Borneol Alleviates Polyethylene Microsphere-Induced Cerebral Microcirculatory Dysfunction with Reduced NET-Related Markers

Background/Objectives: Neutrophil extracellular traps (NETs) contribute to thromboinflammation and microvascular obstruction after ischemic brain injury. Borneol has anti-inflammatory and microcirculation-related pharmacological activities, but its effects on cerebral microcirculatory dysfunction and NET-related changes remain unclear. This study aimed to determine whether borneol attenuates polyethylene microsphere-induced cerebral microcirculatory dysfunction and to examine its association with NET-related markers. Methods: Rat bone marrow-derived neutrophils were stimulated with PMA with or without borneol. Male Sprague–Dawley rats were subjected to polyethylene microsphere-induced cerebral microcirculatory dysfunction and treated intragastrically with borneol (0.1, 0.2, or 0.4 g/kg). NET formation, neurological deficits, hemodynamics, cerebral microvascular perfusion, hemorheology, histopathology, inflammatory and oxidative stress markers, and NET-related molecules were assessed by immunofluorescence, ELISA, quantitative PCR, and Western blotting. Results: Borneol reduced PMA-induced NET formation in vitro. In vivo, borneol improved neurological scores, hemodynamic indices, microvascular perfusion, hemorheological parameters, and histopathological injury. It also reduced serum TNF-α, IL-1β, and ROS, decreased cerebral MPO/CitH3 signals, and downregulated MPO, PADI4/PAD4, CitH3, TNF-α, IL-6, IL-8, ICAM-1, and MIP2. Conclusions: These findings suggest that borneol alleviates polyethylene microsphere-induced cerebral microcirculatory dysfunction, accompanied by reductions in NET-related markers. However, as borneol was administered prophylactically before model induction, these results should be interpreted with caution and do not directly support a post-insult therapeutic application.