piperidines and apixaban

Neural inflammation is linked to coagulation. Low levels of thrombin have a neuroprotective effect, mediated by activated protein C (APC). We describe a sensitive novel method for the measurement of APC activity at the low concentrations found in neural tissue.. APC activity was measured using a fluorogenic substrate, Pyr-Pro-Arg-AMC, cleaved preferentially by APC. Selectivity was assessed using specific inhibitors and activators. APC levels were measured in human plasma, in glia cell lines, in mice brain slices following mild traumatic brain injury (mTBI) and systemic lipopolysaccharide (LPS) injection, and in cerebrospinal fluid (CSF) taken from viral meningoencephalitis patients and controls.. Selectivity required apixaban and alpha-naphthylsulphonylglycyl-4-amidinophenylalanine piperidine (NAPAP). APC levels were easily measurable in plasma and were significantly increased by Protac and CaCl. This method is selective and sensitive for the measurement of APC activity that significantly changes during inflammation in cell lines, animal models and human CSF.

Topics: Animals; Brain; Brain Concussion; Cell Line; Cerebrospinal Fluid; Dipeptides; Endothelial Protein C Receptor; Humans; Inflammation; Lipopolysaccharides; Male; Mice; Mice, Inbred ICR; Models, Animal; Neuroglia; Piperidines; Protein C; Pyrazoles; Pyridones; Receptor, PAR-1; Thrombin

Topics: Aged; Anticoagulants; Azetidines; Drug Interactions; Hemorrhage; Humans; Male; Piperidines; Pyrazoles; Pyridones; Syndrome