Lycopene Exerts Neuroprotective Effects After Hypoxic-Ischemic Brain Injury in Neonatal Rats via the Nuclear Factor Erythroid-2 Related Factor 2/Nuclear Factor-κ-Gene Binding Pathway.

Changchang Fu,Xiaoqin Fu,Jinjin Zhu,Kun Lin,Peijun Li,Wei Lin,Binwen Chen,Jianghu Zhu,Zhenlang Lin,Shangqin Chen,Yihui Zheng

doi:10.3389/fphar.2020.585898

Abstract

Neonatal hypoxic-ischemic encephalopathy (HIE) is a brain injury caused by perinatal asphyxia and is the main cause of neonatal death and chronic neurological diseases. Protection of neuron after hypoxic-ischemic (HI) brain injury is considered as a potential therapeutic target of HI brain injury. To date, there are no effective medicines for neonatal HI brain injury. Lycopene (Lyc), a member of the carotenoids family, has been reported to have anti-oxidative and anti-inflammatory effects. However, its effects and potential mechanisms in HI brain injury have not yet to be systematically evaluated. In this study, we investigated whether Lyc could ameliorate HI brain injury and explored the associated mechanism both in vivo and in vitro experiments. In vivo study, Lyc significantly reduced infarct volume and ameliorated cerebral edema, decreased inflammatory response, promoted the recovery of tissue structure, and improved prognosis following HI brain injury. In vitro study, results showed that Lyc reduced expression of apoptosis mediators in oxygen-glucose deprivation (OGD)-induced primary cortical neurons. Mechanistically, we found that Lyc-induced Nrf2/NF-κB pathway could partially reversed by Brusatol (an Nrf2 inhibitor), indicated that the Nrf2/NF-κB pathway was involved in the therapy of Lyc. In summary, our findings indicate that Lyc can attenuated HI brain injury in vivo and OGD-induced apoptosis of primary cortical neurons in vitro through the Nrf2/NF-κB signaling pathway.

Highlights

Hypoxic-ischemic (HI) brain injury is associated with high morbidity and mortality rate in neonates
Girard et al found that administration of the anti-IL-1 receptor can improve the neuroprotective effects in HI brain injury. inducible nitric oxide synthase (iNOS), one of the nitric oxide synthase (NOS) family of enzymes, which could promote the synthesis of NO (Girard et al, 2012)
In vivo experiments of this study, we found that Lyc significantly decreased the brain infarct volume, attenuated apoptosis, inhibited inflammatory response, recovered histomorphology, increased body weights and improved behavior disorders after HI injury

Summary

INTRODUCTION

Hypoxic-ischemic (HI) brain injury is associated with high morbidity and mortality rate in neonates. Phosphorylation of P65 allows it to be translocated from the cytoplasm into the nucleus where it upregulates expression of inflammatory factors such as tumor necrosis factor α (TNF-α), Interleukin- 6 (IL-6) and inducible nitric oxide synthase (iNOS) (Liang et al, 2017) These inflammatory factors are considered to be the chief contributors to ischemic brain injury (Williams et al, 2006). Some studies demonstrated that the mechanism of Lyc protects Leydig cell from damage may be that the Nrf pathway was regulated to exert anti-inflammation and antioxidant effect (Zhao Y. et al, 2020). We conducted a study to investigate the neuroprotective effect of Lyc in neonatal brain damage induced by HI injury, and determined whether the Nrf2/NFκB signaling pathway is involved in this process

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ETHICS STATEMENT