Towards a dynamical network view of brain ischemia and reperfusion. Part I: background and preliminaries

DeGracia, Donald J.

doi:10.4172/1939-067x.1000121

Cited by 3 publications

(4 citation statements)

References 31 publications

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“…Current basic and clinical data do not confirm this assumption, and for this reason, the subtractive suppressive strategy for neuroprotection therapies has failed. This failure occurs because the interference between DM and EDA has not been properly considered but not because the key cell death pathway has not yet been discovered [11]. Even from empirical molecular pathways models, we know that it is impossible to interfere with the DM without influencing EDA.…”

Section: Damage Mechanism and Endogenous Defence Activitymentioning

confidence: 99%

Towards a roadmap in brain protection and recovery

Mureșanu

Buzoianu

Florian

et al. 2012

J Cellular Molecular Medi

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This article briefly reviews some of the mechanisms involved in the pathogenesis of neurological diseases, i.e. damage mechanisms (DM), and their interactions and overlap with protection and reparatory processes (i.e. endogenous defence activities). A relationship between DM and endogenous defence activity (EDA) regarding therapy principles will also be described. Currently, it is difficult to find the correct therapeutic approach for brain protection and recovery, especially because we do not fully understand all of the endogenous neurobiological processes, the complete nature of the pathophysiological mechanisms and the links between these two categories. Moreover, we continue to use a simplistic and reductionist approach in this respect. Endogenous neurobiological processes, such as neurotrophicity, neuroprotection, neuroplasticity and neurogenesis, are central to protection and recovery and represent the background of EDA. The biological reality of the nervous system is far more complex. In fact, there is an endogenous holistic process of neuroprotection and neurorecovery that should be approached therapeutically in an integrated way. The current tendency to exclusively frame drug activity in terms of single mechanisms and single focus effect might distract from other paradigms with greater explanatory power and hinder the development of more effective treatment strategies. A change of concept is required in pharmacological brain protection and recovery. Prospective considerations include an integrated pharmacological approach, focusing on drugs with multimodal activity and pleiotropic neuroprotective effect which are biological drugs, rather than single mechanism drugs, which usually are chemical drugs.

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Section: Damage Mechanism and Endogenous Defence Activitymentioning

confidence: 99%

Towards a roadmap in brain protection and recovery

Mureșanu

Buzoianu

Florian

et al. 2012

J Cellular Molecular Medi

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“…It is increasingly understood that an excessive inflammatory response and oxidative stress are closely related to the patho-genesis of cerebral ischemia-reperfusion (I/R) injury [3]. One of the early and most important components of cerebral I/R is reactive oxygen species-(ROS-) induced tissue damage [4]. Due to the complex structure of the brain, its relatively low antioxidant capacity, its high oxidative metabolism activity, insufficient cell repair activity of neurons, and high polyunsaturated fatty acid (PUFA) content, the brain is extremely susceptible to oxidative stress-induced damage [5].…”

Section: Introductionmentioning

confidence: 99%

Metformin Protects against Oxidative Stress Injury Induced by Ischemia/Reperfusion via Regulation of the lncRNA-H19/miR-148a-3p/Rock2 Axis

Zeng

Zhu

Liu

et al. 2019

Oxidative Medicine and Cellular Longevity

109

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Previous studies have shown that metformin not only is a hypoglycemic agent but also has neuroprotective effects. However, the mechanism of action of metformin in ischemic stroke is unclear. Oxidative stress is an important factor in the pathogenesis of cerebral ischemia-reperfusion injury. It has been reported that metformin is associated with stroke risk in the clinical population. This study is aimed at investigating the effect and mechanism of metformin in an experimental model of oxidative stress induced by ischemia/reperfusion (I/R) in vivo and oxygen glucose deprivation/reperfusion (OGD/R) in vitro. Metformin (100, 200, and 300 mg/kg) was administered intraperitoneally immediately after induction of cerebral ischemia. The indicators of oxidative stress selected were antioxidant enzyme activities of catalase, malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), and glutathione peroxidation enzyme (GSHPx). First, we demonstrated that metformin can significantly alleviate acute and chronic cerebral I/R injury and it has a strong regulatory effect on stroke-induced oxidative stress. It can reduce the elevated activities of MDA and NO and increase the levels of GSHPx and SOD in the cerebrum of mice and N2a cells exposed to I/R. Furthermore, real-time PCR and western blot were used to detect the expression of long noncoding RNA H19 (lncRNA-H19), microRNA-148a-3p (miR-148a-3p), and Rho-associated protein kinase 2 (Rock2). The direct interaction of lncRNA-H19, miR-148a-3p, and Rock2 was tested using a dual luciferase reporter assay. lncRNA-H19 altered OGD/R-induced oxidative stress by modulating miR-148a-3p to increase Rock2 expression. The expression of lncRNA-H19 and Rock2 could be downregulated with metformin in vivo and in vitro. In conclusion, our study confirmed that metformin exerts neuroprotective effects by regulating ischemic stroke-induced oxidative stress injury via the lncRNA-H19/miR-148a-3p/Rock2 axis. These results provide new evidence that metformin may represent a potential treatment for stroke-related brain injury.

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“…(DeGracia 2010a;DeGracia 2010b;DeGracia 2010c;DeGracia 2010d) The complexity of this model may be so advanced that few may appreciate the details yet this conceptual approach is truly innovative, providing a great example of what may be currently lacking in the field. The author takes an introspective viewpoint on the chronicle of colossal efforts that have aimed to extend effective therapies for acute ischemic stroke.…”

Section: Letters To the Editormentioning

confidence: 99%

“…In sum, stroke imaging holds the potential to test the innovative concepts advanced in these articles. (DeGracia 2010a;DeGracia 2010b;DeGracia 2010c;DeGracia 2010d) The complexity of cerebral ischemia will undoubtedly require use of complex models and detailed imaging approaches to disclose potential breakthroughs. The articles are solely the first steps in re-examining…”

Section: Letters To the Editormentioning

confidence: 99%

Complex models for the complexity of cerebral ischemia

Liebeskind¹

2010

J Exp Stroke Transl Med

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Towards a dynamical network view of brain ischemia and reperfusion. Part I: background and preliminaries

Cited by 3 publications

References 31 publications

Towards a roadmap in brain protection and recovery

Towards a roadmap in brain protection and recovery

Metformin Protects against Oxidative Stress Injury Induced by Ischemia/Reperfusion via Regulation of the lncRNA-H19/miR-148a-3p/Rock2 Axis

Complex models for the complexity of cerebral ischemia

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