Fibroblast growth factor 2 contributes to the effect of salidroside on dendritic and synaptic plasticity after cerebral ischemia/reperfusion injury.

Sisi Li,Yechen Lu,Xuyun Hua,Xiangxin Xing,Daofang Ding,Zhenzhen Ma,Jianguang Xu

doi:10.18632/aging.103308

Sisi Li, Yechen Lu + Show 5 more

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https://doi.org/10.18632/aging.103308

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Abstract

Ischemic stroke, a serious neurological disease, is associated with cell death, axonal and dendritic plasticity, and other activities. Anti-inflammatory, anti-apoptotic, promote dendritic and synaptic plasticity are critical therapeutic targets after ischemic stroke. Fibroblast growth factor-2 (FGF2), which is involved in the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/CAMP response element (CRE)-binding protein (CREB) pathway, has been shown to facilitate dendritic and synaptic plasticity. Salidroside (Sal) has been reported to have anti-inflammatory, anti-oxidative, and anti-apoptotic effects; however, the underlying mechanisms of Sal in promoting dendritic and synaptic plasticity remain unclear. Here, the anti-inflammatory, anti-apoptotic, dendritic and synaptic plasticity effects of Sal were investigated in vitro in PC12 cells under oxygen-glucose deprivation/reoxygenation (OGD/R) conditions and in vivo in rats with middle cerebral artery occlusion/reperfusion (MCAO/R). We investigated the role of Sal in promoting dendritic and synaptic plasticity in the ischemic penumbra and whether the FGF2-mediated cAMP/PKA/CREB pathway was involved in this process. The present study demonstrated that Sal could significantly inhibit inflammation and apoptosis, and promote dendritic and synaptic plasticity. Overall, our study suggests that Sal is an effective treatment for ischemic stroke that functions via the FGF2-mediated cAMP/PKA/CREB pathway to promote dendritic and synaptic plasticity.

Highlights

Stroke is currently the second leading cause of death worldwide and can be classified into haemorrhagic and ischemic stroke
The results showed the protein and mRNA levels of proinflammatory mediators, including tumor necrosis factor alpha (TNF-α), interleukin-1β (IL1β) and IL-6 were increased after oxygen-glucose deprivation/reoxygenation (OGD/R), Sal significantly reversed the inflammation induced by OGD/R (Figure 2)
We evaluated the expression of cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), CREB, pCREB, Fibroblast growth factor-2 (FGF2) and FGF receptor 1 (FGFR1) in the ischemic penumbra by western blot and qPCR, revealing that the expression levels of cAMP, PKA, p-CREB, FGF2 and FGFR1 were markedly increased in the middle cerebral artery occlusion/reperfusion (MCAO/R) group compared with the sham group

Summary

Introduction

Stroke is currently the second leading cause of death worldwide and can be classified into haemorrhagic and ischemic stroke. Recent studies have shown that acute ischemic stroke leads to diverse pathophysiological changes, such as brain oedema, neuronal damage and synaptic dysfunction [3]. The behavioural changes and functional recovery after ischemic stroke are closely related to dendrite and synaptic plasticity [4]. A phenomenon that is governed by the temporal www.aging-us.com patterns of presynaptic and postsynaptic activity. Postsynaptic activity can be determined by the properties of dendrites, indicating that dendrites play an important role in, and, to a certain extent, dominate synaptic plasticity [5]. Available treatment interventions may be able to retard early dendritic degeneration to prevent the death of injured neurons

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