Neuronal CD200 Loss in the Rostral Ventrolateral Medulla Exacerbates Neuroinflammation and Promotes Stress-Induced Hypertension.

Abstract

Stress-induced hypertension (SIH) is a prevalent public health concern, and brain-immune crosstalk, particularly neuroinflammation-mediated sympathetic overactivation, dominates its pathogenesis. Our previous proteomic screening of the rostral ventrolateral medulla (RVLM) in SIH rats revealed significant CD200 downregulation, suggesting its regulatory function in SIH development. This study investigated CD200's role, underlying mechanisms, and the therapeutic potential of targeting CD200. We performed RVLM proteomic profiling in SIH rats, injected LV-shCD200 into the RVLM of normal rats to knock down CD200, and microinjected CD200Fc (a CD200 receptor agonist) into the RVLM of SIH rats to test its efficacy; Western blot, qRT-PCR, and immunofluorescence confirmed specific CD200 reduction in the RVLM neurons of SIH rats. Functional assays demonstrated that RVLM CD200 silencing induced neuroinflammation, M1 microglial polarization, and elevated blood pressure, whereas local CD200Fc administration reduced blood pressure and ameliorated neuroinflammation in SIH rats. Mechanistically, CD200 loss promoted M1 microglial polarization, enhancing RVLM neuronal excitability and excessive sympathetic outflow to sustain hypertension. Collectively, CD200 confers critical protection against SIH by modulating RVLM neuroinflammation and neuronal activity, and CD200Fc-activated CD200 signaling remodels RVLM brain immune crosstalk through anti-inflammatory and neuromodulatory effects as a promising therapeutic strategy for SIH.

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