Electrical Stimulation of Somatosensory Nerves Alleviates Neuroinflammation and Hypertension Potentially by Reducing M1-Microglia in the Rostral Ventral Lateral Medulla

Introduction: Low-grade chronic inflammation contributes to the pathophysiology of hypertension (HTN), with neuroinflammation playing a critical role in essential HTN. We have reported that electrical stimulation of both deep peroneal nerve and tibial nerve, using electroacupuncture (EA) at two sets of acupoints ST36-37 and SP6-7, reduced chronic inflammation and attenuated HTN in dahl salt-sensitive hypertensive (DSSH) rats. Yet it remained unclear if and how neuroinflammation was affected by EA’s action. Microglia, the resident macrophages of the central nervous system, play a key role in neuroinflammation by polarization into a pro-inflammatory, neurotoxic M1 subtype upon activation. Meanwhile, the rostral ventral lateral medulla (rVLM), the sympathetic outflow center, plays a crucial role in blood pressure (BP) regulation. Therefore, we hypothesized that EA attenuated neuroinflammation and elevated BP in DSSH rats by reducing M1-microglia in the rVLM. Methods: 8 DSS rats were fed a 4% salt diet to develop hypertension, and randomly allocated to EA and Sham-EA (no electrical stimulation) treatments (n=4/group). Another 4 rats were fed a standard rat chow and served as normotensive controls. Systolic/diastolic blood pressure (SBP/DBP) were measured with non-invasive tail-cuff once weekly. EA or Sham-EA was applied twice weekly for five weeks once SBP reached 160±5 mmHg in DSSH rats. The normotensive control rats received restraining treatments (no needle-poking) throughout the experimental timeline. After five weeks of treatments, rats’ plasmas were drawn from the left ventricular, and cardiac perfusion was performed using 0.01M PBS and 4% paraformaldehyde, followed by brain harvesting. Concentrations of pro-inflammatory cytokines including high-sensitivity C-reaction protein (hs-CRP) and interlukin-6 (IL-6) in the rats’ plasmas was quantified by enzyme-linked immunosorbent assay (ELISA). Brain tissues sliced at 40-μm thickness were stained using anti-Iba1 and anti-CD86 antibodies. M1-microglia in the rVLM were identified by colocalization of Iba1 and CD86 expressions, and then were counted in EA vs. Sham-EA rats (4 rats/group, 2 sections/rat) using Z-stacked images captured by confocal microscopy. Results: Sham-EA treated DSSH rats showed significantly higher BPs (SBP: 188.6±5.6 mmHg, DBP: 136.6±4.9 mmHg) at the end of experiments compared to the EA-treated and normotensive groups. Meanwhile, five weeks of EA treatments decreased SBP by 25.7% and DBP by 32.6% compared to Sham-EA (SBP: 140.2±3.5 mmHg, DBP: 92.1±5.4 mmHg, p<0.01). The BPs of normotensive rats remained in normal range throughout the experiments. Additionally, EA reduced concentrations of hs-CRP by 68% and IL-6 by 54% in plasma compared to Sham-EA. No statistical differences of hs-CRP and IL-6 concentrations were detected between EA and normotensive groups. Furthermore, after five weeks of treatments, EA-treated rats showed a 34.6% reduction in M1-microglia in the rVLM (34±6 cells/4x10 5 μm 2 ) compared to Sham-EA treated DSSH rats (52±5 cells/4x10 5 μm 2 ) (p=0.003). No statistical differences in the total number of microglial cells were detected between EA-treated rats (67±6 cells/4x10 5 μm 2 ) and Sham-EA treated rats (64±10 cells/4x10 5 μm 2 ) at the end of experiments. Conclusion: Electrical stimulation of the deep peroneal nerve and tibial nerve decreases neuroinflammation and alleviates hypertension potentially through reducing pro-inflammatory M1-microglia in the rVLM of DSSH rats. This study was supported by NIH 1RO1AT011306-01A1 and SSIHI Pilot Award Program 2023, University of California-Irvine. This abstract was presented at the American Physiology Summit 2025 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.