scholarly journals Substantiation for the Use of Curcumin during the Development of Neurodegeneration after Brain Ischemia

2020 ◽  
Vol 21 (2) ◽  
pp. 517 ◽  
Author(s):  
Marzena Ułamek-Kozioł ◽  
Stanisław J. Czuczwar ◽  
Sławomir Januszewski ◽  
Ryszard Pluta
Keyword(s):  
Brain Injury ◽  
Brain Ischemia ◽  
Clinical Symptoms ◽  
Therapeutic Potential ◽  
Ischemia Reperfusion ◽  
Misfolded Proteins ◽  
Comprehensive Overview ◽  
Ischemic Brain ◽  
Neuronal Membranes ◽  
Limited Effectiveness

Currently available pharmacological treatment of post-ischemia-reperfusion brain injury has limited effectiveness. This review provides an assessment of the current state of neurodegeneration treatment due to ischemia-reperfusion brain injury and focuses on the role of curcumin in the diet. The purpose of this review was to provide a comprehensive overview of what was published about the benefits of curcumin influence on post-ischemic brain damage. Some data on the clinical benefits of curcumin treatment of post-ischemic brain in terms of clinical symptoms and adverse reactions have been reviewed. The data in this review contributes to a better understanding of the potential benefits of curcumin in the treatment of neurodegenerative changes after ischemia and informs scientists, clinicians, and patients, as well as their families and caregivers about the possibilities of such treatment. Due to the pleotropic properties of curcumin, including anti-amyloid, anti-tau protein hyperphosphorylation, anti-inflammatory, anti-apoptotic, and neuroprotective action, as well as increasing neuronal lifespan and promoting neurogenesis, curcumin is a promising candidate for the treatment of post-ischemic neurodegeneration with misfolded proteins accumulation. In this way, it may gain interest as a potential therapy to prevent the development of neurodegenerative changes after cerebral ischemia. In addition, it is a safe substance and inexpensive, easily accessible, and can effectively penetrate the blood–brain barrier and neuronal membranes. In conclusion, the evidence available in a review of the literature on the therapeutic potential of curcumin provides helpful insight into the potential clinical utility of curcumin in the treatment of neurological neurodegenerative diseases with misfolded proteins. Therefore, curcumin may be a promising supplementary agent against development of neurodegeneration after brain ischemia in the future. Indeed, there is a rational scientific basis for the use of curcumin for the prophylaxis and treatment of post-ischemic neurodegeneration.

scholarly journals Brain Ischemia as a Prelude to Alzheimer's Disease

2021 ◽  
Vol 13 ◽  
Author(s):  
Ryszard Pluta ◽  
Sławomir Januszewski ◽  
Stanisław J. Czuczwar
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Injury ◽  
White Matter ◽  
Brain Ischemia ◽  
Tau Protein ◽  
Ischemia Reperfusion ◽  
Acute Stage ◽  
Ischemic Brain Injury ◽  
Ischemic Brain

Transient ischemic brain injury causes massive neuronal death in the hippocampus of both humans and animals. This was accompanied by progressive atrophy of the hippocampus, brain cortex, and white matter lesions. Furthermore, it has been noted that neurodegenerative processes after an episode of ischemia-reperfusion in the brain can continue well-beyond the acute stage. Rarefaction of white matter was significantly increased in animals at 2 years following ischemia. Some rats that survived 2 years after ischemia developed severe brain atrophy with dementia. The profile of post-ischemic brain neurodegeneration shares a commonality with neurodegeneration in Alzheimer's disease. Furthermore, post-ischemic brain injury is associated with the deposition of folding proteins, such as amyloid and tau protein, in the intracellular and extracellular space. Recent studies on post-ischemic brain neurodegeneration have revealed the dysregulation of Alzheimer's disease-associated genes such as amyloid protein precursor, α-secretase, β-secretase, presenilin 1, presenilin 2, and tau protein. The latest data demonstrate that Alzheimer's disease-related proteins and their genes play a key role in the development of post-ischemic brain neurodegeneration with full-blown dementia in disease types such as Alzheimer's. Ongoing interest in the study of brain ischemia has provided evidence showing that ischemia may be involved in the development of the genotype and phenotype of Alzheimer's disease, suggesting that brain ischemia can be considered as a useful model for understanding the mechanisms responsible for the initiation of Alzheimer's disease.

scholarly journals Influence of exercise training on ischemic brain injury in type 1 diabetic rats

2012 ◽  
Vol 113 (7) ◽  
pp. 1121-1127 ◽  
Author(s):  
Denise M. Arrick ◽  
Hong Sun ◽  
William G. Mayhan
Keyword(s):  
Brain Injury ◽  
Exercise Training ◽  
Vascular Function ◽  
Ischemia Reperfusion ◽  
Diabetic Rats ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Cerebrovascular Function ◽  
Pial Arterioles

While exercise training (ExT) appears to influence cerebrovascular function during type 1 diabetes (T1D), it is not clear whether this beneficial effect extends to protecting the brain from ischemia-induced brain injury. Thus our goal was to examine whether modest ExT could influence transient focal ischemia-induced brain injury along with nitric oxide synthase (NOS)-dependent dilation of cerebral (pial) arterioles during T1D. Sprague-Dawley rats were divided into four groups: nondiabetic sedentary, nondiabetic ExT, diabetic (streptozotocin; 50 mg/kg ip) sedentary, and diabetic ExT. In the first series of studies, we measured infarct volume in all groups of rats following right MCA occlusion for 2 h, followed by 24 h of reperfusion. In a second series of studies, a craniotomy was performed over the parietal cortex, and we measured responses of pial arterioles to an endothelial NOS (eNOS)-dependent, a neuronal NOS (nNOS)-dependent, and a NOS-independent agonist in all groups of rats. We found that sedentary diabetic rats had significantly larger total, cortical, and subcortical infarct volumes following ischemia-reperfusion than sedentary nondiabetic, nondiabetic ExT, and diabetic ExT rats. Infarct volumes were similar in sedentary nondiabetic, ExT nondiabetic, and ExT diabetic rats. In contrast, ExT did not alter infarct size in nondiabetic compared with sedentary nondiabetic rats. In addition, ExT diabetic rats had impaired eNOS- and nNOS-dependent, but not NOS-independent, vasodilation that was restored by ExT. Thus ExT of T1D rats lessened ischemic brain injury following middle cerebral artery occlusion and restored impaired eNOS- and nNOS-dependent vascular function. Since the incidence of ischemic stroke is increased during T1D, we suggest that our finding are significant in that modest ExT may be a viable preventative therapeutic approach to lessen ischemia-induced brain injury that may occur in T1D subjects.

scholarly journals AMP-Dependent Hypothermia Affords Protection from Ischemic Brain Injury

2012 ◽  
Vol 33 (2) ◽  
pp. 171-174 ◽  
Author(s):  
Mirko Muzzi ◽  
Francesco Blasi ◽  
Alberto Chiarugi
Keyword(s):  
Brain Injury ◽  
Brain Ischemia ◽  
Adenosine Monophosphate ◽  
Artery Occlusion ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Stroke Treatment ◽  
Adenosine A1 ◽  
A1 Receptor ◽  
Cerebral Artery Occlusion

In light of the relevance of therapeutic hypothermia to stroke treatment, we investigated whether 5′-adenosine monophosphate (AMP)-dependent cooling affords protection from ischemic brain injury. We show that hypothermia by AMP is because of adenosine A1 receptor (A1R) activation and is not invariantly associated with hypotension. Inhibition of ecto-5′-nucleotidase-dependent constitutive degradation of brain extracellular AMP by methylene-ADP (AMPCP) also suffices to prompt A1R-dependent hypothermia without hypotension. Both intraischemic and postischemic hypothermia by AMP or AMPCP reduce infarct volumes and mortality of mice subjected to transient middle cerebral artery occlusion. Data disclose that AMP-dependent hypothermia is of therapeutic relevance to treatment of brain ischemia.

The LPA-CDK5-Tau Pathway Mediates Neuronal Injury in an In Vitro Model of Ischemia-Reperfusion Insult

2021 ◽  
Author(s):  
Yaya Wang ◽  
Jie Zhang ◽  
Liqin Huang ◽  
Yanhong Mo ◽  
Changyu Wang ◽  
...  
Keyword(s):  
Brain Injury ◽  
Molecular Mechanisms ◽  
Biological Effects ◽  
Ischemia Reperfusion ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Ischemic Brain ◽  
Pathophysiological Process ◽  
Vitro Model

Abstract Lysophosphatidic acid (LPA) is a common glycerol phospholipid and an important extracellular signaling molecule. LPA binds to its receptors and mediates a variety of biological effects, including the pathophysiological process underlying ischemic brain damage and traumatic brain injury. However, the molecular mechanisms mediating the pathological role of LPA are not clear. Here, we found that LPA activates cyclin-dependent kinase 5 (CDK5). CDK5 phosphorylates tau, which leads to neuronal cell death. Inhibition of LPA production or blocking its receptors reduced the abnormal activation of CDK5 and phosphorylation of tau, thus reversing the death of neurons. Our data indicate that the LPA-CDK5-Tau pathway plays an important role in the pathophysiological process after ischemic stroke. Inhibiting the LPA pathway may be a potential therapeutic target for treating ischemic brain injury.

scholarly journals 5′-Adenosine Monophosphate-Induced Hypothermia Attenuates Brain Ischemia/Reperfusion Injury in a Rat Model by Inhibiting the Inflammatory Response

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Yi-Feng Miao ◽  
Hui Wu ◽  
Shao-Feng Yang ◽  
Jiong Dai ◽  
Yong-Ming Qiu ◽  
...  
Keyword(s):  
Brain Injury ◽  
Reperfusion Injury ◽  
Brain Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Neuronal Cells ◽  
Adenosine Monophosphate ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Induced Hypothermia

Hypothermia treatment is a promising therapeutic strategy for brain injury. We previously demonstrated that 5′-adenosine monophosphate (5′-AMP), a ribonucleic acid nucleotide, produces reversible deep hypothermia in rats when the ambient temperature is appropriately controlled. Thus, we hypothesized that 5′-AMP-induced hypothermia (AIH) may attenuate brain ischemia/reperfusion injury. Transient cerebral ischemia was induced by using the middle cerebral artery occlusion (MCAO) model in rats. Rats that underwent AIH treatment exhibited a significant reduction in neutrophil elastase infiltration into neuronal cells and matrix metalloproteinase 9 (MMP-9), interleukin-1 receptor (IL-1R), tumor necrosis factor receptor (TNFR), and Toll-like receptor (TLR) protein expression in the infarcted area compared to euthermic controls. AIH treatment also decreased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling- (TUNEL-) positive neuronal cells. The overall infarct volume was significantly smaller in AIH-treated rats, and neurological function was improved. By contrast, rats with ischemic brain injury that were administered 5′-AMP without inducing hypothermia had ischemia/reperfusion injuries similar to those in euthermic controls. Thus, the neuroprotective effects of AIH were primarily related to hypothermia.

scholarly journals The Many Faces of Post-Ischemic Tau Protein in Brain Neurodegeneration of the Alzheimer’s Disease Type

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2213
Author(s):  
Ryszard Pluta ◽  
Stanisław J. Czuczwar ◽  
Sławomir Januszewski ◽  
Mirosław Jabłoński
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Injury ◽  
Cerebral Ischemia ◽  
Tau Protein ◽  
Ischemia Reperfusion ◽  
Disease Type ◽  
Dependent Manner ◽  
Ischemic Brain ◽  
The Brain

Recent data suggest that post-ischemic brain neurodegeneration in humans and animals is associated with the modified tau protein in a manner typical of Alzheimer’s disease neuropathology. Pathological changes in the tau protein, at the gene and protein level due to cerebral ischemia, can lead to the development of Alzheimer’s disease-type neuropathology and dementia. Some studies have shown increased tau protein staining and gene expression in neurons following ischemia-reperfusion brain injury. Recent studies have found the tau protein to be associated with oxidative stress, apoptosis, autophagy, excitotoxicity, neuroinflammation, blood-brain barrier permeability, mitochondrial dysfunction, and impaired neuronal function. In this review, we discuss the interrelationship of these phenomena with post-ischemic changes in the tau protein in the brain. The tau protein may be at the intersection of many pathological mechanisms due to severe neuropathological changes in the brain following ischemia. The data indicate that an episode of cerebral ischemia activates the damage and death of neurons in the hippocampus in a tau protein-dependent manner, thus determining a novel and important mechanism for the survival and/or death of neuronal cells following ischemia. In this review, we update our understanding of proteomic and genomic changes in the tau protein in post-ischemic brain injury and present the relationship between the modified tau protein and post-ischemic neuropathology and present a positive correlation between the modified tau protein and a post-ischemic neuropathology that has characteristics of Alzheimer’s disease-type neurodegeneration.

scholarly journals Moderate low temperature protects the ischemic brain injury by activating SIRT1 through inhibition of FOXO1/PINK1/Parkin axis mediated mitophagy in a mouse

2020 ◽  
Author(s):  
Yaobin Zhu ◽  
Yaping Zhang ◽  
Nan Ding ◽  
Hanlu Yi ◽  
Xing Fan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Brain Injury ◽  
Low Temperature ◽  
Ischemia Reperfusion ◽  
Cerebral Injury ◽  
Brain Maturation ◽  
Ischemic Brain Injury ◽  
Biological Functions ◽  
Brain Protection ◽  
Ischemic Brain

Abstract Background: Several evidences suggested that the protective effect of hypothermia on brain injury is related to the inhibition of apoptosis and depends on the onset time of hypothermia and the degree of brain maturation. We performed many experiments aimed to comprehensively explore the biological functions of moderate low temperature protects the ischemic brain injury in a mouse and its underlying mechanism.Methods: 12 normal healthy C57BL6 mouse were selected, and moderate low temperature model mouse were selected. The biological functions of moderate low temperature protect the ischemic brain injury in a mouse and its underlying mechanism were performed to explore.Results: Based on our results, we found that moderate hypothermia brain protection could alleviate cerebral injury caused by ischemia reperfusion in mouse. Hypothermic brain protection reduced the level of oxidative stress induced by ischemia reperfusion in mouse. Meso-hypothermic cerebral protection could inhibit excessive mitochondrial autophagy induced by ischemia reperfusion in mouse. Medium-low temperature brain protection could activate SIRT1 and inhibit FOXO1/PINK1/Parkin pathway. Activation of SIRT1 in the hypoxia/reoxygenation model of hippocampal neurons could inhibit autophagy and oxidative stress by inhibiting the FOXO1/PINK1/Parkin pathway.Conclusions : Moderate low temperature protects the ischemic brain injury by activating SIRT1 through inhibition of FOXO1/PINK1/Parkin axis mediated mitophagy in a mouse.

TIGAR alleviates ischemia/reperfusion-induced autophagy and ischemic brain injury

2019 ◽  
Vol 137 ◽  
pp. 13-23 ◽  
Author(s):  
Ding-Mei Zhang ◽  
Tian Zhang ◽  
Ming-Ming Wang ◽  
Xin-Xin Wang ◽  
Yuan-Yuan Qin ◽  
...  
Keyword(s):  
Brain Injury ◽  
Ischemia Reperfusion ◽  
Ischemic Brain Injury ◽  
Ischemic Brain

Abstract TP264: MicroRNA-15a/16-1 Antagomir Ameliorates Ischemic Brain Injury in Experimental Stroke

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Xinxin Yang ◽  
Kai Liu ◽  
Jun Chen ◽  
Ke-Jie Yin
Keyword(s):  
Ischemic Stroke ◽  
Brain Injury ◽  
Therapeutic Potential ◽  
Specific Inhibitor ◽  
Inflammatory Factors ◽  
Experimental Stroke ◽  
Separate Experiment ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Mrna Targets

MicroRNAs (miRs) are small endogenous RNA molecules that repress gene translation by hybridizing to 3’-UTRs of mRNAs. Accumulating evidence has shown that miRs play a critical regulatory role in the pathogenesis of ischemic stroke. MiR-15a and miR-16-1 are two highly conserved miRs, which act similarly by binding to their common mRNA targets, thus forming both a structural and functional cluster. Dysregulated plasma levels of miR-15a/16-1 have been reported in stroke patients. Inhibition of miR-15a has been shown to protect against myocardial infarction and selected by pharmaceutical companies as one of the most attractive miR-based therapeutics. Up to now, the essential role and therapeutic potential of the miR-15a/16-1 cluster in ischemic stroke are poorly understood. In this study, adult male miR-15a/16-1 knockout and wildtype mice were subjected to 45 min of middle cerebral artery occlusion (MCAO) and 72h of reperfusion. In a separate experiment, miR-15a/16-1 specific inhibitor (antagomir, 30 pmol/g) was injected into tail vein of stroke mice and the animals were allowed to survive for 72h. The neurological scores, brain infarct volume, and edema content were then evaluated and analyzed. To explore the underlying mechanism, inflammatory factors were measured by qPCR or ELISA and anti-apoptotic proteins were examined by western blotting. We found that genetic deletion of miR-15a/16-1 or intravenous delivery of miR-15a/16-1 antagomir significantly reduced cerebral infarct size, decreased brain edema and improved neurological outcomes in stroke mice. Mechanistically, treatment of miR-15a/16-1 antagomir significantly ameliorated the expression of several key inflammatory factors and increased the Bcl-2 and Bcl-w levels in the ischemic brain regions. These results demonstrated that pharmacological inhibition of miR-15a/16-1 reduces ischemic brain injury via both anti-apoptotic and anti-inflammatory mechanisms and the miR-15a/16-1 cluster is a novel therapeutic target for ischemic stroke.

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