Toll‐like receptor‐4 knockout mice are more resistant to optic nerve crush damage than wild‐type mice

Morzaev, Dana; Nicholson, James D.; Caspi, Tomm; Weiss, Shirel; Hochhauser, Edith; Goldenberg-Cohen, Nitza

doi:10.1111/ceo.12521

Cited by 30 publications

(29 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These results suggested the potential anti-apoptotic effect of wogonin in the prevention of retinal diseases. Brn3a is a nuclear protein expressed exclusively in RGCs and has been widely used as a reliable and efficient marker to identify and quantify RGCs in normal and injured retina [13, 37]. In this work, we demonstrated that the number of Brn3a-positive RGCs and the Brn3a protein level were much lower in retina after ONC than those in control group, which were markedly increased after wogonin treatment, especially in the dose of 30 mg/kg.…”

Section: Discussionmentioning

confidence: 56%

“…Recent studies have shown that activated neuroglial cells dramatically induced the activation of toll-like receptor 4-nuclear factor-kappa B (TLR4-NF-κB) pathways, which may play a vital role in promoting the release of pro-inflammatory cytokines, causing RGCs death in retina after optic nerve (ON) injury [11, 12]. There was evidence to show a reduced inflammatory responses and improved RGCs preservation following optic nerve crush (ONC) in TLR4-deficient mice, which indicated that the presence of TLR4-dependent pathway induced the RGCs death [13]. Furthermore, reducing TLR4-NF-κB pathways dependent glial activation with medical treatment could promote RGCs survival after ON injury [14, 15].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Wogonin prevents TLR4-NF-κB-medicated neuro-inflammation and improves retinal ganglion cells survival in retina after optic nerve crush

Yang

et al. 2016

Oncotarget

View full text Add to dashboard Cite

Chronic neuro-inflammation is involved in the death of retinal ganglion cells (RGCs) in glaucoma. The aim of this study is to determine whether wogonin can suppress inflammatory responses and rescue RGCs death after optic nerve crush (ONC), an ideal animal model of glaucoma. Wogonin was administered intraperitoneally 10 min after establishment of ONC model. In this study, wogonin treatment reduced RGCs loss and inhibited RGCs apoptosis demonstrated by the increased Brn3a labeling RGCs at day 14 and the decreased cleaved caspase-3 expression at day 7 after ONC, respectively. In ONC model, number of GFAP-positive glial cells and iba1-positive microglial cells were increased, combined of the elevated level of pro-inflammatory cytokines released in retina at day 7. However, most of these responses were inhibited after wogonin treatment. The level of TLR4 expression, NF-κB-P65 nucleus location and NF-κB-P65 phosphorylation were increased in retina at day 1 after ONC, which was significantly reduced after wogonin treatment. These results demonstrated that wogonin protected RGCs survival and suppressed neuro-inflammation in retina after ONC by inhibiting TLR4-NF-κB pathways. We conclude that wogonin could be a possible strategy for the treatment of glaucoma.

show abstract

Section: Discussionmentioning

confidence: 56%

Section: Introductionmentioning

confidence: 99%

Wogonin prevents TLR4-NF-κB-medicated neuro-inflammation and improves retinal ganglion cells survival in retina after optic nerve crush

Yang

et al. 2016

Oncotarget

View full text Add to dashboard Cite

show abstract

“…This is supported by three lines of experimental evidence. Retinal microglia upregulate TLR expression as an early response to glaucomatous damage [ 107 ], polymorphisms in both TLR2 and TLR4 are risk alleles for glaucoma [ 108 , 109 ], and deletion of Tlr4 in mice reduces RGC death after optic nerve damage [ 110 ] and ischemia-reperfusion [ 111 ]. TLRs respond to endogenously derived “damage-associated molecular pattern” (DAMP) molecules released from damaged or dying cells [ 3 ].…”

Section: Discussionmentioning

confidence: 99%

Retinal glial responses to optic nerve crush are attenuated in Bax-deficient mice and modulated by purinergic signaling pathways

Nair

Schlamp

Montgomery

et al. 2016

J Neuroinflammation

View full text Add to dashboard Cite

Background: Retinal ganglion cell (RGC) soma death is a consequence of optic nerve damage, including in optic neuropathies like glaucoma. The activation of the innate immune network in the retina after nerve damage has been linked to RGC pathology. Since the eye is immune privileged, innate immune functions are the responsibility of the glia, specifically the microglia, astrocytes, and Müller cells that populate the retina. Glial activation, leading to the production of inflammatory cytokines, is a hallmark feature of retinal injury resulting from optic nerve damage and purported to elicit secondary degeneration of RGC somas.

show abstract

“…TLR1, TLR2 and TLR4 are reported to respond to nerve injury, they are upregulated in the CNS, and are positively associated with the production of pro-inflammatory cytokines TNF-α and IL-1β (27). TLR4 knockout mice and rats that were intrathecally administered with TLR4 antisense oligonucleotides exhibited downregulated spinal microglia activation and spinal pro-inflammatory cytokines, and reduced neuropathic pain (28). TLR4 is expressed specifically by microglia (29), while LPS is an agonist to TLR4 (30).…”

Section: Discussionmentioning

confidence: 99%

Protective role of fentanyl in lipopolysaccharide‑induced neuroinflammation in BV‑2 cells

Wang

Ying-jie

2018

Exp Ther Med

View full text Add to dashboard Cite

Neurosurgery always results in neuroinflammation, which may activate microglial cells. Previous studies have demonstrated that fentanyl could be used for the induction or maintenance of anesthesia prior to surgery. However, it is unknown if fentanyl attenuates neuroinflammation prophylactically. Cell viability in groups that were treated with different concentrations of fentanyl (0.01, 0.1, 1 or 5 µmol/l) was analyzed by an MTT assay. BV-2 microglial cells were treated with lipopolysaccharide (LPS) at a concentration of 1 µg/ml to mimic neuroinflammation . BV-2 cells were pretreated with 5 µmol/l fentanyl prior to stimulation by LPS. The protein levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-10 in the culture medium were assessed by ELISA. The mRNA level of toll-like receptor (TLR)4 was evaluated by reverse transcription-quantitative polymerase chain reaction analysis. The protein levels of TLR4, glycogen synthase kinase (GSK)-3β and phosphorylated (p)-GSK-3β in BV-2 cells were assessed by western blot analysis. The MTT assay demonstrated that low concentrations of fentanyl (0.01, 0.1 or 1 µmol/l) did not affect the cell viability of BV-2 cells, while 5 µmol/l fentanyl significantly reduced BV-2 cell viability. The results of ELISA revealed that LPS significantly upregulated the release of TNF-α, IL-1β and IL-10, which were repressed by fentanyl pretreatment. Fentanyl pretreatment significantly reduced the LPS-induced elevation of TLR4 at mRNA and protein levels as well as p-GSK-3β protein levels in BV-2 cells. In conclusion, fentanyl pretreatment protects BV-2 cells from LPS-induced neuroinflammation by inhibiting TLR4 expression and GSK-3β activation. Neuroinflammation induced by surgery serves an important role in the development of postoperative cognitive dysfunction (POCD) and targeting the TLR4 and GSK-3β signaling pathway may provide a novel therapeutic approach for the treatment of POCD.

show abstract

Toll‐like receptor‐4 knockout mice are more resistant to optic nerve crush damage than wild‐type mice

Abstract: Background: This study aims to investigate the role of the inflammatory response following optic nerve crush (ONC) in knockout mice for the toll-like receptor-4 gene (TLR4−/−) compared to wild-type (WT) mice.

Cited by 30 publications

References 59 publications

Wogonin prevents TLR4-NF-κB-medicated neuro-inflammation and improves retinal ganglion cells survival in retina after optic nerve crush

Wogonin prevents TLR4-NF-κB-medicated neuro-inflammation and improves retinal ganglion cells survival in retina after optic nerve crush

Retinal glial responses to optic nerve crush are attenuated in Bax-deficient mice and modulated by purinergic signaling pathways

Protective role of fentanyl in lipopolysaccharide‑induced neuroinflammation in BV‑2 cells

Contact Info

Product

Resources

About