scholarly journals Role of Spleen-Derived Monocytes/Macrophages in Acute Ischemic Brain Injury

2014 ◽  
Vol 34 (8) ◽  
pp. 1411-1419 ◽  
Author(s):  
Eunhee Kim ◽  
Jiwon Yang ◽  
Cesar D Beltran ◽  
Sunghee Cho
Keyword(s):  
Infarct Size ◽  
Mononuclear Phagocytes ◽  
Ischemic Brain Injury ◽  
Monocyte Subsets ◽  
Ischemic Brain ◽  
Acute Infarct ◽  
Pathologic Assessment ◽  
The Individual ◽  
The Brain

Monocytes/macrophages (MMs), mononuclear phagocytes, have been implicated in stroke-induced inflammation and injury. However, the presence of pro-inflammatory Ly-6Chigh and antiinflammatory Ly-6Clow monocyte subsets raises uncertainty regarding their role in stroke pathologic assessment. With recent identification of the spleen as an immediate reservoir of MMs, this current study addresses whether the spleen-derived MMs are required for stroke pathologic assessment. We observed that the spleen was contracted in poststroke animals and the contraction was accompanied by decreased number of Ly-6Chigh and Ly-6Clow subsets in the spleen. The deployment of these subsets from the spleen temporally coincided with respective increases in the ischemic brain. Compared to mice with the spleen, mice receiving a splenectomy just before the stroke displayed less accumulation of Ly-6Chigh and Ly-6Clow MMs in the brain. Despite the reduced accumulation of both subsets, infarct size and swelling were not reduced in the asplenic mice. The dissociative findings of infarct size and extent of MM infiltration in the postischemic brain indicate minimal involvement of spleen-derived total MMs in acute infarct development. Selective Ly-6Chigh or Ly-6Clow MM targeting is suggested to address the contribution of the individual subset to acute stroke pathologic assessment.

Molecular Mechanisms of Ischemic Cerebral Edema: Role of Electroneutral Ion Transport

Physiology ◽  
2009 ◽  
Vol 24 (4) ◽  
pp. 257-265 ◽  
Author(s):  
Kristopher T. Kahle ◽  
J. Marc Simard ◽  
Kevin J. Staley ◽  
Brian V. Nahed ◽  
Pamela S. Jones ◽  
...  
Keyword(s):  
Cerebral Edema ◽  
Molecular Mechanisms ◽  
Cell Volume Regulation ◽  
Cell Swelling ◽  
Ischemic Brain Injury ◽  
Edema Formation ◽  
Ischemic Brain ◽  
The Brain ◽  
Permeability Alterations

The brain achieves homeostasis of its intracellular and extracellular fluids by precisely regulating the transport of solute and water across its major cellular barriers: endothelia of the blood-brain barrier (BBB), choroid plexus epithelia, and neuroglial cell membranes. Cerebral edema, the pathological accumulation of fluid in the brain’s intracellular and extracellular spaces, is a major cause of morbidity and mortality following stroke and other forms of ischemic brain injury. Until recently, mechanisms of cerebral edema formation have been obscure; consequently, its treatment has been empiric and suboptimal. Here, we provide a paradigm for understanding ischemic cerebral edema, showing that its molecular pathogenesis is a complex yet step-wise process that results largely from impaired astrocytic cell volume regulation and permeability alterations in the cerebral microvasculature, both of which arise from pathological changes in the activities of specific ion channels and transporters. Recent data has implicated the bumetanide-sensitive NKCC1, an electroneutral cotransporter expressed in astrocytes and the BBB, in cerebral edema formation in several different rodent models of stroke. Pharmacological inhibition or genetic deficiency of NKCC1 decreases ischemia-induced cell swelling, BBB breakdown, cerebral edema, and neurotoxicity. Combination pharmacological strategies that include NKCC1 as a target might thus prove beneficial for the treatment of ischemic, and potentially other types of, cerebral edema.

scholarly journals Ion Channels and Zinc: Mechanisms of Neurotoxicity and Neurodegeneration

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Deborah R. Morris ◽  
Cathy W. Levenson
Keyword(s):  
Brain Injury ◽  
Ion Channels ◽  
Kainate Receptors ◽  
Zinc Toxicity ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
The Central Nervous System ◽  
Excitatory Neurotransmission ◽  
The Brain

Ionotropic glutamate receptors, such as NMDA, AMPA and kainate receptors, are ligand-gated ion channels that mediate much of the excitatory neurotransmission in the brain. Not only do these receptors bind glutamate, but they are also regulated by and facilitate the postsynaptic uptake of the trace metal zinc. This paper discusses the role of the excitotoxic influx and accumulation of zinc, the mechanisms responsible for its cytotoxicity, and a number of disorders of the central nervous system that have been linked to these neuronal ion channels and zinc toxicity including ischemic brain injury, traumatic brain injury, and epilepsy.

scholarly journals Cell Type-Specific Mechanisms in the Pathogenesis of Ischemic Stroke: The Role of Apoptosis Signal-Regulating Kinase 1

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
So Yeong Cheon ◽  
Eun Jung Kim ◽  
Jeong Min Kim ◽  
Bon-Nyeo Koo
Keyword(s):  
Ischemic Stroke ◽  
Brain Injury ◽  
Cerebral Ischemia ◽  
Cell Types ◽  
Ischemic Brain Injury ◽  
Cell Type ◽  
Ischemic Brain ◽  
Cell Type Specific ◽  
The Brain

Stroke has become a more common disease worldwide. Despite great efforts to develop treatment, little is known about ischemic stroke. Cerebral ischemia activates multiple cascades of cell type-specific pathomechanisms. Ischemic brain injury consists of a complex series of cellular reactions in various cell types within the central nervous system (CNS) including platelets, endothelial cells, astrocytes, neutrophils, microglia/macrophages, and neurons. Diverse cellular changes after ischemic injury are likely to induce cell death and tissue damage in the brain. Since cells in the brain exhibit different functional roles at distinct time points after injury (acute/subacute/chronic phases), it is difficult to pinpoint genuine roles of cell types after brain injury. Many experimental studies have shown the association of apoptosis signal-regulating kinase 1 (ASK1) with cellular pathomechanisms after cerebral ischemia. Blockade of ASK1, by either pharmacological or genetic manipulation, leads to reduced ischemic brain injury and subsequent neuroprotective effects. In this review, we present the cell type-specific pathophysiology of the early phase of ischemic stroke, the role of ASK1 suggested by preclinical studies, and the potential use of ASK suppression, either by pharmacologic or genetic suppression, as a promising therapeutic option for ischemic stroke recovery.

scholarly journals In Vivo and in Vitro Evaluation of the Anti-inflammatory Effect of Thymoquinone Toward Ischemic Brain Injury Alleviation via Nrf2/HO-1 Pathway

2020 ◽  
Author(s):  
Nashwa Amin ◽  
Xiaoxue Du ◽  
Shijia Chen ◽  
Qiannan Ren ◽  
Azhar Badry ◽  
...  
Keyword(s):  
Cell Death ◽  
Cerebral Ischemia ◽  
Brain Damage ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Chronic Dose ◽  
The Brain

Abstract Background - In recent years, considerable efforts have been devoted to exploring effective therapy for cerebral ischemia. Reactive oxygen species (ROS) mediated - inflammation plays a crucial role in ischemic brain injury. Triptolide (TP) has been widely used for ischemic therapy although administrating a chronic dose of this therapy may cause serious drawbacks and higher liver toxicity. Considering these critical side effects, here we demonstrate the employment of thymoquinone (TQ) as a new alternative drug for alleviating ischemic brain damage via suppression of inflammatory cytokines by inducing Nrf2/HO-1 under a chronic dose without toxicity. Methods- We assessed a photo-thrombosis mouse model of focal cerebral ischemia to investigate the impact of the chronic dose of TQ to alleviates ischemic brain damage, meanwhile, we used Pc12 to determine the efficiency of TQ to attenuate the OGD/R induces cell death. Results- Our in vivo and in vitro results indicate that the administration of TQ drug can sufficiently mitigate the brain damage after stroke by increasing the Nrf2/HO-1 expression and thereby modulate the cell death and inflammation resulting from cerebral ischemia. The observation based on YFP mice elucidates the role of TQ therapy in recovering the brain status after injury through increasing the dendrite spines density and the ratio of YFP reporter cells with NeuN expression. Conclusions- Our study is the first to focus on the crucial role of the Nrf2/HO-1 pathway as a promising ischemic therapy under a chronic dose of TQ by increasing proliferating protein expression, decreasing inflammation and neuronal cell death as well as controlling the autophagy process.

scholarly journals Effects of sevoflurane on rats with ischemic brain injury and the role of the TREK-1 channel

2017 ◽  
Vol 14 (4) ◽  
pp. 2937-2942 ◽  
Author(s):  
Lixiao Pan ◽  
Fengyun Yang ◽  
Caixia Lu ◽  
Changxin Jia ◽  
Qing Wang ◽  
...  
Keyword(s):  
Brain Injury ◽  
Ischemic Brain Injury ◽  
Ischemic Brain

scholarly journals Pathophysiological role of zinc in ischemic brain injury

Oncotarget ◽  
2016 ◽  
Vol 8 (4) ◽  
pp. 5670-5671
Author(s):  
Zhifeng Qi ◽  
Ke Jian Liu
Keyword(s):  
Brain Injury ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Pathophysiological Role
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