Nitric oxide (NO) is a free radical gas that has a Janus nature. As indicated by the literature and by our studies, in the cell, NO can either function as a beneficial physiological agent utilized for essential functions such as differentiation or neurotransmission, or as a pathological agent that causes ...

Inflammation of the CNS is usually locally limited to avoid devastating consequences. Critical players involved in this immune regulatory process are the resident immune cells of the brain, the microglia. Interactions between the growing family of B7 costimulatory ligands and their receptors are increasingly recognized as important pathways for costimulation ...

A major problem for neuroscience has been to find a means to achieve reliable regeneration of synaptic connections following injury to the adult CNS. This problem has been solved by the leech, where identified neurons reconnect precisely with their usual targets following axotomy, re-establishing in the adult the connections formed ...

Exposure to apparently unrelated neurotoxicants can nevertheless converge on common neurodevelopmental events. We examined the long-term effects of developmental exposure of rats to terbutaline, a beta-adrenoceptor agonist used to arrest preterm labor, and the organophosphorus insecticide chlorpyrifos (CPF) separately and together. Treatments mimicked the appropriate neurodevelopmental stages for human exposures: ...

Glutamate in excessive amounts is a major contributor to neuronal degeneration, and its removal is attributed mainly to astrocytes. Traumatic injury to the central nervous system (CNS) is often accompanied by disappearance of astrocytes from the lesion site and failure of the remaining cells to withstand the ensuing toxicity. Microglia ...

Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL) is a recessively inherited disease characterized by early onset dementia associated with bone cysts. Our group has recently established the molecular background of PLOSL by identifying mutations in DAP12 and TREM2 genes. To understand how loss of function of the immune cell activating ...

Methylmercury (MeHg) is a common environmental pollutant due to both natural and anthropogenic sources. Although the central nervous system (CNS) is considered the critical organ for the toxic effect of MeHg, it has recently been suggested that the immune system might be at least as sensitive as the CNS. We ...

PURPOSE: Although the clinical efficacy of cyclosporin A (CSA) in retinoblastoma (RB) has been attributed to multidrug resistance reversal activity, the authors hypothesized that CSA is also directly toxic to RB cells through inhibition of calcineurin (CN)/nuclear factor of activated T-cells (NFAT) signaling. METHODS: Antiproliferative effects of CSA, PSC-833 (a ...

Condensation is a process whereby a tissue undergoes a coordinated decrease in size and increase in cellular density during development. Although it occurs in many developmental contexts, the mechanisms underlying this process are largely unknown. Here, we investigate condensation in the embryonic Drosophila ventral nerve cord (VNC). Two major events ...

Central nervous system (CNS) development requires mechanisms for the regulation of cell number. Although growth factors are essential determinants of the proliferation and apoptosis that determine final numbers, the long-range nature of signals from diffusible growth factors makes them insufficient for the provision of the precise and localized signals required. ...

BACKGROUND: In neuropathological processes associated with neutrophilic infiltrates, such as experimental allergic encephalitis and traumatic injury of the brain, the CXC chemokine, macrophage inflammatory protein-2 (MIP-2) is thought to play a pivotal role in the induction and perpetuation of inflammation in the central nervous system (CNS). The origin of MIP-2 ...

Freshly isolated or culture-expanded human umbilical cord blood mononuclear cells (CBMNCs) have been known to express neural phenotypes in vitro and to differentiate into neural cells and improve neurological function recovery after being administrated into rodent models of neurological diseases. However, the mechanism of action remains unclear. The present study ...

BACKGROUND: Schizophrenia, a relatively common psychiatric syndrome, affects virtually all brain functions yet has eluded explanation for more than 100 years. Whether by developmental and/or degenerative processes, abnormalities of neurons and their synaptic connections have been the recent focus of attention. However, our inability to fathom the pathophysiology of schizophrenia ...

Activation of microglia/macrophages after injury occurs limitedly in the CNS, which finding may explain unsuccessful axonal regeneration. Therefore, the relationship between lipopolysaccharide (LPS)-induced inflammation and recovery of locomotor function of rats after spinal cord injury was examined. High-dose LPS improved locomotor function greater than low-dose LPS, being consistent with the ...

Wallerian degeneration in the CNS and PNS consists of degradation and phagocytosis of axons and their myelin sheath distal to the site of injury. This process of degeneration, which requires an effective macrophage response, occurs rapidly in peripheral nerves but is slow in the CNS. Rapid Wallerian degeneration in peripheral ...

Evidence and inferences from clinical research, clinical observation, and literature review support an etiologic paradigm for the pathophysiology of spinal cord injury (SCI). According to this paradigm, changes in immunoregulation and in the activation of cytokines or intercellular adhesion molecules (ICAMs) contribute to many of the comorbidities, metabolic changes, and ...

Classically, the central nervous system (CNS) and the immune system are thought to operate independently of each other. This simplistic view has been corrected in recent years, first with the recognition that the brain dynamically modulates the immune system, and later with the reverse; that is, that the immune system ...

Cryptococcus neoformans is a yeast that causes cryptococcosis, a life-threatening disease that develops following inhalation and dissemination of the organisms. C. neoformans has a predilection for the central nervous system (CNS) and mortality is most frequently associated with meningoencephalitis. Susceptibility to cryptococcosis is increased in patients with deficiencies in cell-mediated ...

The immunologic privilege of the central nervous system (CNS) makes it crucial that CNS resident cells be capable of responding rapidly to infection. Astrocytes have been reported to express Toll-like receptors (TLRs), hallmark pattern recognition receptors of the innate immune system, and respond to their ligation with cytokine production. Astrocytes ...

Although microglial activation occurs in inflammatory, degenerative and neoplastic central nervous system (CNS) disorders, its role in pathogenesis is unclear. We studied this question by generating CD11b-HSVTK transgenic mice, which express herpes simplex thymidine kinase in macrophages and microglia. Ganciclovir treatment of organotypic brain slice cultures derived from CD11b-HSVTK mice ...

In the central nervous system (CNS), the cellular processes of astrocytes make intimate contact with essentially all areas of the brain. They have also been shown to be functionally coupled to neurons, oligodendrocytes, and other astrocytes via both contact-dependent and non-contact-dependent pathways. These observations have led to the suggestion that ...

We report that B cell-activating factor of the tumor necrosis factor (TNF) family (BAFF) is expressed in the normal human brain at approximately 10% of that in lymphatic tissues (tonsils and adenoids) and is produced by astrocytes. BAFF was regularly detected by enzyme-linked immunosorbent assay in brain tissue lysates and ...

In the Central Nervous System (CNS), Gram-positive bacterial infections represent about 50% of the bacterial diseases and are often associated with high mortality and severe permanent neurological consequences. The major immunostimulatory principles of Gram-positive bacteria are the constituents of bacterial cell walls, lipoteichoic acid (LTA) and peptidoglycan (PGN). In contrast ...

Cytokines circulating in the blood affect CNS function through a variety of pathways. One of these pathways is by being transported directly across the blood-brain barrier (BBB). Transport of blood-borne cytokines across the BBB is now known to be an operational pathway by which cytokines can directly affect CNS functions. ...

This study summarizes the possible effects on prenatal development of physiologically weak electric fields induced in the body by exposure to extremely low frequency (ELF) electromagnetic fields and of elevated temperature levels that might result from exposure to radiofrequency (RF) radiation. Both topics have been discussed at recent international workshops ...

Poliovirus (PV) is the causal agent of paralytic poliomyelitis, an acute disease of the central nervous system (CNS) resulting in flaccid paralysis. The development of new animal and cell models has allowed the key steps of the pathogenesis of poliomyelitis to be investigated at the molecular level. In particular, it ...

Until recently the central nervous system (CNS) was considered an immune-privileged site, however, technological and immunological advances have resulted in the CNS being reclassified as an "immune-specialized site." The immune cells, particularly T-cells, continuously patrol the brain and are involved in neuroimmune responses. As such, any changes in the brain ...

In recent years, increasing evidence has indicated that immune and inflammatory reactions occur in brain in various central nervous system (CNS) diseases. Furthermore, inflammatory processes, such as the production of proinflammatory cytokines and related molecules, have been described in brain after seizures induced in experimental models and in clinical cases ...

HIV-1-associated dementia (HAD) is an important complication of HIV-1 infection. Reactive astrogliosis is a key pathological feature in HAD brains and in other central nervous system (CNS) diseases. Activated astroglia may play a critical role in CNS inflammatory diseases such as HAD. In order to test the hypothesis that activated ...

Spine cord injury (SCI) leads to devastating functional loss below the level of injury. Partially explained by the presence of a non-permissive environment, the injured spinal cord does not mount adequate regeneration to re-establish functional connections. Therefore, it is important to identify the cellular and molecular factors and their interactions ...

Immunity is required to eliminate dangerous or degenerated material and to support regeneration, but also causes significant parenchymal damage. In the eye and the brain, in which cornea and lens poorly regenerate and neurons are hardly replaceable, early transplantation experiments demonstrated remarkable tolerance to various grafts. This "immunologically privileged status" ...

Encapsulation of cells has the potential to provide a protective barrier against host immune cell interactions after grafting. Previously we have shown that alginate encapsulated BDNF-producing fibroblasts (Fb/BDNF) survived for one month in culture, made bioactive neurotrophins, survived transplantation into the injured spinal cord in the absence of immune suppression, ...

Disabled-2 (Dab-2) functions in the mitogenic signal transduction pathway, and is expressed in a variety of tissues. We investigated the roles of Dab-2 expression in the rat brain following experimental cryoinjury in relation to central nervous system (CNS) inflammation. Western blot analysis showed that Dab-2 expression increased significantly (p < ...

T-cell cytokines are involved in beneficial immune responses, pathological autoimmunity, and tissue inflammation. In this review, we focus on the role of interferon-gamma, interleukin (IL)-2, IL-4, IL-6, and IL-10 in autoimmune diseases such as multiple sclerosis, and primarily "nonimmune" injury of the central nervous system (CNS), in particular focal ischemia ...

Spinal cord trauma activates the immune system and elicits leukocyte recruitment to the site of injury. This increase in immunological activity contributes to acute lesion expansion over a period of days to weeks following the initial trauma. At the same time, inflammatory cells and mediators facilitate endogenous repair processes such ...

The Uncaria genus is an important source of medicinal natural products, particularly alkaloids and triterpenes. The collected information is an attempt to cover the more recent developments in the ethnobotany, pharmacology and phytochemistry of this genus. During the past 20 years, alkaloids, terpenes, quinovic acid glycosides, flavonoids and coumarins have ...

Experimental autoimmune encephalomyelitis (EAE) disease was accelerated iNOS-deficient (KO) mice: coinciding with greatly increased numbers of Ag-specific Th1 cells in the periphery that appeared to rapidly shift from the spleen to the CNS during onset of disease symptoms. iNOS KO mice had significantly increased Th1 cells in the CNS versus ...

Transected axons can regenerate beyond the site of injury in the peripheral but not in the central nervous system (CNS). Increasing evidence implicates inflammatory processes as modulators of axon regeneration after injury. In this study, we addressed a possible role of the matricellular glycoprotein osteopontin (OPN) using crush lesions of ...

The secondary cascade of cell death that follows central nervous system (CNS) injury or ischemia has long been considered a target for neuroprotective agents aimed at sparing tissue and function. Recently, several laboratories have shown remarkable protection and recovery of function in rodent models of spinal cord injury using treatments ...

Proteoglycan is a family of glycoproteins which carry covalently-linked glycosaminoglycan chains, such as chondroitin sulfate and heparan sulfate. Proteoglycans are believed to play important roles in morphogenesis and maintenance of various tissues including the central nervous system (CNS) through interactions with cell adhesion molecules and growth factors. In the CNS, ...

Recent studies have shown inflammatory markers in affected neural tissues of amyotrophic lateral sclerosis (ALS) patients. We examined immunocytochemically spinal cord tissues of six patients with ALS, two with corticospinal tract degeneration secondary to cerebral infarcts and three control subjects without neuropathologic abnormalities. ALS spinal cords had dense macrophage infiltration ...

Microglia--the macrophage equivalent of the CNS--safeguards and supports neuronal functions. Threats to the CNS homeostasis can trigger a rapid transformation of these cells from a normally "resting" into alerted and "activated" states. Microglia primarily serves the tissue defence and protection when participating in mechanisms of innate and adaptive immunity. On ...

Ciliary neurotrophic factor (CNTF) is a cytokine whose neurotrophic and differentiating effects over cells in the central nervous system (CNS) have been clearly demonstrated. This article summarizes the general characteristics of CNTF, its receptor and the signaling pathway that it activates and focuses on its effects over skeletal muscle, one ...

The contribution of inflammation to the pathogenesis of several nervous system disorders has long been established. Other observations, however, indicate that both inflammatory cells and mediators may also have beneficial functions, assisting in repair and recovery processes. There is compelling evidence to indicate that in the injured nervous system, as ...

Astroglial cells are the most abundant cells in the mammalian central nervous system (CNS), yet our knowledge about their function in health and disease has been limited. This review focuses on the recent work addressing the function of intermediate filaments in astroglial cells under severe mechanical or osmotic stress, in ...

Mice transgenic for human P301S tau protein exhibit many characteristics of the human tauopathies, including the formation of abundant filaments made of hyperphosphorylated tau protein and neurodegeneration leading to nerve cell loss. At 5 months of age, the pathological changes are most marked in brainstem and spinal cord. Here we ...

Sodium hyaluronate (HA) is widely distributed in extracellular matrixes and can play a role in orchestrating cell function. Consequently, many investigators have looked at the effect of exogenous HA on cell behavior in vitro. HA can be isolated from several sources (e.g., bacterial, rooster comb, umbilical cord) and therefore can ...

Endothelin (ET) is a potent autocrine mitogen produced by reactive and neoplastic astrocytes. ET has been implicated in the induction of astrocyte proliferation and other transformations engendered by brain pathology, and in promoting the malignant behavior of astrocytomas. Reactive astrocytes containing ET are found in the periphery/penumbra of a wide ...

Inflammatory cytokines in the central nervous system are largely modulated by glial cells and influence neuronal responses to CNS injury. The protein tyrosine phosphatase SHP-1, an intracellular regulator of many cytokine signaling pathways, has been implicated in mediating the activation of glia. There is a direct correlation between abnormally activated ...

The central nervous system (CNS) is a major dose-limiting organ in clinical radiotherapy (XRT). The underlying mechanisms of radiation-induced injury in this organ remain unclear. For many years, research has focused on identifying the major target cells of damage, and depletion of target cells due to reproductive or clonogenic cell ...