About
87
Publications
14,961
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
4,883
Citations
Introduction
Additional affiliations
January 2009 - present
January 2006 - December 2011
January 2005 - December 2008
Linkoping University
Publications
Publications (87)
Many neuroscientists use the term Blood–Brain Barrier (BBB) to emphasize restrictiveness, often equating or reducing the notion of BBB properties to tight junction molecules physically sealing cerebral endothelial cells, rather than pointing out the complexity of this biological interface with respect to its selectivity and variety of exchange betw...
Children that survive leukemia are at an increased risk for cognitive difficulties. A better understanding of the neurobiological changes in response to early life chemotherapy will help develop therapeutic strategies to improve quality of life for leukemia survivors. To that end, we used a translationally-relevant mouse model consisting of leukemi...
In spite of the brain-protecting tissues of the skull, meninges, and blood-brain barrier, some forms of injury to or infection of the CNS can give rise to cerebral cytokine production and action and result in drastic changes in brain function and behavior. Interestingly, peripheral infection-induced systemic inflammation can also be accompanied by...
Sickness behavior, characterized by on overall reduction in behavioral activity, is commonly observed after bacterial infection. Sickness behavior can also be induced by the peripheral administration of Gram-negative bacterial lipopolysaccharide (LPS) or interleukin-1beta (IL-1β), a pro-inflammatory cytokine released by LPS-activated macrophages. I...
Survivors of acute lymphoblastic leukemia (ALL), the most common childhood cancer, are at increased risk for long-term cognitive problems, including executive function deficits. The chemotherapeutic agent methotrexate (MTX) is used to treat most ALL patients, and is closely associated with cognitive deficits. To address how early life cancer chemot...
Background
Magnetic resonance imaging (MRI) of rodents combined with histology allows to determine what mechanisms underlie functional and structural brain changes during sepsis‐associated encephalopathy. However, the effects of MRI performed in isoflurane‐anesthetized rodents on modifications of the blood‐brain barrier and the production of vasoac...
Animals, including human beings, modify their behavior when they fall sick. Interestingly, sociology, biology, and psychology have at different times in their history developed constructs of illness or sickness behavior. The aims of the present paper are to consider sickness behavior in animals and humans and to evaluate to what extent the notions...
Much of the debates surrounding the concept of health in philosophy of medicine has been between ‘naturalism’ and ‘normativism’. Here, the aim is to apply the revisionist naturalists’ recommendation and to look for definitions of health in the biomedical literature. Based on our own research experience with neuroendocrinology, neuroimmunology, psyc...
Increasing evidence from animal and human studies suggests that inflammation may be involved in mood disorders. Sickness behavior and emotional changes induced by experimental inflammatory stimuli have been extensively studied in humans and rodents to better understand the mechanisms underlying inflammation-driven mood alterations. However, researc...
Sepsis-associated encephalopathy (SAE) refers to brain dysfunction, including delirium, occurs during severe infection and is associated with development of post-traumatic stress disorder. SAE has been proposed to be related to reduced cerebral blood flow (CBF), blood-brain barrier breakdown (BBB), white matter edema and disruption and glia cell ac...
A reduction in food intake is commonly observed after bacterial infection, a phenomenon that can be reproduced by peripheral administration of Gram-negative bacterial lipopolysaccharide (LPS) or interleukin-1beta (IL-1β), a pro-inflammatory cytokine released by LPS-activated macrophages. The arcuate nucleus of the hypothalamus (ARH) plays a major r...
The possibility that inflammation plays a causal role in major depression is an important claim in the emerging field of immunopsychiatry and has generated hope for new treatments. The aims of the present review are first to provide some historical background and to consider the evidence in favor of the claim that inflammation is causally involved...
Our analysis of microbiota-gut-brain (MGB) research took MGB to task for some of its methods, concepts, and interpretations. Commentators then raised numerous issues about the neuroscientific and microbiome aspects of MGB and how it can be understood as a field. We respond by addressing the dimensionality (scope and depth) and causal focus of MGB.
Microbiota-gut-brain (MGB) research is a fast-growing field of inquiry with important implications for how human brain function and behaviour are understood. Researchers manipulate gut microbes (‘microbiota’) to reveal connections between intestinal microbiota and normal brain functions (e.g., cognition, emotion, memory) or pathological states (e.g...
Although the immune and nervous systems have long been considered independent biological systems, they turn out to mingle and interact extensively. The present review summarizes recent insights into the neural pathways activated by and involved in infection-induced inflammation and discusses potential clinical applications. The simplest activation...
In this chapter, we describe the role of water channel proteins, aquaporins (AQPs), in brain edema formation. The recent knowledge on the three main AQPs expressed in the brain (AQP1, AQP4, and AQP9) is summarized; however, AQP4 is the most studied in the central nervous system. Thus, AQPs, and in particular AQP4, have important roles both in the f...
Gases have been long known to have essential physiological functions in the CNS such as respiration or regulation of vascular tone. Since gases have been classically considered to freely diffuse, research in gas biology has so far focused on mechanisms of gas synthesis and gas reactivity, rather than gas diffusion and transport. However, the discov...
Traumatic brain injury (TBI) is the leading cause of death and disability in children. Indeed, the acute mechanical injury often evolves to a chronic brain disorder with long-term cognitive, emotional and social dysfunction even in the case of mild TBI. Contrary to the commonly held idea that children show better recovery from injuries than adults,...
Brain dysfunction is a frequent complication of the systemic inflammatory response to bacterial infection or sepsis. In the present work, the effects of intravenous bacterial lipopolysaccharide (LPS) administration on cerebral arterial blood flow were assessed with time-of-flight (TOF)-based magnetic resonance angiography (MRA) in mice. Cerebral ex...
Sepsis-associated encephalopathy (SAE) refers to brain dysfunction during systemic inflammation, which can range from mild delirium to coma. Despite its clinical relevance and poor outcome, SAE remains poorly understood even though magnetic resonance imaging (MRI) in septic patients has provided indications of cerebral vasospasms and diffuse edema....
Within the framework of a political economy approach, the paper analyses the social construction of both markets and illnesses in the field of mental health, linked with the recent debates associated to the publication of the latter classification of mental disorders (DSM-5). Illustrated by the example of attention deficit and hyperactivity disorde...
The tumor microenvironment is an interesting target for anticancer therapies but modifying this compartment is challenging. Here, we demonstrate the feasibility of a gene therapy strategy that combined targeting to bone marrow-derived tumor microenvironment using genetically modified bone-marrow derived cells and control of transgene expression by...
Aim: Peripheral cytokines contribute to arthritis and bone cancer pain through sensory nerve actions. However, increased spinal cytokine and glial filament expression, coined neuroinflammation, has also been proposed to play part in chronic pain. Spinal cord, dorsal root ganglia and circulating cytokines were therefore compared in murine arthritis...
“Brain Disorders in Critical Illness”, edited by Robert Stevens, Tarek Sharshar and Wes Ely, offers an overview of critical illness brain dysfunction (delirium, coma, encephalopathy), a major problem in intensive care with potentially debilitating long-term consequences. Chapters on epidemiology, outcomes, relevant behavioral neurology and biologic...
Biomedical findings mature from uncertain observations to validated facts. Although subsequent studies often refute initial appealing findings, newspapers privilege the latter and often fail to cover refutations. Thus, biomedical knowledge and media reporting may diverge with time. Here we investigated how French television reported on three scient...
Increased physical activity is present in 30-80% of anorexia nervosa patients. To explain the paradox of low food intake and excessive exercise in humans and other animals, it has been proposed that increased physical activity along with food restriction activates brain reward circuits and is addictive. Alternatively, the fleeing-famine hypothesis...
A growing body of evidence suggests that pro-inflammatory cytokines contribute to the pathogenesis of depression. Previously, it has been shown that cytokines (e.g. interferon-α therapy) induce major depression in humans. In addition, administration of the cytokine-inducer lipopolysaccharide (LPS) provokes anhedonia (i.e. the inability to experienc...
CONTEXT: Because positive biomedical observations are more often published than those reporting no effect, initial observations are often refuted or attenuated by subsequent studies. OBJECTIVE: To determine whether newspapers preferentially report on initial findings and whether they also report on subsequent studies. METHODS: We focused on attenti...
Chronic stress is associated with negative health outcomes and is linked with neuroendocrine changes, suppressed immunity, and central nervous system neuropathology. While human studies have illustrated the benefits of stress reduction, mechanistic understanding of how decreasing stress affects health, and disease progression remains unclear. Furth...
Chronic stress is associated with negative health outcomes and is linked with neuroendocrine changes, deleterious effects on innate and adaptive immunity, and central nervous system neuropathology. Although stress management is commonly advocated clinically, there is insufficient mechanistic understanding of how decreasing stress affects disease pa...
A knowledge of the spatial localization of cell vehicles used in gene therapy against glioma is necessary before launching therapy. For this purpose, MRI cell tracking is performed by labeling the cell vehicles with contrast agents. In this context, the goal of this study was to follow noninvasively the chemoattraction of therapeutic microglial cel...
Lack of compensatory or even reduced food intake is frequently observed in weight-losing cancer patients and contributes to increased morbidity and mortality. Our previous work has shown increased transcription factor expression in the hypothalamus and ventral striatum of anorectic rats bearing small tumors. mRNA expression of molecules known to be...
Evidence has accumulated over the years indicating that cytokines produced by immune cells can act on the nervous system and that neurotransmitters can modify immune cell functioning. In the present chapter, we will adopt a broad view on neuroimmunomodulation and provide an outline of how immune signals may be channeled to neural circuits that medi...
Interleukin-1beta acts on the CNS to induce fever, neuroendocrine activation, and behavioral changes, but cannot passively cross the blood-brain barrier. According to a widely accepted hypothesis interleukin-1beta induces the synthesis of cyclooxygenase-2 at the blood-brain interface, which produces prostaglandins that diffuse into brain parenchyma...
Erythropoietin (Epo) is an endogenous cytokine that regulates hematopoiesis and is widely used to treat anemia. In addition, it has recently increased interest in the neurosciences since the new concept of Epo as a neuroprotective agent has emerged. The potential protective effect of human recombinant Epo (r-hu-Epo) on a hypoxic-ischemic (HI) pup r...
Glucocorticoids are released after hypothalamus-pituitary-adrenal axis stimulation by stress and act both in the periphery and in the brain to bring about adaptive responses that are essential for life. Dysregulation of the stress response can precipitate psychiatric diseases, in particular depression. Recent genetic studies have suggested that the...
Methotrexate is a widely used cytostatic in chemotherapy cocktails for the treatment of cancer but is associated with cognitive impairment. Previous animal studies indicated that methorexate decreases hippocampal cell proliferation, which might contribute to the observed cognitive impairment. However, clinical studies have shown that cognitive impa...
Although receptors for the pro-inflammatory cytokine interleukin-1 have long been known to be expressed in the brain, their role in fever and behavioural depression observed during the acute phase response (APR) to tissue infection remains unclear. This may in part be due to the fact that interleukin-1 in the brain is bioactive only several hours a...
There is evidence from in vitro studies that inflammatory messengers influence the release of stress hormone via direct effects on the adrenal gland; however, the mechanisms underlying these effects in the intact organism are unknown. Here we demonstrate that systemic inflammation in rats elicited by iv injection of lipopolysaccharide results in dy...
The brain parenchyma has long been considered immunologically privileged based on the lack of a true lymphoid system. It is, however, clear now that brain infection or injury elicits innate immune responses including the release of cytokines, such as interleukin-1 beta(IL-1 beta). Interestingly, low levels of IL-1 beta are already present in the de...
In response to tissue injury or infection, the peripheral tissue macrophage induces an inflammatory response through the release of IL-1beta (interleukin-1beta) and TNFalpha (tumour necrosis factor alpha). These cytokines stimulate macrophages and endothelial cells to express chemokines and adhesion molecules that attract leucocytes into the periph...
The brain parenchyma has long been considered immunologically privileged based on the lack of a true lymphoid system. It is, however, clear now that brain infection or injury elicits innate immune responses including the release of cytokines, such as interleukin-1β (IL-1β). Interestingly, low levels of IL-1β are already present in the developing an...
Forebrain structures are necessary for the initiation of food intake and its coupling to energy expenditure. The cancer-related anorexia-cachexia syndrome is typified by a prolonged increase in metabolic rate resulting in body weight loss which, paradoxically, is accompanied by reduced food intake. The aim of the present work was to study the foreb...
Systemic inflammation is accompanied by changes in body temperature, either fever or hypothermia. Over the past decade, the rat and mouse have become the predominant animal models, and new species-specific tools (recombinant antibodies and other proteins) and genetic manipulations have been applied to study fever and hypothermia. Remarkable progres...
Interleukin-1 beta (IL-1 beta) is thought to act on the brain to induce fever, neuroendocrine activation, and behavioral changes during disease through induction of prostaglandins at the blood-brain barrier (BBB). However, despite the fact that IL-1 beta induces the prostaglandin-synthesizing enzyme cyclooxygenase-2 (COX-2) in brain vascular cells,...
IntroductionNeurobiology of Eating Cholecystokinin Acts as a Satiety Signal Reducing Meal SizeLeptin Constitutes an Adiposity Signal Inhibiting Long-term Meal SizeThe Adiposity Signal Leptin Interacts with the Satiety Signal CCK, but Inhibits Long-term Food Intake by Its ActionThe Arcuate Hypothalamus Contains Two Neuronal Populations Exerting Oppo...
The antidepressant tianeptine has been shown to decrease the response of the hypothalamic-pituitary-adrenal (HPA) axis to stress and to attenuate the behavioral effects of the cytokine inducer, lipopolysaccharide (LPS). Since LPS also activates the HPA axis, the objective of this study was to assess the effects of tianeptine on the HPA axis activat...
"Cytokines and the ageing brain". Held in Palais de Congres, Arcachon, France on 1-3 June 2002.
Sickness behaviour represents the expression of the adaptive reorganization of the priorities of the host during an infectious episode. This process is triggered by pro-inflammatory cytokines produced by peripheral phagocytic cells in contact with invading micro-organisms. The peripheral immune message is relayed to the brain via a fast neural path...
Anorexia is one of the most common symptoms associated with illness and constitutes an adaptive strategy in fighting acute infectious diseases. However, prolonged reduction in food intake and an increase in metabolic rate, as seen in the anorexia-cachexia syndrome, lead to depletion of body fat and protein reserves, thus worsening the organism's co...
The CNS melanocortin (MC) system is implicated as a mediator of the central effects of leptin, and reduced activity of the CNS MC system promotes obesity in both rodents and humans. Because activation of CNS MC receptors has direct effects on autonomic outflow and metabolism, we hypothesized that food intake-independent mechanisms contribute to dev...
The first studies carried out on the mechanisms by which peripheral immune stimuli signal the brain to induce fever, activation of the hypothalamic-pituitary-adrenal axis and sickness behavior emphasized the importance of fenestrated parts of the blood-brain barrier known as circumventricular organs for allowing blood-borne proinflammatory cytokine...
Binding of the pro-inflammatory cytokine interleukin-1 (IL-1) in the brain was first shown a decade ago [1]. Interleukin-1 receptors (IL-1R) in the brain were, at that time, proposed to play a role in mediating symptoms of sickness such as fever, activation of the hypothalamo-pituitary adrenal (HPA)-axis, behavioural depression and increased sleepi...
Cytokines act on the brain to induce fever and behavioural depression after infection. Although several mechanisms of cytokine-to-brain communication have been proposed, their physiological significance is unclear. We propose that behavioural depression is mediated by the vagus nerve activating limbic structures, while fever would primarily be due...
Vagal afferent signals, have been implicated in cytokine mediated interactions between the periphery and the central nervous system. Studies in experimental animals have shown that cytokine induced activation of brain mediated responses to infection such as fever, sickness behaviour and pituitary-adrenal activation, are inhibited by subdiaphragmati...
Interleukin-1 (IL-1) and tumor necrosis factor alpha (TNFalpha) are proinflammatory cytokines that are constitutively expressed in healthy, adult brain where they mediate normal neural functions such as sleep. They are neuromodulators expressed by and acting on neurons and glia. IL-1 and TNFalpha expression is upregulated in several important disea...
Cytokines act on the brain to induce fever and behavioural depression after infection. Although several mechanisms of cytokine-to-brain communication have been proposed, their physiological significance is unclear. We propose that behavioural depression is mediated by the vagus nerve activating limbic structures, while fever would primarily be due...
Interleukin-1beta acts on the CNS to induce fever, neuroendocrine activation and behavioural depression. We have previously demonstrated that interleukin-1beta is synthesized in glial cells and macrophages of circumventricular organs and choroid plexus after intraperitoneal administration of bacterial lipopolysaccharide. Whether, and how, interleuk...
Hans Seyle constateerde als student medicijnen in de jaren dertig al dat ziektes met uiteenlopende oorzaken vaak vergezeld gaan van dezelfde symptomen, zoals een verhoogde lichaamstemperatuur als mede een gebrek aan eetlust en ambitie. Het is echter pas kort geleden dat de factoren verantwoordelijk voor deze symptomen zijn ontdekt. Toediening van c...
Interleukin-1beta plays an important role in mediating central components of the host response to peripheral infection such as fever and neuroendocrine activation by acting in the brain. The present study assessed whether interleukin-1beta produced in the brain is relevant to neuronal activation and the fever response induced by intraperitoneal inj...
Sickness behavior refers to the coordinated set of behavioral changes that develop in sick individuals during the course of
an infection. A sick individual typically displays depressed locomotor activity and little or no interest in his physical
and social environment. Body care activities are usually absent and ingestive behavior is profoundly dep...
Roman-high (RHA/Verh) and low (RLA/Verh) avoidance rats are selected and bred for rapid learning versus non-acquisition of two-way, active avoidance behavior in a shuttle box. RHA/Verh rats generally show a more active coping style than do their RLA/Verh counterparts when exposed to various environmental challenges. The central nucleus of the amygd...
Roman high (RHA/Verh)- and low (RLA/Verh)-avoidance rats are selected and bred for rapid versus nonacquisition of two-way, active avoidance behavior in the shuttle box. RHA/Verh rats generally show a more active coping style than do their RLA/Verh counterparts when exposed to various environmental challenges. The central nucleus of the amygdala (Ce...
Interleukin-1 (IL-1), IL-6 and tumour necrosis factor-alpha (TNFα) are multifunctional cytokines which are released by activated monocytes and macrophages and play a pivotal role in inflammation and infection [1]. Although their biological activities widely overlap, each cytokine has its own characteristic properties. IL-1 exists in two molecular f...
