Giamal N. Luheshi

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The cytokine interleukin 1 (IL-1) has diverse actions in the brain. In normal brain the IL-1 system is expressed at low levels and is upregulated rapidly in response to local or peripheral insults. IL-1 mediates host defence responses to local and systemic disease and injury (e.g. fever, slow-wave sleep, appetite suppression and neuroendocrine responses)(More)
Maternal infections with bacterial or viral agents during pregnancy are associated with an increased incidence of schizophrenia in the offspring at adulthood although little is known about the mechanism by which maternal infection might affect fetal neurodevelopment. Exposure of pregnant rodents to the bacterial endotoxin, lipopolysaccharide (LPS), results(More)
Polyinosinic:polycytidylic acid (poly I:C) is a synthetic double-stranded RNA that is used experimentally to model viral infections in vivo. Previous studies investigating the inflammatory properties of this agent in rodents demonstrated that it is a potent pyrogen. However, the mechanisms underlying this response have not been fully elucidated. In the(More)
The cytokine interleukin-1beta (IL-1beta) contributes to ischemic, excitotoxic, and traumatic brain injury. IL-1beta actions depend on interaction with a single receptor (IL-1RI), which associates with an accessory protein (IL-1RAcP), and is blocked by IL-1 receptor antagonist (IL-1ra). Here we show that in normal mice [wild-type (WT)],(More)
An increased incidence of schizophrenia has been associated with several perinatal insults, most notably maternal infection during pregnancy and perinatal hypoxia. This study used a rat model to directly test if maternal exposure to bacterial endotoxin (lipopolysaccharide, LPS) during pregnancy alters behaviors relevant to schizophrenia, in offspring at(More)
Leptin regulates energy balance through its actions in the brain on appetite and energy expenditure and also shares properties with cytokines such as IL-1. We report here that leptin, injected into rats intracerebroventricularly or peripherally, induces significant dose-dependent increases in core body temperature as well as suppression of appetite. Leptin(More)
Maternal infection during pregnancy is a risk factor for some psychiatric illnesses of neurodevelopmental origin such as schizophrenia and autism. In experimental animals, behavioral and neuropathological outcomes relevant to schizophrenia have been observed in offspring of infected dams. However, the type of infectious agent used and gestational age at(More)
Numerous cytokines and their receptors have been identified in the brain, where they act as mediators of host defence responses and have direct effects on neuronal and glial function. Experimental tools for studying cytokine actions, their source and control of synthesis in the brain, actions and mechanisms of action will be reviewed here. In particular,(More)
Although a number of studies indicate that the pyrogenic activity of lipopolysaccharide (LPS) and/or interleukin (IL)-1 is mediated via induction of IL-6, this has been questioned by recent evidence demonstrating a dissociation between fever and circulating IL-6. The present study reexamines this relationship by use of human recombinant interleukin-1(More)
Interleukin (IL)-6 is an important mediator of the host response to disease and has been proposed, largely based upon circumstantial evidence, as the principal endogenous circulating pyrogen responsible for activating CNS mechanisms in fever during infection and inflammation. In the present investigation, we studied the role of peripheral IL-6 in fever and(More)