title: Pyrrolidine Dithiocarbamate Prevents Neuroinflammation and Cognitive Dysfunction after Endotoxemia in Rats.
abstract: Systemic inflammation, for example as a result of infection, often contributes to long-term complications. Neuroinflammation and cognitive decline are key hallmarks of several neurological conditions, including advance age. The contribution of systemic inflammation to the central nervous system (CNS) remains not fully understood. Using a model of peripheral endotoxemia with lipopolysaccharide (LPS) we investigated the role of nuclear factor-κB (NF-κB) activity in mediating long-term neuroinflammation and cognitive dysfunction in aged rats. Herein we describe the anti-inflammatory effects of pyrrolidine dithiocarbamate (PDTC), a selective NF-κB inhibitor, in modulating systemic cytokines including tumor necrosis factor (TNF)-α and interleukin-1β (IL-1β) and CNS markers after LPS exposure in aged rats. In the hippocampus, PDTC not only reduced neuroinflammation by modulating canonical NF-κB activity but also affected IL-1β expression in astrocytes. Parallel effects were observed on behavior and postsynaptic density-95 (PSD95), a marker of synaptic function. Taken together these changes improved acute and long-term cognitive function in aged rats after LPS exposure.
authors: Department of Anesthesiology, Xuanwu Hospital, Capital Medical UniversityBeijing, China; Department of Anatomy, Capital Medical UniversityBeijing, China.
authors: Min Hui
authors: MH
authors: Kan
authors: Department of Medicine, Division of Nephrology, Durham VA and Duke University Medical Centers Durham, NC, USA.
authors: Ting
authors: T
authors: Yang
authors: Department of Anesthesiology, Xuanwu Hospital, Capital Medical University Beijing, China.
authors: Hui Qun
authors: HQ
authors: Fu
authors: Department of Anesthesiology, Xuanwu Hospital, Capital Medical University Beijing, China.
authors: Long
authors: L
authors: Fan
authors: Department of Anatomy, Capital Medical University Beijing, China.
authors: Yan
authors: Y
authors: Wu
authors: Department of Anesthesiology, Basic Science Division, Duke University Medical Center Durham, NC, USA.
authors: Niccolò
authors: N
authors: Terrando
authors: Department of Anesthesiology, Xuanwu Hospital, Capital Medical University Beijing, China.
authors: Tian-Long
authors: TL
authors: Wang
keywords: IL-1β; NF-κB; PSD-95; ageing; astrocytes; lipopolysaccharide