scholarly journals DSIP-Like KND Peptide Reduces Brain Infarction in C57Bl/6 and Reduces Myocardial Infarction in SD Rats When Administered during Reperfusion

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 407
Author(s):  
Elena A. Tukhovskaya ◽  
Elvira R. Shaykhutdinova ◽  
Alina M. Ismailova ◽  
Gulsara A. Slashcheva ◽  
Igor A. Prudchenko ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Brain Infarction ◽  
Cerebral Stroke ◽  
Structural Analogue ◽  
Sd Rats ◽  
Infarction Volume ◽  
Reperfusion Period ◽  
The Brain

A structural analogue of the DSIP, peptide KND, previously showed higher detoxification efficacy upon administration of the cytotoxic drug cisplatin, compared to DSIP. DSIP and KND were investigated using the model of acute myocardial infarction in male SD rats and the model of acute focal stroke in C57Bl/6 mice. A significant decrease in the myocardial infarction area was registered in KND-treated animals relative to saline-treated control animals (19.1 ± 7.3% versus 42.1 ± 9.2%). The brain infarction volume was significantly lower in animals intranasally treated with KND compared to the control saline-treated animals (7.4 ± 3.5% versus 12.2 ± 5.6%). Injection of KND in the first minute of reperfusion in the models of myocardial infarction and cerebral stroke reduced infarction of these organs, indicating a pronounced cardioprotective and neuroprotective effect of KND and potentiality for the treatment of ischemia-reperfusion injuries after transient ischemic attacks on the heart and brain, when administered during the reperfusion period. A preliminary pilot study using the model of myocardial infarction with the administration of DSIP during occlusion, and the model of cerebral stroke with the administration of KND during occlusion, resulted in 100% mortality in animals. Thus, in the case of ischemia-reperfusion injuries of the myocardium and the brain, use of these peptides is only possible during reperfusion.

scholarly journals Neuroprotective Effect of Phosphocreatine on Focal Cerebral Ischemia-Reperfusion Injury

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Tiegang Li ◽  
Nana Wang ◽  
Min Zhao
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Focal Cerebral Ischemia ◽  
Protective Efficacy ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Creatine Phosphate ◽  
High Energy ◽  
Aquaporin 4 ◽  
Neurological Score ◽  
Infarction Volume

Phosphocreatine (PCr) is a natural compound, which can donate high-energy phosphate group to ADP to synthesize ATP, even in the absence of oxygen and glucose. At present, it is widely used in cardiac and renal ischemia-reperfusion (IR) disease. In this study, to examine the protective efficacy of PCr against cerebral IR, disodium creatine phosphate was injected intravenously into rats before focal cerebral IR. Intracranial pressure (ICP), neurological score, cerebral infarction volume, and apoptotic neurons were observed. Expression of caspase-3 and aquaporin-4 (AQP4) was analyzed. Compared with IR group, rats pretreated with PCr had better neurologic score, less infarction volume, fewer ultrastructural histopathologic changes, reduced apoptosis, and lower aquaporin-4 level. In conclusion, PCr is neuroprotective after transient focal cerebral IR injury. Such a protection might be associated with apoptosis regulating proteins.

Inhibitory Effect of Dauricine on Inflammatory Process Following Focal Cerebral Ischemia/Reperfusion in Rats

2007 ◽  
Vol 35 (03) ◽  
pp. 477-486 ◽  
Author(s):  
Xiao-Yan Yang ◽  
Shi-Qin Jiang ◽  
Li Zhang ◽  
Qiang-Ni Liu ◽  
Pei-Li Gong
Keyword(s):  
Inflammatory Process ◽  
Acute Inflammation ◽  
Focal Cerebral Ischemia ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Experimental Studies ◽  
Inhibitory Effect ◽  
Tnf Α ◽  
Underlying Mechanisms ◽  
The Brain

Our previous experimental studies showed that dauricine could protect the brain from ischemic damage, but the underlying mechanisms were unknown. In this study, we investigated the effect of dauricine on the changes of the inflammation process induced by ischemia/reperfusion (I/R). After I/R, the enzyme activity of MPO, the expression of ICAM-1 and the transcription of IL-1β and TNF-α mRNA were all significantly increased (p < 0.01). And after treatment with dauricine, they were all significantly reduced compared to the vehicle-treated I/R group (p < 0.05 or p < 0.01). These results suggest that dauricin attenuates the inflammation process induced by I/R. The neuroprotective effect of dauricine may partly due to the inhibition acute inflammation induced by I/R.

scholarly journals Delta Sleep-Inducing Peptide Recovers Motor Function in SD Rats after Focal Stroke

Molecules ◽  
2021 ◽  
Vol 26 (17) ◽  
pp. 5173
Author(s):  
Elena A. Tukhovskaya ◽  
Alina M. Ismailova ◽  
Elvira R. Shaykhutdinova ◽  
Gulsara A. Slashcheva ◽  
Igor A. Prudchenko ◽  
...  
Keyword(s):  
Motor Performance ◽  
Motor Coordination ◽  
Brain Infarction ◽  
Mutual Effect ◽  
Rotarod Test ◽  
Sd Rats ◽  
Infarction Volume ◽  
Delta Sleep ◽  
The Difference ◽  
Delta Sleep Inducing Peptide

Background and Objectives: Mutual effect of the preliminary and therapeutic intranasal treatment of SD rats with DSIP (8 days) on the outcome of focal stroke, induced with intraluminal middle cerebral occlusion (MCAO), was investigated. Materials and Methods: The groups were the following: MCAO + vehicle, MCAO + DSIP, and SHAM-operated. DSIP or vehicle was applied nasally 60 (±15) minutes prior to the occlusion and for 7 days after reperfusion at dose 120 µg/kg. The battery of behavioral tests was performed on 1, 3, 7, 14, and 21 days after MCAO. Motor coordination and balance and bilateral asymmetry were tested. At the end of the study, animals were euthanized, and their brains were perfused, serial cryoslices were made, and infarction volume in them was calculated. Results: Although brain infarction in DSIP-treated animals was smaller than in vehicle-treated animals, the difference was not significant. However, motor performance in the rotarod test significantly recovered in DSIP-treated animals. Conclusions: Intranasal administration of DSIP in the course of 8 days leads to accelerated recovery of motor functions.

scholarly journals Genome-Wide Transcription Analysis of Electroacupuncture Precondition-Induced Ischemic Tolerance on SD Rat With Ischemia–Reperfusion Injury

2021 ◽  
Vol 12 ◽  
Author(s):  
Shuping Fu ◽  
Meiling Yu ◽  
Houxi Xu ◽  
Qing Liu ◽  
Xiaoxiao Li ◽  
...  
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Brain Infarction ◽  
Ischemic Tolerance ◽  
Neurological Deficits ◽  
Transcription Analysis ◽  
Ischemic Brain ◽  
Rehabilitative Treatment ◽  
Genome Wide ◽  
Infarction Volume

Acupuncture promotes the recovery of neurological function by the overall improvement of ischemic brain injury. It is not only regarded as a rehabilitative treatment but also a pretreatment method for stroke. However, its mechanism has not been fully elucidated. In this study, rats were treated with electroacupuncture (EA) at Baihui (GV20) for 30 min/day for 6 days, ahead of conducting cerebral ischemia–reperfusion (I/R) injury. Infarction volume, Evans blue leakage, and neurological deficits were evaluated at 24 h after I/R injury. Then, the ipsilateral ischemic brain was isolated for RNA sequencing (RNA-Seq) to identify molecular consequences. The results showed that EA pretreatment decreased blood–brain barrier (BBB) permeability, reduced brain infarction volume, and improved neurological outcomes. EA pretreatment could upregulate expression of antivirus and immunity activity-associated genes (such as Ifit1, Ifit3, Irf7, and Oasla) and downregulate expression of matrix disruption-associated genes (Col24a1, Col11a1, Col27a1, etc.) in healthy rats. In addition, it could partially reverse or ameliorate genome-wide transcription changes of the ipsilateral ischemic brain. For the first time, this study provides insight into genomic network modulation of a healthy rat with EA treatment and a EA-preconditioned rat under subsequent I/R injury, which is helpful in explaining acupuncture precondition-induced ischemic tolerance of stroke. It also provides new strategies and targets for the prevention of ischemic stroke.

Abstract WP321: The Role of Neuronal Sirt1 in Ischemic Stroke: Regulation of the Metabolic Imbalance

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Ge Li ◽  
Xiu-Jun Ren ◽  
Su-In Cho ◽  
Wenliang Zhong ◽  
Yong-Joo Ahn ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Test Strip ◽  
Littermate Control ◽  
Knock Out ◽  
Injury Model ◽  
Infarction Volume ◽  
Metabolic Imbalance

Introduction: Sirt1 is a NAD+ dependent deacetylase that is known as an important metabolic regulator for type 2 diabetes melitus. To determine the role of Sirt1 in ischemic stroke-induced metabolic imbalance, we generated the neuronal specific Sirt1 knock-in (nSirt1 KI) and knock-out (Sirt1 KO) mice and examined its effect and mechanism. Methods: To determine the role of Sirt1 in ischemic stroke-induced impaired metabolic actions including insulin and glucose abnormality, we tested the pharmacological effects of Metformin and Sirtinol as Sirt1 activator and inhibitor. To determine the genetic role of neuronal Sirt1 in the brain, we generated the nSirt1 KI mice and Sirt1 KO. We used the Ischemia/Reperfusion (I/R: 1h middle cerebral artery occlusion (MCAO)/23h reperfusion) injury model to induce the abnormal metabolic changes. Infarction volume was measured by TTC staining and we determined neurological deficit score (NDS) at 23h after 1h MCAO. The level of glucose and insulin were measured by a drop of tail blood using test-strip and ELISA Kit before, during (every 10 minutes interval), and after MCAO. Results: Metformin reduced infarction volume and Sirtinol worsened the infarction volume via Sirt1 signaling pathway. Heterozygous Sirt1 KO (Sirt1 +/-) mice showed decreased relative cerebral blood flow (rCBF) and worsen infarction volume in ischemic areas, whereas nSirt1 KI mice exhibited increased rCBF, improved NDS, regulating abnormal blood glucose and insulin, and reduced infarction volume by 42% compare to that of littermate control in I/R injury model (n=7, p<0.05). Based on western blotting analysis of brain lysates in nSirt1 KI mice, the expression of Sirt1 was significantly increased. Glucose regulation by overexpression of Sirt1 and reduced infarction volume in nSirt1 KI mice were reversed by Sirtinol. Conclusion: These findings indicate that the important neuroprotective effect of neuronal cells is mediated by Sirt1 overexpression and suggest that upregulation of neuronal Sirt1 may be an important therapeutic target for ischemic stroke via regulating metabolic imbalance.

scholarly journals EARLY AND REMOTE RESPONSE OF HIF-1Α PROTEIN IN THE HIPPOCAMPUS FIELDS TO ISCHEMIA-REPERFUSION IN RATS WITH DIABETES MELLITUS

2021 ◽  
Vol 9 (1) ◽  
pp. 101-106
Author(s):  
O.M. Nika ◽  
O.V. Zaliavska ◽  
O.V. Kaushanska
Keyword(s):  
Diabetes Mellitus ◽  
Transcription Factor ◽  
Ischemia Reperfusion ◽  
Control Group ◽  
Experimental Conditions ◽  
Ischemic Reperfusion ◽  
Reperfusion Period ◽  
Ischemic Period ◽  
The Brain ◽  
Activity Indices

The role of the transcription factor Hif-1α in pathogenesis of hypoxic lesions and diabetes mellitus (DM) has been confirmed, though molecular mechanisms underlying dysfunctions of the factor in the association of DM with ischemic-reperfusion lesion of the brain remain unknown. Objective: the investigation of Hif-1α protein content in the neurons of the hippocampus fields of rats with experimental DM in the dynamics of ischemic-reperfusion lesion of the brain. The study was conducted on 60 6-month rats with DM simulated at the age of 2 months by means of a single administration of streptozotocin (60 mg/kg of the body weight) (Sigma, USA). Disorders of the cerebral circulation were simulated by means of occlusion of both carotid arteries for 20 minutes. The content of Hif1-α protein was determined by means of fluoroimmunoassay after 20-minute ischemia with one hour reperfusion, and on the 12th day of the post-ischemic period in the hippocampus fields: СА1, СА2, СА3, СА4. In rats without DM 20-minute ischemia with one hour reperfusion increases the content of Hif-1α protein in all the hippocampus fields. On the 12th day of ischemic-reperfusion period in СА2-СА4 hippocampus fields the values of certain examined activity indices of the transcription factor Hif-1α continue to increase, and in СА1 field they are normalized or come closer to the values of animals from the control group. In rats with DM at the early post-ischemic period changes of Hif-1α protein content are lacking in СА1 field, the signs of its reduced activity are found in СА2 field, in СА3 field they are limited by the response of one index, and in СА4 field they are similar to those of the control rats under the experimental conditions. On the 12th day of ischemic-reperfusion period all the activity indices of the transcription factor Hif-1α increase in СА1 filed. They are higher than the corresponding indices in animals from the control group by absolute values under similar experimental conditions; changes of the examined parameters are limited in СА2 and СА3 fields in comparison with those from the control group; the parameters, which increased in the control group of animals, decreased in СА4 field. DM restricts Hif-1α protein response to ischemia-reperfusion in the neurons of СА1-СА3 field at the early ischemic-reperfusion period and in the neurons of СА2-СА4 fields — on the 12th day of the observation.

Betaine Ameliorates Brain Damage in a Rat Model of Ischemia/Reperfusion Injury

2022 ◽  
Author(s):  
Qian Li ◽  
Mingwei Qu ◽  
Ningning Wang ◽  
Limin Wang ◽  
Guimei Fan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ischemia Reperfusion Injury ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Methionine Sulfoxide ◽  
The Elderly ◽  
Artery Occlusion ◽  
Oxidative Enzymes ◽  
The Brain

Brain ischemia and reperfusion (I/R) injury may lead to a poor prognosis for ischemic stroke, which could be alleviated by anti-oxidants with diminished oxidative stress. Betaine is a natural nutrient found in beetroot and seafood to improve cognitive performance in the elderly. The present study investigated whether betaine could protect the brain from I/R injury. Results showed that betaine treatment could reduce H2O2-induced cell death in the PC12 cell line. Pretreatment with betaine reduced the brain infarct volume and neuronal apoptosis in a rat I/R injury model induced by two-hour middle cerebral artery occlusion (MCAO). Biochemical analyses indicated that betaine treatment decreased pro-inflammatory cytokine production and reduced oxidative stress after I/R injury. Betaine increased the expression of anti-oxidative enzymes, such as glutathione peroxidase 4 (Gpx4) and superoxide dismutase 1 (Sod1), and anti-oxidative non-enzymatic genes, such as 3-mercaptopyruvate sulfurtransferase (Mpst), methionine sulfoxide reductases b1 (Msrb1), and Msrb2. These data suggest that betaine exerts a neuroprotective effect in I/R injury through enzymatic and non-enzymatic anti-oxidative systems and anti-inflammatory mechanisms.

Scutellaria baicalensis Extract-Phospholipid Complex: Preparation and Initial Pharmacodynamics Research in Rats

2021 ◽  
Vol 22 ◽  
Author(s):  
Shibin Chen ◽  
Qiujie Xie ◽  
Ming Yang ◽  
Yajun Shi ◽  
Junhui Shi ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Scutellaria Baicalensis ◽  
Phospholipid Complex ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion Injury ◽  
The Brain

Background: Baicalin, a flavonoid glycoside compound present in Scutellaria baicalensis, has shown a wide spectrum of biological activities, but its liposolubility, water-solubility and mucosal permeability are all very poor, which lead to the low concentration in brain and poor bioavailability by oral or intravenous injective administration. Objective: The primary objective of this study was to formulate the Scutellaria baicalensis extract (SBE) with phospholipid to yield Scutellaria baicalensis extract-phospholipid complex (SBEPC) and to screen the appropriate administration and dose of SBEPC through the pharmacodynamics experiment. Methods: The optimal preparation process of SBEPC was obtained through single-factor test and central composite design-response surface methodology (CCD-RSM), and was characterized with various analytical techniques including SEM, FT-IR and NMR. The storage conditions of SBEPC were established through stability study and the middle cerebral artery occlusion (MCAO) rat model was investigated through conducting pharmacodynamic studies to screen the appropriate administration and dose of SBEPC as well as to verify the neuroprotective effect of SBEPC on cerebral ischemia-reperfusion injury. Results: The optimized preparation conditions of SBEPC were summarized as follows: the ratio of phospholipids to drug was 2:1, the drug concentration was 3.5 mg/ml, the reaction temperature was 50 °C, the entrapment efficiency was over 93.00%. Stability studies have demonstrated that SBEPC should be stored under 40 °C in a dry and ventilated place away from light and below 37% humidity. Furthermore, pharmacodynamic studies have found that, compared with SBE, SBEPC could introduce drugs into the brain and better exert the neuroprotective effect on MCAO rats, and the optimal administration and dose concentration of SBEPC were nasal administration and 40 mg/ml, respectively. Conclusion: These findings demonstrate that SBEPC was successfully prepared by CCD-RSM. SBEPC can enhance the ability of drugs entering the brain and improve the bioavailability of drugs in brain, and can effectively exert the neuroprotective effect on cerebral ischemia-reperfusion injury as compared with SBE.

scholarly journals Ischemic stroke and myocardial infarction: promising therapeutic goals for protecting the brain and heart

2018 ◽  
pp. 26-32
Author(s):  
N. Svyrydova
Keyword(s):  
Oxidative Stress ◽  
Myocardial Infarction ◽  
Treatment Effectiveness ◽  
Inflammatory Diseases ◽  
Neuroprotective Effect ◽  
Integrated Treatment ◽  
Antioxidant Therapy ◽  
Therapeutic Goals ◽  
Irreversible Effects ◽  
The Brain

During the last decade of medical practice, the issue of integrated treatment of ischemic heart and brain damage is actively discussed, therefore the attention of scientists is increasingly of interest in the creation of potentially new models of treatment in the acute period of illness. Many researchers today actively pursue various pharmacological modulations with a complex of pathogenetically validated effects of various isoforms that are involved in the development of stroke, myocardial infarction, diabetes mellitus, atherosclerosis, Alzheimer's disease, Parkinson's disease, tumor growth, inflammatory diseases, heart failure and hypertrophy of the myocardium. In recent years, progress in treatment tactics has been achieved in studies that affect oxidative stress, which leads to irreversible effects of damage to the gray and white matter of the brain, which entails swelling and massive cell death, and therefore justifies the use of antioxidant therapy. The concept of the use of antioxidants in the early stages of the disease demonstrates promising direction and requires further study in various pathological conditions, since the potential for treatment effectiveness is quite high. The use of antioxidant therapy aimed at preventing or reducing oxidative stress has become widely used in the field of prevention and treatment of acute and chronic conditions, where the use of drugs with a pliotropic effect is of strategic importance. To study the evaluation of the neuroprotective effect of ethyl methylhydroxypyridine succinate recently, cytological studies of the effect of glutamate stress on cerebellum cells have been performed and it has been shown that the drug affects the increase in neuronal survival (p <0.05), where the focus is on pharmacotherapy of the combination of neuroprotective treatment of cerebrovascular pathology.

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