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Front. Physiol. | doi: 10.3389/fphys.2019.01186

Experimental Pulmonary Hypertension is Associated with Neuroinflammation in the Spinal Cord

Mylene Vaillancourt1, Pamela Chia1, Nancy Cao1,  Gregoire Ruffenach1,  David Younessi1 and  Soban Umar1, 2*
  • 1UCLA David Geffen School of Medicine, United States
  • 2University of California, Los Angeles, United States

Rationale: Pulmonary hypertension (PH) is a rare but fatal disease characterized by elevated pulmonary pressures and vascular remodeling, leading to right ventricular failure and death. Recently, neuroinflammation has been suggested to be involved in the sympathetic activation in experimental PH. Whether PH is associated with neuroinflammation in the spinal cord has never been investigated.
Methods/Results: PH was well-established in adult male Wistar rats 3-weeks after pulmonary endothelial toxin Monocrotaline (MCT) injection. Using the thoracic segments of the spinal cord, we found a 5-fold increase for the glial fibrillary acidic protein (GFAP) in PH rats compared to controls (p<0.05). To further determine the region of the spinal cord where GFAP was expressed, we performed immunofluorescence and found a 3 to 3.5-fold increase of GFAP marker in the grey matter, and a 2 to 3-fold increase in the white matter in the spinal cord of PH rats compared to controls. This increase was due to PH (MCT vs. Control; p<0.01), and there was no difference between the dorsal versus ventral region. PH rats also had an increase in the pro-inflammatory marker chemokine (C-C motif) ligand 3 (CCL3) protein expression (~ 3-fold) and (2.8 to 4-fold, p<0.01) in the white matter. Finally, angiogenesis was increased in PH rat spinal cords assessed by the adhesion molecule CD31 expression (1.5 to 2.3-fold, p<0.01).
Conclusion: We report for the first time evidence for neuroinflammation in the thoracic spinal cord of pulmonary hypertensive rats. The impact of spinal cord inflammation on cardiopulmonary function in PH remains elusive.

Keywords: Pulmonary hypertension (PH), Monocrotaline (MCT), Neuroinflammation, Spinal Cord, Oxidative Stress, Sympathetic Nervous System, sympathetic activation

Received: 16 Dec 2018; Accepted: 02 Sep 2019.

Copyright: © 2019 Vaillancourt, Chia, Cao, Ruffenach, Younessi and Umar. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Soban Umar, University of California, Los Angeles, Los Angeles, United States, sumar@mednet.ucla.edu