LPS Induced Coagulation and Neuronal Damage in a Mice Model is Attenuated by Enoxaparin

Abstract Neuroinflammation and coagulation interact, therefore, the neural effects of lipopolysaccharide (LPS)-induced inflammation (1 mg/kg, intraperitoneal (IP), n = 20) and enoxaparin treatment (1 mg/kg, IP, 15 minutes, and 12 hours following LPS, n = 20) were studied in C57BL/6J mice. One week after LPS injection, sensory, motor, and cognitive functions were assessed by a hot plate, rotarod, Open-Field test (OFT), and Y-maze. We measured thrombin activity with a fluorometric assay, hippocampal mRNA expression of coagulation and inflammation factors by real-time- PCR and serum neurofilament-light-chain (NfL), and tumor necrosis factor-α (TNF-α) by a single-molecule array (Simoa) assay. Reduced crossing center frequency was observed in both LPS groups in the OFT (p = 0.02) along with a minor motor deficit between controls and LPS indicated by the rotarod (p = 0.057). Increased hippocampal thrombin activity (p = 0.038), and protease-activated receptor 1 (PAR1) mRNA (p = 0.01) were measured in LPS compared to controls but not in enoxaparin LPS treated mice (p = 0.4, p = 0.9, respectively). Serum NfL and TNF-α levels were elevated in LPS mice (p < 0.05) and normalized by enoxaparin treatment. These results indicate that inflammation, coagulation, neuronal structure, and function are linked and may regulate each other, suggesting another pharmacological mechanism for intervention in neuroinflammation.