Alterations in the time course of expression of the Nox family in the brain in a rat experimental cerebral ischemia and reperfusion model: effects of melatonin

2014 ◽  
Vol 57 (1) ◽  
pp. 110-119 ◽  
Author(s):  
Haiying Li ◽  
Yang Wang ◽  
Dongxia Feng ◽  
Yin Liu ◽  
Min Xu ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Time Course ◽  
Ischemia And Reperfusion ◽  
Cerebral Ischemia And Reperfusion ◽  
Nox Family ◽  
The Brain ◽  
Experimental Cerebral Ischemia

Abstract P801: Impact of Oxidized Phospholipids on Outcomes From Cerebral Ischemia and Reperfusion Injury

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Jin Yu ◽  
Hong Zhu ◽  
Calvin Yeang ◽  
Joseph L Witztum ◽  
Sotirios Tsimikas ◽  
...  
Keyword(s):  
Cell Death ◽  
Cerebral Ischemia ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Ischemia And Reperfusion ◽  
Oxidized Phospholipids ◽  
Ischemia And Reperfusion Injury ◽  
Cerebral Ischemia And Reperfusion ◽  
The Brain

The mechanisms leading to oxidative stress and cellular dysfunction during stroke are not well understood. To test the hypothesis that transient cerebral artery occlusion (MCAo) in mice results in the generation of oxidized phospholipids (oxPLs) that contribute to neuronal cell death and glial activation. Both in vitro and in vivo cerebral ischemia and reperfusion injury (IRI) resulted in the elevation of specific oxPLs. Neuronal cell death was determined in the presence of oxPLs and the natural oxPL E06 antibody protected the cells from the toxic effects. IRI in mice gave rise to increased immunoreactivity of oxPLs in the brain. E06 reduced inflammatory markers in the brain following IRI, including iba-1, GFAP and inflammatory cytokines. In addition, oxPLs gave rise to M1 and Mox microglial phenotypes which was reversed in the presence of E06 and elicited a more M2 phenotype. Nrf2 deficient mice show increased infarct volumes and microglia from Nrf2 -/- mice show a reduction in Mox gene expression, and E06 protects both mice and cells from the Nrf2 deficit. Cerebral IRI generates oxPLs which triggers neuronal cell loss and inflammation and inactivation of oxPLs in vivo reduces infarct volume and improves outcomes.

scholarly journals Yi-Zhi-Fang-Dai Formula Exerts Neuroprotective Effects Against Pyroptosis and Blood–Brain Barrier–Glymphatic Dysfunctions to Prevent Amyloid-Beta Acute Accumulation After Cerebral Ischemia and Reperfusion in Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhongkuan Lyu ◽  
Qiyue Li ◽  
Zhonghai Yu ◽  
Yuanjin Chan ◽  
Lei Fu ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Blood Brain Barrier ◽  
Amyloid Beta ◽  
Neuronal Damage ◽  
Cerebral Infarct ◽  
Brain Barrier ◽  
Ischemia And Reperfusion ◽  
Neuroprotective Effects ◽  
Cerebral Ischemia And Reperfusion ◽  
The Brain

Background: The dysfunctional blood–brain barrier (BBB)–glymphatic system is responsible for triggering intracerebral amyloid-beta peptide (Aβ) accumulation and acts as the key link between ischemic stroke and dementia dominated by Alzheimer’s disease (AD). Recently, pyroptosis in cerebral ischemia and reperfusion (I/R) injury is demonstrated as a considerable mechanism causing BBB–glymphatic dysfunctions and Aβ acute accumulation in the brain. Targeting glial pyroptosis to protect BBB–glymphatic functions after cerebral I/R could offer a new viewpoint to prevent Aβ accumulation and poststroke dementia. Yi-Zhi-Fang-Dai formula (YZFDF) is an herbal prescription used to cure dementia with multiple effects of regulating inflammatory responses and protecting the BBB against toxic Aβ-induced damage. Hence, YZFDF potentially possesses neuroprotective effects against cerebral I/R injury and the early pathology of poststroke dementia, which evokes our current study.Objectives: The present study was designed to confirm the potential efficacy of YZFDF against cerebral I/R injury and explore the possible mechanism associated with alleviating Aβ acute accumulation.Methods: The models of cerebral I/R injury in rats were built by the method of middle cerebral artery occlusion/reperfusion (MCAO/R). First, neurological function assessment and cerebral infarct measurement were used for confirming the efficacy of YZFDF on cerebral I/R injury, and the optimal dosage (YZFDF-H) was selected to conduct the experiments, which included Western blotting detections of pyroptosis, Aβ1-42 oligomers, and NeuN, immunofluorescence observations of glial pyroptosis, aquaporin-4 (AQP-4), and Aβ locations, brain water content measurement, SMI 71 (a specific marker for BBB)/AQP-4 immunohistochemistry, and Nissl staining to further evaluate BBB–glymphatic functions and neuronal damage.Results: YZFDF obviously alleviated neurological deficits and cerebral infarct after cerebral I/R in rats. Furthermore, YZFDF could inactivate pyroptosis signaling via inhibiting caspase-1/11 activation and gasdermin D cleavage, ameliorate glial pyroptosis and neuroinflammation, protect against BBB collapse and AQP-4 depolarization, prevent Aβ acute accumulation and Aβ1-42 oligomers formation, and reduce neuronal damage and increase neurons survival after reperfusion.Conclusion: Our study indicated that YZFDF could exert neuroprotective effects on cerebral I/R injury and prevent Aβ acute accumulation in the brain after cerebral I/R associated with inhibiting neuroinflammation-related pyroptosis and BBB–glymphatic dysfunctions.

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