المؤلفون: Huang, Dou, Chen, Changwei, Zuo, Yunxia, Du, Lei, Liu, Ting, Abbott, Geoffrey W, Hu, Zhaoyang

المصدر: PLOS ONE. 17(5)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Digestive Diseases, Lung, Liver Disease, Diabetes, Aetiology, Development of treatments and therapeutic interventions, 2.1 Biological and endogenous factors, 5.1 Pharmaceuticals, Metabolic and endocrine, Animals, Diabetes Mellitus, Experimental, Ischemic Postconditioning, Ischemic Preconditioning, Liver, Lung Injury, Male, Rats, Rats, Sprague-Dawley, Reperfusion Injury, General Science & Technology

الوصف: Pulmonary ischemia and reperfusion (I/R) injury occurs in many clinical conditions and causes severe damage to the lungs. Diabetes mellitus (DM) predisposes to pulmonary I/R injury. We previously found that remote liver ischemia preconditioning protected lungs against pulmonary I/R injury. The aim of the present study was to investigate whether remote liver ischemic postconditioning (RLIPost) attenuates pulmonary damage induced by I/R injury in non-diabetic or diabetic rats. Male Sprague-Dawley rats were assigned into non-diabetic and diabetic groups. All rats except for the sham were exposed to 45 min of left hilum occlusion followed by 2 h of reperfusion. RLIPost was conducted at the onset of pulmonary reperfusion by four cycles of 5 min of liver ischemia and reperfusion. Lung injury was assessed by the wet/dry weight ratio, pulmonary oxygenation, histopathological changes, apoptosis and the expression of inflammatory cytokines. Reperfusion-associated protein phosphorylation states were determined. RLIPost offered strong pulmonary-protection in both non-diabetic and diabetic rats, as reflected in reduced water content and pulmonary structural damage, recovery of lung function, inhibition of apoptosis and inflammation after ischemia-reperfusion. RLIPost induced the activation of pulmonary STAT-3, a key component in the SAFE pathway, but not activation of the proteins in the RISK pathway, in non-diabetic rats. In contrast, RLIPost-induced pulmonary protection in diabetic lungs was independent of SAFE or RISK pathway activation. These results demonstrate that RLIPost exerts pulmonary protection against I/R-induced lung injury in non-diabetic and diabetic rats. The underlying mechanism for protection may be different in non-diabetic (STAT-3 dependent) versus diabetic (STAT-3 independent) rats.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/1p05x989Test

المؤلفون: Hamed, MO, Barlow, AD, Dolezalova, N, Khosla, S, Sagar, A, Gribble, FM, Davies, S, Murphy, MP, Hosgood, SA, Nicholson, ML, Saeb-Parsy, K

مصطلحات موضوعية: Animals, Intestine, Small, Ischemic Postconditioning, Ischemic Preconditioning, Male, Organ Preservation, Perfusion, Swine

الوصف: BACKGROUND: There is an unmet need for suitable ex vivo large animal models in experimental gastroenterology and intestinal transplantation. This study details a reliable and effective technique for ex vivo normothermic perfusion (EVNP) of segmental porcine small intestine. METHODS: Segments of small intestine, 1.5-3.0 m in length, were retrieved from terminally anaesthetized pigs. After a period of cold ischaemia, EVNP was performed for 2 h at 37°C with a mean pressure of 80 mmHg using oxygenated autologous blood diluted with Ringer's solution. The duration of EVNP was extended to 4 h for a second set of experiments in which two segments of proximal to mid-ileum (1.5-3.0 m) were retrieved from each animal and reperfused with whole blood (control) or leucocyte-depleted blood to examine the impact of leucocyte depletion on reperfusion injury. RESULTS: After a mean cold ischaemia time of 5 h and 20 min, EVNP was performed in an initial group of four pigs. In the second set of experiments, five pigs were used in each group. In all experiments bowel segments were well perfused and exhibited peristalsis during EVNP. Venous glucose levels significantly increased following luminal glucose stimulation (mean(s.e.m.) basal level 1.8(0.6) mmol/l versus peak 15.5(5.8) mmol/l; P < 0.001) and glucagon-like peptide 1 (GLP-1) levels increased in all experiments, demonstrating intact absorptive and secretory intestinal functions. There were no significant differences between control and leucocyte-depleted animals regarding blood flow, venous glucose, GLP-1 levels or histopathology at the end of 4 h of EVNP. CONCLUSIONS: This novel model is suitable for the investigation of gastrointestinal physiology, pathology and ischaemia reperfusion injury, along with evaluation of potential therapeutic interventions.

وصف الملف: Print; application/pdf

العلاقة: https://www.repository.cam.ac.uk/handle/1810/321625Test

الإتاحة: https://doi.org/10.17863/CAM.68743Test
https://www.repository.cam.ac.uk/handle/1810/321625Test

المؤلفون: Basalay, Maryna V., Wiart, Marlene, Chauveau, Fabien, Dumot, Chloe, Leon, Christelle, Amaz, Camille, Bolbos, Radu, Cash, Diana, Kim, Eugene, Mechtouff, Laura, Cho, Tae Hee, Nighoghossian, Norbert, Davidson, Sean M., Ovize, Michel, Yellon, Derek M.

المصدر: Basalay , M V , Wiart , M , Chauveau , F , Dumot , C , Leon , C , Amaz , C , Bolbos , R , Cash , D , Kim , E , Mechtouff , L , Cho , T H , Nighoghossian , N , Davidson , S M , Ovize , M & Yellon , D M 2020 , ' Neuroprotection by remote ischemic conditioning in the setting of acute ischemic stroke : a preclinical two-centre study ' , Scientific Reports , vol. 10 , no. 1 , 16874 . https://doi.org/10.1038/s41598-020-74046-4Test

مصطلحات موضوعية: Animals, Disease Models, Animal, Ischemic Postconditioning/methods, Ischemic Preconditioning/methods, Ischemic Stroke/therapy, Male, Neuroprotection, Rats, Sprague-Dawley, Recovery of Function, Safety, Treatment Outcome

الوصف: Reperfusion is the only existing strategy for patients with acute ischemic stroke, however it causes further brain damage itself. A feasible therapy targeting reperfusion injury is remote ischemic conditioning (RIC). This was a two-centre, randomized, blinded international study, using translational imaging endpoints, aimed to examine the neuroprotective effects of RIC in ischemic stroke model. 80 male rats underwent 90-min middle cerebral artery occlusion. RIC consisted of 4 × 5 min cycles of left hind limb ischemia. The primary endpoint was infarct size measured on T2-weighted MRI at 24 h, expressed as percentage of the area-at-risk. Secondary endpoints were: hemispheric space-modifying edema, infarct growth between per-occlusion and 24 h MRI, neurofunctional outcome measured by neuroscores. 47 rats were included in the analysis after applying pre-defined inclusion criteria. RIC significantly reduced infarct size (median, interquartile range: 19% [8%; 32%] vs control: 40% [17%; 59%], p = 0.028). This effect was still significant after adjustment for apparent diffusion coefficient lesion size in multivariate analysis. RIC also improved neuroscores (6 [3; 8] vs control: 9 [7; 11], p = 0.032). Other secondary endpoints were not statistically different between groups. We conclude that RIC in the setting of acute ischemic stroke in rats is safe, reduces infarct size and improves functional recovery.

الإتاحة: https://doi.org/10.1038/s41598-020-74046-4Test
https://kclpure.kcl.ac.uk/portal/en/publications/d31797e3-c99e-4813-9082-f7821c43ebd8Test
http://www.scopus.com/inward/record.url?scp=85092292281&partnerID=8YFLogxKTest

المؤلفون: Hui-Sheng, Chen, Yu, Cui, Xiao-Qiu, Li, Xin-Hong, Wang, Yu-Tong, Ma, Yong, Zhao, Jing, Han, Chang-Qing, Deng, Mei, Hong, Ying, Bao, Li-Hong, Zhao, Ting-Guang, Yan, Ren-Lin, Zou, Hui, Wang, Zhuo, Li, Li-Shu, Wan, Li, Zhang, Lian-Qiang, Wang, Li-Yan, Guo, Ming-Nan, Li, Dong-Qing, Wang, Qiang, Zhang, Da-Wei, Chang, Hong-Li, Zhang, Jing, Sun, Chong, Meng, Zai-Hui, Zhang, Li-Ying, Shen, Li, Ma, Gui-Chun, Wang, Run-Hui, Li, Ling, Zhang, Cheng, Bi, Li-Yun, Wang, Duo-Lao, Wang, Juan, Feng

المصدر: JAMA

مصطلحات موضوعية: Male, China, General Medicine, Recovery of Function, Middle Aged, Article, Upper Extremity, Treatment Outcome, Humans, Female, Nervous System Diseases, Ischemic Postconditioning, Aged, Ischemic Stroke

الوصف: Preclinical and clinical studies have suggested a neuroprotective effect of remote ischemic conditioning (RIC), which involves repeated occlusion/release cycles on bilateral upper limb arteries; however, robust evidence in patients with ischemic stroke is lacking.To assess the efficacy of RIC for acute moderate ischemic stroke.This multicenter, open-label, blinded-end point, randomized clinical trial including 1893 patients with acute moderate ischemic stroke was conducted at 55 hospitals in China from December 26, 2018, through January 19, 2021, and the date of final follow-up was April 19, 2021.Eligible patients were randomly assigned within 48 hours after symptom onset to receive treatment with RIC (using a pneumatic electronic device and consisting of 5 cycles of cuff inflation for 5 minutes and deflation for 5 minutes to the bilateral upper limbs to 200 mm Hg) for 10 to 14 days as an adjunct to guideline-based treatment (n = 922) or guideline-based treatment alone (n = 971).The primary end point was excellent functional outcome at 90 days, defined as a modified Rankin Scale score of 0 to 1. All end points had blinded assessment and were analyzed on a full analysis set.Among 1893 eligible patients with acute moderate ischemic stroke who were randomized (mean [SD] age, 65 [10.3] years; 606 women [34.1%]), 1776 (93.8%) completed the trial. The number with excellent functional outcome at 90 days was 582 (67.4%) in the RIC group and 566 (62.0%) in the control group (risk difference, 5.4% [95% CI, 1.0%-9.9%]; odds ratio, 1.27 [95% CI, 1.05-1.54]; P = .02). The proportion of patients with any adverse events was 6.8% (59/863) in the RIC group and 5.6% (51/913) in the control group.Among adults with acute moderate ischemic stroke, treatment with remote ischemic conditioning compared with usual care significantly increased the likelihood of excellent neurologic function at 90 days. However, these findings require replication in another trial before concluding efficacy for this intervention.ClinicalTrials.gov Identifier: NCT03740971.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2399207d9f2e5419af1b5da42eee94d9Test
https://pubmed.ncbi.nlm.nih.gov/35972503Test

المؤلفون: Marte Wennemo, Mikhail Gordeev, Øyvind Jakobsen, Mikhail Galagudza, Kathrine Nergaard Aas, Cathrine Brunborg, Paweł Czub, Adam Arendarczyk, Mari-Liis Kaljusto, Torvind Næsheim, Jarle Vaage, Andrey Bautin, Lyudmila Karpova, Radosław Wilimski, Svein Aslak Landsverk

المصدر: European Journal of Cardio-Thoracic Surgery. 61:1144-1152

مصطلحات موضوعية: Adult, Male, Pulmonary and Respiratory Medicine, Cardiac function curve, Cardiac output, Mean arterial pressure, medicine.medical_specialty, Cardiac index, Aortic valve replacement, Internal medicine, medicine, Creatine Kinase, MB Form, Humans, Prospective Studies, Ischemic Postconditioning, Heart Valve Prosthesis Implantation, Troponin T, business.industry, Atrial fibrillation, General Medicine, medicine.disease, Treatment Outcome, Aortic Valve, Ventricular fibrillation, Heart Arrest, Induced, Cardiology, Female, Surgery, Cardiology and Cardiovascular Medicine, business

الوصف: OBJECTIVES The effect of ischaemic postconditioning (IPost) on postcardioplegic cardiac function is not known. We hypothesized that IPost was cardioprotective in adult patients undergoing elective aortic valve replacement. METHODS In a multicentre, prospective, randomized trial, patients (n = 209) were randomized to either a standard operation (controls) or postconditioning. Immediately before the cross-clamp was released, patients in the postconditioning group underwent 3 cycles of flow/non-flow (2 min each) of normothermic blood via the antegrade cardioplegia line. The primary end point was cardiac index. Secondary end points included additional haemodynamic measurements, biomarkers of cardiomyocyte injury, renal function parameters, intra- and postoperative arrhythmias and use of inotropic agents. RESULTS There was no significant difference between the groups regarding cardiac index [mean between-group difference, 95% confidence interval (CI), 0.11 (−0.1 to 0.3), P = 0.27]. Postconditioning had no effect on other haemodynamic parametres. There was no between-group difference regarding troponin T or creatine kinase MB. Postconditioning reduced the relative risk for arrhythmias by 45% (P = 0.03) when postoperative atrial fibrillation and intraoperative ventricular fibrillation were combined. There were no differences in patients with/without diabetes, patients above/below 70 years of age or between the centres. However, after postconditioning, the cardiac index [95% CI, 0.46 (0.2–0.7), P = 0.001], cardiac output (P CONCLUSIONS IPost had no overall cardioprotective effects in patients undergoing aortic valve replacement but improved postoperative cardiac performance in men compared to women.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::55cc3d80e254f42e24c849d7de9960faTest
https://doi.org/10.1093/ejcts/ezab500Test

المؤلفون: Lubica Macakova, Michal Virag, Miroslava Nemethova, Marek Furman, Peter Berek, Rastislav Mucha, Ivan Kopolovets, Vladimir Sihotsky

المصدر: Molecular Biology Reports. 49:477-485

مصطلحات موضوعية: Male, Ischemia, Stimulation, Pharmacology, CREB, Neuroprotection, Brain Ischemia, Brain ischemia, Gene expression, Genetics, Animals, Medicine, Ischemic Postconditioning, Molecular Biology, Stroke, TM4SF1 Gene, biology, business.industry, Gene Expression Profiling, General Medicine, medicine.disease, Rats, Disease Models, Animal, Gene Expression Regulation, biology.protein, Disease Susceptibility, business, Biomarkers

الوصف: A stroke is an acute damage to a certain area of a nerve tissue of the brain. In developed countries, it ranks second among the most often causes of death and is also the leading cause of disability. Recent findings emphasize the significant neuroprotective effect of conditioning on the course and rate of recovery after ischemic attack; however the molecular mechanism of ischemic tolerance induced by conditioning is still not completely explored. The purpose of this study is an identification of changes in gene expression induced by stimulation of reaction cascades after activation of the neuroprotective mechanism using an experimental rat model of global ischemia. The induction of neuroprotective cascades was stimulated by the application of early and delayed form of remote ischemic postconditioning. The quantitative qRT-PCR method was used to assess the rate of change in ADM, BDNF, CDKN1A, CREB, GADD45G, IL6, nNOS, and TM4SF1 gene expression levels 72 h after ischemic attack. The detected results confirm the neuroprotective effect of both forms of postconditioning. Participation of neuroprotection-related gene expression changes was observed once as an early one (CREB, GADD45G), once as a delayed one (ADM, IL6), or both (BDNF, CDKN1A, nNOS, TM4SF1) postconditioning forms, depending on the particular gene. Our results characterize impact of ischemic tolerance on the molecular level. We predict ischemic tolerance to be consisted of complex combination of early and delayed remote postconditioning.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b3fc3f64d93508a9d77000ef78ea4af0Test
https://doi.org/10.1007/s11033-021-06899-5Test

المؤلفون: Yingshi Ji, Jinghong Ren, Li Sun, Huanyu Liu, Yuan Yao, Rajesh Khanna

المصدر: Molecular Brain, Vol 14, Iss 1, Pp 1-20 (2021)
Molecular Brain

مصطلحات موضوعية: Male, Programmed cell death, Neurotoxins, Excitotoxicity, Glutamic Acid, Calcium-Calmodulin-Dependent Protein Kinase Kinase, Nerve Tissue Proteins, Apoptosis, AMP-Activated Protein Kinases, Pharmacology, medicine.disease_cause, Neuroprotection, Brain Ischemia, Rats, Sprague-Dawley, Cellular and Molecular Neuroscience, Cell Line, Tumor, Autophagy, Animals, Humans, Medicine, Ischemic Postconditioning, RC346-429, Molecular Biology, PI3K/AKT/mTOR pathway, CaMKKβ/AMPK/mTOR pathway, business.industry, Research, Glutamate receptor, AMPK, Infarction, Middle Cerebral Artery, medicine.disease, Peptide Fragments, Cerebral ischemia injury, CRMP2, Reperfusion Injury, Intercellular Signaling Peptides and Proteins, Calcium, Neurology. Diseases of the nervous system, Glutamate, business, Reperfusion injury, Signal Transduction

الوصف: Cerebral ischemia, a common cerebrovascular disease, is characterized by functional deficits and apoptotic cell death. Autophagy, a type of programmed cell death, plays critical roles in controlling neuronal damage and metabolic homeostasis, and has been inextricably linked to cerebral ischemia. We previously identified a short peptide aptamer from collapsin response mediator protein 2 (CRMP2), designated the Ca2+ channel-binding domain 3 (CBD3) peptide, that conferred protection against excitotoxicity and traumatic brain injury. ST2-104, a nona-arginine (R9)-fused CBD3 peptide, exerted beneficial effects on neuropathic pain and was neuroprotective in a model of Alzheimer’s disease; however, the effect of ST2-104 on cerebral ischemia and its mechanism of action have not been studied. In this study, we modeled cerebral ischemia–reperfusion injury in rats with the middle cerebral artery occlusion (MCAO) as well as challenged SH-SY5Y neuroblastoma cells with glutamate to induce toxicity to interrogate the effects of ST2-104 on autophagy following ischemic/excitotoxic insults. ST2-104 reduced the infarct volume and improved the neurological score of rats subjected to MCAO. ST2-104 protected SH-SY5Y cells from death following glutamate exposure via blunting apoptosis and autophagy as well as limiting excessive calcium entry. 3-Methyladenine (3-MA), an inhibitor of autophagy, promoted the effects of ST2-104 in inhibiting apoptosis triggered by glutamate while rapamycin, an activator of autophagy, failed to do so. ST2-104 peptide reversed glutamate-induced apoptosis via inhibiting Ca2+/CaM-dependent protein kinase kinase β (CaMKKβ)-mediated autophagy, which was partly enhanced by STO-609 (an inhibitor of CaMKKβ). ST2-104 attenuated neuronal apoptosis by inhibiting autophagy through CaMKKβ/AMPK/mTOR pathway. Our results suggest that the neuroprotective effect of ST2-104 are due to actions on the crosstalk between apoptosis and autophagy via the CaMKKβ/AMPK/mTOR signaling pathway. The findings present novel insights into the potential neuroprotection of ST2-104 in cerebral ischemia.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ecc441d25f3b491b6f926bc51332bd85Test
https://doaj.org/article/1b51f0a80ad6417c8a7c616f6dc23fdcTest

المؤلفون: Xiaokun Geng, Melissa Wills, Fengwu Li, Qingzhu Wang, Yuchuan Ding

المصدر: Neurological Research. 43:874-883

مصطلحات موضوعية: Male, 0301 basic medicine, Angiogenesis, medicine.medical_treatment, Morris water navigation task, Rats, Sprague-Dawley, 03 medical and health sciences, 0302 clinical medicine, Physical Conditioning, Animal, Ischemic conditioning, Neuroplasticity, medicine, Animals, Ischemic Postconditioning, Stroke, Ischemic Stroke, Functional rehabilitation, Rehabilitation, business.industry, Stroke Rehabilitation, General Medicine, medicine.disease, Rats, 030104 developmental biology, Neurology, Anesthesia, Ischemic stroke, Neurology (clinical), business, 030217 neurology & neurosurgery

الوصف: Objective: Exercise is an essential rehabilitative strategy after stroke butits implementation is limited as its very early use can exacerbate damage and is restricted by patient disability. Remote Ischemic Conditioning (RIC) is a safe alternative for post-stroke neuroprotetion. The present study investigated the neurorehabilitative benefits of early RIC followed by exercise (RICE) therapy.Methods: 48 adult male Sprague-Dawley rats were divided into groups: 1) sham, 2) stroke, 3) stroke with RICE at day 3 (RIC 6 hours after reperfusion followed by exercise days 3 to 28), 4) stroke with exercise at day 3 (exercise days 3 to 28), and 5) stroke with RICE at day 1 (RIC 6 hours after reperfusion followed by exercise days 1 to 28), 6) stroke with exercise at day 1 (exercise days 1 to 28 after reperfusion). Long-term functional outcomes were determined by grid walk, rota-rod, adhesive tape touch, and Morris water maze. Levels of mRNA and proteins of neuroplasticity, synaptogenesis, and angiogenesis, were determined.Results: As compared to exercise only, animals that underwent RICE had significant improvements in functional outcomes after stroke. These improvements were most significant in groups that had the later initiation of exercise. In addition, all treatment groups showed significant increases in mRNA and protein expression of the target molecules for neuroplasticity, synaptogenesis, and angiogenesis, while further significant increases were observed after RICE following ischemic stroke.Conclusions: RICE, a novel therapy that supplements RIC prior to exercise, is superiorly effective in inducing rehabilitation after stroke as compared to the traditional exercise monotherapy rehabilitation in rats with ischemic brain injury.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0877542e641b8df1af999bcf0434fc95Test
https://doi.org/10.1080/01616412.2021.1939489Test

المؤلفون: Anthony Carter, Matthew W. McDonald, Gergely Silasi, Matthew S. Jeffers, Angela Dykes, Ralph Nevins, Dale Corbett, Allyson Ripley

المصدر: Neurorehabilitation and Neural Repair

مصطلحات موضوعية: Male, Time Factors, medicine.medical_treatment, Ischemia, Hindlimb, Tissue plasminogen activator, Neuroprotection, Rats, Sprague-Dawley, 03 medical and health sciences, 0302 clinical medicine, Sex Factors, hemic and lymphatic diseases, Original Research Articles, medicine, Animals, Ischemic Postconditioning, Ischemic Preconditioning, Stroke, medicine.diagnostic_test, business.industry, brain repair, 030208 emergency & critical care medicine, Magnetic resonance imaging, General Medicine, Cerebral Infarction, medicine.disease, Magnetic Resonance Imaging, Rats, Disease Models, Animal, cell death, Anesthesia, Cuff, neuroprotection, Female, Stroke recovery, business, 030217 neurology & neurosurgery, medicine.drug

الوصف: Remote ischemic conditioning (RIC) is a noninvasive procedure whereby several periods of ischemia are induced in a limb. Although there is growing interest in using RIC to improve stroke recovery, preclinical RIC research has focused exclusively on neuroprotection, using male animals and the intraluminal suture stroke model, and delivered RIC at times not relevant to either brain repair or behavioral recovery. In alignment with the Stroke Recovery and Rehabilitation Roundtable, we address these shortcomings. First, a standardized session (5-minute inflation/deflation, 4 repetitions) of RIC was delivered using a cuff on the contralesional hindlimb in both male and female Sprague-Dawley rats. Using the endothelin-1 stroke model, RIC was delivered once either prestroke (18 hours before, pre-RIC) or poststroke (4 hours after, post-RIC), and infarct volume was assessed at 24 hours poststroke using magnetic resonance imaging. RIC was delivered at these times to mimic the day before a surgery where clots are possible or as a treatment similar to tissue plasminogen activator, respectively. Pre-RIC reduced infarct volume by 41% compared with 29% with post-RIC. RIC was neuroprotective in both sexes, but males had a 46% reduction of infarct volume compared with 23% in females. After confirming the acute efficacy of RIC, we applied it chronically for 4 weeks, beginning 5 days poststroke. This delayed RIC failed to enhance poststroke behavioral recovery. Based on these findings, the most promising application of RIC is during the hyperacute and early acute phases of stroke, a time when other interventions such as exercise may be contraindicated.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::28d471d688f40b1449437bb35de8757aTest
http://europepmc.org/articles/PMC8135236Test

المؤلفون: Xunming Ji, Xiaokun Geng, Yuchuan Ding, Hangil Lee, Qingzhu Wang, Christian Huber, Melissa Wills, Kenneth Elkin, Fengwu Li

المصدر: Molecular Neurobiology

مصطلحات موضوعية: Male, 0301 basic medicine, medicine.medical_specialty, Neurology, Neuroscience (miscellaneous), Ischemia/reperfusion, Morris water navigation task, Physical exercise, Tropomyosin receptor kinase B, Neuroprotection, Article, Brain Ischemia, Postconditioning, Rats, Sprague-Dawley, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Neuroplasticity, Physical Conditioning, Animal, Internal medicine, medicine, Animals, Ischemic Postconditioning, Stroke, Neurorehabilitation, business.industry, Stroke Rehabilitation, Brain, medicine.disease, Rats, 030104 developmental biology, Exercise Test, Cardiology, Angiogenesis, Synaptogenesis, business, 030217 neurology & neurosurgery

الوصف: There remain debates on neuroprotection and rehabilitation techniques for acute ischemic stroke patients. Therapeutic physical exercise following stroke has shown promise but is challenging to apply clinically. Ischemic conditioning, which has several clinical advantages, is a potential neuroprotective method for stroke rehabilitation that is less understood. In the present study, the rehabilitative properties and mechanisms of physical exercise and remote ischemic postconditioning (RIPostC) after stroke were compared and determined. A total of 248 adult male Sprague-Dawley rats were divided into five groups: (1) sham, (2) stroke, (3) stroke with intense treadmill exercise, (4) stroke with mild treadmill exercise, and (5) stroke with RIPostC. Focal ischemia was evaluated by infarct volume and neurological deficit. Long-term functional outcomes were represented through neurobehavioral function tests: adhesive removal, beam balance, forelimb placing, grid walk, rota-rod, and Morris water maze. To further understand the mechanisms underlying neurorehabilitation and verify the presence thereof, we measured mRNA and protein levels of neuroplasticity factors, synaptic proteins, angiogenesis factors, and regulation molecules, including HIF-1α, BDNF, TrkB, and CREB. The key role of HIF-1α was elucidated by using the inhibitor, YC-1. Both exercise intensities and RIPostC significantly decreased infarct volumes and neurological deficits and outperformed the stroke group in the neurobehavioral function tests. All treatment groups showed significant increases in mRNA and protein expression levels of the target molecules for neurogenesis, synaptogenesis, and angiogenesis, with intermittent further increases in the RIPostC group. HIF-1α inhibition nullified most beneficial effects and indicative molecule expressions, including HIF-1α, BDNF, TrkB, and CREB, in both procedures. RIPostC is equally, or superiorly, effective in inducing neuroprotection and rehabilitation compared to exercise in ischemic rats. HIF-1α likely plays an important role in the efficacy of neuroplasticity conditioning, possibly through HIF-1α/BDNF/TrkB/CREB regulation.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4f49ee1a2f730b359fbd27bd71eea61cTest
https://doi.org/10.1007/s12035-021-02329-6Test