Paraventricular oxytocin neurons attenuate post-ischemic brain injury by suppressing microglia-mediated neuroinflammation.
Level 5 - mechanism / opinion, no new human data
Preclinical animal and in vitro laboratory study
PubMed 42310721 · doi:10.1186/s12964-026-03007-7
What was done
Transient middle cerebral artery occlusion (tMCAO) was performed in mice. Oxytocin (OXT) levels were measured in peri-infarct cortex, serum, and cerebrospinal fluid, and oxytocin receptor (OXTR) expression was assessed in the peri-infarct cortex. Chemogenetic approaches were applied to selectively activate paraventricular nucleus (PVN) OXT neurons in OXT-Cre mice, followed by assessments of neurological function, infarct volume, and blood-brain barrier integrity. RNA sequencing of the ipsilateral ischemic hemisphere, flow cytometry, molecular assays, and Transwell migration assays were used to examine downstream mechanisms.
What was found
Following tMCAO, OXT levels decreased in the peri-infarct cortex, serum, and CSF, while OXTR expression increased in the peri-infarct cortex. Chemogenetic activation of PVN OXT neurons elevated brain and circulating OXT levels, decreased infarct volume, and improved neurological outcomes. Transcriptomic analysis identified CXCL3 as significantly downregulated following PVN OXT activation, correlating with reduced neutrophil chemotaxis. Mechanistic testing confirmed that PVN OXT neurons inhibit microglial CXCL3 expression via an OXTR-ERK pathway to limit neutrophil infiltration, whereas recombinant CXCL3 administration promoted neutrophil recruitment and exacerbated brain injury. The abstract does not report numerical values or effect sizes.
Why it matters
This study outlines a central neuroendocrine pathway through which hypothalamic oxytocin neurons suppress microglial chemokine expression and subsequent neutrophil infiltration after cerebral ischemia. It highlights PVN OXT neuron signaling and microglial CXCL3 as potential mechanistic targets to lessen secondary neuroinflammatory damage.
Limits
The study is limited to rodent models and cell culture assays, lacking human validation. The abstract does not report sample sizes, quantitative estimates, variance, or long-term functional recovery.
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