Splenic sympathetic signaling contributes to acute neutrophil infiltration of the injured spinal cord
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(2020) 17:282
RESEARCH
Open Access
Splenic sympathetic signaling contributes to acute neutrophil infiltration of the injured spinal cord Susana Monteiro1,2, Andreia G. Pinho1,2, Mara Macieira1,2, Cláudia Serre-Miranda1,2, Jorge R. Cibrão1,2, Rui Lima1,2, Carina Soares-Cunha1,2, Natália L. Vasconcelos1,2, José Lentilhas-Graça1,2, Sara Duarte-Silva1,2, Alice Miranda1,2, Margarida Correia-Neves1,2, António J. Salgado1,2 and Nuno A. Silva1,2*
Abstract Background: Alterations in the immune system are a complication of spinal cord injury (SCI) and have been linked to an excessive sympathetic outflow to lymphoid organs. Still unknown is whether these peripheral immune changes also contribute for the deleterious inflammatory response mounted at the injured spinal cord. Methods: We analyzed different molecular outputs of the splenic sympathetic signaling for the first 24 h after a thoracic compression SCI. We also analyzed the effect of ablating the splenic sympathetic signaling to the innate immune and inflammatory response at the spleen and spinal cord 24 h after injury. Results: We found that norepinephrine (NE) levels were already raised at this time-point. Low doses of NE stimulation of splenocytes in vitro mainly affected the neutrophils’ population promoting an increase in both frequency and numbers. Interestingly, the interruption of the sympathetic communication to the spleen, by ablating the splenic nerve, resulted in reduced frequencies and numbers of neutrophils both at the spleen and spinal cord 1 day post-injury. Conclusion: Collectively, our data demonstrates that the splenic sympathetic signaling is involved in the infiltration of neutrophils after spinal cord injury. Our findings give new mechanistic insights into the dysfunctional regulation of the inflammatory response mounted at the injured spinal cord. Keywords: Spinal cord injury, Spleen, Sympathetic fibers, Neutrophils
Background Spinal cord injury (SCI), especially when affecting upper anatomical levels, can impair the immune system function leading to increased susceptibility for infections [1–5]. Trauma to the cervical or thoracic part of the spinal cord damages supraspinal autonomic projections and sympathetic preganglionic neurons located at the intermediolateral nucleus (IML). These are crucial for relaying autonomic information from the central nervous system * Correspondence: [email protected] 1 Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal 2 ICVS/3B’s—PT Government Associate Laboratory, Braga, Portugal
to the peripheral sympathetic postganglionic neurons innervating lymphoid organs. The sympathetic signaling can become further compromised by the increased intraspinal plasticity following the primary injury that through the reorganization of sympathetic pathways results in erroneous reflexive circuits [4, 5]. This maladaptive plasticity has been shown to underlie autonomic dysreflexia causing immunosuppression [4, 5] through alterations in th
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