12/15 Lipoxygenase as a Therapeutic Target in Stroke

Karataş, Hülya; Cakir-Aktas, Canan

doi:10.29399/npa.23646

Cited by 7 publications

(6 citation statements)

References 49 publications

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“…LOX activity, particularly the 12/15-LOX isoform, is enriched in leukocytes, which contributes to oxidative injury in the brain. 148 In experimental SAH, 12/15-LOX is increased in macrophages adjacent to the subarachnoid blood, and its inhibition and gene deletion decrease brain injury and improve short-term functional outcome after SAH. 149 Another study reported increased neuronal expression of 5-LOX‚ with 5-LOX inhibition reducing neuroinflammation and neuronal cell death after experimental SAH.…”

Section: Inflammation In the Development Of DCImentioning

confidence: 99%

Role of Inflammatory Processes in Hemorrhagic Stroke

Ohashi

DeLong

Kozberg

et al. 2023

Stroke

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Hemorrhagic stroke is the deadliest form of stroke and includes the subtypes of intracerebral hemorrhage and subarachnoid hemorrhage. A common cause of hemorrhagic stroke in older individuals is cerebral amyloid angiopathy. Intracerebral hemorrhage and subarachnoid hemorrhage both lead to the rapid collection of blood in the central nervous system and generate inflammatory immune responses that involve both brain resident and infiltrating immune cells. These responses are complex and can contribute to both tissue recovery and tissue injury. Despite the interconnectedness of these major subtypes of hemorrhagic stroke, few reviews have discussed them collectively. The present review provides an update on inflammatory processes that occur in response to intracerebral hemorrhage and subarachnoid hemorrhage, and the role of inflammation in the pathophysiology of cerebral amyloid angiopathy–related hemorrhage. The goal is to highlight inflammatory processes that underlie disease pathology and recovery. We aim to discuss recent advances in our understanding of these conditions and identify gaps in knowledge with the potential to develop effective therapeutic strategies.

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Section: Inflammation In the Development Of DCImentioning

confidence: 99%

Role of Inflammatory Processes in Hemorrhagic Stroke

Ohashi

DeLong

Kozberg

et al. 2023

Stroke

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“…Lipoxygenases (LOX) are a family of enzymes responsible for the oxidation of lipids and the generation of a range of metabolites such as eicosanoids and PUFA-related compounds. These metabolites play diverse physiological and pathological roles in inflammatory, neurodegenerative, and cardiovascular diseases, as well as, in defence mechanisms [ 20 , 21 ]. Lipoxygenases have also been reported in cell differentiation [ 22 , 23 ], apoptosis [ 24 ], and play an important role in the immune response by helping to regulate cytokine secretion [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Brain fatty acid and transcriptome profiles of pig fed diets with different levels of soybean oil

et al. 2023

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Background The high similarity in anatomical and neurophysiological processes between pigs and humans make pigs an excellent model for metabolic diseases and neurological disorders. Lipids are essential for brain structure and function, and the polyunsaturated fatty acids (PUFA) have anti-inflammatory and positive effects against cognitive dysfunction in neurodegenerative diseases. Nutrigenomics studies involving pigs and fatty acids (FA) may help us in better understanding important biological processes. In this study, the main goal was to evaluate the effect of different levels of dietary soybean oil on the lipid profile and transcriptome in pigs’ brain tissue. Results Thirty-six male Large White pigs were used in a 98-day study using two experimental diets corn-soybean meal diet containing 1.5% soybean oil (SOY1.5) and corn-soybean meal diet containing 3.0% soybean oil (SOY3.0). No differences were found for the brain total lipid content and FA profile between the different levels of soybean oil. For differential expression analysis, using the DESeq2 statistical package, a total of 34 differentially expressed genes (DEG, FDR-corrected p-value < 0.05) were identified. Of these 34 DEG, 25 are known-genes, of which 11 were up-regulated (log2 fold change ranging from + 0.25 to + 2.93) and 14 were down-regulated (log2 fold change ranging from − 3.43 to -0.36) for the SOY1.5 group compared to SOY3.0. For the functional enrichment analysis performed using MetaCore with the 34 DEG, four pathway maps were identified (p-value < 0.05), related to the ALOX15B (log2 fold change − 1.489), CALB1 (log2 fold change − 3.431) and CAST (log2 fold change + 0.421) genes. A “calcium transport” network (p-value = 2.303e-2), related to the CAST and CALB1 genes, was also identified. Conclusion The results found in this study contribute to understanding the pathways and networks associated with processes involved in intracellular calcium, lipid metabolism, and oxidative processes in the brain tissue. Moreover, these results may help a better comprehension of the modulating effects of soybean oil and its FA composition on processes and diseases affecting the brain tissue.

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“…12/15-LOX is found to be upregulated after stroke, resulting in neuronal death and leakage of BBB and BRB [ 134 ]. Inhibition of 12/15-LOX was also shown to reduce infarct volume and edema in the stroke area, suggesting its potential role as an effective and viable therapeutic option for ischemia [ 92 , 135 , 136 ]. Furthermore, the protection of BBB and BRB help preserves the microenvironment at the injured site from disruption by systemic immunity and secondary inflammatory responses caused by degeneration.…”

Section: Pathways Targeted By Baicalein Baicalin and Wogonin During Neuroprotective Processesmentioning

confidence: 99%

Baicalein, Baicalin, and Wogonin: Protective Effects against Ischemia‐Induced Neurodegeneration in the Brain and Retina

Pan

Cho

et al. 2021

Oxidative Medicine and Cellular Longevity

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Ischemia is a common pathological condition present in many neurodegenerative diseases, including ischemic stroke, retinal vascular occlusion, diabetic retinopathy, and glaucoma, threatening the sight and lives of millions of people globally. Ischemia can trigger excessive oxidative stress, inflammation, and vascular dysfunction, leading to the disruption of tissue homeostasis and, ultimately, cell death. Current therapies are very limited and have a narrow time window for effective treatment. Thus, there is an urgent need to develop more effective therapeutic options for ischemia-induced neural injuries. With emerging reports on the pharmacological properties of natural flavonoids, these compounds present potent antioxidative, anti-inflammatory, and antiapoptotic agents for the treatment of ischemic insults. Three major active flavonoids, baicalein, baicalin, and wogonin, have been extracted from Scutellaria baicalensis Georgi (S. baicalensis); all of which are reported to have low cytotoxicity. They have been demonstrated to exert promising pharmacological capabilities in preventing cell and tissue damage. This review focuses on the therapeutic potentials of these flavonoids against ischemia-induced neurotoxicity and damage in the brain and retina. The bioactivity and bioavailability of baicalein, baicalin, and wogonin are also discussed. It is with hope that the therapeutic potential of these flavonoids can be utilized and developed as natural treatments for ischemia-induced injuries of the central nervous system (CNS).

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12/15 Lipoxygenase as a Therapeutic Target in Stroke

Cited by 7 publications

References 49 publications

Role of Inflammatory Processes in Hemorrhagic Stroke

Role of Inflammatory Processes in Hemorrhagic Stroke

Brain fatty acid and transcriptome profiles of pig fed diets with different levels of soybean oil

Baicalein, Baicalin, and Wogonin: Protective Effects against Ischemia‐Induced Neurodegeneration in the Brain and Retina

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