title: Lipopolysaccharide-induced preconditioning against ischemic injury is associated with changes in toll-like receptor 4 expression in the rat developing brain.
abstract: Lipopolysaccharide (LPS) preconditioning reduces ischemic injury in adult brain by activating Toll-like receptor 4 (TLR-4). We sought to investigate the effect of brain maturity on the efficacy of LPS preconditioning against hypoxic-ischemic (HI) injury in the developing rat brain. Rat pups at the specified age were randomly assigned to LPS-treated (0.1 mg/kg) or saline-treated groups. HI injury was induced 48 h later by occluding the right common carotid artery followed by transient hypoxia. Brains were removed 1 wk after HI injury, and infarct volumes were compared between the two groups. TLR-4 expression was also compared among different ages. We found that LPS treated P7, P9, and P14 rat pups had significantly smaller infarct volume compared with saline-treated pups (p = 0.006, 0.03, and 0.01, respectively). This significant reduction in infarct volume was not observed in P3 and P5 rats. TLR-4 expression was significantly higher in older rats compared with P3 and P5 rats (p < 0.01). These findings indicate that LPS-induced preconditioning is a robust neuroprotective phenomenon in the ischemic developing brain that is age dependent. Pattern of TLR-4 expression is also affected by brain maturity and likely to be responsible for differences in the efficacy of LPS preconditioning.
authors.affiliation: Department of Surgery, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.
authors.forename: Edward
authors.initials: E
authors.lastname: Hickey
authors.forename: Hui
authors.initials: H
authors.lastname: Shi
authors.forename: Glen
authors.initials: G
authors.lastname: Van Arsdell
authors.forename: Rand
authors.initials: R
authors.lastname: Askalan
mesh_terms: D000367:Age Factors; D000375:Aging; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects* / Q000254:growth & development / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D020925:Hypoxia-Ischemia, Brain / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000819:agonists* / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; C440499:lipopolysaccharide, Escherichia coli O111 B4