Programmed Cell Deaths and Potential Crosstalk With Blood–Brain Barrier Dysfunction After Hemorrhagic Stroke

Fang, Yuanjian; Gao, Shiqi; Wang, Xiaoyu; Cao, Yang; Lu, Jianing; Chen, Sheng; Lenahan, Cameron; Zhang, Junyi; Shao, Anwen; Zhang, Jianmin

doi:10.3389/fncel.2020.00068

Cited by 77 publications

(65 citation statements)

References 165 publications

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“…Previous studies have shown that inflammation precipitated by neuroglia and infiltrating leukocytes is a significant mechanism that participates in ICH-induced brain injury. Inflammation contributes to the breakdown of the blood-brain barrier (BBB), which in turn exacerbates the inflammation by allowing the infiltration of immunocytes ( 3 – 5 ). Besides, blood components, such as red blood cells (RBCs), leukocytes, and plasma proteins enter the brain immediately following the hemorrhage and these infiltrations may also play a role in the progress of the disease ( 6 ).…”

Section: Introductionmentioning

confidence: 99%

The Changes of Leukocytes in Brain and Blood After Intracerebral Hemorrhage

et al. 2021

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Preclinical and clinical research has demonstrated that inflammation is a critical factor regulating intracerebral hemorrhage (ICH)-induced brain injury. Growing evidence suggests that myeloid cells and lymphocytes have an effect on the pathophysiological processes associated with ICH, such as inflammation, immune responses, perihematomal edema formation, blood–brain barrier (BBB) integrity, and cell death. However, the underlying mechanisms remain largely unknown. We aimed to explore the role immune cells played at different stages of the ICH. To achieve this, novel bioinformatics algorithms were employed to analyze the gene expression profiles and three different analytical tools were utilized to predict the abundances of cell types. In this study, we found that natural killer (NK) cells infiltrated into the brain parenchyma after ICH. Infiltrating NK cells may mediate brain injury through degranulation and recruitment of other cells. Besides, in the acute phase of ICH, monocytes in peripheral blood carried out phagocytosis and secretion of cytokines. On the other hand, in the subacute stage, non-classical monocytes were activated and showed a stronger ability to carry out heme metabolism, wound healing, and antigen processing and presentation. In conclusion, our findings emphasize the significance of intracerebral infiltrating immunocytes in ICH and demonstrate that ICH is a systemic disease affected by peripheral blood. The hub genes identified might be promising therapeutic targets. We also provide a reference on how to use bioinformatics approaches to explore non-neoplastic immune-related diseases.

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Section: Introductionmentioning

confidence: 99%

The Changes of Leukocytes in Brain and Blood After Intracerebral Hemorrhage

et al. 2021

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“…In addition, impaired mitochondrial function generates the production of superoxide radicals, reducing antioxidant activity and causing oxidative stress, which in turn results in the oxidation of proteins and lipids in the cell membrane and DNA fragmentation, ultimately leading to cell necrosis [30]. On the other hand, the events that lead to cell death in the penumbra area are more complex and can extend for weeks after ischemia [30][31][32].…”

Section: Stroke Pathophysiology 21 Overviewmentioning

confidence: 99%

Microglial Plasticity Contributes to Recovery of Bone Marrow Mononuclear Cells during Experimental Stroke

Franco¹,

Cardoso²,

Souza³

et al. 2021

Macrophages

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Brain stroke is an acute neural disorder characterized by obstruction (ischemic) or rupture (hemorrhagic) of blood vessels causing neural damage and subsequent functional impairment. Its pathophysiology is complex and involves a multitude of pathological events including energetic collapse, excitotoxicity, oxidative stress, metabolic acidosis, cell death and neuroinflammation. Despite its clinical importance, there is no effective pharmacological therapies available to diminish secondary damage avowing functional deficits. Considering the failure of pharmacological approaches for stroke, cell therapy came as promising alternative. Different cell types have been investigated in different experimental models with promising results. An important issue regarding the transplantation of stem cells into the damaged CNS tissue is how the pathological environment influences the transplanted cells. It has been established that an exacerbated inflammation in the pathological environment is detrimental to the survival of the transplanted stem cells. This prompted us to develop an experimental strategy to improve the therapeutic actions of bone marrow mononuclear cells (BMMCs) transplanted into the acute phase of brain stroke by modulating microglial activation with minocycline. In this chapter, we first review the basic pathophysiology of ischemic stroke with emphasis on the role of microglia to the pathological outcome. We then review the experimental approach of modulating microglia activation in order to enhance therapeutic actions of BMMCS for experimental stroke. We suggest that such an approach may be applied as an adjuvant therapy to control excessive neuroinflammation in the pathological environment allowing acute transplants and improving therapeutic actions of different kind of stem cells.

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“…Necroptosis and pyroptosis are two additional and important forms of programmed cell death after ischemia or hemorrhage in the brain. Both necroptosis and pyroptosis could be a result of inflammatory factors or DAMPs [4]. Recently, a paper revealed that PACAP is involved in the inhibition of necroptosis in atherosclerosis, and functions by mediating receptor interacting protein 3 (RIP3) expression, a key protein of necroptosis [159].…”

Section: Pacap and Cell Deathmentioning

confidence: 99%

“…The function and structure of BBB would be damaged after stroke, further aggravating the pathological changes. The BBB consists of the neurovascular unit, including endothelial cells, astrocytes, pericytes, neurons, and microglia [4,165]. Among them, endothelial cells and astrocytes function as the most important components of the BBB.…”

Section: Pacap and Bbb Dysfunctionmentioning

confidence: 99%

“…Cell death, considered a terminal point of many pathophysiological changes, contributes an important role of outcome after stroke [ 155 ]. The main cell death after stroke includes apoptosis and autophagy, as well as the programmed necrosis such as necroptosis and pyroptosis [ 155 ]. Apoptosis is widely studied as a downstream target of PACAP.…”

Section: Pacap and Potential Mechanism Of Neuroprotection In Strokementioning

confidence: 99%

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Pituitary Adenylate Cyclase-Activating Polypeptide: A Promising Neuroprotective Peptide in Stroke

et al. 2020

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The search for viable, effective treatments for acute stroke continues to be a global priority due to the high mortality and morbidity. Current therapeutic treatments have limited effects, making the search for new treatments imperative. Pituitary adenylate cyclase-activating polypeptide (PACAP) is a well-established cytoprotective neuropeptide that participates in diverse neural physiological and pathological activities, such as neuronal proliferation, differentiation, and migration, as well as neuroprotection. It is considered a promising treatment in numerous neurological diseases. Thus, PACAP bears potential as a new therapeutic strategy for stroke treatment. Herein, we provide an overview pertaining to the current knowledge of PACAP, its receptors, and its potential neuroprotective role in the setting of stroke, as well as various mechanisms of neuroprotection involving ionic homeostasis, excitotoxicity, cell edema, oxidative stress, inflammation, and cell death, as well as the route of PACAP administration.

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Programmed Cell Deaths and Potential Crosstalk With Blood–Brain Barrier Dysfunction After Hemorrhagic Stroke

Cited by 77 publications

References 165 publications

The Changes of Leukocytes in Brain and Blood After Intracerebral Hemorrhage

The Changes of Leukocytes in Brain and Blood After Intracerebral Hemorrhage

Microglial Plasticity Contributes to Recovery of Bone Marrow Mononuclear Cells during Experimental Stroke

Pituitary Adenylate Cyclase-Activating Polypeptide: A Promising Neuroprotective Peptide in Stroke

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