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Abstract
Brain dysfunction is a common but not well-understood complication of sepsis. It often appears prior to the failure of other organs. Multiple factors could contribute to the development of acute brain dysfunction associated with sepsis including oxidative stress, proinflammatory mediators, endothelial activation and blood brain barrier disruption. In the present work, we aimed to test the beneficial anti-inflammatory and antioxidant properties of both 3-(1{u2032}1{u2032}-dimethylbutyl)-1-deoxy-x8-THC ( JWH 133), cannabinoid receptor (CB2R) agonist, and physostigmine (Esrine), cholinesterase enzyme inhibitor, on early LPS induced behavioural changes. In addition, the role of cholinergic and cannabinoid systems were also investigated on the LPS modulating effect on the p-glycoprotein, an ATP-driven drug efflux transporter, expression in the blood brain barrier (BBB). Rats were treated with a single intraperitoneal injection of lipopolysaccharide LPS (4 mg/kg) or vehicle. LPS treated rats were further subdivided in to 5 subgroups: None treated LPS and treated LPS with either saline, Eserine, JWH133 or Eserine+JWH133.