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

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.

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Increased Calbindin D28k Expression via Long-Term Alternate-Day Fasting Does Not Protect against Ischemia-Reperfusion Injury: A Focus on Delayed Neuronal Death, Gliosis and Immunoglobulin G Leakage

International Journal of Molecular Sciences ◽

10.3390/ijms22020644 ◽

2021 ◽

Vol 22 (2) ◽

pp. 644

Author(s):

Hyejin Sim ◽

Tae-Kyeong Lee ◽

Yeon Ho Yoo ◽

Ji Hyeon Ahn ◽

Dae Won Kim ◽

...

Keyword(s):

Immunoglobulin G ◽

Pyramidal Neurons ◽

Short Term Memory ◽

Forebrain Ischemia ◽

Short Term ◽

Term Memory ◽

Transient Forebrain Ischemia ◽

Ca1 Pyramidal Neurons ◽

Ca1 Region ◽

Calbindin D28k

Calbindin-D28k (CB), a calcium-binding protein, mediates diverse neuronal functions. In this study, adult gerbils were fed a normal diet (ND) or exposed to intermittent fasting (IF) for three months, and were randomly assigned to sham or ischemia operated groups. Ischemic injury was induced by transient forebrain ischemia for 5 min. Short-term memory was examined via passive avoidance test. CB expression was investigated in the Cornu Ammonis 1 (CA1) region of the hippocampus via western blot analysis and immunohistochemistry. Finally, histological analysis was used to assess neuroprotection and gliosis (microgliosis and astrogliosis) in the CA1 region. Short-term memory did not vary significantly between ischemic gerbils with IF and those exposed to ND. CB expression was increased significantly in the CA1 pyramidal neurons of ischemic gerbils with IF compared with that of gerbils fed ND. However, the CB expression was significantly decreased in ischemic gerbils with IF, similarly to that of ischemic gerbils exposed to ND. The CA1 pyramidal neurons were not protected from ischemic injury in both groups, and gliosis (astrogliosis and microgliosis) was gradually increased with time after ischemia. In addition, immunoglobulin G was leaked into the CA1 parenchyma from blood vessels and gradually increased with time after ischemic insult in both groups. Taken together, our study suggests that IF for three months increases CB expression in hippocampal CA1 pyramidal neurons; however, the CA1 pyramidal neurons are not protected from transient forebrain ischemia. This failure in neuroprotection may be attributed to disruption of the blood–brain barrier, which triggers gliosis after ischemic insults.

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Antioxidant-like protein 1 is altered in non-pyramidal cells and expressed in astrocytes in the gerbil hippocampal CA1 region after transient forebrain ischemia

Brain Research ◽

10.1016/j.brainres.2005.09.022 ◽

2005 ◽

Vol 1062 (1-2) ◽

pp. 111-119 ◽

Cited By ~ 4

Author(s):

In Koo Hwang ◽

Li Hua ◽

Ki-Yeon Yoo ◽

Dae Won Kim ◽

Tae-Cheon Kang ◽

...

Keyword(s):

Pyramidal Cells ◽

Forebrain Ischemia ◽

Transient Forebrain Ischemia ◽

Ca1 Region ◽

Hippocampal Ca1 Region ◽

Hippocampal Ca1

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

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/00004647-200111000-00003 ◽

2001 ◽

Vol 21 (11) ◽

pp. 1268-1280 ◽

Cited By ~ 73

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.

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Laminarin Pretreatment Provides Neuroprotection against Forebrain Ischemia/Reperfusion Injury by Reducing Oxidative Stress and Neuroinflammation in Aged Gerbils

Marine Drugs ◽

10.3390/md18040213 ◽

2020 ◽

Vol 18 (4) ◽

pp. 213 ◽

Cited By ~ 3

Author(s):

Joon Ha Park ◽

Ji Hyeon Ahn ◽

Tae-Kyeong Lee ◽

Cheol Woo Park ◽

Bora Kim ◽

...

Keyword(s):

Oxidative Stress ◽

Inflammatory Cytokines ◽

Pyramidal Neurons ◽

Ischemia Reperfusion Injury ◽

Neuroprotective Effect ◽

Ischemia Reperfusion ◽

Forebrain Ischemia ◽

Ca1 Pyramidal Neurons ◽

Before And After ◽

Anti Inflammatory

Laminarin is a polysaccharide isolated from brown algae that has various biological and pharmacological activities, such as antioxidant and anti-inflammatory properties. We recently reported that pretreated laminarin exerted neuroprotection against transient forebrain ischemia/reperfusion (IR) injury when we pretreated with 50 mg/kg of laminarin once a day for seven days in adult gerbils. However, there have been no studies regarding a neuroprotective effect of pretreated laminarin against IR injury in aged animals and its related mechanisms. Therefore, in this study, we intraperitoneally inject laminarin (50 mg/kg) once a day to aged gerbils for seven days before IR (5-min transient ischemia) surgery and examine the neuroprotective effect of laminarin treatment and the mechanisms in the gerbil hippocampus. IR injury in vehicle-treated gerbils causes loss (death) of pyramidal neurons in the hippocampal CA1 field at five days post-IR. Pretreatment with laminarin effectively protects the CA1 pyramidal neurons from IR injury. Regarding the laminarin-treated gerbils, production of superoxide anions, 4-hydroxy-2-nonenal expression and pro-inflammatory cytokines [interleukin(IL)-1β and tumor necrosis factor-α] expressions are significantly decreased in the CA1 pyramidal neurons after IR. Additionally, laminarin treatment significantly increases expressions of superoxide dismutase and anti-inflammatory cytokines (IL-4 and IL-13) in the CA1 pyramidal neurons before and after IR. Taken together, these findings indicate that laminarin can protect neurons from ischemic brain injury in an aged population by attenuating IR-induced oxidative stress and neuroinflammation.

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Persistent degenerative state of non-pyramidal neurons in the ca1 region of the gerbil hippocampus following transient forebrain ischemia

Neuroscience ◽

10.1016/0306-4522(93)90281-j ◽

1993 ◽

Vol 53 (1) ◽

pp. 23-38 ◽

Cited By ~ 34

Author(s):

T. Fukuda ◽

S. Nakano ◽

I. Yoshiya ◽

P.H. Hashimoto

Keyword(s):

Pyramidal Neurons ◽

Forebrain Ischemia ◽

Transient Forebrain Ischemia ◽

Ca1 Region

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Altered Expression of the Glutamate Transporter EAAC1 in Neurons and Immature Oligodendrocytes after Transient Forebrain Ischemia

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/00004647-200004000-00005 ◽

2000 ◽

Vol 20 (4) ◽

pp. 678-687 ◽

Cited By ~ 40

Author(s):

M. Gottlieb ◽

M. Domercq ◽

C. Matute

Keyword(s):

Cerebral Cortex ◽

Pyramidal Neurons ◽

Glutamate Uptake ◽

Glutamate Transporter ◽

Subcortical White Matter ◽

Moderate Increase ◽

Forebrain Ischemia ◽

Altered Expression ◽

Transient Forebrain Ischemia ◽

Ca1 Region

Glutamate uptake is reduced during ischemia because of perturbations of ionic gradients across neuronal and glial membranes. Using immunohistochemical and Western blot analyses, the authors examined the expression of the glutamate transporters EAAC1, GLAST, and GLT-1 in the rat hippocampus and cerebral cortex 8 hours and 1 to 28 days after transient forebrain ischemia. Densitometric analysis of immunoblots of CA1 homogenates showed a moderate increase in EAAC1 protein levels early after the insult. Consistently, it was observed that EAAC1 immunostaining in CA1 pyramidal neurons was more intense after 8 hours and 1 day of reperfusion and reduced at later postischemia stages. A similar transient increase of EAAC1 immunolabeling was detected in layer V pyramidal neurons of the cerebral cortex. In addition, the authors observed that EAAC1 also was located in oligodendroglial progenitor cells in subcortical white matter. The number of EAAC1-labeled cells in this region was increased after 3 and 28 days of reperfusion. Finally, changes in GLAST and GLT-1 expression were not observed in the CA1 region after ischemia using immunohistochemical study or immunoblotting. Enhanced expression of EAAC1 may be an adaptive response to increased levels of extracellular glutamate during ischemia.

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