The calcimimetic R-568 attenuates subarachnoid hemorrhage-induced vasospasm through PI3K/Akt/eNOS signaling pathway in the rat model

Güleç, İlker; Şengelen, Aslıhan; Karagöz-Güzey, Feyza; Uçar, Evren Önay; Eren, Burak; G., Vahabova; Karacan, Murat Kemal; Özcan, Tevhide Bilgen

doi:10.1016/j.brainres.2021.147508

Cited by 4 publications

(1 citation statement)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Activation of this pathway has caused antiinflammatory and anti-apoptotic effects through downregulation of molecules including TNFα, and NF-κB [86]. Several studies have demonstrated improved mortality rates and attenuated cerebral vasospasm following PI3K/Akt/eNOS activation in murine models of SAH [86,87]. Similarly, treatment with low concentrations of carbon monoxide (CO) has the potential to exert neuroprotective effects by reducing inflammation and restoring normal blood flow [88].…”

Section: Emerging Preclinical Treatmentsmentioning

confidence: 99%

Prevention and treatment of cerebral vasospasm following aneurysmal subarachnoid hemorrhage

McGrath,

Hey,

Ebrahim

et al. 2023

Academia Biology

View full text Add to dashboard Cite

Cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH) remains a significant cause of morbidity and mortality. Posthemorrhage cerebral vasospasm (PHCV) occurs through a complex pathophysiology, and numerous pharmacologic agents, including vasodilators, anti-inflammatories, and fibrinolytics, as well as endovascular techniques have been used to prevent and/or treat PHCV. Nimodipine continues to be the only agent with level 1 evidence, but other vasodilators have demonstrated promising results. Endovascular therapy likely has a role in treating severe/refractory PHCV, but randomized trials are needed to establish stronger evidence for this therapy. Numerous preclinical investigations highlight novel targets related to the immune response that could prove effective at improving outcomes in clinical trials. Further investigation of the glymphatic system and its role in PHCV pathogenesis could result in novel pharmacologic targets. Future trials of these therapies and combinations of existing therapies are needed, and functional outcomes should be included as an endpoint. Further exploration of the neuroinflammatory reaction following aSAH will continue to identify targetable molecules involved in PHCV pathogenesis.

show abstract

Section: Emerging Preclinical Treatmentsmentioning

confidence: 99%

Prevention and treatment of cerebral vasospasm following aneurysmal subarachnoid hemorrhage

McGrath,

Hey,

Ebrahim

et al. 2023

Academia Biology

View full text Add to dashboard Cite

show abstract

Poor expression of miR‐195‐5p can assist the diagnosis of cerebral vasospasm after subarachnoid hemorrhage and predict adverse outcomes

et al. 2022

View full text Add to dashboard Cite

Objective: Patients with spontaneous subarachnoid hemorrhage (SAH) may develop refractory arterial cerebral vasospasm (CVS), which is the leading cause of death in SAH patients. This study explored the clinical diagnostic value of serum miR-195-5p levels in CVS after SAH (SAH + CVS) and its relationship with the prognosis of SAH + CVS. Methods: A total of 110 patients with spontaneous SAH were divided into the SAH group (N = 62) and SAH + CVS group (N = 58), with 60 healthy subjects as controls. The clinical data of blood glucose, blood sodium fluctuation, and serum lactic acid were recorded. miR-195-5p serum level was detected by RT-qPCR and its diagnostic value on SAH + CVS was analyzed by receiver operating characteristic curve. Serum levels of PDGF/IL-6/ET-1 and their correlation with miR-195-5p were analyzed using RT-qPCR, enzyme-linked immunosorbent assay, and Pearson's method. The patient prognosis was evaluated by Glasgow Outcome Scale. The effect of miR-195-5p levels on adverse prognosis was analyzed by Kaplan-Meier method and Cox regression analysis. Results: miR-195-5p was lowly expressed in the serum of SAH patients and lower in SAH + CVS patients. Serum miR-195-5p level assisted the diagnosis of SAH and SAH+ CVS and was negatively correlated with PDGF/IL-6/ET-1 levels and was an independent risk factor together with ET-1 and blood glucose for SAH + CVS. miR-195-5p low expression predicted a higher cumulative incidence of adverse outcomes and was an independent predictor of adverse outcomes. Conclusion:Poor expression of miR-195-5p can assist the diagnosis of SAH + CVS and predict higher adverse outcomes.

show abstract

Calcium‐sensing receptor regulates the angiogenic differentiation of LPS‐treated human dental pulp cells via the phosphoinositide 3‐kinase/Akt pathway in vitro

Yang,

Liu,

Qiu

et al. 2024

Int Endodontic J

View full text Add to dashboard Cite

AimThe purpose of this study was to investigate the role of calcium‐sensing receptor (CaSR) in the angiogenic differentiation of lipopolysaccharide (LPS)‐treated human dental pulp cells (hDPCs).MethodologyThe LPS‐induced hDPCs were cultured in the medium with different combinations of CaSR agonist R568 and antagonist Calhex231. The cell proliferation, migration, and angiogenic capacity were measured by Cell Counting Kit‐8 (CCK‐8), scratch wound healing, and tube formation assays, respectively. Enzyme‐linked immunosorbent assay (ELISA), quantitative real‐time polymerase chain reaction (qRT‐PCR), and western blot were conducted to determine the gene/protein expression of CaSR, inflammatory mediators, and angiogenic‐associated markers. The activation of phosphoinositide 3‐kinase (PI3K) and protein kinase B (Akt) was assessed by western blot analysis.ResultsThe cell proliferation was elevated in response to R568 or Calhex231 exposure, but an enhanced cell migration was only found in cultures supplemented with Calhex231. Furthermore, R568 was found to potentiate the formation of vessel‐like structure, up‐regulated the protein expression of tumour necrosis factor (TNF)‐α, vascular endothelial growth factor (VEGF), and stromal cell‐derived factor (SDF)‐1; comparable influences were also observed in R568‐stimulated cells in the presence of PI3K inhibitor LY294002. In contrast, Calhex231 obviously inhibited the tube formation and VEGF protein level, whereas promoted the production of IL‐6, TNF‐α, and eNOS; however, in the presence of LY294002, Calhex231 showed a significant promotion on the protein expression of CaSR, VEGF, and SDF‐1. In addition, R568 exhibited a promotive action on the Akt phosphorylation, which can be reversed by LY294002.ConclusionsOur results demonstrated that CaSR can regulate the angiogenic differentiation of LPS‐treated hDPCs with an involvement of the PI3K/Akt signalling pathway.

show abstract

The calcimimetic R-568 attenuates subarachnoid hemorrhage-induced vasospasm through PI3K/Akt/eNOS signaling pathway in the rat model

Cited by 4 publications

References 53 publications

Prevention and treatment of cerebral vasospasm following aneurysmal subarachnoid hemorrhage

Prevention and treatment of cerebral vasospasm following aneurysmal subarachnoid hemorrhage

Poor expression of miR‐195‐5p can assist the diagnosis of cerebral vasospasm after subarachnoid hemorrhage and predict adverse outcomes

Calcium‐sensing receptor regulates the angiogenic differentiation of LPS‐treated human dental pulp cells via the phosphoinositide 3‐kinase/Akt pathway in vitro

Contact Info

Product

Resources

About