Chronic Stress Alters Medial Prefrontal Control of Peripheral Vasomotion

Medial prefrontal cortex (MPFC) is an important hub for appraising stress and regulating coping responses to stressors. Human and animal research support the role of MPFC activation in the reduction of cardiovascular reactivity to acute stressors. While studies have interrogated the link between MPFC buffering of stress induced cardiovascular reactivity via central hemodynamics (median arterial pressure, heart rate), there is a very limited understanding on the role of MPFC control of peripheral hemodynamics (vasomotion) in the skeletal muscles, especially after chronic stress. The goal of this study was to examine the hypothesis that chronic stress alters MPFC control of vasomotion accompanied by changes in blood volume distribution across both hindlimb and forelimb skeletal limb musculature in a rodent model of chronic restraint stress. Male Wistar rats (300-400g) received chronic immobilization stress in a restrainer tube for 28 days (5 days/ week; 6 hours/day chronic stress; CS, N=7). All comparisons were made against age matched control animals (C, N=7). Stress induced behavioral and neuroendocrine responses were quantified with open field, elevated plus maze and blood biomarkers (e.g., corticosterone, glucose and inflammatory biomarkers TNF alpha & IL-6) respectively. Animals were anesthetized with urethane (1.2-1.6 g/kg) and instrumented with a catheter in the aortic arch to measure blood pressure, in addition to noninvasive photoplethysmography (PPG) sensors over both forelimb and hindlimb musculature bilaterally. Intracortical microstimulation was utilized to map the organization of vasomotor control in the right MPFC spanning the prelimbic, infralimbic, cingulate, and dorsal peduncular cortices. Changes in arterial vasomotion (AM) in response to MPFC stimulation were estimated by extracting the pulsatile component >4 hertz in the PPG, while changes in local venous blood volume (BL) was estimated by extracting the DC component <1 hertz of the PPG, similar to previous studies. Stimulation induced changes in blood volume distribution in the skeletal musculature assessed by PPG were also further validated using laser speckle contrast imaging. We found that MPFC stimulation in CS animals induced significant blood volume redistribution accompanied by increase in venous blood volume vasoconstriction magnitude in the contralateral hindlimb (p = 0.04, d = 1.2), increased vasodilation magnitude in venous blood volume (p = 0.012, d =1.58) and decrease in arterial vasoconstriction magnitude (p = 0.028, d = 1.32) in the contralateral forelimb. These results indicate that chronic stress alters neuroplasticity in MPFC in a manner that causes peripheral blood flow redistribution that may contribute to the overall coping response during stress. Future studies should also assess the impact of this chronic stress paradigm on cardiovascular dysfunction and coping responses. Funding sources: This study was supported by: NIH (R01 NS131493) 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.