We developed a low‑cost SCX‑membrane‑based DiskTip microproteomics workflow, integrated with LCM and DIA‑MS, to profile six brain regions in LPS‑induced neuroinflammation. We uncovered a molecular boundary between hippocampal CA1 and CA3 with opposing MAPK activity, and proposed the Spatial Heterogeneity Index (SHI) to quantify regional variation. The IgSF CAM–RHOA–MAPK axis may drive region‑selective lesions, providing new insights and targets for neuroinflammation.