scholarly journals Neuroprotective and Anti-Inflammatory Effects of Pinus densiflora Bark Extract in Gerbil Hippocampus Following Transient Forebrain Ischemia

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4592
Author(s):  
Joon Ha Park ◽  
Jong Dai Kim ◽  
Tae-Kyeong Lee ◽  
Xionggao Han ◽  
Hyejin Sim ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Pinus Densiflora ◽  
Ischemic Injury ◽  
Bark Extract ◽  
Forebrain Ischemia ◽  
Neuroprotective Effects ◽  
Transient Forebrain Ischemia ◽  
Brain Ischemic Injury ◽  
Anti Inflammatory ◽  
Pre Treatment

Korean red pine (Pinus densiflora) belongs to the Genus Pinus, and its bark contains a great amount of naturally occurring phenolic compounds. Until now, few studies have been conducted to assess the neuroprotective effects of Pinus densiflora bark extract against brain ischemic injury. The aim of this study was to investigate the neuroprotective effects of pre-treatment with the extract in the hippocampus following 5-min transient forebrain ischemia in gerbils. Furthermore, this study examined the anti-inflammatory effect as a neuroprotective mechanism of the extract. Pinus densiflora bark was extracted by pure water (100 °C), and this extract was quantitatively analyzed and contained abundant polyphenols, flavonoids, and proanthocyanidins. The extract (25, 50, and 100 mg/kg) was orally administered once a day for seven days before the ischemia. In the gerbil hippocampus, death of the pyramidal neurons was found in the subfield cornu ammonis 1 (CA1) five days after the ischemia. This death was significantly attenuated by pre-treatment with 100 mg/kg, not 25 or 50 mg/kg, of the extract. The treatment with 100 mg/kg of the extract markedly inhibited the activation of microglia (microgliosis) and significantly decreased the expression of pro-inflammatory cytokines (interleukin 1β and tumor necrosis factor α). In addition, the treatment significantly increased anti-inflammatory cytokines (interleukin 4 and interleukin 13). Taken together, this study clearly indicates that pre-treatment with 100 mg/kg of Pinus densiflora bark extract in gerbils can exert neuroprotection against brain ischemic injury by the attenuation of neuroinflammatory responses.

scholarly journals Experimental Pretreatment with Chlorogenic Acid Prevents Transient Ischemia-Induced Cognitive Decline and Neuronal Damage in the Hippocampus through Anti-Oxidative and Anti-Inflammatory Effects

Molecules ◽  
2020 ◽  
Vol 25 (16) ◽  
pp. 3578 ◽  
Author(s):  
Tae-Kyeong Lee ◽  
Il-Jun Kang ◽  
Bora Kim ◽  
Hye Jin Sim ◽  
Dae- Won Kim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Chlorogenic Acid ◽  
Western Blotting ◽  
Inflammatory Cytokines ◽  
Ischemia Reperfusion ◽  
Forebrain Ischemia ◽  
Transient Forebrain Ischemia ◽  
Fluoro Jade B ◽  
Anti Inflammatory

Chlorogenic acid (CGA), an ester of caffeic acid and quinic acid, is among the phenolic acid compounds which can be naturally found in green coffee extract and tea. CGA has been studied since it displays significant pharmacological properties. The aim of this study was to investigate the effects of CGA on cognitive function and neuroprotection including its mechanisms in the hippocampus following transient forebrain ischemia in gerbils. Memory and learning following the ischemia was investigated by eight-arm radial maze and passive avoidance tests. Neuroprotection was examined by immunohistochemistry for neuronal nuclei-specific protein and Fluoro-Jade B histofluorescence staining. For mechanisms of the neuroprotection, alterations in copper, zinc-superoxide dismutase (SOD1), SOD2 as antioxidant enzymes, dihydroethidium and 4-hydroxy-2-nonenal as indicators for oxidative stress, and anti-inflammatory cytokines (interleukin (IL)-4 and IL-13) and pro-inflammatory cytokines (tumor necrosis factor α (TNF-α) and IL-2) were examined by Western blotting and/or immunohistochemistry. As a result, pretreatment with 30 mg/kg CGA attenuated cognitive impairment and displayed a neuroprotective effect against transient forebrain ischemia (TFI). In Western blotting, the expression levels of SOD2 and IL-4 were increased due to pretreatment with CGA and, furthermore, 4-HNE production and IL-4 expressions were inhibited by CGA pretreatment. Additionally, pretreated CGA enhanced antioxidant enzymes and anti-inflammatory cytokines and, in contrast, attenuated oxidative stress and pro-inflammatory cytokine expression. Based on these results, we suggest that CGA can be a useful neuroprotective material against ischemia-reperfusion injury due to its antioxidant and anti-inflammatory efficacies.

scholarly journals Pycnogenol® Supplementation Attenuates Memory Deficits and Protects Hippocampal CA1 Pyramidal Neurons via Antioxidative Role in a Gerbil Model of Transient Forebrain Ischemia

Nutrients ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2477
Author(s):  
Bora Kim ◽  
Tae-Kyeong Lee ◽  
Cheol Woo Park ◽  
Dae Won Kim ◽  
Ji Hyeon Ahn ◽  
...  
Keyword(s):  
Pyramidal Neurons ◽  
Neuroprotective Effect ◽  
Ischemic Injury ◽  
Pyramidal Cells ◽  
Acid Oxidation ◽  
Forebrain Ischemia ◽  
Transient Forebrain Ischemia ◽  
Ca1 Region ◽  
Pine Tree ◽  
Before And After

Pycnogenol® (an extract of the bark of French maritime pine tree) is used for dietary supplement and known to have excellent antioxidative efficacy. However, there are few reports on neuroprotective effect of Pycnogenol® supplementation and its mechanisms against ischemic injury following transient forebrain ischemia (TFI) in gerbils. Now, we examined neuroprotective effect and its mechanisms of Pycnogenol® in the gerbils with 5-min TFI, which evokes a significant death (loss) of pyramidal cells located in the cornu ammonis (CA1) region of gerbil hippocampus from 4–5 days post-TFI. Gerbils were pretreated with 30, 40, and 50 mg/kg of Pycnogenol® once a day for 7 days before TFI surgery. Treatment with 50 mg/kg, not 30 or 40 mg/kg, of Pycnogenol® potently protected learning and memory, as well as CA1 pyramidal cells, from ischemic injury. Treatment with 50 mg/kg Pycnogenol® significantly enhanced immunoreactivity of antioxidant enzymes (superoxide dismutases and catalase) in the pyramidal cells before and after TFI induction. Furthermore, the treatment significantly reduced the generation of superoxide anion, ribonucleic acid oxidation and lipid peroxidation in the pyramidal cells. Moreover, interestingly, its neuroprotective effect was abolished by administration of sodium azide (a potent inhibitor of SODs and catalase activities). Taken together, current results clearly indicate that Pycnogenol® supplementation can prevent neurons from ischemic stroke through its potent antioxidative role.

scholarly journals Neuroprotective Effect of Sodium Orthovanadate on Delayed Neuronal Death after Transient Forebrain Ischemia in Gerbil Hippocampus

2001 ◽  
Vol 21 (11) ◽  
pp. 1268-1280 ◽  
Author(s):  
Takayuki Kawano ◽  
Kohji Fukunaga ◽  
Yusuke Takeuchi ◽  
Motohiro Morioka ◽  
Shigetoshi Yano ◽  
...  
Keyword(s):  
Neuronal Death ◽  
Neuroprotective Effect ◽  
Delayed Neuronal Death ◽  
Intraventricular Injection ◽  
Mongolian Gerbils ◽  
Sodium Orthovanadate ◽  
Forebrain Ischemia ◽  
Neuroprotective Effects ◽  
Transient Forebrain Ischemia ◽  
Ca1 Region

In transient forebrain ischemia, sodium orthovanadate as well as insulinlike growth factor-1 (IGF-1) rescued cells from delayed neuronal death in the hippocampal CA1 region. Adult Mongolian gerbils were subjected to 5-minute forebrain ischemia. Immunoblotting analysis with anti–phospho-Akt/PKB (Akt) antibody showed that phosphorylation of Akt at serine-473 (Akt-Ser-473) in the CA1 region decreased immediately after reperfusion, and in turn transiently increased 6 hours after reperfusion. The decreased phosphorylation of Akt-Ser-473 was not observed in the CA3 region. The authors then tested effects of intraventricular injection of orthovanadate and IGF-1, which are known to activate Akt. Treatment with orthovanadate or IGF-1 30 minutes before ischemia blocked delayed neuronal death in the CA1 region. The neuroprotective effects of orthovanadate and IGF-1 were associated with preventing decreased Akt-Ser-473 phosphorylation in the CA1 region observed immediately after reperfusion. Immunohistochemical studies with the anti–phospho-Akt-Ser-473 antibody also demonstrated that Akt was predominantly in the nucleus and was moderately activated in the cell bodies and dendrites of pyramidal neurons after orthovanadate treatment. The orthovanadate treatment also prevented the decrease in phosphorylation of mitogen-activated protein kinase (MAPK). Pretreatment with combined blockade of phosphatidylinositol 3-kinase and MAPK pathways totally abolished the orthovanadate-induced neuroprotective effect. These results suggest that the activation of both Akt and MAPK activities underlie the neuroprotective effects of orthovanadate on the delayed neuronal death in the CA1 region after transient forebrain ischemia.

scholarly journals CX3CL1/CX3CR1-Mediated Microglia Activation Plays a Detrimental Role in Ischemic Mice Brain via p38MAPK/PKC Pathway

2015 ◽  
Vol 35 (10) ◽  
pp. 1623-1631 ◽  
Author(s):  
Yong Liu ◽  
Xiao-Mei Wu ◽  
Qian-Qian Luo ◽  
Suna Huang ◽  
Qing-Wu Qian Yang ◽  
...  
Keyword(s):  
White Matter ◽  
Protein Kinase ◽  
Inflammatory Cytokines ◽  
White Matter Lesions ◽  
Ischemic Injury ◽  
Microglia Activation ◽  
Tnf Α ◽  
Brain Ischemic Injury ◽  
Mice Brain

The exact roles of activated microglia and fractalkine (CX3CL1)/fractalkine receptor (CX3CR1) signaling are not fully understood in brain ischemic injury and the findings reported are controversial. Here, we investigated the effects of CX3CR1 siRNA on the expression of CX3CR1, p38 mitogen-activated protein kinase (p38MAPK), Protein Kinase C (PKC) and inflammatory cytokines, microglia activation, white matter lesions, and cognitive function in mice treated with bilateral common carotid artery stenosis (BCAS) in vivo as well as effects of exogenous CX3CL1, CX3CR1 siRNA, and SB2035080 on expression of inflammatory cytokines in BV2 microglia treated with oxygen–glucose deprivation (OGD) in vitro. We showed that CX3CR1 siRNA significantly inhibited the increased expression of CX3CR1, p38MAPK, PKC as well as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6, and also attenuated microglia activation, white matter lesions, and cognitive deficits induced by BCAS in mice brain. We also showed that exogenous CX3CL1 could induce a further enhancement in TNF-α and IL-1β expression, which could be suppressed by CX3CR1 siRNA or by the p38MAPK inhibitor in OGD-treated BV2 microglial cells in vitro. Our findings indicated that CX3CL1/CX3CR1-mediated microglial activation plays a detrimental role in ischemic brain via p38MAPK/PKC signaling and also suggested that CX3CL1/CX3CR1 axis might be a putative therapeutic target to disrupt the cascade of deleterious events that lead to brain ischemic injury.

Fisetin has Inhibitory Effects on the TLR 4/NF-κB-Mediated Inflammatory Pathway After Traumatic Brain Injury in Mice: A Potential Neuroprotective Role

2021 ◽  
Author(s):  
Chenhui Zhou ◽  
Sheng Nie ◽  
Zhepei Wang ◽  
Fanyong Gong ◽  
Jingmi Wu ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Brain Edema ◽  
Inflammatory Cytokines ◽  
Nuclear Factor Κb ◽  
Neuroprotective Effects ◽  
Inflammatory Pathway ◽  
Mortality And Morbidity ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

Abstract Inflammatory response contributes to the high mortality and morbidity of traumatic brain injury (TBI). Potent anti-inflammatory effects can alleviate brain injury after TBI. Fisetin has anti-inflammatory properties in several brain injury models, but the effects of fisetin on inflammation after TBI is still unclear. Our study aimed to investigate the neuroprotective effects of fisetin against inflammation after TBI in mice.Fisetin (25 mg/kg, 50 mg/kg or 75 mg/kg) or equal volume of vehicle was given via intraperitoneal injection 30 min after TBI. The neurological severity score, brain edema and blood brain barrier (BBB) permeability were assayed after TBI. In further mechanistic studies, changes in the toll-like receptor 4 (TLR 4)/nuclear factor-κB (NF-κB) pathway and the expression of pro-inflammatory cytokines were measured. Fisetin significantly improved behavioral outcomes and reduced brain edema after TBI. These changes were associated with significant reductions in TLR 4 expression and NF-κB activity. In addition, changes in the expression of pro-inflammatory cytokines were detected 24 h after TBI. Our study provided the first evidence that fisetin exerted neuroprotective effects by inhibiting the TLR 4/NF-κB–mediated inflammatory pathway after TBI in mice.

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