The role of extracellular ionic changes in upregulating the mRNA for glial fibrillary acidic protein following spreading depression

Bonthius, Daniel J.; Lothman, Eric W.; Steward, Oswald

doi:10.1016/0006-8993(95)00035-o

Cited by 17 publications

(5 citation statements)

References 44 publications

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“…SD by itself can trigger astrocyte reactivity. SD induces an upregulation in GFAP mRNA and protein levels in vivo in the absence of tissue injury (Bonthius et al, ; Kraig et al, ). The spatial distribution of GFAP upregulation matches the observed spatial pattern of SD and signs of reactivity were not observed in animals where SD propagation was prevented by the NMDAR antagonist MK801.…”

Section: Changes In Astrocyte Phenotypementioning

confidence: 99%

Multifaceted roles for astrocytes in spreading depolarization: A target for limiting spreading depolarization in acute brain injury?

Seidel

Escartin

Ayata

et al. 2015

Glia

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Spreading depolarizations (SD) are coordinated waves of synchronous depolarization, involving large numbers of neurons and astrocytes as they spread slowly through brain tissue. The recent identification of SDs as likely contributors to pathophysiology in human subjects has led to a significant increase in interest in SD mechanisms, and possible approaches to limit the numbers of SDs or their deleterious consequences in injured brain. Astrocytes regulate many events associated with SD. SD initiation and propagation is dependent on extracellular accumulation of K+ and glutamate, both of which involve astrocytic clearance. SDs are extremely metabolically demanding events, and signaling through astrocyte networks is likely central to the dramatic increase in regional blood flow that accompanies SD in otherwise healthy tissues. Astrocytes may provide metabolic support to neurons following SD, and may provide a source of adenosine that inhibits neuronal activity following SD. It is also possible that astrocytes contribute to the pathophysiology of SD, as a consequence of excessive glutamate release, facilitation of NMDA receptor activation, brain edema due to astrocyte swelling, or disrupted coupling to appropriate vascular responses after SD. Direct or indirect evidence has accumulated implicating astrocytes in many of these responses, but much remains unknown about their specific contributions, especially in the context of injury. Conversion of astrocytes to a reactive phenotype is a prominent feature of injured brain, and recent work suggests that the different functional properties of reactive astrocytes could be targeted to limit SDs in pathophysiological conditions.

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Section: Changes In Astrocyte Phenotypementioning

confidence: 99%

Multifaceted roles for astrocytes in spreading depolarization: A target for limiting spreading depolarization in acute brain injury?

Seidel

Escartin

Ayata

et al. 2015

Glia

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“…Exposure of the cerebral cortex to a solution containing 60 mM K + followed by spreading depression produces a dramatic upregulation of GFAP mRNA levels [3]. This indicates that CNS tissue incubation in high K + might be a useful model for studying astrocyte swelling and the early events of astrocytic activation.…”

Section: Introductionmentioning

confidence: 98%

High extracellular K+ evokes changes in voltage-dependent K+ and Na+ currents and volume regulation in astrocytes

Neprašová

Andĕrová

Petrik

et al. 2006

Pflugers Arch - Eur J Physiol

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[K(+)](e) increase accompanies many pathological states in the CNS and evokes changes in astrocyte morphology and glial fibrillary acidic protein expression, leading to astrogliosis. Changes in the electrophysiological properties and volume regulation of astrocytes during the early stages of astrocytic activation were studied using the patch-clamp technique in spinal cords from 10-day-old rats after incubation in 50 mM K(+). In complex astrocytes, incubation in high K(+) caused depolarization, an input resistance increase, a decrease in membrane capacitance, and an increase in the current densities (CDs) of voltage-dependent K(+) and Na(+) currents. In passive astrocytes, the reversal potential shifted to more positive values and CDs decreased. No changes were observed in astrocyte precursors. Under hypotonic stress, astrocytes in spinal cords pre-exposed to high K(+) revealed a decreased K(+) accumulation around the cell membrane after a depolarizing prepulse, suggesting altered volume regulation. 3D confocal morphometry and the direct visualization of astrocytes in enhanced green fluorescent protein/glial fibrillary acidic protein mice showed a smaller degree of cell swelling in spinal cords pre-exposed to high K(+) compared to controls. We conclude that exposure to high K(+), an early event leading to astrogliosis, caused not only morphological changes in astrocytes but also changes in their membrane properties and cell volume regulation.

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“…In recent decades, however, evidence has begun to emerge of regional differences among astrocytes. For example, we have shown that astrocytes in the cerebral cortex and subfields of the hippocampus differ in their responses to spreading depression and reverberatory seizures (Bonthius and Oswald, 1993; Bonthius et al, 1994; 1995). Others have demonstrated regional differences among astrocytes in the expression of cytoskeletal elements and neuropeptides, and in the uptake of neurotransmitters (Wilkin et al, 1990).…”

Section: Discussionmentioning

confidence: 99%

“…For example, we have shown that astrocytes in the cerebral cortex and subfields of the hippocampus differ in their responses to spreading depression and reverberatory seizures. 4,14,15 Others have demonstrated regional differences among astrocytes in the expression of cytoskeletal elements and neuropeptides, and in the uptake of neurotransmitters. 13 Regional differences in astrocytes have been observed in a variety of disease states, including Alzheimer’s disease, amyotrophic lateral sclerosis, and major depression.…”

Section: Discussionmentioning

confidence: 99%

Alexander Disease

Bonthius

Karaçay

2015

J Child Neurol

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Alexander disease is a genetically-induced leukodystrophy, due to dominant mutations in the glial fibrillary acidic protein (GFAP) gene, causing dysfunction of astrocytes. We have identified a novel GFAP mutation, associated with a novel phenotype for Alexander disease. A boy with global developmental delay and hypertonia was found to have a leukodystrophy. Genetic analysis revealed a heterozygous point mutation in exon 6 of the GFAP gene. The guanine-to-adenine change causes substitution of the normal glutamic acid codon (GAG) with a mutant lysine codon (AAG) at position 312 (E312K mutation). At the age of four years, the child developed epilepsia partialis continua, consisting of unabating motor seizures involving the unilateral perioral muscles. Epilepsia partialis continua has not previously been reported in association with Alexander disease. Whether and how the E312K mutation produces pathologic changes and clinical signs that are unique from other Alexander disease-inducing mutations in GFAP remain to be determined.

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The role of extracellular ionic changes in upregulating the mRNA for glial fibrillary acidic protein following spreading depression

Cited by 17 publications

References 44 publications

Multifaceted roles for astrocytes in spreading depolarization: A target for limiting spreading depolarization in acute brain injury?

Multifaceted roles for astrocytes in spreading depolarization: A target for limiting spreading depolarization in acute brain injury?

High extracellular K+ evokes changes in voltage-dependent K+ and Na+ currents and volume regulation in astrocytes

Alexander Disease

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