Abstract
Traumatic spinal cord injury (SCI) leads to disruption of sensory, motor and autonomic function, and triggers structural, physiological and biochemical changes that cause reorganization of existing circuits that affect functional recovery. Propriospinal neurons (PN) appear to be very plastic within the inhibitory microenvironment of the injured spinal cord by forming compensatory circuits that aid in relaying information across the lesion site and, thus, are being investigated for their potential to promote locomotor recovery after experimental SCI. Yet the role of PN plasticity in autonomic dysfunction is not well characterized, notably, the disruption of supraspinal modulatory signals to spinal sympathetic neurons after SCI at the sixth thoracic spinal segment or above resulting in autonomic dysreflexia (AD). This condition is characterized by unmodulated sympathetic reflexes triggering sporadic hypertension associated with baroreflex mediated bradycardia in response to noxious yet unperceived stimuli below the injury to reduce blood pressure. AD is frequently triggered by pelvic visceral distension (bowel and bladder), and there are documented structural relationships between injury-induced sprouting of pelvic visceral afferent C-fibers. Their excitation of lumbosacral PN, in turn, sprout and relay noxious visceral sensory stimuli to rostral disinhibited thoracic sympathetic preganglionic neurons (SPN) that manifest hypertension. Herein, we review evidence for maladaptive plasticity of PN in neural circuits mediating heightened sympathetic reflexes after complete high thoracic SCI that manifest cardiovascular dysfunction, as well as contemporary research methodologies being employed to unveil the precise contribution of PN plasticity to the pathophysiology underlying AD development.
Highlights
Propriospinal neurons (PN) have intraspinal origins and project to interneurons in other spinal cord segments as reported in electrophysiological and tract-tracing studies in feline and rodent models (Alstermark et al, 1981; Chung and Coggeshall, 1983; Skinner et al, 1989; Jankowska, 1992; Flynn et al, 2011)
The severity of experimental autonomic dysreflexia (AD) in mice is correlated with the level of serotonergic inputs in the spinal cord that innervate the intermediolateral cell column (IML) (Cormier et al, 2010), and grafting of neural stem cells derived from embryonic brainstem into T4 spinal transection sites in rats reduced the severity of experimentally induced AD (Hou et al, 2013b). These findings indicate that improving serotonergic connections between the brainstem and regions of IML below the lesion may aid in alleviating severity of AD
While adrenergic hypersensitivity is a noted contributing factor peripherally, we focus on the role of intraspinal plasticity in AD development
Summary
Propriospinal neurons (PN) have intraspinal origins and project to interneurons in other spinal cord segments as reported in electrophysiological and tract-tracing studies in feline and rodent models (Alstermark et al, 1981; Chung and Coggeshall, 1983; Skinner et al, 1989; Jankowska, 1992; Flynn et al, 2011). Both corticospinal and intraspinal circuits are reorganized following SCI (Tandon et al, 2009; Ghosh et al, 2010; Asboth et al, 2018), and such sudden increases in neuronal sprouting without suitable axon guidance cues and supraspinal modulation leads to an imbalance of inhibitory and excitatory signaling (see Brown and Weaver, 2012).
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