Anatomical plasticity of spinal afferents in sympathetic prevertebral ganglia of adult mice following high thoracic spinal cord injury Restricted; Files & ToC
Jarrar, Nadine (Spring 2024)
Published
Abstract
Patients with high thoracic spinal cord injury (SCIHT) lose descending control from the brainstem to the sympathetic nervous system, resulting in autonomic dysfunction across various organ systems, including autonomic dysreflexia (AD). AD is characterized by uncontrolled hypertensive crises triggered by nociceptive stimuli. Current understanding of AD mechanisms predominantly revolve around changes within the spinal cord or in blood vessels. Prevertebral sympathetic postganglionic neurons (SPNs), particularly those in the celiac/superior mesenteric ganglia (CSMG), provide the final neuronal output to modulate visceral organ sympathetic function and regulate their vasculature. Given that approximately 30% of total blood volume is stored in viscera at rest, heightened sympathetic output from prevertebral SPNs to visceral vasculature may hypothetically increase circulating blood volume, potentially contributing to AD. An essential anatomical feature of prevertebral SPNs is their integration of sympathetic preganglionic input and visceral sensory input. One type of input to prevertebral SPNs are the sensory afferents arising from visceral structures, termed spinal afferents. These spinal afferents send collaterals to prevertebral SPNs before innervating the spinal cord, release neuropeptides such as calcitonin gene-related peptide (CGRP) and are implicated in the activation of pain circuits. Whether they sprout within the prevertebral ganglia to induce enhanced SPNs sympathetic output after SCIHT remains unstudied. To address this gap, this study investigated the anatomical plasticity of spinal afferents in the spinal cord and prevertebral ganglia after SCIHTusing vesicular glutamate transporter 2 (vGluT2)TdTomato transgenic mice to fluorescently-label sensory afferents. Animals with chronic SCIHT, laminectomy (sham injured), and age-matched naive were examined. The spinal cord and CSMG were processed with TdTomato antibody to amplify fluorescent signal in vGluT2+ spinal afferents, CGRP antibody to label CGRP+ nociceptive spinal afferents, and tyrosine hydroxylase antibody to label SPNs. The results revealed an increase in the density of CGRP+ afferents in the spinal cord superficial dorsal horn and their innervation into deeper dorsal laminae at chronic stage of SCIHT, consistent with prior studies in rat. Strikingly, an increase in both vGluT2+ and CGRP+ afferent area around prevertebral SPNs were observed after SCIHT, with vGluT2+ spinal afferent area increasing 53.1% in celiac ganglia (P= 0.033) and 32.7% in superior mesenteric ganglia, while CGRP+ afferents increased by 56% and 33.3%, respectively. These findings established a new peripheral mechanism of plasticity in spinal sensory afferents after SCIHT that should increase reflex amplification of sympathetic output to visceral organs, including vasomotor induced increases in blood pressure as seen with AD.
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