scholarly journals Propofol Ameliorates Ischemic Brain Injury by Blocking Toll-like Receptor 4-dependent Pathway and Suppressing Consequent Inflammatory Cytokine Production

2020 ◽  
Author(s):  
Kazuha Mitsui ◽  
Masakazu Kotoda ◽  
Sohei Hishiyama ◽  
Ayasa Takamino ◽  
Sho Morikawa ◽  
...  
Keyword(s):  
Brain Injury ◽  
Inflammatory Cytokine ◽  
Neuroprotective Effect ◽  
Ischemic Brain Injury ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Neuroprotective Effects ◽  
Inflammatory Cytokine Production ◽  
Ischemic Brain ◽  
Dependent Pathway

Abstract BackgroundIschemic stroke is one of the leading causes of mortality and morbidity worldwide. Accumulated evidence suggests that the consequent excessive inflammation plays detrimental roles in the pathogenesis of secondary injury after cerebral infarction and exacerbates the brain tissue damage. Although regulation of the inflammation would be the potential strategy for the novel treatment option, effective methods that control the cerebral inflammation have not yet been established. Recent studies have suggested that propofol, a sedative agent widely used for management of patients with acute stroke, suppresses excessive inflammation and may have neuroprotective effects against ischemic brain injury. However, the available evidence is still limited and controversial, and the underlying mechanism remains unclear. This study aimed to investigate the neuroprotective effects of propofol against ischemic brain injury, with a specific focus on Toll-like receptor 4 (TLR4), the critical mediator of inflammation in the ischemic brain.ResultsTreatment with propofol significantly reduced infarct volume in wild-type mice (7.9 ± 1.4 vs. 12.6 ± 1.1 mm3, n = 10 each, p < 0.05). The propofol-treated mice exhibited lower levels of pro-inflammatory cytokine expressions compared with the control mice (IL-6: 0.57 ± 0.23 vs. 1.00 ± 0.39, p < 0.05, IL-1β: 0.53 ± 0.24 vs. 1.00 ± 0.36, p = 0.087, n = 15 each). The neuroprotective effect of propofol was abrogated by TLR4 gene knockout. Propofol treatment had no significant effects on hemodynamic parameters.ConclusionsPropofol attenuates brain injury by blocking the TLR4-dependent pathway and suppressing pro-inflammatory cytokine production. This insight into the mechanism underlying the neuroprotective effect of propofol against ischemic brain injury may lead to a new strategy for preventing exacerbation of cerebral infarction.

scholarly journals Neuroprotective Effects of Salicin in a Gerbil Model of Transient Forebrain Ischemia by Attenuating Oxidative Stress and Activating PI3K/Akt/GSK3β Pathway

Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 629
Author(s):  
Joon Ha Park ◽  
Tae-Kyeong Lee ◽  
Dae Won Kim ◽  
Hyejin Sim ◽  
Jae-Chul Lee ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Brain Injury ◽  
Pyramidal Neurons ◽  
Glycogen Synthase ◽  
Neuroprotective Effect ◽  
Pyramidal Cells ◽  
Ischemic Brain Injury ◽  
Neuroprotective Effects ◽  
Ischemic Brain ◽  
Ca1 Pyramidal Neurons

Salicin is a major natural compound of willow bark and displays diverse beneficial biological properties, such as antioxidant activity. However, little information available for the neuroprotective potential of salicin against ischemic brain injury has been reported. Thus, this study was performed to investigate the neuroprotective potential of salicin against ischemia and reperfusion (IR) injury and its mechanisms in the hippocampus using a gerbil model of 5-min transient ischemia (TI) in the forebrain, in which a massive loss (death) of pyramidal neurons cells occurred in the subfield Cornu Ammonis 1 (CA1) among the hippocampal subregions (CA1-3) at 5 days after TI. To examine neuroprotection by salicin, gerbils were pretreated with salicin alone or together with LY294002, which is a phosphatidylinositol 3-kinase (PI3K) inhibitor, once daily for 3 days before TI. Treatment with 20 mg/kg of salicin significantly protected CA1 pyramidal neurons against the ischemic injury. Treatment with 20 mg/kg of salicin significantly reduced the TI-induced increase in superoxide anion generation and lipid peroxidation in the CA1 pyramidal neurons after TI. The treatment also reinstated the TI-induced decrease in superoxide dismutases (SOD1 and SOD2), catalase, and glutathione peroxidase in the CA1 pyramidal cells after TI. Moreover, salicin treatment significantly elevated the levels of phosphorylation of Akt and glycogen synthase kinase-3β (GSK3β), which is a major downstream target of PI3K, in the ischemic CA1. Notably, the neuroprotective effect of salicin was abolished by LY294002. Taken together, these findings clearly indicate that salicin protects against ischemic brain injury by attenuating oxidative stress and activating the PI3K/Akt/GSK3β pathway.

scholarly journals Effect of curcumin in the acute phase of ischemia in chronic cerebral hypoperfusion in rats

2018 ◽  
Vol 17 (1) ◽  
pp. 69-73
Author(s):  
N. S. Shcherbak ◽  
M. A. Popovetskiy ◽  
G. Yu. Yukina ◽  
M. M. Galagudza
Keyword(s):  
Brain Injury ◽  
Acute Phase ◽  
Wistar Rats ◽  
Neuroprotective Effect ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Ischemic Brain Injury ◽  
Protective Effects ◽  
Single Application ◽  
Ischemic Brain

Curcumin presents antioxidant and anti-inflammatory properties and can be considered as a neuroprotector. Data on doses and duration of application of curcumin to achieve protective effects in various types of ischemic brain injury is controversial. The purpose was to study the neuroprotective properties of curcumin in the acute phase of ischemia in chronic cerebral hypoperfusion in rats. It is shown that a single application of curcumin (300 mg/kg, i.p.) is not has neuroprotective effect in the acute phase of ischemia in chronic hypoperfusion in Wistar rats. The results allow to conclude that the neuroprotective effect of a single application of curcumin.

scholarly journals Previous Adaptation Period Modulates Pregnancy Swimming Neuroprotective Effects on the Offspring Following Neonatal Hypoxic‐Ischemic Brain Injury

2019 ◽  
Vol 33 (S1) ◽  
Author(s):  
Isadora Davila Tassinari ◽  
Eduardo Farias Sanches ◽  
Rafael Bandeira Fabres ◽  
Mirella Kielek Galvan Andrade ◽  
Thais Lopes Rodrigues ◽  
...  
Keyword(s):  
Brain Injury ◽  
Ischemic Brain Injury ◽  
Adaptation Period ◽  
Neuroprotective Effects ◽  
Ischemic Brain ◽  
Hypoxic Ischemic Brain Injury

scholarly journals Neuroactive Steroids in Hypoxic–Ischemic Brain Injury: Overview and Future Directions

2020 ◽  
Author(s):  
Nicolas Toro-Urrego ◽  
Marco Avila-Rodriguez ◽  
María Inés Herrera ◽  
Andrea Aguilar ◽  
Lucas Udovin ◽  
...  
Keyword(s):  
Brain Injury ◽  
Estrogenic Activity ◽  
Neuroactive Steroids ◽  
Ischemic Brain Injury ◽  
Neuroprotective Effects ◽  
Future Directions ◽  
Ischemic Brain ◽  
Public Health Burden ◽  
Hypoxic Ischemic Brain Injury ◽  
Underlying Mechanisms

Hypoxic–ischemic brain injury is a number one cause of long-term neurologic disability and death worldwide. This public health burden is mainly characterized by a decrease in oxygen concentration and blood flow to the tissues, which lead to an inefficient supply of nutrients to the brain. This condition induces cell death by energy depletion and increases free radical generation and inflammation. Hypoxic–ischemic brain injury may occur in ischemic-stroke and over perinatal asphyxia, being both leading causes of morbidity in adults and children, respectively. Currently, there are no effective pharmaceutical strategies to prevent the triggering of secondary injury cascades, including oxidative stress and metabolic dysfunction. Neuroactive steroids like selective estrogen receptor modulators, SERMs, and selective tissue estrogenic activity regulators, STEARs, exert several neuroprotective effects. These encompass mitochondrial survival, a decrease in reactive oxygen species, and maintenance of cell viability, among others. In this context, these neurosteroids constitute promising molecules, which could modify brain response to injury. Here we show an updated overview of the underlying mechanisms of hypoxic–ischemic brain injury. We also highlight the neuroprotective effects of neurosteroids and their future directions.

Neuroprotective Effects of AG490 in Neonatal Hypoxic-Ischemic Brain Injury

2019 ◽  
Vol 56 (12) ◽  
pp. 8109-8123 ◽  
Author(s):  
Feiya Li ◽  
Raymond Wong ◽  
Zhengwei Luo ◽  
Lida Du ◽  
Ekaterina Turlova ◽  
...  
Keyword(s):  
Brain Injury ◽  
Ischemic Brain Injury ◽  
Neuroprotective Effects ◽  
Ischemic Brain ◽  
Hypoxic Ischemic Brain Injury

scholarly journals Neuroprotective effects of inter-alpha inhibitor proteins after hypoxic-ischemic brain injury in neonatal rats

2019 ◽  
Vol 317 ◽  
pp. 244-259 ◽  
Author(s):  
Xiaodi Chen ◽  
Sakura Nakada ◽  
John E. Donahue ◽  
Ray H. Chen ◽  
Richard Tucker ◽  
...  
Keyword(s):  
Brain Injury ◽  
Ischemic Brain Injury ◽  
Neonatal Rats ◽  
Neuroprotective Effects ◽  
Ischemic Brain ◽  
Hypoxic Ischemic Brain Injury

scholarly journals CYP3A Excipient-Based Microemulsion Prolongs the Effect of Magnolol on Ischemia Stroke Rats

Pharmaceutics ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 737 ◽  
Author(s):  
Jiun-Wen Guo ◽  
Chih-Cheng Chien ◽  
Jiann-Hwa Chen
Keyword(s):  
Brain Injury ◽  
Water Solubility ◽  
Neuroprotective Effect ◽  
Ischemic Brain Injury ◽  
Microemulsion Formulation ◽  
Brain Infarct ◽  
Time Curve ◽  
Release Formulation ◽  
Ischemic Brain ◽  
Effective Delivery

Magnolol, which is a CYP3A substrate, is a well-known agent that can facilitate neuroprotection and reduce ischemic brain damage. However, a well-controlled release formulation is needed for the effective delivery of magnolol due to its poor water solubility. In this study, we have developed a formulation for a CYP3A-excipient microemulsion, which can be administrated intraperitoneally to increase the solubility and bioavailability of magnolol and increase its neuroprotective effect against ischemic brain injury. The results showed a significant improvement in the area under the plotted curve of drug concentration versus time curve (AUC0–t) and mean residence time (MRT) of magnolol in microemulsion compared to when it was dissolved in dimethyl sulfoxide (DMSO). Both magnolol in DMSO and microemulsion, administrated after the onset of ischemia, showed a reduced visual brain infarct size. As such, this demonstrates a therapeutic effect on ischemic brain injury caused by occlusion, however it is important to note that a pharmacological effect cannot be concluded by this study. Ultimately, our study suggests that the excipient inhibitor-based microemulsion formulation could be a promising concept for the substrate drugs of CYP3A.

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