scholarly journals Neuroinflammation as a Key Driver of Secondary Neurodegeneration Following Stroke?

2021 ◽  
Vol 22 (23) ◽  
pp. 13101
Author(s):  
Shannon M. Stuckey ◽  
Lin Kooi Ong ◽  
Lyndsey E. Collins-Praino ◽  
Renée J. Turner
Keyword(s):  
Ischaemic Stroke ◽  
Tissue Damage ◽  
Inflammatory Cells ◽  
Rapid Onset ◽  
Neurological Dysfunction ◽  
Infarct Core ◽  
Neuronal Tissue ◽  
Post Stroke ◽  
Brain Stroke ◽  
Anti Inflammatory

Ischaemic stroke involves the rapid onset of focal neurological dysfunction, most commonly due to an arterial blockage in a specific region of the brain. Stroke is a leading cause of death and common cause of disability, with over 17 million people worldwide suffering from a stroke each year. It is now well-documented that neuroinflammation and immune mediators play a key role in acute and long-term neuronal tissue damage and healing, not only in the infarct core but also in distal regions. Importantly, in these distal regions, termed sites of secondary neurodegeneration (SND), spikes in neuroinflammation may be seen sometime after the initial stroke onset, but prior to the presence of the neuronal tissue damage within these regions. However, it is key to acknowledge that, despite the mounting information describing neuroinflammation following ischaemic stroke, the exact mechanisms whereby inflammatory cells and their mediators drive stroke-induced neuroinflammation are still not fully understood. As a result, current anti-inflammatory treatments have failed to show efficacy in clinical trials. In this review we discuss the complexities of post-stroke neuroinflammation, specifically how it affects neuronal tissue and post-stroke outcome acutely, chronically, and in sites of SND. We then discuss current and previously assessed anti-inflammatory therapies, with a particular focus on how failed anti-inflammatories may be repurposed to target SND-associated neuroinflammation.

scholarly journals The immune response of T cells and therapeutic targets related to regulating the levels of T helper cells after ischaemic stroke

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Tian-Yu Lei ◽  
Ying-Ze Ye ◽  
Xi-Qun Zhu ◽  
Daniel Smerin ◽  
Li-Juan Gu ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune System ◽  
Immune Responses ◽  
Ischaemic Stroke ◽  
Immune Cells ◽  
Tissue Injury ◽  
Recovery Period ◽  
Vital Functions ◽  
Anti Inflammatory

AbstractThrough considerable effort in research and clinical studies, the immune system has been identified as a participant in the onset and progression of brain injury after ischaemic stroke. Due to the involvement of all types of immune cells, the roles of the immune system in stroke pathology and associated effects are complicated. Past research concentrated on the functions of monocytes and neutrophils in the pathogenesis of ischaemic stroke and tried to demonstrate the mechanisms of tissue injury and protection involving these immune cells. Within the past several years, an increasing number of studies have elucidated the vital functions of T cells in the innate and adaptive immune responses in both the acute and chronic phases of ischaemic stroke. Recently, the phenotypes of T cells with proinflammatory or anti-inflammatory function have been demonstrated in detail. T cells with distinctive phenotypes can also influence cerebral inflammation through various pathways, such as regulating the immune response, interacting with brain-resident immune cells and modulating neurogenesis and angiogenesis during different phases following stroke. In view of the limited treatment options available following stroke other than tissue plasminogen activator therapy, understanding the function of immune responses, especially T cell responses, in the post-stroke recovery period can provide a new therapeutic direction. Here, we discuss the different functions and temporal evolution of T cells with different phenotypes during the acute and chronic phases of ischaemic stroke. We suggest that modulating the balance between the proinflammatory and anti-inflammatory functions of T cells with distinct phenotypes may become a potential therapeutic approach that reduces the mortality and improves the functional outcomes and prognosis of patients suffering from ischaemic stroke.

scholarly journals Anti-inflammatory genes in PBMCs post-spontaneous intracerebral hemorrhage

2021 ◽  
Vol 12 (1) ◽  
pp. 58-66
Author(s):  
Doan Nguyen ◽  
Vi Tran ◽  
Alireza Shirazian ◽  
Cruz Velasco-Gonzalez ◽  
Ifeanyi Iwuchukwu
Keyword(s):  
Intracerebral Hemorrhage ◽  
Negative Correlation ◽  
Mononuclear Cells ◽  
Inflammatory Cells ◽  
Favorable Outcome ◽  
Hospital Length Of Stay ◽  
Spontaneous Intracerebral Hemorrhage ◽  
Hematoma Volume ◽  
Peripheral Blood Mononuclear ◽  
Anti Inflammatory

Abstract Background Neuroinflammation is important in the pathophysiology of spontaneous intracerebral hemorrhage (ICH) and peripheral inflammatory cells play a role in the clinical evolution and outcome. Methodology Blood samples from ICH patients (n = 20) were collected at admission for 5 consecutive days for peripheral blood mononuclear cells (PBMCs). Frozen PBMCs were used for real-time PCR using Taqman probes (NFKB1, SOD1, PPARG, IL10, NFE2L2, and REL) and normalized to GAPDH. Data on hospital length of stay and modified Rankin score (MRS) were collected with 90-day MRS ≤ 3 as favorable outcome. Statistical analysis of clinical characteristics to temporal gene expression from early to delayed timepoints was compared for MRS groups (favorable vs unfavorable) and hematoma volume. Principle findings and results IL10, SOD1, and REL expression were significantly higher at delayed timepoints in PBMCs of ICH patients with favorable outcome. PPARG and REL increased between timepoints in patients with favorable outcome. NFKB1 expression was not sustained, but significantly decreased from higher levels at early onset in patients with unfavorable outcome. IL10 expression showed a negative correlation in patients with high hematoma volume (>30 mL). Conclusions and significance Anti-inflammatory, pro-survival regulators were highly expressed at delayed time points in ICH patients with a favorable outcome, and IL10 expression showed a negative correlation to high hematoma volume.

scholarly journals Hyaluronic Acid-Modified and TPCA-1-Loaded Gold Nanocages Alleviate Inflammation

Pharmaceutics ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 143 ◽  
Author(s):  
Jingnan Zhao
Keyword(s):  
Hyaluronic Acid ◽  
Inflammatory Cells ◽  
Oxygen Species ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Nanogold Particles ◽  
Gold Nanocages ◽  
Factor Alpha ◽  
Anti Inflammatory ◽  
Necrosis Factor

Gold nanocages (AuNCs) are biocompatible and porous nanogold particles that have been widely used in biomedical fields. In this study, hyaluronic acid (HA) and peptide- modified gold nanocages (HA-AuNCs/T/P) loaded with 2-[(aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide (TPCA-1) were prepared to investigate their potential for combating inflammation. TPCA-1 was released from AuNCs, intracellularly when HA was hydrolyzed by hyaluronidase. HA-AuNCs/T/P show a much higher intracellular uptake than AuNCs/T/P, and exhibit a much higher efficacy on the suppression of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) than free TPCA-1, suggesting great improvement to the anti-inflammatory efficacy of TPCA-1 through the application of AuNCs. HA-AuNCs/T/P can also reduce the production of reactive oxygen species in inflammatory cells. This study suggests that HA-AuNCs/T/P may be potential agents for anti-inflammatory treatment, and are worthy of further investigation.

scholarly journals Association between insulin resistance and post-ischaemic stroke outcome in patients without diabetes: protocol for a systematic review and meta-analysis

BMJ Open ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. e044771
Author(s):  
Jeremiah Hadwen ◽  
Woojin Kim ◽  
Brian Dewar ◽  
Tim Ramsay ◽  
Alexandra Davis ◽  
...  
Keyword(s):  
Systematic Review ◽  
Insulin Resistance ◽  
Ischaemic Stroke ◽  
Functional Outcome ◽  
Recurrent Stroke ◽  
Meta Analysis ◽  
Secondary Outcome ◽  
Stroke Outcome ◽  
Post Stroke ◽  
Meta Analyses

IntroductionInsulin resistance is an independent risk factor for atherosclerosis, coronary artery disease and ischaemic stroke. Currently, insulin resistance is not usually included in post-stroke risk stratification. This systematic review and meta-analysis intends to determine if available scientific knowledge supports an association between insulin resistance and post-stroke outcomes in patients without diabetes.Methods and analysisThe authors will conduct a literature search in Medline, Embase, Web of Science and Cochrane Central. The review will include studies that assess the association between elevated insulin homeostasis model of insulin resistance (HOMA-IR) and post-stroke outcome (functional outcome and recurrent stroke). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines will be used. The primary outcome will be post-stroke functional outcome (Modified Rankin Scale), and the secondary outcome will be recurrent ischaemic stroke. Comparison of outcome will be made between highest and lowest HOMA-IR range (as defined in each article included in this systematic review). Risk of bias will be assessed qualitatively. Meta-analysis will be performed if sufficient homogeneity exists between studies. Heterogeneity of outcomes will be assessed by I².Ethics and disseminationNo human or animal subjects or samples were/will be used. The results will be published in a peer-reviewed journal, and will be disseminated at local and international neurology conferences.PROSPERO registration numberCRD42020173608.

scholarly journals Local Serpin Treatment via Chitosan-Collagen Hydrogel after Spinal Cord Injury Reduces Tissue Damage and Improves Neurologic Function

2020 ◽  
Vol 9 (4) ◽  
pp. 1221 ◽  
Author(s):  
Jacek M. Kwiecien ◽  
Liqiang Zhang ◽  
Jordan R. Yaron ◽  
Lauren N. Schutz ◽  
Christian J. Kwiecien-Delaney ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Tissue Damage ◽  
Low Dose ◽  
Dorsal Column ◽  
Neurological Deficits ◽  
Sustained Delivery ◽  
Post Surgery ◽  
Cord Injury ◽  
Anti Inflammatory

Spinal cord injury (SCI) results in massive secondary damage characterized by a prolonged inflammation with phagocytic macrophage invasion and tissue destruction. In prior work, sustained subdural infusion of anti-inflammatory compounds reduced neurological deficits and reduced pro-inflammatory cell invasion at the site of injury leading to improved outcomes. We hypothesized that implantation of a hydrogel loaded with an immune modulating biologic drug, Serp-1, for sustained delivery after crush-induced SCI would have an effective anti-inflammatory and neuroprotective effect. Rats with dorsal column SCI crush injury, implanted with physical chitosan-collagen hydrogels (CCH) had severe granulomatous infiltration at the site of the dorsal column injury, which accumulated excess edema at 28 days post-surgery. More pronounced neuroprotective changes were observed with high dose (100 µg/50 µL) Serp-1 CCH implanted rats, but not with low dose (10 µg/50 µL) Serp-1 CCH. Rats treated with Serp-1 CCH implants also had improved motor function up to 20 days with recovery of neurological deficits attributed to inhibition of inflammation-associated tissue damage. In contrast, prolonged low dose Serp-1 infusion with chitosan did not improve recovery. Intralesional implantation of hydrogel for sustained delivery of the Serp-1 immune modulating biologic offers a neuroprotective treatment of acute SCI.

scholarly journals NEW APPROACHES TO POSTOPERATIVE TREATMENT PERITONITIS

2020 ◽  
Vol 19 (4) ◽  
pp. 43-46
Author(s):  
V. Maksymyuk ◽  
M. Sheremet
Keyword(s):  
Inflammatory Cytokines ◽  
Tissue Damage ◽  
Postoperative Treatment ◽  
Antioxidant Systems ◽  
Control Group ◽  
Septic Complications ◽  
Antigenic Properties ◽  
Anticytokine Therapy ◽  
Anti Inflammatory ◽  
Experimental Group

A significant role in the pathogenesis of peritonitis is attributed to free radical mechanisms of tissue damage. Due to inhibition of a number of membrane-bound enzymes and FRO of lipids of plasma membranes, foci of secondary necrosis appear in the peritoneum. Oxidized lipids have antigenic properties, and therefore stimulate autoimmune processes of tissue damage. In the pathogenesis of peritonitis, an important role is played by inflammatory mediators - cytokines. Their biological activity is manifested by the action on highly specific receptors located on cells. At the same time, interleukins and tumor necrosis factor act on all cells, exhibiting a systemic effect. It was found that the activity of ceruloplasmin in the blood plasma of patients in the control group progressively decreased from the first to the fifth day of the postoperative period, from 77.2 ± 5.61 to 59.32 ± 4.42 o.o. / g of protein, and in the patients of the experimental group it increased highly reliably - from 77.2 ± 5.61 to 97.31 ± 4.42 o.o. / h protein (p <0.001). The same pattern is characteristic of catalase activity. The activity of glutathione peroxidase in patients of both groups significantly decreased up to 3 days after the operation and increased on the fifth day, and it was more pronounced in the patients of the experimental group. When studying the level of cytokines, it was found that the expression of proinflammatory cytokines IL-1b, IL-8, TNFa exceeded the control values, while the expression of anti-inflammatory cytokines IL-1Ra was "delayed" (almost twofold). The highest expression of IL-1b, IL-8 potentiated further chain of pro-inflammatory reactions indicates the adequacy of the anti-inflammatory response and the relative balance between pro-inflammatory and anti-inflammatory cytokines and the adequacy of anticytokine therapy. The total number of septic complications (PBS) in the control group was 82.4%, and in the experimental group it was 66.7%. In dynamics study of pro- and antioxidant systems and serum concentra-tions of cytokine in the patients with acute peritonitis was high prognostic significance of results this study, which allows defining treatment tactic of these patients. To include in complex post-operative treatment of these pa-tients with evaluated antioxidant and anticytokine therapy allowed reducing the development of purulent-septic complications from 82.4 to 66.7%, which increased effectively of treatment in such patients and reduced the term of hospitality.

scholarly journals Diffusion-weighted Imaging Reversibility In Stroke After Successful Mechanical Recanalization. Case report

2020 ◽  
Vol 29 (2) ◽  
Author(s):  
Matías Negrotto ◽  
Alejandro M. Spiotta ◽  
Aquilla S. Turk ◽  
Raymond D. Turner ◽  
Jonathan Lena ◽  
...  
Keyword(s):  
Case Report ◽  
Clinical Outcome ◽  
Thrombolytic Therapy ◽  
Tissue Damage ◽  
Diffusion Weighted Imaging ◽  
Lesion Size ◽  
Infarct Core ◽  
Mechanical Recanalization ◽  
Diffusion Weighted ◽  
Imaging Characteristics

Increased use of Diffusion-weighted imaging (DWI) in acute stroke has led to observations of early diffusion normalization in lesions thatinitially show diffusion slowing. The “renormalization” of DWI may be spontaneous or the result of thrombolytic therapy, thus, acuteslowing of diffusion is not necessarily an indicator of irreversible tissue damage. The perfusion-diffusion mismatch concept is attractiveas it assumes that DWI lesion size reflects the infarct core whilst the mismatch area reflects the penumbra. However, this concept maybe an oversimplification. This paper shows a case with Diffusion Lesion Reversal after successful neuroendovascular treatment andexcellent clinical outcome, and discuss the imaging characteristics associated with this phenomenon.

scholarly journals The RIG-I Signal Pathway Mediated Panax notoginseng Saponin Anti-Inflammatory Effect in Ischemia Stroke

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Chujun Zhang ◽  
Sai Zhang ◽  
Lanxiang Wang ◽  
Soyeon Kang ◽  
Jiabao Ma ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Molecular Mechanisms ◽  
Chinese Herb ◽  
Inflammatory Cells ◽  
Panax Notoginseng ◽  
Artery Occlusion ◽  
Blue Staining ◽  
Bioactive Constituents ◽  
Anti Inflammatory ◽  
Cerebral Artery Occlusion

Panax notoginseng saponins (PNS), the main bioactive constituents of a traditional Chinese herb Panax notoginseng, were commonly used for ischemic stroke in China. However, the associated cellular and molecular mechanisms of PNS have not been well examined. This study aimed to decipher the underlying molecular target of PNS in the treatment of cerebral ischemia. The oxygen-glucose-deprived (OGD) model of rat brain microvascular endothelial cells (BMECs) was used in this study. The alteration of gene expression in rat BMECs after PNS treatment was measured by microarray and indicated that there were 38 signaling pathways regulated by PNS. Among them, RIG-I receptor and related signaling molecules TNF receptor-associated factor 2 (Traf2) and nuclear factor-kappa B (NF-κB) were significantly suppressed by PNS, which was verified again in OGD-induced BMECs measured by FQ-PCR and western blotting and in middle cerebral artery occlusion (MCAO) rats measured by immunohistochemistry. The levels of TNF-α, IL-8, and the downstream cytokines regulated by RIG-I receptor pathway were also decreased by PNS. Meanwhile, the neurological evaluation, hematoxylin and eosin (HE) staining, and Evans blue staining were conducted to evaluate the effect of PNS in MCAO rats. Results showed PNS significantly improved functional outcome and cerebral vascular leakage. Flow cytometry showed the number of the inflammatory cells infiltrated in brain tissue was decreased in PNS treatment. Our results identified that RIG-I signaling pathway mediated anti-inflammatory properties of PNS in cerebral ischemia, which provided the novel insights of PNS application in clinics.

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