scholarly journals Exploring the role of microglia in cortical spreading depression in neurological disease

2017 ◽  
Vol 37 (4) ◽  
pp. 1182-1191 ◽  
Author(s):  
Mamoru Shibata ◽  
Norihiro Suzuki
Keyword(s):  
Cortical Neurons ◽  
Neurological Disease ◽  
Cortical Spreading Depression ◽  
Microglial Activation ◽  
Spreading Depression ◽  
Traumatic Injury ◽  
The Relationship ◽  
The Brain ◽  
Microglial Development

Microglia play a pivotal role in innate immunity in the brain. During development, they mature from myeloerythroid progenitor cells in the yolk sac and colonize the brain to establish a resident population of tissue macrophages. In the postnatal brain, they exert phagocytosis and induce inflammatory response against invading pathogens. Microglia also act as guardians of brain homeostasis by surveying the microenvironment using motile processes. Cortical spreading depression (CSD) is a slowly propagating (2–5 mm/min) wave of rapid, near-complete depolarization of neurons and astrocytes followed by a period of electrical suppression of a distinct population of cortical neurons. Not only has CSD been implicated in brain migraine aura, but CSD-like events have also been detected in stroke and traumatic injury. CSD causes a considerable perturbation of the ionic environment in the brain, which may be readily detected by microglia. Although CSD is known to activate microglia, the role of microglial activation in CSD-related neurological disorders remains poorly understood. In this article, we first provide an overview of microglial development and the multiple functions of microglia. Then, we review existing data on the relationship between microglia and CSD and discuss the relevance of CSD-induced microglial activation in neurological disease.

scholarly journals High-mobility group box 1 is an important mediator of microglial activation induced by cortical spreading depression

2016 ◽  
Vol 37 (3) ◽  
pp. 890-901 ◽  
Author(s):  
Tsubasa Takizawa ◽  
Mamoru Shibata ◽  
Yohei Kayama ◽  
Toshihiko Shimizu ◽  
Haruki Toriumi ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Cortical Spreading Depression ◽  
Microglial Activation ◽  
Spreading Depression ◽  
High Mobility ◽  
High Mobility Group ◽  
Migraine Aura ◽  
Double Knockout ◽  
Activated Microglia ◽  
Important Mediator

Single episodes of cortical spreading depression (CSD) are believed to cause typical migraine aura, whereas clusters of spreading depolarizations have been observed in cerebral ischemia and subarachnoid hemorrhage. We recently demonstrated that the release of high-mobility group box 1 (HMGB1) from cortical neurons after CSD in a rodent model is dependent on the number of CSD episodes, such that only multiple CSD episodes can induce significant HMGB1 release. Here, we report that only multiple CSD inductions caused microglial hypertrophy (activation) accompanied by a greater impact on the transcription activity of the HMGB1 receptor genes, TLR2 and TLR4, while the total number of cortical microglia was not affected. Both an HMGB1-neurtalizing antibody and the HMGB1 inhibitor glycyrrhizin abrogated multiple CSD-induced microglial hypertrophy. Moreover, multiple CSD inductions failed to induce microglial hypertrophy in TLR2/4 double knockout mice. These results strongly implicate the HMGB1–TLR2/4 axis in the activation of microglia following multiple CSD inductions. Increased expression of the lysosomal acid hydrolase cathepsin D was detected in activated microglia by immunostaining, suggesting that lysosomal phagocytic activity may be enhanced in multiple CSD-activated microglia.

Prostanoids attenuate pial arteriolar dilation induced by cortical spreading depression in rabbits

1991 ◽  
Vol 261 (4) ◽  
pp. R828-R834 ◽  
Author(s):  
M. Shibata ◽  
C. W. Leffler ◽  
D. W. Busija
Keyword(s):  
Cerebrospinal Fluid ◽  
Cortical Spreading Depression ◽  
Spreading Depression ◽  
Brain Vessels ◽  
Cranial Window ◽  
Baseline Levels ◽  
Fluid Levels ◽  
The Brain ◽  
Arteriolar Diameter

The role of prostanoids in mediating cerebrovascular responses to cortical spreading depression (CSD) was examined in anesthetized rabbits. CSD was elicited by KCl microinjection, and its propagation was monitored electrophysiologically. Pial arterial diameter was determined using a closed cranial window and intravital microscopy, and regional cerebral blood flow (rCBF) was determined using laser flowmetry. Levels of peri-arachnoid cerebrospinal fluid prostanoids were determined by radioimmunoassay. CSF increased pial arteriolar diameter 62% and rCBF 354% over the baseline levels. Locations of propagating CSD, dilating pial arteriole, and increased rCBF were always closely associated spatiotemporally. Cerebrospinal fluid prostanoid levels increased during single CSD-induced arteriolar dilation, and they were further augmented during multiple CSDs. Indomethacin enhanced both CSD-induced vasodilation (88%) and rCBF increase (580%), but it decreased the cerebrospinal fluid levels of prostanoids below the baseline levels and prevented their increase during CSD-induced vasodilation. These results indicate that prostanoids are synthesized from neurons or glial cells and/or the brain vessels and, as the net result, counteract pial arteriolar dilation and rCBF increase during CSD. In addition, they support the hypothesis that the vasodilation is caused primarily by neurogenic factors associated with CSD.

scholarly journals Effect of serotonin depletion on cortical spreading depression evoked cerebrovascular changes

2010 ◽  
Vol 4 (5) ◽  
pp. 731-738 ◽  
Author(s):  
Supang Maneesri le Grand ◽  
Weera Supornsilpchai ◽  
Chonlawan Saengjaroentham ◽  
Juntima Pleumsamran ◽  
Anan Srikiatkhachorn
Keyword(s):  
Cortical Neurons ◽  
Cortical Spreading Depression ◽  
Spreading Depression ◽  
Control Group ◽  
Cerebral Microvessels ◽  
Doppler Flowmetry ◽  
Pathological Conditions ◽  
Migraine Pathophysiology ◽  
The Relationship ◽  
Cerebral Cortical Blood Flow

Abstract Background: The cortical spreading depression (CSD) is a phenomenon associated with several pathological conditions including migraine. It can induce alterations in both neural and vascular compartments. Serotonin (5-HT) depletion is known as a condition involved in migraine pathophysiology. The hyper-excitability of the cortical neurons to the CSD activation in the low 5-HT state has been previously reported. However, the cerebrovascular responses to CSD activation in this condition have never been studied yet. Objectives: Determine the effect of 5-HT depletion on the cerebrovascular responses to CSD activation. Methods: Wistar rats (weighing 250-300 grams) were divided into three groups: control, CSD, and low 5-HT with CSD group (five rats per group). To induce the low 5-HT state, the para-chlorophenylalanine was injected intraperitoneally into the rats three days before the experiment. CSD was induced by the application of solid KCl (3 mg) on the parietal cortex. NaCl instead of KCl was applied to the control group. Cerebral cortical blood flow was monitored using Laser Doppler flowmetry. The ultrastructure of cerebral microvessels was examined using electron microscopy to determine the cerebral microcirculatory responses to CSD. Results: Depletion of serotonin induced a significant increase in the peak amplitude of CSD-evoked cerebral hyperaemia. This condition also enhanced the development of CSD-induced endothelial pinocytosis and microvillus formation in cerebrocortical microvessels. Conclusion: 5-HT was an important neurotransmitter involved in the control of cerebrovascular responses to CSD activation. The hypersensitivity of the cerebrovascular responses observed in the 5-HT depleted state may explain the relationship between headache and 5-HT depletion.

scholarly journals Cortical Spreading Depression—New Insights and Persistent Questions

Cephalalgia ◽  
2009 ◽  
Vol 29 (10) ◽  
pp. 1115-1124 ◽  
Author(s):  
A Charles ◽  
KC Brennan
Keyword(s):  
Brain Injury ◽  
Animal Models ◽  
Cortical Spreading Depression ◽  
Spreading Depression ◽  
Exact Role ◽  
Definitive Evidence ◽  
Meaningful Information ◽  
Human Disorders ◽  
Functional Consequences

Since its original extensive description by Leao in 1944, thousands of publications have characterized the phenomenon of cortical spreading depression (CSD). Despite the attention that CSD has received over more than six decades, however, many fundamental questions regarding its initiation, propagation, functional consequences, and relationship to migraine and other human disorders remain unanswered. Advances in genetics and cellular imaging have led to important insights into the basic mechanisms of CSD, with increasing attention focused on specific neuronal ion channels, neurotransmitters and neuromodulators. In addition, there is growing recognition that astrocytes and the vasculature may play an active, rather than simply a passive or reactive role in CSD. Several recent descriptions of CSD in humans in the setting of brain injury provide definitive evidence that this phenomenon can occur and have important functional consequences in the human brain. Although the exact role of CSD in migraine has yet to be conclusively established, there is strong evidence that the investigation of CSD in animal models can provide meaningful information about migraine that can be translated into the clinical setting. This review will briefly address the extensive work that has been done on CSD over more than half a century, but focus primarily on more recent studies with a particular emphasis on relevance to migraine.

scholarly journals Death Receptors in the Selective Degeneration of Motoneurons in Amyotrophic Lateral Sclerosis

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Julianne Aebischer ◽  
Nathalie Bernard-Marissal ◽  
Brigitte Pettmann ◽  
Cédric Raoul
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Immune Cells ◽  
Microglial Activation ◽  
Death Receptors ◽  
Strong Body ◽  
Als Patients ◽  
Brain And Spinal Cord ◽  
The Brain ◽  
Lateral Sclerosis

While studies on death receptors have long been restricted to immune cells, the last decade has provided a strong body of evidence for their implication in neuronal death and hence neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS). ALS is a fatal paralytic disorder that primarily affects motoneurons in the brain and spinal cord. A neuroinflammatory process, associated with astrocyte and microglial activation as well as infiltration of immune cells, accompanies motoneuron degeneration and supports the contribution of non-cell-autonomous mechanisms in the disease. Hallmarks of Fas, TNFR, LT-βR, and p75NTR signaling have been observed in both animal models and ALS patients. This review summarizes to date knowledge of the role of death receptors in ALS and the link existing between the selective loss of motoneurons and neuroinflammation. It further suggests how this recent evidence could be included in an ultimate multiapproach to treat patients.

Ethanol and Cortical Spreading Depression: The Protective Role of α-Tocopherol

2019 ◽  
pp. 109-117
Author(s):  
Rubem Carlos Araújo Guedes ◽  
Ranilson de Souza Bezerra ◽  
Ricardo Abadie-Guedes
Keyword(s):  
Cortical Spreading Depression ◽  
Spreading Depression ◽  
Protective Role

Electrical and Vascular Concomitants of Spreading Depression

1957 ◽  
Vol 189 (1) ◽  
pp. 159-166 ◽  
Author(s):  
A. Van Harreveld ◽  
Sidney Ochs
Keyword(s):  
Spreading Depression ◽  
Potential Change ◽  
Vascular Changes ◽  
Convulsive Activity ◽  
Slow Potential ◽  
Narrow Region ◽  
Transport Of Ions ◽  
The Relationship ◽  
The Brain

Spreading depression is accompanied by a slow potential change, a drop in cortical conductivity and by vascular changes. The latter were investigated in histological preparations of cortex frozen while a spreading depression was in progress. In the cat and rabbit a broad wave of vasodilatation was observed. In the rabbit this appeared to be preceded by a narrow region of vasoconstriction. Spreading depression can be changed into spreading convulsive activity by administering CO2 in the respiratory air (7–12%). CO2 markedly decreased the drop in cortical conductivity but affected the magnitude of the slow potential change only moderately. It is postulated that both the conductivity drop during spreading depression and a similar drop observed after asphyxiation of the brain are caused by a transport of ions from the intercellular compartment into cortical cellular elements. The relationship between the slow potential change, conductivity drop, vascular changes and the changes in the electrocorticogram during spreading depression is discussed.

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