Biotechnology-based therapeutics for management of cerebral stroke

Patel, Dhrumi; Wairkar, Sarika

doi:10.1016/j.ejphar.2021.174638

Cited by 7 publications

(4 citation statements)

References 92 publications

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“…The pathogenesis of ischemic stroke is complex. At present, reported pathological mechanisms of CIS include abnormal energy metabolism, excitotoxicity of amino acids, oxidative damage of free radicals and apoptosis 40 – 44 . At the cellular level, hypoperfusion, hypoxia, and glucose deficiency cause insufficient energy production in brain metabolism, thus leading to some toxic metabolites accumulating locally, such as excitatory toxic products, acidic metabolites, oxidative stress products, and inflammatory mediators, resulting in cerebral cell dysfunction or death 45 .…”

Section: Discussionmentioning

confidence: 99%

Molecular subtype identification of cerebral ischemic stroke based on ferroptosis-related genes

Wang,

Xu,

Shui

et al. 2024

Sci Rep

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Cerebral ischemic stroke (CIS) has the characteristics of a high incidence, disability, and mortality rate. Here, we aimed to explore the potential pathogenic mechanisms of ferroptosis-related genes (FRGs) in CIS. Three microarray datasets from the Gene Expression Omnibus (GEO) database were utilized to analyze differentially expressed genes (DEGs) between CIS and normal controls. FRGs were obtained from a literature report and the FerrDb database. Weighted gene co-expression network analysis (WGCNA) and protein–protein interaction (PPI) network were used to screen hub genes. The receiver operating characteristic (ROC) curve was adopted to evaluate the diagnostic value of key genes in CIS, followed by analysis of immune microenvironment, transcription factor (TF) regulatory network, drug prediction, and molecular docking. In total, 128 CIS samples were divided into 2 subgroups after clustering analysis. Compared with cluster A, 1560 DEGs were identified in cluster B. After the construction of the WGCNA and PPI network, 5 hub genes, including MAPK3, WAS, DNAJC5, PRKCD, and GRB2, were identified for CIS. Interestingly, MAPK3 was a FRG that differentially expressed between cluster A and cluster B. The expression levels of 5 hub genes were all specifically highly in cluster A subtype. It is noted that neutrophils were the most positively correlated with all 5 real hub genes. PRKCD was one of the target genes of FASUDIL. In conclusion, five real hub genes were identified as potential diagnostic markers, which can distinguish the two subtypes well.

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Section: Discussionmentioning

confidence: 99%

Molecular subtype identification of cerebral ischemic stroke based on ferroptosis-related genes

Wang,

Xu,

Shui

et al. 2024

Sci Rep

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“…Tissue plasminogen activator (tPA) is a thrombolytic drug that decomposed thrombus. It is currently the only drug approved by FDA for the treatment of ischemic stroke. − However, only about 7% of patients are eligible for tPA treatment . In addition, tPA had an obvious effect on small and medium-sized stroke but not a good effect on macrovascular obstruction. , With the development of cell transplantation, the application of stem cells after stroke had been further explored .…”

Section: Strokementioning

confidence: 99%

Application of Nanotechnology-Based Products in Stroke

Cai

Sun

Chen

et al. 2023

ACS Chem. Neurosci.

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Stroke is a disease with high disability and high mortality in the world. Due to the existence of the blood-brain barrier (BBB), complex brain structure, and numerous neural signal pathways, the treatment methods are limited, so new drugs and new treatments need to be developed urgently. Thankfully, the advent of nanotechnology offered a new opportunity for biomedical development because of the unique properties of nanoparticles that give them the ability to traverse the BBB and accumulate in relevant regions of the brain. More importantly, nanoparticles could be modified on the surface to meet a variety of specific properties that people need. Some could be used for effective drug delivery, including tissue plasminogen activator (tPA), neuroprotective agents, genes, and cytokines; some nanoparticles were used as contrast agents and biosensors in medical imaging for further diagnosis of stroke; some were used to track target cells for prognosis of stroke; and some were used to detect pathological markers of stroke that appear at different stages. This Review looks at the application and research progress of nanoparticles in the diagnosis and treatment of stroke, hoping to bring some help to researchers.

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“…This is despite the fact that many antibody-based treatment platforms for cerebral ischemia are still in development. However, there is a lack of appropriate animal models to test the safety and efficacy of antibody-based drugs in the treatment of cerebral ischemia [ 177 , 178 ]. This makes it difficult to determine whether these drugs are effective.…”

Section: Clinical Translation Of Antibody-based Drugs For Cerebral Is...mentioning

confidence: 99%

Advances in Antibody-Based Therapeutics for Cerebral Ischemia

et al. 2022

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Cerebral ischemia is an acute disorder characterized by an abrupt reduction in blood flow that results in immediate deprivation of both glucose and oxygen. The main types of cerebral ischemia are ischemic and hemorrhagic stroke. When a stroke occurs, several signaling pathways are activated, comprising necrosis, apoptosis, and autophagy as well as glial activation and white matter injury, which leads to neuronal cell death. Current treatments for strokes include challenging mechanical thrombectomy or tissue plasminogen activator, which increase the danger of cerebral bleeding, brain edema, and cerebral damage, limiting their usage in clinical settings. Monoclonal antibody therapy has proven to be effective and safe in the treatment of a variety of neurological disorders. In contrast, the evidence for stroke therapy is minimal. Recently, Clone MTS510 antibody targeting toll-like receptor-4 (TLR4) protein, ASC06-IgG1 antibody targeting acid sensing ion channel-1a (ASIC1a) protein, Anti-GluN1 antibodies targeting N-methyl-D-aspartate (NMDA) receptor associated calcium influx, GSK249320 antibody targeting myelin-associated glycoprotein (MAG), anti-High Mobility Group Box-1 antibody targeting high mobility group box-1 (HMGB1) are currently under clinical trials for cerebral ischemia treatment. In this article, we review the current antibody-based pharmaceuticals for neurological diseases, the use of antibody drugs in stroke, strategies to improve the efficacy of antibody therapeutics in cerebral ischemia, and the recent advancement of antibody drugs in clinical practice. Overall, we highlight the need of enhancing blood–brain barrier (BBB) penetration for the improvement of antibody-based therapeutics in the brain, which could greatly enhance the antibody medications for cerebral ischemia in clinical practice.

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Biotechnology-based therapeutics for management of cerebral stroke

Cited by 7 publications

References 92 publications

Molecular subtype identification of cerebral ischemic stroke based on ferroptosis-related genes

Molecular subtype identification of cerebral ischemic stroke based on ferroptosis-related genes

Application of Nanotechnology-Based Products in Stroke

Advances in Antibody-Based Therapeutics for Cerebral Ischemia

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