107. Bacterial lipopolysaccharide-induced systemic inflammation alters cerebral blood flow: Relationship to prostaglandin and NO production

Abstract

Delirium is a DSM-IVR diagnosis characterized by disturbed consciousness and changes in cognition over a short period of time. Cognition requires finely-regulated cerebral blood flow. Cerebral blood flow alterations may explain frequent delirium occurrence during bacterial sepsis. In the present work we studied the effect of systemic inflammation on cerebral blood flow. Magnetic resonance angiography revealed lower blood flow in the rostral part of the circle of Willis as well as in the middle and anterior cerebral arteries and downstream branches from 1 h after bacterial lipopolysaccharide (LPS) injection onwards as compared to saline administration. Two and a half hours after injection animals were killed and their brains analyzed for Nuclear Factor Kappa-B (NFkB) expression and for prostaglandin and NO production as enzymes for these vasoactive mediators are known to be upregulated by LPS. RT-PCR analyses showed increased expression of cyclooxygenase-2, prostaglandin E synthase and inducible NO synthase in the brains of LPS-treated animals. Immunohistochemistry indicated augmented nuclear NFkB in LPS-injected mice, but no frank increases in cyclooxygenase-2 protein or nitrotyrosine expression in the middle and anterior cerebral arteries. In conclusion, our work indicates that cerebral arterial blood flow is rapidly altered after intravenous bacterial LPS administration. The neuroimmune mechanisms underlying this effect remain elusive even though sustained changes in cerebral blood flow may involve prostaglandin and NO production.