Histological Correlates of Improved Baroreflex Function After SCI: Serotonergic Input to Sympathetic Preganglionic Neurons

Spinal cord injury (SCI) disrupts descending pathways to sympathetic preganglionic neurons (SPNs) that normally regulate sympathetic baroreflex regulation of blood pressure, contributing to orthostatic hypotension. SCI also reduces bulbospinal serotonin (5-hydroxytryptamine, 5-HT) availability below the lesion, and 5-HT is a key modulator of sympathetic and motor circuits. Importantly, we have previously shown that sympathetic baroreflex regulation of blood pressure partially recovers over the first 8 weeks after SCI. However, the anatomical substrates that could support this functional improvement remain unclear. Therefore, the objective of this study is to histologically characterize the recovery and potential reorganization of descending serotonergic input to SPNs caudal to injury. We hypothesize that because SCI reduces sympathetic and serotonergic signaling below the lesion, that 1 week post-injury will show diminished 5-HT input and SPN-associated labeling, and that 8 weeks will show partial but incomplete improvement, consistent with neuroplastic reorganization. To test this hypothesis, adult rats received a left T7 spinal hemisection and were studied for 1 week or 8 weeks post-injury. SPNs were identified in the thoracic spinal cord immunohistochemically using choline acetyltransferase (ChAT) immunolabeling, and descending 5-HT input was assessed in the sympathetic region caudal to the lesion. Sections were imaged using fluorescence microscopy and 3D deconvolution in standardized regions of interest within the intermediolateral cell column containing the SPNs. Quantification includes 5-HT immunoreactive fiber density and putative 5-HT appositions within the SPN region, compared across time points and relative to the ipsilateral versus contralateral sides. Lesion extent was verified histologically in each rat to confirm a consistent left hemisection and to define the segments included for analysis. Within each rat, IHC density caudal to injury is normalized to rostral thoracic segments to reduce variability and to provide an internal control for labelling and imaging conditions. ChAT-positive somata confirmed SPN identity in the intermediolateral cell column. We also quantified the spatial distribution of 5-HT fibers within the SPN region to detect selective remodeling. Preliminary data at 1 week post-SCI show a substantial reduction in 5-HT immunoreactivity below the lesion, along with diminished ChAT labeling, consistent with severely reduced descending input and reduced sympathetic baroreflex regulation during early recovery. These early post-injury deficits are expected to impair SPN activity and contribute to cardiovascular instability. Analysis of the 8-week cohort is ongoing and will directly test whether serotonergic labeling partially recovers in parallel with the established time course of baroreflex recovery. Together, this work leverages a known physiological recovery trajectory to identify histological correlates of autonomic improvement after SCI and may inform targeted strategies to enhance serotonergic support of sympathetic circuits and improve cardiovascular activity. This study was supported by the National Institutes of Health (R03NS140993 to MZ) and the East Tennessee State University’s (ETSU) Student Faculty Collaborative Grant and ETSU Research Enhancement Grant. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.