Emerging Treatment Strategies for Cerebral Ischemia–Reperfusion Injury

Li, Mengxing; Tang, He-Yong; Li, Zhen; Tang, Wei

doi:10.1016/j.neuroscience.2022.10.020

Cited by 27 publications

(11 citation statements)

References 165 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the present study, FOXO4 silencing promoted ZO-1, claudin-5 and occludin expression, indicating that FOXO4 downregulation improved the barrier dysfunction in OGD/R-exposed HCMEC/D3 cells. Oxidative stress and inflammatory response are common events responsible for CIRI ( 29 ). Oxidative stress-activated FOXO proteins ( 30 ) regulate the expression of oxidative stress-related genes ( 31 ).…”

Section: Discussionmentioning

confidence: 99%

Knockdown of FOXO4 protects against OGD/R‑induced cerebral microvascular endothelial cell injury and regulates the AMPK/Nrf2/HO‑1 pathway through transcriptional activation of CTRP6

Cui,

Li,

Yuan

2024

Exp Ther Med

View full text Add to dashboard Cite

Cerebral ischemia is a type of cerebrovascular disease with high disability and mortality rates. The expression of forkhead box protein O4 (FOXO4) in the brain is increased following traumatic brain injury. To the best of our knowledge, however, the role of FOXO4 as well as its mechanism in cerebral ischemia has not been reported so far. For the establishment of an in vitro cellular injury model, human brain microvascular endothelial HCMEC/D3 cells were induced by oxygen-glucose deprivation/reoxygenation (OGD/R). mRNA and protein expressions of FOXO4 and C1q/tumor necrosis factor-related protein 6 (CTRP6) in OGD/R-induced HCMEC/D3 cells were detected by reverse transcription-quantitative (RT-q)PCR and western blotting. The transfection efficacy of small interfering (si)- and overexpression (Ov)-FOXO4 and si-CTRP6 was assessed using RT-qPCR and western blotting. Cell Counting Kit-8 and TUNEL assay were used to assess viability and apoptosis of HCMEC/D3 cells induced by OGD/R, respectively. A FITC-Dextran assay kit was applied to determine endothelial permeability and immunofluorescence assay was used for the measurement of the tight junction protein zonula occludens-1. The levels of oxidative stress markers and inflammatory cytokines were assessed with corresponding assay kits. The binding sites of transcription factor, FOXO4 and CTRP6 promoter were predicted using HDOCK SERVER. Luciferase reporter assay was used to detect the activity of the CTRP6 promoter while chromatin immunoprecipitation assay was used to evaluate the binding ability of the FOXO4 and CTRP6 promoter. Western blotting was used for the detection of apoptosis- and AMPK/Nrf2/heme oxygenase-1 (HO-1) pathway-associated proteins, along with tight junction proteins. The expression of FOXO4 was increased in OGD/R-induced HCMEC/D3 cells. After interfering with FOXO4 in cells, the viability of the OGD/R-induced HCMEC/D3 cells was increased while apoptosis was decreased. Furthermore, FOXO4 interference improved cellular barrier dysfunction but inhibited oxidative stress and the inflammatory response in HCMEC/D3 cells induced by OGD/R. FOXO4 knockdown regulated CTRP6 transcription in HCMEC/D3 cells. Knockdown of FOXO4 regulated expression of CTRP6 and protected OGD/R-induced HCMEC/D3 cell injury via the AMPK/Nrf2/HO-1 pathway. The present study indicated that FOXO4 knockdown activated CTRP6 to protect against cerebral microvascular endothelial cell injury induced by OGD/R via the AMPK/Nrf2/HO-1 pathway.

show abstract

Section: Discussionmentioning

confidence: 99%

Knockdown of FOXO4 protects against OGD/R‑induced cerebral microvascular endothelial cell injury and regulates the AMPK/Nrf2/HO‑1 pathway through transcriptional activation of CTRP6

Cui,

Li,

Yuan

2024

Exp Ther Med

View full text Add to dashboard Cite

show abstract

“…The study demonstrates that PEx-4 has a potent antioxidant activity and sustained bioavailability, suggesting that it may ameliorate IR-induced brain damage in diabetic rats by inhibiting OS and nerve cell apoptosis [ 71 ]. Mitochondrial malfunction and ROS overproduction damage neurons in CIR [ 103 ]. Curcumin can prevent the oxidative damage due to CIR, but free curcumin has a low BBB passage rate and a poor bioavailability.…”

Section: Applications Of Plga-based Nanostructures In Drug Delivery A...mentioning

confidence: 99%

The Recent Applications of PLGA-Based Nanostructures for Ischemic Stroke

Yan,

Huang,

Feng

et al. 2023

Pharmaceutics

View full text Add to dashboard Cite

With the accelerated development of nanotechnology in recent years, nanomaterials have become increasingly prevalent in the medical field. The poly (lactic acid–glycolic acid) copolymer (PLGA) is one of the most commonly used biodegradable polymers. It is biocompatible and can be fabricated into various nanostructures, depending on requirements. Ischemic stroke is a common, disabling, and fatal illness that burdens society. There is a need for further improvement in the diagnosis and treatment of this disease. PLGA-based nanostructures can facilitate therapeutic compounds’ passage through the physicochemical barrier. They further provide both sustained and controlled release of therapeutic compounds when loaded with drugs for the treatment of ischemic stroke. The clinical significance and potential of PLGA-based nanostructures can also be seen in their applications in cell transplantation and imaging diagnostics of ischemic stroke. This paper summarizes the synthesis and properties of PLGA and reviews in detail the recent applications of PLGA-based nanostructures for drug delivery, disease therapy, cell transplantation, and the imaging diagnosis of ischemic stroke.

show abstract

“…They may affect functionally, as well as anatomically, any component of the neurovascular unit or BBB that is composed of tight junctions, endothelium, astrocytes, pericytes, microglia, and neurons [1][2][3][4]. Minimizing BBB disruption, which is a major injury resulting from ischemia-reperfusion, may lead to a more favorable neurological outcome following a stroke [5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Leucine Reduced Blood–Brain Barrier Disruption and Infarct Size in Early Cerebral Ischemia-Reperfusion

Chi,

Liu,

Magsino

et al. 2023

Brain Sciences

View full text Add to dashboard Cite

A disruption of the blood–brain barrier (BBB) is a crucial pathophysiological change that can impact the outcome of a stroke. Ribosomal protein S6 (S6) and protein kinase B (Akt) play significant roles in early cerebral ischemia-reperfusion injury. Studies have suggested that branched-chain amino acids (BCAAs) may have neuroprotective properties for spinal cord or brain injuries. Therefore, we conducted research to investigate if leucine, one of the BCAAs, could offer neuroprotection and alter BBB disruption, along with its effects on the phosphorylation of S6 and Akt during the early phase of cerebral ischemia-reperfusion, specifically within the thrombolytic therapy time window. In rats, ten min after left middle cerebral artery occlusion (MCAO), 5 µL of 20 mM L-leucine or normal saline was injected into the left lateral ventricle. After two hours of reperfusion following one hour of MCAO, we determined the transfer coefficient (Ki) of 14C-α-aminoisobutyric acid to assess the BBB disruption, infarct size, and phosphorylation of S6 and Akt. Ischemia-reperfusion increased the Ki (+143%, p < 0.001) and the intra-cerebroventricular injection of leucine lowered the Ki in the ischemic-reperfused cortex (−34%, p < 0.001). Leucine reduced the percentage of cortical infarct (−42%, p < 0.0001) out of the total cortical area. Ischemia-reperfusion alone significantly increased the phosphorylation of both S6 and Akt (p < 0.05). However, the administration of leucine had no further effect on the phosphorylation of S6 or Akt in the ischemic-reperfused cortex. This study suggests that an acute increase in leucine levels in the brain during early ischemia-reperfusion within a few hours of stroke may offer neuroprotection, possibly due to reduced BBB disruption being one of the major contributing factors. Leucine did not further increase the already elevated phosphorylation of S6 or Akt by ischemia-reperfusion under the current experimental conditions. Our data warrant further studies on the effects of leucine on neuronal survival and its mechanisms in the later stages of cerebral ischemia-reperfusion.

show abstract

Emerging Treatment Strategies for Cerebral Ischemia–Reperfusion Injury

Cited by 27 publications

References 165 publications

Knockdown of FOXO4 protects against OGD/R‑induced cerebral microvascular endothelial cell injury and regulates the AMPK/Nrf2/HO‑1 pathway through transcriptional activation of CTRP6

Knockdown of FOXO4 protects against OGD/R‑induced cerebral microvascular endothelial cell injury and regulates the AMPK/Nrf2/HO‑1 pathway through transcriptional activation of CTRP6

The Recent Applications of PLGA-Based Nanostructures for Ischemic Stroke

Leucine Reduced Blood–Brain Barrier Disruption and Infarct Size in Early Cerebral Ischemia-Reperfusion

Contact Info

Product

Resources

About