Apigenin protects blood–brain barrier and ameliorates early brain injury by inhibiting TLR4-mediated inflammatory pathway in subarachnoid hemorrhage rats

2015 ◽  
Vol 28 (1) ◽  
pp. 79-87 ◽  
Author(s):  
Tingting Zhang ◽  
Jingyuan Su ◽  
Bingyu Guo ◽  
Kaiwen Wang ◽  
Xiaoming Li ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Blood Brain Barrier ◽  
Early Brain Injury ◽  
Brain Barrier ◽  
Inflammatory Pathway ◽  
Blood Brain

scholarly journals COG133 Attenuates the Early Brain Injury Induced by Blood-Brain Barrier Disruption in Experimental Subarachnoid Hemorrhage

2022 ◽  
Vol 2022 ◽  
pp. 1-13
Author(s):  
Yongfa Zhang ◽  
Baocheng Gao ◽  
Jingsong Ouyang ◽  
Bai Tai ◽  
Shuai Zhou
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Blood Brain Barrier ◽  
Barrier Function ◽  
Early Brain Injury ◽  
Brain Barrier ◽  
Inflammasome Activation ◽  
Mimetic Peptide ◽  
Blood Brain ◽  
Experimental Subarachnoid Hemorrhage

Subarachnoid hemorrhage (SAH) is a kind of severe hemorrhagic stroke, and early brain injury acted as one of the main causes of death and delayed neurological deficit in patients with subarachnoid hemorrhage. In this process, the function and structural integrity of the blood-brain barrier play an important role. In this study, we have observed whether the apolipoprotein E (apoE) mimetic peptide, COG133, can alleviate early brain injury after subarachnoid hemorrhage. For this purpose, an experimental subarachnoid hemorrhage model was constructed in mice and treated by intravenous injection of COG133 at a dosage of 1 mg/kg. Then, the function and integrity of the blood-brain barrier were detected, and the pyroptosis level of the neuron was determined. The results showed that COG133 could protect blood-brain barrier function and structure integrity, reduce early brain injury, and ameliorate neurological function after subarachnoid hemorrhage. In terms of molecular mechanism, COG133 inhibits blood-brain barrier destruction through the proinflammatory CypA-NF-κB-MMP9 pathway and reduces neuronal pyroptosis by inhibiting NLRP3 inflammasome activation. In conclusion, this study demonstrated that apoE-mimetic peptide, COG133, can play a neuroprotective role by protecting blood-brain barrier function and inhibiting brain cell pyroptosis to reduce early brain injury after subarachnoid hemorrhage.

scholarly journals The Updated Role of the Blood Brain Barrier in Subarachnoid Hemorrhage: From Basic and Clinical Studies

2020 ◽  
Vol 18 (12) ◽  
pp. 1266-1278
Author(s):  
Sheng Chen ◽  
PengLei Xu ◽  
YuanJian Fang ◽  
Cameron Lenahan
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Cerebral Ischemia ◽  
Clinical Outcome ◽  
Blood Brain Barrier ◽  
Ct Perfusion ◽  
Delayed Cerebral Ischemia ◽  
Early Brain Injury ◽  
Brain Barrier ◽  
Blood Brain

Subarachnoid hemorrhage (SAH) is a type of hemorrhagic stroke associated with high mortality and morbidity. The blood-brain-barrier (BBB) is a structure consisting primarily of cerebral microvascular endothelial cells, end feet of astrocytes, extracellular matrix, and pericytes. Post-SAH pathophysiology included early brain injury and delayed cerebral ischemia. BBB disruption was a critical mechanism of early brain injury and was associated with other pathophysiological events. These pathophysiological events may propel the development of secondary brain injury, known as delayed cerebral ischemia. Imaging advancements to measure BBB after SAH primarily focused on exploring innovative methods to predict clinical outcome, delayed cerebral ischemia, and delayed infarction related to delayed cerebral ischemia in acute periods. These predictions are based on detecting abnormal changes in BBB permeability. The parameters of BBB permeability are described by changes in computed tomography (CT) perfusion and magnetic resonance imaging (MRI). Kep seems to be a stable and sensitive indicator in CT perfusion, whereas Ktrans is a reliable parameter for dynamic contrast-enhanced MRI. Future prediction models that utilize both the volume of BBB disruption and stable parameters of BBB may be a promising direction to develop practical clinical tools. These tools could provide greater accuracy in predicting clinical outcome and risk of deterioration. Therapeutic interventional exploration targeting BBB disruption is also promising, considering the extended duration of post-SAH BBB disruption.

scholarly journals Hyperbaric Oxygen Intervention Modulates Early Brain Injury after Experimental Subarachnoid Hemorrhage in Rats: Possible Involvement of TLR4/NF-κ B-Mediated Signaling Pathway

2016 ◽  
Vol 38 (6) ◽  
pp. 2323-2336 ◽  
Author(s):  
Hao Liu ◽  
Ming Yang ◽  
Li Pan ◽  
Peng Liu ◽  
Lianting Ma
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Signaling Pathway ◽  
Brain Edema ◽  
Blood Brain Barrier ◽  
Hyperbaric Oxygen ◽  
Early Brain Injury ◽  
Brain Barrier ◽  
Enzyme Linked Immunosorbent Assay ◽  
Blood Brain

Background/Aims: Previous studies have proved that the activation of TLR4/NF-κ B signaling pathway is involved in inflammatory processes in early brain injury (EBI) after subarachnoid hemorrhage (SAH). Hyperbaric oxygen (HBO) intervention has successfully been used to treat several animal models of tissue injury via its anti-inflammation property. This study was undertaken to investigate the influence of HBO administration on the TLR4/NF-κ B signaling pathway in rats at the early stage of SAH. Methods: Male Sprague-Dawley rats (n = 150) were randomly divided into 5 groups: the sham, the sham + 2.8 atmospheres absolute (ATA) HBO group, the SAH group, the SAH + 2.0ATA HBO group, the SAH + 2.8ATA HBO group. Each group (n = 30) was randomly subdivided into three subgroups that were examined at the following time points: 24 h, 48 h and 72 h post-injury. HBO (100% O2, 2.0ATA or 2.8ATA for 90mins) was initiated 12 h after injury. Neurological deficit, brain edema and blood-brain barrier (BBB) permeability were assessed to evaluate the development of EBI. The expressions of TLR4, NF-κ B and pro-inflammatory cytokines in the cortical were determined by real time polymerase chain reaction (RT-PCR), western blot, immunohistochemistry, or enzyme-linked immunosorbent assay (ELISA). Results: Our study showed that treatment with HBO significantly decreased the expressions of TLR4, NF-κ B and the downstream inflammatory agents, such as TNF-α, IL-6, IL-1β and ICAM-1, and also improved brain edema, blood-brain barrier permeability and neurologic function. Conclusions: These findings indicate that HBO treatment may result in abatement of the development of EBI after SAH, possibly through suppression of TLR4/NF-κ B signaling pathway.

scholarly journals Baicalin Attenuates Subarachnoid Hemorrhagic Brain Injury by Modulating Blood-Brain Barrier Disruption, Inflammation, and Oxidative Damage in Mice

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Xianqing Shi ◽  
Yongjian Fu ◽  
SongSong Zhang ◽  
Hao Ding ◽  
Jin Chen
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Oxidative Damage ◽  
Blood Brain Barrier ◽  
Real Time Pcr ◽  
Microglial Cell ◽  
Brain Barrier ◽  
Blood Brain Barrier Disruption ◽  
Blood Brain ◽  
Brain Barrier Disruption

In subarachnoid hemorrhagic brain injury, the early crucial events are edema formation due to inflammatory responses and blood-brain barrier disruption. Baicalin, a flavone glycoside, has antineuroinflammatory and antioxidant properties. We examined the effect of baicalin in subarachnoid hemorrhagic brain injury. Subarachnoid hemorrhage was induced through filament perforation and either baicalin or vehicle was administered 30 min prior to surgery. Brain tissues were collected 24 hours after surgery after evaluation of neurological scores. Brain tissues were processed for water content, real-time PCR, and immunoblot analyses. Baicalin improved neurological score and brain water content. Decreased levels of tight junction proteins (occludin, claudin-5, ZO-1, and collagen IV) required for blood-brain barrier function were restored to normal level by baicalin. Real-time PCR data demonstrated that baicalin attenuated increased proinflammatory cytokine (IL-1β, IL-6, and CXCL-3) production in subarachnoid hemorrhage mice. In addition to that, baicalin attenuated microglial cell secretion of IL-1βand IL-6 induced by lipopolysaccharide (100 ng/ml) dose dependently. Finally, baicalin attenuated induction of NOS-2 and NOX-2 in SAH mice at the mRNA and protein level. Thus, we demonstrated that baicalin inhibited microglial cell activation and reduced inflammation, oxidative damage, and brain edema.

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