Autonomic Dysreflexia in Spinal Cord Injury: Mechanisms and Prospective Therapeutic Targets.
Cameron T TruebloodAnurag SinghMarissa A CusimanoShaoping HouPublished in: The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry (2023)
High-level spinal cord injury (SCI) often results in cardiovascular dysfunction, especially the development of autonomic dysreflexia. This disorder, characterized as an episode of hypertension accompanied by bradycardia in response to visceral or somatic stimuli, causes substantial discomfort and potentially life-threatening symptoms. The neural mechanisms underlying this dysautonomia include a loss of supraspinal control to spinal sympathetic neurons, maladaptive plasticity of sensory inputs and propriospinal interneurons, and excessive discharge of sympathetic preganglionic neurons. While neural control of cardiovascular function is largely disrupted after SCI, the renin-angiotensin system (RAS), which mediates blood pressure through hormonal mechanisms, is up-regulated after injury. Whether the RAS engages in autonomic dysreflexia, however, is still controversial. Regarding therapeutics, transplantation of embryonic presympathetic neurons, collected from the brainstem or more specific raphe regions, into the injured spinal cord may reestablish supraspinal regulation of sympathetic activity for cardiovascular improvement. This treatment reduces the occurrence of spontaneous autonomic dysreflexia and the severity of artificially triggered dysreflexic responses in rodent SCI models. Though transplanting early-stage neurons improves neural regulation of blood pressure, hormonal regulation remains high and baroreflex dysfunction persists. Therefore, cell transplantation combined with selected RAS inhibition may enhance neuroendocrine homeostasis for cardiovascular recovery after SCI.
Keyphrases
- spinal cord injury
- spinal cord
- blood pressure
- heart rate
- neuropathic pain
- heart rate variability
- early stage
- cell therapy
- hypertensive patients
- oxidative stress
- polycystic ovary syndrome
- small molecule
- blood glucose
- mesenchymal stem cells
- type diabetes
- squamous cell carcinoma
- metabolic syndrome
- transcription factor
- depressive symptoms
- sentinel lymph node
- copy number
- dna methylation
- stem cells
- weight loss
- weight gain
- adipose tissue
- physical activity