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Astrocyte Activation (astrocyte + activation)

Distribution by Scientific Domains

Life Sciences	72%
Medical Sciences	27%

Selected Abstracts

Astrocyte Activation and Apoptosis: Their Roles in the Neuropathology of HIV Infection

BRAIN PATHOLOGY, Issue 1 2003
Farideh Sabri
Astrogliosis is a common neuropathological finding in the brains of HIV infected individuals; both activation and apoptosis of astrocytes are seen. This review aims to discuss the Fas pathway in the context of proliferation and apoptosis of astrocytes during HIV infection, and as a result of astrogliosis, the dysregulation of astrocyte-neuron networks. The presence of molecules reflecting astrocyte activation, which are derived from the sol-ubilization of receptor/ligand from the surface of proliferating astrocytes, in the cerebrospinal fluid may be used to evaluate the degree of brain cell activation during HAART therapy. A better understanding of the molecular pathway(s) leading to increase activation and apoptosis of astrocytes, in parallel with studies conducted to unravel the molecules involved in T-cell apoptosis during HIV infection, may lead to the development of new therapeutic strategies for controlling HIV replication and tissue damage. [source]

Protective effects of naloxone in two-hit seizure model

EPILEPSIA, Issue 3 2010
Lu Yang
Summary Purpose:, Early life status epilepticus (SE) could enhance the vulnerability of the immature brain to a second SE in adulthood (two-hit seizure model). Naloxone has been proved to possess inflammation inhibitory effects in nervous system. This study was designed to evaluate the dose-dependent protective effects of naloxone in kainic acid (KA),induced two-hit seizure model. Methods:, After KA-induced SE at postnatal day 15 (P15), Sprague-Dawley rats were infused with either saline or different doses (1.92, 3.84, 5.76, and 7.68 mg/kg) of naloxone continuously for 12 h. De novo synthesis of cytokines (interleukin-1, [IL-1,], S100B) was assessed by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA) at 12 h after P15 SE. Glial activation states were analyzed by western blotting of glial markers (glial fibrillary acidic protein [GFAP], S100B, Iba1) both at 12 h after P15 SE and at P45. After a second SE at P45, cognitive deteriorations were evaluated by Morris water tests and neuron injuries were evaluated by TdT-mediated dUTP nick end labeling (TUNEL) assays. Results:, Naloxone reduced IL-1, synthesis and microglial activation most potently at a dose of 3.84 mg/kg. Attenuation of S100B synthesis and astrocyte activation were achieved most dramatically by naloxone at a dose of 5.76 mg/kg, which is equal to the most powerful dose in ameliorating cognitive injuries and neuron apoptosis after second SE. Conclusions:, Naloxone treatment immediately after early life SE could dose-dependently reduce cytokine production, glial activation, and further lower the vulnerability of immature brains to a second hit in adulthood. [source]

The induction of HIF-1 reduces astrocyte activation by amyloid beta peptide

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2009
David Schubert
Abstract Reduced glucose metabolism and astrocyte activation in selective areas of the brain are pathological features of Alzheimer's disease (AD). The underlying mechanisms of low energy metabolism and a molecular basis for preventing astrocyte activation are not, however, known. Here we show that amyloid beta peptide (A,)-dependent astrocyte activation leads to a long-term decrease in hypoxia-inducible factor (HIF)-1, expression and a reduction in the rate of glycolysis. Glial activation and the glycolytic changes are reversed by the maintenance of HIF-1, levels with conditions that prevent the proteolysis of HIF-1,. A, increases the long-term production of reactive oxygen species (ROS) through the activation of nicotinamide adenine dinucleotide phosphate oxidase and reduces the amount of HIF-1, via the activation of the proteasome. ROS are not required for glial activation, but are required for the reduction in glycolysis. These data suggest a significant role for HIF-1,-mediated transcription in maintaining the metabolic integrity of the AD brain and identify the probable cause of the observed lower energy metabolism in afflicted areas. They may also explain the therapeutic success of metal chelators in animal models of AD. [source]

In the hypoxic central nervous system, endothelial cell proliferation is followed by astrocyte activation, proliferation, and increased expression of the ,6,4 integrin and dystroglycan

GLIA, Issue 10 2010
Longxuan Li
Abstract Cerebral hypoxia induces a profound angiogenic response in the central nervous system (CNS). Using a mouse model of chronic cerebral hypoxia, we previously demonstrated that angiogenic vessels in the hypoxic CNS show marked upregulation of the extracellular matrix (ECM) protein fibronectin, along with increased expression of its major receptor, ,5,1 integrin on brain endothelial cells (BEC). As cerebral hypoxia also leads to glial activation, the aim of the current study was to define the temporal relationship between BEC responses and glial cell activation in this model of cerebral hypoxia. This revealed that BEC fibronectin/,5,1 integrin expression and proliferation both reached maximal level after 4-day hypoxia. Interestingly, up to 4-day hypoxia, all dividing cells were BEC, but at later time-points proliferating astrocytes were also observed. GFAP staining revealed that hypoxia induced marked astrocyte activation that reached maximal level between 7- and 14-day hypoxia. As newly formed cerebral capillaries require ensheathment by astrocyte end-feet to acquire mature brain endothelium characteristics, we next examined how expression of astrocyte end-feet adhesion molecules is regulated by hypoxia. This showed that the astrocyte adhesion receptors ,6,4 integrin and dystroglycan were both markedly upregulated, with a time-course that closely resembled astrocyte activation. Taken together, this evidence shows that cerebral hypoxia promotes first an endothelial response, in which fibronectin promotes BEC proliferation. This is then followed by an astrocyte response, involving astrocyte activation, proliferation, and reorganization of astrocyte end-feet, which correlates with increased expression of astrocyte end-feet adhesion molecules. © 2010 Wiley-Liss, Inc. [source]

Astrocyte modulation of in vitro ,-amyloid neurotoxicity

GLIA, Issue 3 2004
Silvia Paradisi
Abstract In Alzheimer's disease brain, ,-amyloid (A,) deposition is accompanied by astrocyte activation, whose role in the pathogenesis of the disease is still unclear. To explore the subject, we compared A, neurotoxicity in pure hippocampal cultures and neuronal-astrocytic cocultures, where astrocytes conditioned neurons but were not in contact with them or A,. In the presence of astrocytes, neurons were protected from A, neurotoxicity. Neuritic dystrophy was reduced, synapses were partially preserved, and apoptosis was contrasted. The protection disappeared when astrocytes were also treated with A,, suggesting that A,-astrocyte interaction is deleterious for neurons. This was supported by comparing A, neurotoxicity in pure neurons and neurons grown on astrocytes. In this case, where astrocytes were also in contact with A,, neuritic damage was enhanced and expression of synaptic vesicle proteins decreased. Our results suggest that astrocytes can protect neurons from A, neurotoxicity, but when they interact with A,, the protection is undermined and neurotoxicity enhanced. © 2004 Wiley-Liss, Inc. [source]

Glutamate-mediated astrocyte-to-neuron signalling in the rat dorsal horn

THE JOURNAL OF PHYSIOLOGY, Issue 5 2010
Rita Bardoni
By releasing neuroactive agents, including proinflammatory cytokines, prostaglandins and neurotrophins, microglia and astrocytes are proposed to be involved in nociceptive transmission, especially in conditions of persistent, pathological pain. The specific action on dorsal horn neurons of agents released from astrocytes, such as glutamate, has been, however, poorly investigated. By using patch-clamp and confocal microscope calcium imaging techniques in rat spinal cord slices, we monitored the activity of dorsal horn lamina II neurons following astrocyte activation. Results obtained revealed that stimuli that triggered Ca2+ elevations in astrocytes, such as the purinergic receptor agonist BzATP and low extracellular Ca2+, induce in lamina II neurons slow inward currents (SICs). Similarly to SICs triggered by astrocytic glutamate in neurons from other central nervous system regions, these currents (i) are insensitive to tetrodotoxin (TTX), (ii) are blocked by the NMDA receptor (NMDAR) antagonist d -AP5, (iii) lack an AMPA component, and (iv) have slow rise and decay times. Ca2+ imaging also revealed that astrocytic glutamate evokes NMDAR-mediated episodes of synchronous activity in groups of substantia gelatinosa neurons. Importantly, in a model of peripheral inflammation, the development of thermal hyperalgesia and mechanical allodynia was accompanied by a significant increase of spontaneous SICs in dorsal horn neurons. The NMDAR-mediated astrocyte-to-neuron signalling thus represents a novel pathway that may contribute to the control of central sensitization in pathological pain. [source]