion neurons that mediate penile erection (Dail et al, 1989) and bladder contraction; after hypogastric nerve injury, pelvic nerve activation causes contraction of the vas deferens, an outcome originally mediated by sympathetic spinal nerves (Kihara et al, 1996)
In (D), intense c-Jun immunoreactivity is absent, but some dim labeling is indicated. (e) A c-Jun-positive nucleus within a choline acetyltransferase (ChAT)-positive neuron in the lumbar intermediolateral column (IML) contralateral to hypogastric nerve transection, 1 week after injury. (F) A c-Jun-positive nucleus within a ChAT-negative neuron in the lumbar central autonomic area (CAA), 1 week after hypogastric nerve injury. (g) In the sacral IML, a significant increase in the proportion of ChAT neurons expressing c-Jun was detected ipsilateral to pelvic nerve transection but there was no significant interaction between side and time
Summary
Parasympathetic preganglionic neurons in the sacral spinal cord are essential for urogenital reflexes, including voiding (micturition and defecation), penile erection, and stimulation of secretions from the internal reproductive tract. The proportion of FluoroGold (FG)-positive neurons expressing c-Jun was recorded in horizontal sacral (L6–S1) and lumbar (L1–L2) spinal cord sections 1, 2, or 4 weeks after nerve transection and in naïve controls.
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