Neuroprotective effects of human umbilical cord–derived mesenchymal stromal cells combined with nimodipine against radiation-induced brain injury through inhibition of apoptosis

Wang, Guihua; Liu, Yang; Wu, Xiaobing; Lu, Ying; Jin, Lina; Qin, Ya-Ru; Li, Tong; Duan, Haifeng

doi:10.1016/j.jcyt.2015.10.006

Cited by 31 publications

(18 citation statements)

References 36 publications

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“…The present study investigated the protective effects of eupafolin on cerebral I/R injury in rats and revealed that eupafolin at a dose of 10, 20 and 50 mg/kg all exhibited significant protective effects on cerebral I/R via inhibiting inflammation, oxidative stress and apoptosis. Concurrently, 20 mg/kg eupafolin showed nearly equivalent effects to nimodipine, which is used to improve blood circulation in the recovery period of acute cerebrovascular disease and has been proven to exert anti-inflammation and anti-apoptosis effects (31)(32)(33). These results provided in vivo data for the therapeutic effect of low-dose eupafolin in treating cerebral I/R injury.…”

Section: Discussionmentioning

confidence: 81%

Eupafolin alleviates cerebral ischemia/reperfusion injury in rats via blocking the TLR4/NF‑κB signaling pathway

et al. 2020

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Eupatorium perfoliatum L. (E. perfoliatium) has been used traditionally for treating fever, malaria and inflammation-associated diseases. Eupafolin, the extract of E. perfoliatium, was also reported to suppress inflammation. The present study aimed to investigate the protective effects of eupafolin on cerebral ischemia/reperfusion (I/R) injury in rats and its possible underlying mechanisms. Cerebral I/R injury was induced in rats by middle cerebral artery occlusion (MCAO) for 1.5 h, followed by reperfusion. The rats were randomly assigned into six groups: Control, model, 10 mg/kg eupafolin, 20 mg/kg eupafolin, 50 mg/kg eupafolin and 20 mg/kg nimodipine. Eupafolin and nimodipine were intragastrically administrated to the rats 1 week before MCAO induction. Following reperfusion for 24 h, the neurological deficit was scored, and brain samples were harvested for evaluating encephaledema, infarct volume, oxidative stress, apoptosis, inflammation and the expression of TLR4/NF-κB signaling. The results revealed that eupafolin decreased the neurological score, relieved encephaledema and decreased infarct volume. Eupafolin also attenuated oxidative stress, neuronal apoptosis and inflammation, with decreases in lactate dehydrogenase, malondialdehyde, TUNEL-positive cells, Bax and caspase-3, along with TnF-α, il-1β and IL-6, but increases in superoxide dismutase and Bcl-2 levels. Furthermore, eupafolin may decrease the expression of TLR4 downstream proteins and proteins involved in the NF-κB pathway. Treatment with TLR4 agonist-LPS significantly blunted the protective effect of eupafolin on encephaledema and cerebral infarct. Meanwhile, 20 mg/kg eupafolin showed nearly equivalent effects to the positive-control drug nimodipine. In conclusion, eupafolin protected against cerebral I/R injury in rats and the underlying mechanism may be associated with the suppression of apoptosis and inflammation via inhibiting the TLR4/ nF-κB signaling pathway.

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Section: Discussionmentioning

confidence: 81%

Eupafolin alleviates cerebral ischemia/reperfusion injury in rats via blocking the TLR4/NF‑κB signaling pathway

et al. 2020

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“…Mesenchymal stem cell (MSC) transplants into mouse brains 2 days after 15 Gy X-ray exposure have been shown to reduce inflammation, cell death and cognitive deficits one month later (Liao et al 2017). A similar study combined MSC transplants with antihypertensive drug nimodipine in mice after 15 Gy of gamma radiation, with more success than MSC transplants alone (Wang et al 2016). In comparison, Baulch et al (Baulch et al 2016) conducted transplant experiments with microvesicles (MVs) derived from human neural stem cells (hNSC), rather than with the stem cells themselves.…”

Section: Limiting Tissue Damage and Increasing Repairmentioning

confidence: 99%

Ionizing radiation-induced risks to the central nervous system and countermeasures in cellular and rodent models

Pariset

Malkani

Cekanaviciute

et al. 2020

International Journal of Radiation Biology

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Purpose: Harmful effects of ionizing radiation on the Central Nervous System (CNS) are a concerning outcome in the field of cancer radiotherapy and form a major risk for deep space exploration. Both acute and chronic CNS irradiation induce a complex network of molecular and cellular alterations including DNA damage, oxidative stress, cell death and systemic inflammation, leading to changes in neuronal structure and synaptic plasticity with behavioral and cognitive consequences in animal models. Due to this complexity, countermeasure or therapeutic approaches to reduce the harmful effects of ionizing radiation include a wide range of protective and mitigative strategies, which merit a thorough comparative analysis. Materials and methods: We reviewed current approaches for developing countermeasures to both targeted and non-targeted effects of ionizing radiation on the CNS from the molecular and cellular to the behavioral level. Results: We focus on countermeasures that aim to mitigate the four main detrimental actions of radiation on CNS: DNA damage, free radical formation and oxidative stress, cell death, and harmful systemic responses including tissue death and neuroinflammation. We propose a comprehensive review of CNS radiation countermeasures reported for the full range of irradiation types (photons and particles, low and high linear energy transfer) and doses (from a fraction of gray to several tens of gray, fractionated and unfractionated), with a particular interest for exposure conditions relevant to deep-space environment and radiotherapy. Our review reveals the importance of combined strategies that increase DNA protection and repair, reduce free radical formation and increase their elimination, limit inflammation and improve cell viability, limit tissue damage and increase repair and plasticity. Conclusions: The majority of therapeutic approaches to protect the CNS from ionizing radiation have been limited to acute high dose and high dose rate gamma irradiation, and few are translatable from animal models to potential human application due to harmful side effects and lack of blood-brain barrier permeability that precludes peripheral administration. Therefore, a promising research direction would be to focus on practical applicability and effectiveness in a wider range of irradiation paradigms, from fractionated therapeutic to deep space radiation. In addition to discovering novel therapeutics, it would be worth maximizing the benefits and reducing side effects of those that already exist. Finally, we suggest that novel cellular and tissue models for developing and testing countermeasures in the context of other impairments might also be applied to the field of CNS responses to ionizing radiation.

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“…Next tissues were dissected into 0.4 cm3 pieces, washed in Hank's balanced salt solution (HBSS-1X, Cat#14025, Gibco, Dublin, Ireland), and transferred to Falcon tubes. Collagenase type II enzyme in an amount of 0.375 mg (Cat#17101015, Gibco, Dublin, Ireland) dissolved in a complete medium were added, and the samples were incubated with 5% CO2 at 37 0C overnight (1,10,13,15).…”

Section: Resection Of Tissues and Preparation Of Primary Cell Culturesmentioning

confidence: 99%

“…A cardiotoxicity study was performed on zebrafish that reported "nimodipine treatment resulted in atrial arrest with much slower but regular ventricular heart beating" (1). Pregnant rats were given 10 mg/kg/day during embryogenesis, and no detrimental effects were found (12,13).…”

Section: Introductionmentioning

confidence: 99%

Do we damage nucleus pulposus tissue while treating cerebrovascular ischemic neurological deficits with nimodipine?

Karaarslan¹,

Yılmaz²,

Şirin³

et al. 2018

J Turgut Ozal Med Cent

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Aim: Nimodipine is used to prevent cerebrovascular-originated ischemic neurological deficits, yet its effects on nucleus pulposus (NP) cells or annulus fibrosus (AF) cells weren't studied. This study aimed to examine nimodipine's effects on vitality and proliferation of chondroadherin (CHAD), type II collagen (COL2A1), and hypoxia-inducible factor 1 alpha (HIF 1α) gene expression in human primary NP/AF cells. Material and Methods: NP/AF cell cultures obtained from 6 patients who underwent microdiscectomy were treated with 100 µMolar nimodipine and analyzed at 0, 24, and 48 h. Data were evaluated using one-way ANOVA and post-hoc Tukey HSD with 95% confidence interval. Results: We observed suppressed cell proliferation and increased necrosis in nimodipine-treated NP/AF cell cultures, especially degenerated tissue. COL2A1 gene expression wasn't detected in any experimental groups. CHAD and HIF 1α expression had timedependent decreases in control. CHAD and HIF 1α expression were found to decrease at 24h, but increased at 48h in degenerated tissue. In nimodipine-applied intact tissues, CHAD expression was stable at 24h but 1.62 times higher than control at 48h. HIF 1α levels were lower than control. Conclusion: In nimodipine-treated degenerated AF/NP cultures, CHAD and HIF 1α expressions had time-dependent decreases. However, after complete RT-PCR data evaluation, no correlation between nimodipine application and gene expression occurred.

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Neuroprotective effects of human umbilical cord–derived mesenchymal stromal cells combined with nimodipine against radiation-induced brain injury through inhibition of apoptosis

Cited by 31 publications

References 36 publications

Eupafolin alleviates cerebral ischemia/reperfusion injury in rats via blocking the TLR4/NF‑κB signaling pathway

Eupafolin alleviates cerebral ischemia/reperfusion injury in rats via blocking the TLR4/NF‑κB signaling pathway

Ionizing radiation-induced risks to the central nervous system and countermeasures in cellular and rodent models

Do we damage nucleus pulposus tissue while treating cerebrovascular ischemic neurological deficits with nimodipine?

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