scholarly journals Nrf2 Plays an Essential Role in Long-Term Brain Damage and Neuroprotection of Korean Red Ginseng in a Permanent Cerebral Ischemia Model

Antioxidants ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 273 ◽  
Author(s):  
Lei Liu ◽  
Marie G. Kelly ◽  
Erika L. Wierzbicki ◽  
Iana C. Escober-Nario ◽  
Mary K. Vollmer ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Infarct Volume ◽  
Regulatory Protein ◽  
Reactive Gliosis ◽  
Ischemic Damage ◽  
Red Ginseng ◽  
Korean Red Ginseng ◽  
Cerebral Ischemic ◽  
Cerebral Ischemic Damage

Cerebral ischemia is a devastating disease with a high incidence of death and disability; however, effective therapeutics remain limited. The transcriptional factor Nrf2 has been shown to play a pivotal role in the endogenous defense against brain oxidative stress and inflammation, and therefore represents a promising target for stroke intervention. However, the long-term effects of Nrf2 and the standardized Korean red ginseng (ginseng), a potent Nrf2 natural inducer, on permanent cerebral ischemic damage have not yet been reported. Wildtype (WT) and Nrf2-/- adult mice were pretreated with either vehicle or ginseng, and were subjected to permanent distal middle cerebral artery occlusion (pdMCAO). The infarct volume, the reactive astrocytes and microglia, and the water regulatory protein aquaporin 4 (AQP4) were examined at 28 days after stroke. When compared with the WT matched controls, the Nrf2 disruption significantly enlarged the infarct volume (40.4 ± 10.1%) and exacerbated the progression of reactive gliosis and AQP4 protein levels after pdMCAO. In contrast, ginseng significantly reduced the infarct volume and attenuated the reactive gliosis and AQP4 in the ischemic WT mice (47.3 ± 6.9%), but not in the Nrf2-/- mice (25.5 ± 5.6%). In conclusion, Nrf2 plays an important role in the long-term recovery of permanent cerebral ischemic damage and the neuroprotection of ginseng.

Abstract TP115: Nrf2 Plays an Essential Role in Long-Term Neuroprotection of Ginseng in Permanent Cerebral Ischemia

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Anna Skrobach ◽  
Lei Liu ◽  
Marie G Kelly ◽  
Erika L Wierzbicki ◽  
Iana C Escober-Nario ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Infarct Volume ◽  
Regulatory Protein ◽  
Reactive Gliosis ◽  
Ischemic Damage ◽  
Long Term Effects ◽  
Korean Red Ginseng ◽  
Cerebral Ischemic ◽  
Cerebral Ischemic Damage

Introduction: Cerebral ischemia is a devastating disease with a high incidence of death and disability; however, effective therapeutics remain limited. The transcriptional factor Nrf2 has been shown to play a pivotal role in the endogenous defense against brain oxidative stress and inflammation; therefore, it represents a promising target for stroke intervention. The natural potential Nrf2-inducer ginseng, extracted from the root of Panax ginseng C.A.Meyer, has been widely used in East Asia for thousands of years, exhibiting potent anti-inflammatory and antioxidative properties. However, the long-term effects of Nrf2 and the standardized Korean red ginseng extract (ginseng) on permanent cerebral ischemic damage have not yet been reported. Methods: Wildtype (WT) and Nrf2 –/– adult mice were treated with either vehicle (water) or ginseng for 7 days and subjected to the permanent distal middle cerebral artery occlusion (pdMCAO). The infarct volume, the reactive astrogliosis and microgliosis, and water regulatory protein aquaporin 4 (AQP4) were examined 28 days after the initiation of stroke. Data acquisition and analyses were performed by an observer blinded to the treatment. Results: When compared with the WT matched controls, the Nrf2 disruption significantly enlarged the infarct volume by 40.4±10.1% (n=7 per group; p<0.05), increased levels of reactive gliosis and AQP4 protein after pdMCAO. Interestingly, ginseng significantly reduced the infarct volume and attenuated the reactive gliosis and AQP4 in the ischemic WT mice (47.3±6.9%, n=12; p<0.01), but not in the Nrf2 -/- mice (25.5±5.6%, n=11; p=0.241). Conclusion: Nrf2 plays an important role in the long-term recovery of permanent cerebral ischemic damage and neuroprotection of ginseng.

scholarly journals Time Dependence of Effect of Nitric Oxide Synthase Inhibition on Cerebral Ischemic Damage

1995 ◽  
Vol 15 (4) ◽  
pp. 595-601 ◽  
Author(s):  
Fangyi Zhang ◽  
Sherry Xu ◽  
Costantino Iadecola
Keyword(s):  
Nitric Oxide ◽  
Cerebral Ischemia ◽  
Nitric Oxide Synthase ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Ischemic Damage ◽  
Nitric Oxide Synthesis ◽  
Cerebral Ischemic ◽  
Cerebral Ischemic Damage ◽  
Oxide Synthase

Nitric oxide, a potent vasodilator and an inhibitor of platelet aggregation, may be beneficial in the early stages of focal cerebral ischemia as it may facilitate collateral blood flow to the ischemic territory. Accordingly, the effect of inhibition of nitric oxide synthesis on cerebral ischemic damage may vary depending on the timing of the inhibition relative to the induction of ischemia. We therefore studied the time course of the effect of nitric oxide synthesis inhibition on focal cerebral ischemic damage. The middle cerebral artery was permanently occluded in spontaneously hypertensive rats and the nitric oxide synthase (NOS) inhibitor nitro-l-arginine methyl ester (l-NAME) was administered systemically (3 mg/kg) <5 min or 2, 3, or 6 h later. Arterial pressure, rectal temperature, plasma glucose, and hematocrit were monitored. Infarct volume was determined on thioninstained sections 24 h after induction of ischemia. NOS activity was determined in cerebellum from the conversion of l-[3H]arginine to l-[3H]citrulline. Administration of l-NAME <5 min after arterial occlusion increased the infarct volume by 23 ± 14% (mean ± SD; p < 0.05, analysis of variance), while administration of l-NAME at 2 or 6 h did not affect the size of the infarct (p > 0.05). l-NAME administration 3 h after induction of ischemia reduced neocortical infarct size by 14 ± 11% (p < 0.05). l-NAME decreased cerebellar NOS activity comparably in all groups (range 16–25%). We conclude that the effects of inhibition of nitric oxide synthesis on focal cerebral ischemic damage are time dependent. Thus, inhibition of nitric oxide synthesis worsens ischemic damage when instituted shortly after induction of ischemia and does not affect or reduces damage at later times. The results support the hypothesis that the vascular actions of nitric oxide are beneficial only in the early stages of permanent focal cerebral ischemia.

Cerebrolysin Reduces Infarct Volume in a Rat Model of Focal Cerebral Ischemic Damage

2009 ◽  
Vol 1 (1) ◽  
pp. 60-66 ◽  
Author(s):  
L. R. Hanson ◽  
X. F. Liu ◽  
T. M. Ross ◽  
E. Doppler ◽  
S. Zimmermann-Meinzingen ◽  
...  
Keyword(s):  
Rat Model ◽  
Infarct Volume ◽  
Ischemic Damage ◽  
Cerebral Ischemic ◽  
Cerebral Ischemic Damage

Exploring the Role of Remote Ischemic Preconditioning In Long Term Cognitive Impairment after Global Ischemia-Reperfusion-Induced Vascular Dementia in Mice

2020 ◽  
Author(s):  
Amteshwar Singh Jaggi
Keyword(s):  
Cognitive Impairment ◽  
Cerebral Ischemia ◽  
Vascular Dementia ◽  
Ischemic Preconditioning ◽  
Ischemia Reperfusion ◽  
Remote Ischemic Preconditioning ◽  
Global Cerebral Ischemia ◽  
Cerebral Ischemic ◽  
The Brain

Aim: The aim of the present study is to explore the neuroprotective effects of remote ischemic preconditioning in long term cognitive impairment after global cerebral ischemia induced-vascular dementia in mice. Material and methods: The mice were subjected to global cerebral ischemia by occluding the bilateral common carotid arteries for 12 minutes followed by the 24 hours of the reperfusion. The remote ischemic preconditioning stimulus was delivered in the form of 4 cycles of ischemia/reperfusion for 5 minutes each. The cerebral ischemic injury induced-long term cognitive impairment-related learning and memory alterations was assessed using morris water maze, the motor performances of the animals were evaluated using rota-rod test and neurological severity score. The cerebral infract size of the brain were quantified using triphenyltetrazolium chloride staining. Results: Global cerebral ischemia causes long term memory impairment, decreases motor performances and increases the brain infract size in animals. The delivery of remote ischemic preconditioning stimulus significantly abolished the long-term cognitive impairment and ameliorates the motor performances as well as cerebral infract size in brain. Conclusion: The remote ischemic preconditioning mediates neuro protection against global cerebral ischemic injury induced long-term cognitive impairment.

scholarly journals Curcumin Protects Neuron against Cerebral Ischemia-Induced Inflammation through Improving PPAR-Gamma Function

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Zun-Jing Liu ◽  
Wei Liu ◽  
Lei Liu ◽  
Cheng Xiao ◽  
Yu Wang ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Neuronal Damage ◽  
Infarct Volume ◽  
Critical Role ◽  
Ischemic Injury ◽  
Ppar Gamma ◽  
Neurological Deficits ◽  
Protective Effects ◽  
Cerebral Ischemic Injury ◽  
Cerebral Ischemic

Cerebral ischemia is the most common cerebrovascular disease worldwide. Recent studies have demonstrated that curcumin had beneficial effect to attenuate cerebral ischemic injury. However, it is unclear how curcumin protects against cerebral ischemic injury. In the present study, using rat middle cerebral artery occlusion model, we found that curcumin was a potent PPARγagonist in that it upregulated PPARγexpression and PPARγ-PPRE binding activity. Administration of curcumin markedly decreased the infarct volume, improved neurological deficits, and reduced neuronal damage of rats. In addition, curcumin suppressed neuroinflammatory response by decreasing inflammatory mediators, such as IL-1β, TNF-α, PGE2, NO, COX-2, and iNOS induced by cerebral ischemia of rats. Furthermore, curcumin suppressed IκB degradation that was caused by cerebral ischemia. The present data also showed that PPARγinteracted with NF-κB-p65 and thus inhibited NF-κB activation. All the above protective effects of curcumin on cerebral ischemic injury were markedly attenuated by GW9662, an inhibitor of PPARγ. Our results as described above suggested that PPARγinduced by curcumin may play a critical role in protecting against brain injury through suppression of inflammatory response. It also highlights the potential of curcumin as a therapeutic agent against cerebral ischemia.

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