The possible roles of necroptosis during cerebral ischemia and ischemia / reperfusion injury

Liao, Suchan; Apaijai, Nattayaporn; Chattipakorn, Nipon

doi:10.1016/j.abb.2020.108629

Cited by 69 publications

(54 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Phosphorylation of MLKL leads to its oligomerization, and the oligomerized MLKL then binds to the cell membrane causing its permeabilization and release of cellular components including the DAMPs, which initiate and exacerbate the inflammatory process [12,14]. Necroptosis has been reported to play a role in neuroinflammation in various neurodegenerative diseases such as Alzheimer's disease [15][16][17], Parkinson's disease [18][19][20], multiple sclerosis [21], and amyotrophic lateral sclerosis [22], as well as brain ischemia [23]. However, it is not known if necroptosis plays a role in age-associated neuroinflammation.…”

Section: Introductionmentioning

confidence: 99%

“…The copyright holder for this preprint (which this version posted July 25, 2021. ; https://doi.org/10.1101/2021.07. 23.453580 doi: bioRxiv preprint Previously, we reported that necroptosis increases with age in the white adipose tissue of mice and interventions that delay aging (dietary restriction or Ames dwarf mice), reduced necroptosis and the expression of pro-inflammatory cytokines [24,25]. We also found that necroptosis was increased in a mouse model of accelerated aging (mice deficient in the antioxidant enzyme, Cu/Zn superoxide dismutase, Sod1 -/mice) and blocking necroptosis reduced inflammation in the liver of Sod1 -/mice [26].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Necroptosis increases with age in the brain and contributes to age-related neuroinflammation

Thadathil

Nicklas

Mohammed

et al. 2021

Preprint

View full text Add to dashboard Cite

Chronic inflammation of the central nervous system (CNS), termed neuroinflammation, is a hallmark of aging and a proposed mediator of cognitive decline associated with aging. Neuroinflammation is characterized by the persistent activation of microglia, the innate immune cells of the CNS, with damage-associated molecular patterns (DAMPs) being one of the well-known activators of microglia. Because necroptosis is a cell death pathway that induce inflammation through the release of DAMPs, we hypothesized that an age-associated increase in necroptosis contributes to increased neuroinflammation with age. The marker of necroptosis, phosphorylated form of MLKL (P-MLKL), and kinases in the necroptosis pathway (RIPK1, RIPK3, and MLKL) showed a region-specific increase in the brain with age, specifically in the cortex layer V and the CA3 region of the hippocampus of mice. Similarly, MLKL-oligomers, which causes membrane binding and permeabilization were significantly increased in the cortex and hippocampus of old mice relative to young mice. Nearly 70 to 80% of P-MLKL immunoreactivity was localized to neurons and less than 10% was localized to microglia, whereas no P-MLKL was detected in astrocytes. P-MLKL expression in neurons was detected in the soma, not in the processes. Blocking necroptosis using Mlkl-/- mice reduced markers (Iba-1 and GFAP) of neuroinflammation in the brains of old mice and short-term treatment with the necroptosis inhibitor, necrostatin-1s, reduced expression of proinflammatory cytokines, IL-6 and IL-1β, in the hippocampus of old mice. Thus, our data demonstrate for the first time that brain necroptosis increases with age and contributes to age-related neuroinflammation in mice.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Necroptosis increases with age in the brain and contributes to age-related neuroinflammation

Thadathil

Nicklas

Mohammed

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…The morbidity and mortality of cerebral ischemia can be controlled to a certain degree by the timely reperfusion. However, cerebral reperfusion further aggregated cerebral injuries via inducing inflammation, oxidative stress, and the breakdown of the blood-brain barrier [ 85 , 86 ]. Therefore, it is vital to explore more strategies to protect cerebral functions and pathological developments in cerebral I/R.…”

Section: The Effects Of La On I/r Injuries Of Different Organsmentioning

confidence: 99%

Effects of Lipoic Acid on Ischemia‐Reperfusion Injury

Ding

Zhang

et al. 2021

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Ischemia-reperfusion (I/R) injury often occurred in some pathologies and surgeries. I/R injury not only harmed to physiological functions of corresponding organ and tissue but also induced multiple tissue or organ dysfunctions (even these in distant locations). Although the reperfusion of blood attenuated I/R injury to a certain degree, the risk of secondary damages was difficult to be controlled and it even caused failures of these tissues and organs. Lipoic acid (LA), as an endogenous active substance and a functional agent in food, owns better safety and effects in our body (e.g., enhancing antioxidant activity, improving cognition and dementia, controlling weight, and preventing multiple sclerosis, diabetes complication, and cancer). The literature searching was conducted in PubMed, Embase, Cochrane Library, Web of Science, and SCOPUS from inception to 20 May 2021. It had showed that endogenous LA was exhausted in the process of I/R, which further aggravated I/R injury. Thus, supplements with LA timely (especially pretreatments) may be the prospective way to prevent I/R injury. Recently, studies had demonstrated that LA supplements significantly attenuated I/R injuries of many organs, though clinic investigations were short at present. Hence, it was urgent to summarize these progresses about the effects of LA on different I/R organs as well as the potential mechanisms, which would enlighten further investigations and prepare for clinic applications in the future.

show abstract

“…Brain apoptosis was reported in rats with cardiac I/R injury [ 8 , 9 ]; however, the occurrence of brain necroptosis and ferroptosis has not been investigated. Tumor necrosis factor alpha (TNF-α) can initiate both extrinsic apoptosis and necroptosis [ 10 ]. Caspase 8 is a key determinant of the cell fate.…”

Section: Introductionmentioning

confidence: 99%

Cell death inhibitors protect against brain damage caused by cardiac ischemia/reperfusion injury

et al. 2021

Self Cite

View full text Add to dashboard Cite

Cognitive impairment has been reported in patients with myocardial infarction despite a successful reperfusion therapy. Several modes of cell death are involved in brain damage during cardiac ischemia/reperfusion (I/R) injury. Although apoptosis, necroptosis, and ferroptosis inhibitors provided neuroprotection against cerebral I/R injury, the effects of these cell death inhibitors on the brain following cardiac I/R injury have never been investigated. We hypothesized that apoptosis, necroptosis, and ferroptosis inhibitors attenuate brain damage following cardiac I/R injury. One-hundred and twenty-six male rats were used: 6 rats were assigned to sham operation and 120 rats were subjected to 30-min regional cardiac ischemia and 120-min reperfusion. Rats in cardiac I/R group were pretreated with either vehicle (n = 12) or one of cell death inhibitors. Rats treated with apoptosis, necroptosis, or ferroptosis inhibitor were subdivided into three different doses including low (L), medium (M), and high (H) doses (n = 12/group). Z-VAD, necrostatin-1 (Nec-1), and ferrostatin-1 (Fer-1) were used as apoptosis, necroptosis, and ferroptosis inhibitor, respectively. Rats were sacrificed at the end of reperfusion, and the brain was used to analyze dendritic spine density, Alzheimer’s disease (AD)-related proteins, blood–brain barrier (BBB) tight junction proteins, mitochondrial function, inflammation, and cell death. Our data showed that cardiac I/R led to brain damage and only apoptosis occurred in the hippocampus after cardiac I/R injury. In the cardiac I/R group, treatment with M-Z-VAD and all doses of Nec-1 decreased hippocampal apoptosis and amyloid beta aggregation, thereby reducing dendritic spine loss. M- and H-Fer-1 also reduced dendritic spine loss by suppressing ACSL4, TNF-α, amyloid beta, and tau hyperphosphorylation. Moreover, Bax/Bcl-2 was decreased in all treatment regimen except L-Z-VAD. Additionally, M-Z-VAD and M-Fer-1 partially attenuated mitochondrial dysfunction. Only L-Nec-1 preserved BBB proteins. In conclusion, cell death inhibitors prevented hippocampal dendritic spine loss caused by cardiac I/R injury through different mechanisms.

show abstract

The possible roles of necroptosis during cerebral ischemia and ischemia / reperfusion injury

Cited by 69 publications

References 56 publications

Necroptosis increases with age in the brain and contributes to age-related neuroinflammation

Necroptosis increases with age in the brain and contributes to age-related neuroinflammation

Effects of Lipoic Acid on Ischemia‐Reperfusion Injury

Cell death inhibitors protect against brain damage caused by cardiac ischemia/reperfusion injury

Contact Info

Product

Resources

About