title: Low molecular weight heparin prevents lipopolysaccharide induced-hippocampus-dependent cognitive impairments in mice.
abstract: Sepsis-associated encephalopathy (SAE) is a common complication after sepsis development, which is associated with the poor prognosis. However, no effective agent is currently available to treat this complication. The objective of the present study was to investigate whether low-molecular-weight heparin (LMWH) has protective effects against sepsis-induced cognitive impairments. Male mice were randomly divided into the control + vehicle, control + LMWH, lipopolysaccharide (LPS) + vehicle, or LPS + LMWH group. LMWH was administrated 30 min after the LPS administration (5 mg/kg) and daily afterward for 2 days. The survival rate was estimated by the Kaplan-Meier method. Behavioral tests were performed by open field and fear conditioning tests at day 7 after LPS administration. The levels of tumor necrosis factor alpha, interleukin (IL)-1β, IL-6, IL-10, malondialdehyde, and superoxide dismutase, Toll-like receptor 4, nuclear factor kappa B p65, inducible nitric oxide synthase, cyclooxygenase-2, occluding, high mobility group box-1, brain derived neurotrophic factor, and IBA1 positive cells were assessed at the indicated time points. LMWH attenuated LPS-induced hippocampus-dependent cognitive impairments, which was accompanied by decreased hippocampal IL-1β, malondialdehyde, Toll-like receptor 4, nuclear factor kappa B p65, inducible nitric oxide synthase, cyclooxygenase-2, high mobility group box-1 protein, and IBA1 positive cells, and increased occluding and brain derived neurotrophic factor levels. In conclusion, LMWH treatment protects against sepsis-induced cognitive impairments by attenuating hippocampal microglial activation, cytokine and oxidative stress production, disruption of blood-brain barrier, and the loss of synaptic plasticity related proteins.
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University Nanjing, China.
authors.forename: Renqi
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University Nanjing, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Tong
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University Nanjing, China.
authors.forename: Yuanhui
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University Nanjing, China.
authors.forename: Sihai
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University Nanjing, China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University Nanjing, China.
authors.forename: Muhuo
authors.initials: M
authors.lastname: Ji
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects; D015153:Blotting, Western; D003072:Cognition Disorders / Q000473:pathology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D007150:Immunohistochemistry; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D065166:Sepsis-Associated Encephalopathy / Q000473:pathology*
chemical_list: D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D008070:Lipopolysaccharides
keywords: LMWH; Sepsis; cognitive impairments; hippocampus