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The first description of the inflammatory process appeared as early as the first century AD. Among the first things learned about inflammation is that vascular permeability is increased and leukocyte extravasation occurs. It is now realized that the central nervous system (CNS) is not as devoid of immune cell entrance as once believed and that neuroinflammation can occur. Even in the CNS absence of peripheral immune cells, cytokines from the periphery can influence glial activation in response to endogenous or exogenous stresses. Activated glial cells will secrete proinflammatory cytokines among other factors. The presence of relatively high concentrations of proinflammatory cytokines, such as IL-1, IL-6, and TNF-α, in the brain produces sickness behavior. Neuroinflammation is not only caused by viral or bacterial infection, but can also be the result of physical injury or neurodegenerative diseases, such as Alzheimer΄s disease, Parkinson΄s disease, multiple sclerosis, and cerebral palsy. This chronic neuroinflammation is associated with a number of common factors; most notable among these is the increased concentration of proinflammatory cytokines. In addition to the ones listed above, others have been detected including, IL-18, IL-33, and HMGB1. Although TGF-β1 functions most often as an anti-inflammatory cytokine, under certain circumstances it, too, can have proinflammatory activity. Other common features of neuroinflammation include increased production of reactive oxygen species (ROS) and nitric oxide (NO), which function to increase apoptosis and promote neuronal damage. Activation of astrocytes is detected by elevated GFAP expression. Activated astrocytes promote chemokine expression causing permeability of the blood–brain barrier (BBB), thus allowing leukocytes to enter the brain tissue. The heavy metal Pb accumulates in glial cells and in doing so can potentiate cytokine and glutamate-mediated increases in the BBB permeability, as well as cause chronic glial cell activation. Pb΄s ability to promote gliosis and deficiencies in chaperone protein function has prompted a comparison of Pb toxicity to certain neurodegenerative disorders, such as Alzheimer΄s and Parkinson΄s diseases. Toxicity of other metals, such as, Al, Cu, Cd, Zn, and Hg was also found to share common features with Alzheimer΄s disease. [ABSTRACT FROM AUTHOR]

It is now well established that glial fibrillary acidic protein (GFAP) is the principal 8- to 9-nm intermediate filament in mature astrocytes of the central nervous system (CNS). More than 30 years ago, the value of GFAP as a prototype antigen in nervous tissue identification and as a standard marker for fundamental and applied research at an interdisciplinary level was recognized. As a member of the cytoskeletal protein family, GFAP is thought to be important in modulating astrocyte motility and shape by providing structural stability to astrocytic processes. In the CNS of higher vertebrates, following injury, either as a result of trauma, disease, genetic disorders, or chemical insult, astrocytes become reactive and respond in a typical manner, termed astrogliosis. Astrogliosis is characterized by rapid synthesis of GFAP and is demonstrated by increase in protein content or by immunostaining with GFAP antibody. In addition to the major application GFAP antisera for routine use in astrocyte identification in the CNS, the molecular cloning of the mouse gene in 1985 and the subsequent discovery of the gfa-2 promoter have both opened a new and rich realm for GFAP studies. These include antisense, null mice, and numerous promoter studies. GFAP knockout mice studies have shown the important role of GFA cytoskeleton in the astrocyte. The genetic basis for the only disease due to GFAP mutation, Alexander disease, has been demonstrated and confirmed. While the structural function of GFAP has become more acceptable, the use of GFAP antibodies and promoters continue to be valuable in studying CNS injury, disease, and development. [ABSTRACT FROM AUTHOR]

Propentofylline is a unique methylxanthine with clear cyclic AMP, phosphodiesterase, and adenosine actions, including enhanced synaptic adenosine signaling. Both in vitro and in vivo studies have demonstrated profound neuroprotective, antiproliferative, and anti-inflammatory effects of propentofylline. Propentofylline has shown efficacy in preclinical models of stroke, opioid tolerance, and acute and chronic pain. Clinically, propentofylline has shown efficacy in degenerative and vascular dementia, and as a potential adjuvant treatment for schizophrenia and multiple sclerosis. Possible mechanisms of action include a direct glial modulation to decrease a reactive phenotype, decrease glial production and release of damaging proinflammatory factors, and enhancement of astrocyte-mediated glutamate clearance. This chapter reviews the literature that supports a myriad of protective actions of this small molecule and implicates propentofylline as a potential therapeutic for the treatment of chronic pain. From these studies, we propose a CNS multipartite synaptic action of propentofylline that includes modulation of pre- and postsynaptic neurons, astrocytes, and microglia in the treatment of chronic pain syndromes, including, but not limited to, neuropathic pain. [ABSTRACT FROM AUTHOR]

To determine the cell autonomous and environmental factors that control the differentiation of neurons, astrocytes, and oligodendrocytes, we have used neurospheres made of primary neural progenitor cells. These organoids are amenable to the live cell imaging of several parameters which are central to the proper control of neuron and glial cell differentiation, as well as to the function of the resulting fully differentiated neural cells. Here we report on the methods to study in living cells the connexin-dependent cell-to-cell coupling, the oscillations in intracellular Ca2+, and specifically the intercellular synchronization of such events, and the ATP release by either exocytosis of vesicles or through specialized membrane channels. The methods rely on the combination of a variety of state-of-the art microscopy and biophysical methods. [ABSTRACT FROM AUTHOR]

Central nervous system (CNS) is composed of two major cell types: neuron and glia. Astrocytes and oligodendrocytes belong to the latter category. Astrocytes, through an intricate network surrounding blood vessels, play an important role in supplying food, water and ions from periphery to the CNS and maintain CNS homeostasis. Astrocytes also play an active role in neurogenesis. However, under inflammatory or neurodegenerative conditions, astrocytes produce proinflammatory mediators and take active part in the ongoing events. Neurons in the CNS are covered by myelin sheath that maintains conduction of nerve impulse. Consistently, the CNS houses oligodendrocytes for myelin synthesis. On the other hand, Schwann cells are the myelinating cells in the peripheral nervous system (PNS). Balanced expression of several genes and activation of transcription factors critically regulate the entire complicated functional network of astrocytes, oligodendrocytes and Schwann cells. Keeping a birds΄ eye view, this chapter delineates genesis and functional aspects of astrocytes, oligodendrocytes and Schwann cells. [ABSTRACT FROM AUTHOR]

An encyclopedia entry for "Glia" is presented. Glial proliferation within the epileptogenic zone of patients with focal seizures can influence epiletogenicity. Brain tumor and cortical dysplasia are some of the pathophysiologic lesions that lead to increased neuronal-glial interdigitation and proliferation which may facilitate hyperexcitability occurring with seizures. Particular focus is given to the role of glial cells in neural circuits.

A definition of the term "blood-brain barrier" is presented. It refers to a condition which arises because capillaries are permeable to water, glucose, sodium chloride and non-ionised lipid-soluble molecules. It is because to the presence of tight junctions between endothelial cells as well as the close association of perivascular extensions of astrocytes with the capillaries.

A definition of the term "astrocytes," which refers to a category of glial cells in the vertebrate central nervous system with long radial processes, is presented.

A definition of the term "glioblastoma multiforme" is presented. It refers to the most malignant of astrocytic tumors. Glioblastoma is composed of poorly differentiated astrocytes. The tumor, which usually affects adults, may develop from low grade astrocytoma, but more frequently manifests itself de novo, after a short clinical history without indication of a less malignant precursor lesion.