For many years, the central nervous system (CNS) was considered to be 'immune privileged', neither susceptible to nor contributing to inflammation. It is now appreciated that the CNS does exhibit features of inflammation, and in response to injury, infection or disease, resident CNS cells generate inflammatory mediators, including proinflammatory cytokines, ...

The central nervous system (CNS) is an immunologically specialized organ. The blood-brain barrier regulates the passage of molecules and cells into the CNS. Robust immune responses occur in the CNS even though there is normally an absence of MHC molecules, lack of normal lymphatic drainage, and reduced immune surveillance. This ...

The immune system is designed to defend the organism from hazardous infection. The way by which cells of the immune system perform this function can be dangerous for the survival and function of the neuronal network in the brain. An attack of immune cells inside the brain includes the potential ...

The central nervous system (CNS) has long been regarded as an immune privileged organ implying that the immune system avoids the CNS to not disturb its homeostasis, which is critical for proper function of neurons. Meanwhile, it is accepted that immune cells do in fact gain access to the CNS ...

The cytokines IL-1alpha and IL-1beta are induced rapidly after insults to the CNS, and their subsequent signaling through the type 1 IL-1 receptor (IL-1R1) has been regarded as essential for a normal astroglial and microglial/macrophage response. To determine whether abrogating signaling through the IL-1R1 will alter the cardinal astrocytic responses ...

Multiple sclerosis is a chronic neurologic disorder considered to result from relatively selective immune mediated injury of central nervous system (CNS) myelin and/or its cell of origin, the oligodendrocyte (OGC). Constituents of both the innate and adaptive immune systems are potential contributors to this process. Endogenous (microglia) and infiltrating (macrophages, ...

Immune privilege in the central nervous system (CNS) is not maintained by immune ignorance of the CNS, but by CNS control over inflammatory processes. In this review we examine the role neuropeptides play in maintenance of immune privilege in the CNS. Vasoactive intestinal peptide, alpha-melanocyte-stimulating-hormone, neuropeptide Y, and somatostatin are ...

Progression of HIV encephalitis (HIVE) is associated with neuronal damage and loss because of infiltration of infected and/or activated macrophages into the CNS. We have previously observed increased inactivation of the retinoblastoma susceptibility gene product (pRb) by phosphorylation in neurons and glia of HIVE and the simian model of HIVE ...

The hedgehog (Hh) pathway is a highly conserved signalling cascade involved in many developmental processes, including a key role in morphogenesis of many tissues including the limb bud, lung, gut, hair follicle and the neural tube. Hh role in adult tissue is less well-established, however, it is known that the ...

Cell death in the developing human spinal cord was investigated in 5-12 week human conceptuses using immunohistochemical and TUNEL methods. Expression of pro-apoptotic (Fas-receptor, caspase-3) and anti-apoptotic (bcl-2) markers and marker for internucleosomal fragmentation (TUNEL) were analysed in the cranial and caudal parts of the human spinal cord. In early ...

Chick embryos are capable of functional spinal cord regeneration following crush injury until embryonic day 13. Developmental changes occurring thereafter result in failure to regenerate. Secondary injury mechanisms can result in apoptotic cell death and make a major contribution to cell loss after trauma. We report here that around embryonic ...

Fibroblasts that have been genetically modified to secrete neurotrophins can stimulate axonal regeneration, rescue injured neurons, and improve function when grafted into a spinal cord injury site. These grafts are usually allografts that require immunosuppression to prevent rejection. In this study, we compared the effects of two immunophilin-ligands (cyclosporine A ...

Within the animal kingdom, there are several examples of organisms with remarkable regenerative abilities. Among vertebrates, newts appear to be the most adept at replacing lost structures and injured organs and can regenerate their limbs, tails, spinal cords, jaws, retinas, lenses, optic nerves, intestines, and heart ventricles. This regenerative ability ...

The adult central nervous system (CNS) is generally thought of as a postmitotic organ. However, DNA labeling studies have shown that one major population of nonneuronal cells, called microglia, retain significant mitotic potential. Microglial cell division is prominent during acute CNS injury involving neuronal damage or death. Prior work from ...

Infections are a leading cause of morbidity and mortality in patients with acute CNS injury. It has recently become clear that CNS injury significantly increases susceptibility to infection by brain-specific mechanisms: CNS injury induces a disturbance of the normally well balanced interplay between the immune system and the CNS. As ...

The presence of activated microglia in the spinal cord of amyotrophic lateral sclerosis (ALS) patients is usually accompanied by inflammatory biochemical changes, but these are largely unexplored. Monocyte chemoattractant protein-1 (MCP-1) is critical for recruitment of inflammatory cells of monocytic lineage after inflammation or injury to the central nervous system. ...

Exposure to heavy-ion radiation is considered a potential health risk in long-term space travel. It may result in the loss of critical cellular components in complex systems like the central nervous system (CNS), which could lead to performance decrements that ultimately could compromise mission goals and long-term quality of life. ...

Reactive astrocytosis occurs prominently in response to all forms of CNS injury or disease. The functions of reactive astrocytes are not well understood, and both harmful and beneficial activities have been attributed to these cells. The basic process of reactive astrocytosis is conserved in vertebrate evolution, suggesting fitness-enhancing benefits, but ...

Immunology of the central nervous system (CNS) is a growing field of study. Until recently the brain was considered an 'immunologically privileged' site. It is increasingly apparent that the CNS has a significant but tightly regulated capability to mount an inflammatory and immune response. This article serves as an introduction ...

The generation of intense inflammation in the subarachnoid space in response to meningitis-causing bacteria contributes to brain dysfunction and neuronal injury in bacterial meningitis. Microglia, the major immune effector cells in the central nervous system (CNS), become activated by bacterial components to produce proinflammatory immune mediators. In this study, we ...

Perivascular macrophages (PVM) constitute a subpopulation of resident macrophages in the central nervous system (CNS) that by virtue of their strategic location at the blood-brain barrier potentially lend themselves to a variety of important functions in both health and disease. Functional evidence suggests that PVM play a supportive role during ...

The sensory input to the CNS provides a basis for reflexes that control and coordinate gut function, integrates this with behavioral responses such as the regulation of food intake and also mediate sensations. Diverse sub-populations of afferents have been identified according to the morphologic appearance of their terminal distribution in ...

A dysregulated inflammatory response in the central nervous system (CNS) lies at the heart of many neuropathological conditions such as multiple sclerosis and Alzheimer's disease. A key component of these inflammatory conditions is the accumulation of leukocytes in the CNS. The infiltration of leukocytes into the brain is dependent on ...

AIM: To establish a proinflammatory cytokine profile of the cerebrospinal fluid (CSF) following trauma. BACKGROUND: Trauma is associated with a postinjury syndrome consisting of loss of weight and nitrogen, pyrexia, anorexia and fatigue. It has been proposed that cytokines are pathophysiologically involved in this syndrome but the site of action ...

Glutamate excitotoxicity is increasingly being recognized as a pathogenic mechanism in autoimmune inflammatory disorders of the central nervous system (CNS). Astrocytes are the predominant players in clearing the extracellular space from glutamate and normally have extensive spare capacities in terms of glutamate uptake. We asked what might be the basis ...

Insulin-like growth factor 1 (IGF-1) has been identified as a critical molecule in the induction of myelination in the central nervous system (CNS). Systemic injection of IGF-1 has been shown to have a varied and transiently protective effect on the clinical course of experimental autoimmune encephalomyelitis (EAE). Since systemic IGF-1 ...

Nitric oxide (NO) is a widely recognized mediator of physiological and pathophysiological signal transmission. In an attempt to better understand the molecular actions of NO in astrocytes, stress protein expression in response to NO donor sodium nitroprusside was investigated. Heme oxygenase-1 (HO-1) has been identified as an inducer of manganese ...

Macrophages and microglia are implicated in spinal cord injury, but their precise role is not clear. In the present study, activation of these cells was examined in a spinal cord injury model using 2 different antibodies against ED1 clone and ionized calcium binding adaptor molecule 1 (Iba1). Activation was observed ...

Microglia participate in all phases of the multiple sclerosis (MS) disease process. As members of the innate immune system, these cells have evolved to respond to stranger/danger signals; such a response within the central nervous system (CNS) environment has the potential to induce an acute inflammatory response. Engagement of Toll-like ...

Microglia, one of three glial cell types in the central nervous system (CNS), play an important role as resident immunocompetent and phagocytic cells in the CNS in the event of injury and disease. It was del Rio Hortega in 1927 who determined that microglia belong a distinct glial cell type ...

Multiple sclerosis (MS) and AIDS dementia complex (ADC), also termed HIV-associated dementia (HAD), are two examples of CNS diseases with a strong inflammatory component. In particular, macrophage/microglia activation in the deep white matter (DWM) is a key feature of both diseases. Activated macrophages/microglia have been shown to produce multiple cellular ...

Microglia are a major neuroglial component of the CNS, playing an important role as resident immunocompetent and phagocytic cells in the CNS in the event of injury and disease. To understand the role of microglia in the CNS in health and diseases, we have recently established an immortalized clonal cell ...

Pleiotrophin (PTN) is a member of the family of heparin-binding growth factors that displays mitogenic activities and promotes neurite outgrowth in vitro. In vivo, PTN is widely expressed along pathways of developing axons during the late embryonic and early postnatal period. Although the level of PTN gene expression is very ...

There is evidence that the kynurenine pathway (KP) and particularly one of its end products, quinolinic acid (QUIN) play a role in the pathogenesis of several major neuroinflammatory diseases, and more particularly AIDS dementia complex (ADC). We hypothesized that QUIN may be involved in astrocyte apoptosis because: 1) apoptotic astrocytes ...

In degenerative disorders of the central nervous system (CNS), transplantation of neural multipotent (stem) precursor cells (NPCs) is aimed at replacing damaged neural cells. Here we show that in CNS inflammation, NPCs are able to promote neuroprotection by maintaining undifferentiated features and exerting unexpected immune-like functions. In a mouse model ...

Human herpesvirus-6A (HHV-6A) is a common pathogen whose role in CNS disorders including multiple sclerosis remains controversial. To understand how HHV-6A could influence inflammatory pathways in the CNS, we infected cultured human adult astrocytes and examined the expression of 268 cytokines, chemokines, growth factors and their receptors by gene profiling. ...

Here we review the evidence for immune cells expressing multiple components of the serotonergic and dopaminergic systems that are more commonly associated with the central nervous system (CNS). We discuss where and how peripheral encounters with these biogenic monoamines occur and posit reasons as to why the immune system would ...

There is a growing amount of evidence suggesting that cannabinoids may be neuroprotective in CNS inflammatory conditions. Advances in the understanding of the physiology and pharmacology of the cannabinoid system have increased the interest of cannabinoids as potential therapeutic targets. Cannabinoid receptors and their endogenous ligands, the endocannabinoids, have been ...

Bone marrow cells (BMCs) could correct some pathologic conditions of the central nervous system (CNS) if these cells would effectively repopulate the brain. One such condition is G(M1)-gangliosidosis, a neurodegenerative glycosphingolipidosis due to deficiency of lysosomal beta-galactosidase (beta-gal). In this disease, abnormal build up of G(M1)-ganglioside in the endoplasmic reticulum ...

Astrocytes become activated (reactive) in response to many CNS pathologies, such as stroke, trauma, growth of a tumor, or neurodegenerative disease. The process of astrocyte activation remains rather enigmatic and results in so-called "reactive gliosis," a reaction with specific structural and functional characteristics. In stroke or in CNS trauma, the ...

The retina is one of the best-characterized regions of the central nervous system (CNS) and has served as a model for many of the principles that now form the foundation for CNS development. In the past several years, a number of advances have been made in our understanding of the ...

PURPOSE OF REVIEW: The aim of this article is to describe recent observations regarding the basis for the initiation and disease evolution of multiple sclerosis. RECENT FINDINGS: A current debate is where and what initiates the neuroinflammatory reaction that characterizes the acute multiple sclerosis lesion. Immune sensitization to neural antigens ...

Peripheral nerve injury is normally followed by a robust regenerative response. Here we describe the early changes associated with injury from the initial rise in intracellular calcium and the subsequent activation of transcription factors and cytokines leading to an inflammatory reaction, and the expression of growth factors, cytokines, neuropeptides, and ...

Erythropoietin mediates an evolutionarily conserved, ancient immune response that limits damage to the heart, the nervous system and other tissues following injury. New evidence indicates that erythropoietin specifically prevents the destruction of viable tissue surrounding the site of an injury by signalling through a non-haematopoietic receptor. Engineered derivatives of erythropoietin ...

A well-controlled local immune response is needed for recovery from CNS injury, and autoimmune T cells play a key role in mediating this response. Autoimmunity, at least in the context of the CNS, is the body's fighting force against self-derived destructive compounds, and "tolerance to self" (traditionally though mistakenly equated ...

Macrophages are key components of the inflammatory response to tissue injury, but their activities can exacerbate neuropathology. High-resolution magnetic resonance spectroscopy was used to identify metabolite levels in perchloric acid extracts of cultured cells of the RAW 264.7 murine macrophage line under resting and lipopolysaccharide-activated conditions. Over 25 metabolites were ...

Mechanical spinal cord injury (SCI) initiates a cascade of pathochemical and pathophysiological events, collectively known as the secondary injury. There has been a long-standing interest in understanding the activation and involvement of proteases in this secondary injury process. Several proteases including the calpains, caspases and matrix metalloproteinases are activated by ...

A decade ago the attention of pain scientists was focused on a small number of molecules such as prostaglandin and bradykinin as peripheral pain mediators or modulators. These factors were known to be produced by tissue damage or inflammation, and considered responsible for the activation and sensitization of peripheral pain ...

Several lines of evidence have extensively demonstrated that peroxynitrite plays a pivotal role in Central Nervous System (CNS) injuries. The present study was aimed at elucidating the molecular mechanism by which propofol attenuates peroxynitrite-mediated injury in the brain. Primary cultured astroglial cells were incubated for 18 h with a known ...

PURPOSE OF REVIEW: Preterm infants are at high risk for neurological sequelae and cognitive dysfunction. These problems have been attributed to a high occurrence of central nervous system (CNS) lesions, but suboptimal brain development appears to be just as important. In this brief review we present the hypothesis that systemic ...