Abstract
Astrocyte-mediated inflammation and oxidative stress elicit cerebral ischemia-reperfusion (IR) injury after stroke. Nuclear factor (NF)-κB activates astrocytes and generates pro-inflammatory factors. The purpose of the present study is to elucidate the effect of pterostilbene (PTE, a natural stilbene) on astrocytic inflammation and neuronal oxidative injury following cerebral ischemia-reperfusion injury. A middle cerebral artery occlusion-reperfusion (MCAO/R) mouse model and HT22/U251 co-culture model subjected to oxygen-glucose deprivation and re-introduction (OGD/R) were employed, with or without PTE treatment. The data showed that PTE delivery immediately after reperfusion, at 1 h after occlusion, decreased infarct volume, brain edema, and neuronal apoptosis and improved long-term neurological function. PTE decreased oxidation (i.e., production of reactive oxygen species, malondialdehyde) and inflammatory mediators (tumor necrosis factor-α, interleukin-1β, and interleukin-6) and increased anti-oxidative enzyme activities (i.e., of superoxide dismutase, glutathione peroxidase), by inhibiting phosphorylation and nuclear translocation of NF-κB. In conclusion, PTE attenuated astrocyte-mediated inflammation and oxidative injury following IR via NF-κB inhibition. Overall, PTE is a promising neuroprotective agent.
Highlights
Acute ischemic stroke (AIS) is the main cause of disability worldwide and is one of the leading causes of mortality [1]
We identified that a PTE injection at 10 mg/kg per day for five days had no effect on neurological scores and brain water content in normal mouse brains [11]. 2, 3, 5-triphenyltetrazolium chloride (TTC) staining was used to measure the infarct volume of middle cerebral artery occlusion-reperfusion (MCAO/R) mice (Figure 1)
We investigated the distribution of p-p65 (S536) in astrocytes using immunofluorescent double-staining of p-p65 with GFAP and DAPI 24 h after MCAO/R
Summary
Acute ischemic stroke (AIS) is the main cause of disability worldwide and is one of the leading causes of mortality [1]. We know that inflammation associated with neuronal ischemia and reperfusion (IR) injury (IRI) plays a pathological role in stroke [3]. Pterostilbene Attenuates Cerebral Ischemia-Reperfusion Injury studies have demonstrated that astrocytes contribute to the inflammatory response, which may aggravate the ischemic lesion, and form a glial scar, which may obstruct axonal regeneration and subsequently reduce the functional outcome [5]. Changes in astrocytic functions critically affect neuronal survival following stroke. Cytokines such as interleukin (IL)-6 and IL-1, abundant in brain ischemia [6], are considered to induce astrogliosis [7].
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