Effects of Toll-Like Receptor 4 Antagonists Against Cerebral Vasospasm After Experimental Subarachnoid Hemorrhage in Mice

Kawakita, Fumihiro; Fujimoto, Masashi; Liu, Lei; Nakano, Fumi; Nakatsuka, Yoshinari; Suzuki, Hiroyoshi

doi:10.1007/s12035-016-0178-7

Cited by 50 publications

(35 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The underlying mechanism of DCI development has not been clarified exactly, and nonvasospastic causes of DCI have been attracted attention to recently [4,27,28]. However, inflammation is considered to be an important cause of DCI irrespective of vasospasm [4,[27][28][29][30]. As tissue injury and inflammation induce the expression of POSTN, post-SAH neuroinflammation may cause POSTN upregulation [11,19].…”

Section: Discussionmentioning

confidence: 99%

Plasma Periostin and Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage

et al. 2019

Self Cite

View full text Add to dashboard Cite

Delayed cerebral ischemia (DCI) is a serious complication of aneurysmal subarachnoid hemorrhage (SAH). Matricellular protein periostin (POSTN) has been found to be upregulated and linked with early brain injury after experimental SAH. The aim of the present study was to investigate the relationship between plasma POSTN levels and various clinical factors including serum levels of C-reactive protein (CRP), an inflammatory marker, in 109 consecutive SAH patients whose POSTN levels were measured at days 1-12 after aneurysmal obliteration. DCI developed in 16 patients associated with higher incidence of angiographic vasospasm, cerebral infarction, and 90-day worse outcomes. POSTN levels peaked at days 4-6 before DCI development. Cerebrospinal fluid (CSF) drainage was associated with reduced POSTN levels, but did not influence CRP levels. There was no correlation between POSTN levels and other treatments or CRP levels. To predict DCI development, receiver-operating characteristic curves indicated that the most reasonable cutoff POSTN levels were obtained at days 1-3 in patients without CSF drainage (80.5 ng/ml; specificity, 77.6%; sensitivity, 85.7%). Multivariate analyses using variables obtained by day 3 revealed that POSTN level was an independent predictor of DCI. POSTN levels over the cutoff value were associated with higher incidence of DCI, but not angiographic vasospasm. This study shows for the first time that CSF drainage may reduce plasma POSTN levels, and that POSTN levels may increase prior to the development of DCI with and without vasospasm irrespective of systemic inflammatory reactions in clinical settings. These findings suggest POSTN as a new therapeutic molecular target against post-SAH DCI.

show abstract

Section: Discussionmentioning

confidence: 99%

Plasma Periostin and Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…Therefore, hydrogen inhalation can provide antioxidative protective effect on lipids and proteins after SAH. Inflammation is a significant causal factor in EBI after SAH, as suggested by evidence of the involvement of NLRP3 inflammasome and TLR4/NF-κB in SAH (Kawakita et al, 2017;Zhou et al, 2018), which may related to the early as well as late neuronal injuries (Zhou et al, 2007;You et al, 2013;Kawakita et al, 2017;Okada and Suzuki, 2017). Other study showed that the regulation of TLR4/NF-κB pathway by melatonin alleviated secondary brain damage and neurobehavioral dysfunction in SAH model (Wang et al, 2013).…”

Section: Discussionmentioning

confidence: 95%

Hydrogen Inhalation Attenuates Oxidative Stress Related Endothelial Cells Injury After Subarachnoid Hemorrhage in Rats

et al. 2020

View full text Add to dashboard Cite

Background: Subarachnoid hemorrhage (SAH) is a devastating cerebrovascular disease with poor clinical outcome. Nucleotide binding and oligomerization domainlike receptor family pyrin domain-containing 3 (NLRP3) inflammasome serves a key role in inflammatory response, which may lead to endothelial cell injury and blood-brain barrier (BBB) disruption. Hydrogen (H 2) is considered a neuroprotective antioxidant. This study was set out to explore whether hydrogen inhalation protects against SAH induced endothelial cell injury, BBB disruption, microthrombosis and vasospasm in rats. Methods: One hundred eighty-two male SD rats were used for the study. SAH was induced by endovascular perforation. H2 at a concentration of 3.3% was inhaled beginning at 0.5 h after SAH for duration of 30, 60 or 120 min, followed by single administration or once daily administration for 3 days. The temporal expression of NLRP3 and ASC in the brain was determined, with the effect of hydrogen inhalation evaluated. In addition, brain water content, oxidative stress markers, inflammasome, apoptotic markers, microthrombosis, and vasospasm were evaluated at 24 or 72 h after SAH. Results: The expression of NLRP3 and ASC were upregulated after SAH associated with elevated expression of MDA, 8-OHdG, 4-HNE, HO-1, TLR4/NF-κB, inflammatory and apoptotic makers. Hydrogen inhalation reduced the expression of these inflammatory and apoptotic makers in the vessels, brain edema, microthrombi formation, and vasospasm in rats with SAH relative to control. Hydrogen inhalation also improved short-term and long-term neurological recovery after SAH. Conclusion: Hydrogen inhalation can ameliorate oxidative stress related endothelial cells injury in the brain and improve neurobehavioral outcomes in rats following SAH. Mechanistically, the above beneficial effects might be related to, at least in part, the inhibition of activation of ROS/NLRP3 axis.

show abstract

“…Neurological deficits were evaluated at 96h after the onset of SAH using an 18-point system containing six tests per previous published protocol [22,24]: forelimbs outstretching (0-3), spontaneous activity (0-3), climbing (1)(2)(3), symmetry in the movements of all limbs (0-3), response to vibrissae touch (1-3) and body proprioception (1-3). A higher score indicates an elevated function.…”

Section: Neurological Scorementioning

confidence: 99%

“…Treatment for SAH has primarily focused on the prevention of bleeding in the intracranial aneurysm, a factor contributing to early brain injury (EBI), as well as on the reversal of cerebral vasospasm, a critical cause of delayed brain injury (DBI) [2]. In fact, DBI and delayed cerebral ischemia following EBI are still considered as the most critical and preventable causes of poor prognosis in SAH, whereas inflammation has been considered as the key factor affecting the severity of brain injury [3].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Melatonin affects hypoxia-inducible factor 1α and ameliorates delayed brain injury following subarachnoid hemorrhage via H19/miR-675/HIF1A/TLR4

Xia¹,

Jiang²,

Li³

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: This study was aimed to investigate the molecular mechanism of how melatonin interferes with hypoxia-inducible factor 1α (HIF1A) and TLR4 expression, which is implicated in the management of delayed brain injury (DBI) after subarachnoid hemorrhage (SAH). Method: Luciferase assay, real-time PCR, Western-blot analysis and immunohistochemistry (IHC) assays were utilized to explore the interaction among H19, miR-675, HIF1A and TLR4, and to evaluate the effect of MT on the expression of above transcripts in different groups. Results: MT enhanced H19 expression by promoting the transcription efficiency of H19 promoter, and HIF1A was identified as a target of miR-675. HIF1A enhanced TLR4 expression via promoting the transcription efficiency of TLR4 promoter. Furthermore, administration of MT up-regulated miR-675 but suppressed the expressions of HIF1A and TLR4. Treatment with MT alleviated neurobehavioral deficits and apoptosis induced by SAH. According to the result of IHC, HIF1A and TLR4 protein levels in the SAH group were much higher than those in the SAH+MT group. Therefore, the administration of MT increased the levels of H19 and miR-675 which have been inhibited by SAH. In a similar way, treatment with MT decreased the levels of HIF1A and TLR4 which have been enhanced by SAH. Conclusion: MT could down-regulate the expression of HIF1A and TLR4 via the H19/miR-675/HIF1A/TLR4 signaling pathway, while TLR4 is crucial to the release of pro-inflammatory cytokines. Therefore, the treatment with MT could ameliorate post-SAH DBI.

show abstract

Effects of Toll-Like Receptor 4 Antagonists Against Cerebral Vasospasm After Experimental Subarachnoid Hemorrhage in Mice

Cited by 50 publications

References 35 publications

Plasma Periostin and Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage

Plasma Periostin and Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage

Hydrogen Inhalation Attenuates Oxidative Stress Related Endothelial Cells Injury After Subarachnoid Hemorrhage in Rats

Melatonin affects hypoxia-inducible factor 1α and ameliorates delayed brain injury following subarachnoid hemorrhage via H19/miR-675/HIF1A/TLR4

Contact Info

Product

Resources

About