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Stroke neuroprotective

Yogi Chang-Yo Hsuan, Cheng-Hsien Lin, Ching-Ping Chang, Mao-Tsun Lin
BACKGROUND: Mesenchymal stem cell (MSC) transplantation has been reported to improve neurological function following neural injury. Many physiological and molecular mechanisms involving MSC therapy-related neuroprotection have been identified. METHODS: A review is presented of articles that pertain to MSC therapy and diverse brain injuries including stroke, neural trauma, and heat stroke, which were identified using an electronic search (e.g., PubMed), emphasize mechanisms of MSC therapy-related neuroprotection...
October 2016: Brain and Behavior
Haixia Hu, Xiaoqin Zhu, Ruhui Lin, Zuanfang Li, Lidian Chen
The present study aimed to investigate the inhibitory effects, and underlying mechanisms, of Gua Lou Gui Zhi decoction (GLGZD) in a rat model of neuroinflammation. Sprague-Dawley rats were treated with GLGZD following middle cerebral artery occlusion (MCAO). Neurological function and infarct volume were evaluated to confirm successful generation of the rat model. Subsequently, brain tissues and blood samples were collected for further analysis. Nitric oxide (NO) and prostaglandin E2 (PGE2) were evaluated in peripheral blood samples using the Griess reagent assay and an ELISA, respectively...
October 21, 2016: Molecular Medicine Reports
M A Sotomayor-Sobrino, A Ochoa-Aguilar, L A Méndez-Cuesta, C Gómez-Acevedo
INTRODUCTION: Stroke is one of the leading causes of death in the world; its incidence is increasing due to increased life expectancy. However, treatment options for these patients are limited since no clinically effective drugs have been developed to date. DEVELOPMENT: According to clinical evidence, a number of neurochemical changes take place after stroke, including energy depletion, increased free radical synthesis, calcium accumulation, neurotransmitter imbalance, excitotoxicity, and, at a later stage, immune system activation leading to inflammation...
October 21, 2016: Neurología: Publicación Oficial de la Sociedad Española de Neurología
Lulu Xie, Hongyi Kang, Maiken Nedergaard
BACKGROUND: Stroke is one of the leading causes of death and disability worldwide. As a consequence, several excellent rodent models have been developed to gain insight into the pathophysiology of stroke and testing the efficacy of neuroprotective interventions. However, one potential problem is that albeit roughly 80% of strokes occur in awake patients, all existing murine stroke models employ anesthesia. Moreover, epidemiological studies have shown that stroke injury is more severe in the minority of patients that suffer stroke while asleep...
2016: Journal of Nature and Science
Amutha Selvamani, Farida Sohrabji
With age, stroke prevalence is higher, and stroke outcome, worse, in women. Thus there is an urgent need to identify stroke neuroprotectants for this population. Using a preclinical stroke model, our studies focused on microRNAs (miRNAs), a class of translational repressors, as neuroprotectants. Analysis of circulating miRNA in the acute phase of stroke indicated potential neuroprotective capacity for miR363. Specifically, mir363 is elevated in serum of adult female rats that typically have small infarct volumes, but is deficient in age-matched males or middle-aged males and females, groups that have greater stroke-associated impairment...
October 20, 2016: Neurochemistry International
Svetlana Demyanenko, Anatoly Uzdensky
In ischemic stroke, cell damage propagates from infarct core to surrounding tissue. To reveal proteins involved in neurodegeneration and neuroprotection, we explored the protein profile in penumbra surrounding the photothrombotic infarct core induced in rat cerebral cortex by local laser irradiation after Bengal Rose administration. Using antibody microarrays, we studied changes in expression of 224 signaling proteins 1, 4, or 24 h after photothrombotic infarct compared with untreated contralateral cortex...
October 22, 2016: Molecular Neurobiology
Da-Shi Qi, Jin-Hao Tao, Lian-Qin Zhang, Mei Wang, Rui Qu, Lian-Qin Zhang, Pei Liu, Jian-Cheng Miu, Jing-Yi Ma, Xin-Yu Mei
Cilostazol(CTL) is a phosphodiesterase inhibitor, which has been widely used as anti-platelet agent. It also has preventive effects on various central nervous system (CNS) diseases, including ischemic stroke, Parkinson's disease and Alzheimer disease. However, the molecular mechanism underlying the protective effects of CTL is still unclear, and whether CTL can prevent I/R induced cognitive deficit has not been reported. Transient global brain ischemia was induced by 4-vessel occlusion in adult male Sprague-Dawley rats...
October 18, 2016: Brain Research
Jing Qiu, Min Wang, Jun Zhang, Qing Cai, Dan Lu, Yansong Li, Yushu Dong, Tianzhi Zhao, Huisheng Chen
Neuroinflammation remains the primary cause of morbidity and mortality in stroke-induced secondary brain injury. The NOD-like receptor pyrin 3 (NLRP3) inflammasome is involved in diverse inflammatory diseases, including cerebral ischemia, and is thus considered an effective therapeutic target. In the present study, we investigated the neuroprotection of Sinomenine (SINO), a potent natural anti-apoptotic and anti-inflammatory molecule, against cerebral ischemia in a mouse model of middle cerebral artery occlusion (MCAO) in vivo and in an oxygen glucose deprivation (OGD)-treated astrocytes/microglia model in vitro...
October 18, 2016: International Immunopharmacology
Yuji Kaneko, Colleen Pappas, Naoki Tajiri, Cesar V Borlongan
Oxytocin protects against ischemia-induced inflammation and oxidative stress, and is associated with GABA (γ-aminobutyric acid, an inhibitory neurotransmitter) signaling transduction in neurons. However, the molecular mechanism by which oxytocin affords neuroprotection, especially the interaction between oxytocin receptor and GABAA receptor (GABAAR), remains to be elucidated. Primary rat neural cells were exposed to oxytocin before induction of experimental acute stroke model via oxygen-glucose deprivation-reperfusion (OGD/R) injury...
October 21, 2016: Scientific Reports
Song Hee Lee, Bo Young Choi, Jin Hee Kim, A Ra Kho, Min Sohn, Hong Ki Song, Hui Chul Choi, Sang Won Suh
Choline alfoscerate (α-GPC) is a common choline compound and acetylcholine precursor in the brain, which has been shown to be effective in the treatment of Alzheimer's disease and dementia. α-GPC has been shown to enhance memory and cognitive function in stroke and Alzheimer's patients but currently remains untested in patients suffering from epilepsy. This study aimed to evaluate whether α-GPC treatment after seizure can ameliorate seizure-induced cognitive impairment and neuronal injury. The potential therapeutic effects of α-GPC on seizure-induced cognitive impairment were tested in an animal model of pilocarpine-induced seizure...
October 17, 2016: Brain Research
Neila Maria R de Lima, Emerson de O Ferreira, Mara Yone S D Fernandes, Francisco Arnaldo V de Lima, Kelly Rose T Neves, Marta Regina S do Carmo, Geanne M de Andrade
Inflammation plays a pivotal role in the development of ischemic brain damage. Astrocyte activation promotes the production of several proinflammatory mediators, such as TNF-α and iNOS. Eventually, neuronal death occurs, leading to the development of motor and memory deficits in patients. Boldine is the main alkaloid in the leaves and bark of the Peumus boldus Molina, and has anti-inflammatory and antioxidant properties. The aim of this work was to investigate the neuroprotective effect of boldine on neuroinflammation and memory deficits induced by permanent middle cerebral artery occlusion (pMCAO) in mice...
October 19, 2016: Behavioural Pharmacology
Enerelt Urnukhsaikhan, Tsogbadrakh Mishig-Ochir, Soo-Chan Kim, Jung-Keug Park, Young-Kwon Seo
Low frequency-pulsed electromagnetic fields (LF-PEMFs) affect many biological processes; however, the fundamental mechanisms responsible for these effects remain unclear. Our study aimed to investigate the effect of LF-PEMFs on neuroprotection after ischemic stroke. C57B6 mice were exposed to LF-PEMF (F = 60 Hz, Bm = 10 mT) after photothrombotic occlusion. We measured the BDNF/TrkB/Akt signaling pathway, pro-apoptotic and pro-survival protein and gene expressions, and the expression of inflammatory mediators and performed behavioral tests in both LF-PEMF-treated and untreated ischemic stroke mice...
October 19, 2016: Applied Biochemistry and Biotechnology
Sergio Amaro, Carlos Laredo, Arturo Renú, Laura Llull, Salvatore Rudilosso, Víctor Obach, Xabier Urra, Anna M Planas, Ángel Chamorro
BACKGROUND AND PURPOSE: Identification of neuroprotective therapies in acute ischemic stroke is imperative. We report a predefined analysis of the URICO-ICTUS trial (Efficacy Study of Combined Treatment With Uric Acid and r-tPA in Acute Ischemic Stroke) assessing the efficacy of uric acid (UA) compared with placebo to prevent early ischemic worsening (EIW) and the relevance of collateral circulation. METHODS: URICO-ICTUS was a double-blind, placebo-controlled, phase 2b trial where a total of 411 patients treated with alteplase within 4...
October 6, 2016: Stroke; a Journal of Cerebral Circulation
John H Griffin, Laurent O Mosnier, José A Fernández, Berislav V Zlokovic
APC (activated protein C), derived from the plasma protease zymogen, is antithrombotic and anti-inflammatory. In preclinical injury models, recombinant APC provides neuroprotection for multiple injuries, including ischemic stroke. APC acts directly on brain endothelial cells and neurons by initiating cell signaling that requires multiple receptors. Two or more major APC receptors mediate APC's neuroprotective cell signaling. When bound to endothelial cell protein C receptor, APC can cleave protease-activated receptor 1, causing biased cytoprotective signaling that reduces ischemia-induced injury...
October 6, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
Colin Sumners, Jacob Isenberg, Allison Harmel, Eduardo Candelario-Jalil, Ulrike Steckelings, Douglas Bennion
OBJECTIVE: The renin angiotensin system is a promising target for stroke neuroprotection and therapy through activation of angiotensin type II receptors (AT2R). The selective non-peptide AT2R agonist, Compound 21 (C21), has been shown to exhibit neuroprotection and improve stroke outcomes in preclinical studies, effects that likely involve neurotropic actions. However, these beneficial actions of C21 have not been demonstrated to occur beyond 1 week post stroke. The objective of this study was to determine if systemic administration of C21 would exert sustained neuroprotective effects in aged rats...
September 2016: Journal of Hypertension
M Asunción Barreda-Manso, Natalia Yanguas-Casás, Manuel Nieto-Sampedro, Lorenzo Romero-Ramírez
Following a central nervous system (CNS) injury, restoration of the blood-brain barrier (BBB) integrity is essential for recovering homeostasis. When this process is delayed or impeded, blood substances and cells enter the CNS parenchyma, initiating an additional inflammatory process that extends the initial injury and causes so-called secondary neuronal loss. Astrocytes and profibrotic mesenchymal cells react to the injury and migrate to the lesion site, creating a new glia limitans that restores the BBB. This process is beneficial for the resolution of the inflammation, neuronal survival and the initiation of the healing process...
October 18, 2016: Journal of Cellular Physiology
Haiyun Chen, Guolian Tan, Jie Cao, Gaoxiao Zhang, Peng Yi, Pei Yu, Yewei Sun, Zaijun Zhang, Yuqiang Wang
Oxidative stress plays a crucial role in neurological diseases, resulting in excessive production of reactive oxygen species, mitochondrial dysfunction and cell death. In this work, we designed and synthesized a series of tetramethylpyrazine derivatives and investigated their abilities for scavenging free radicals and preventing against oxidative stress-induced neuronal damage in vitro. Among them, compound 22a, consisted of TMP, caffeic acid and a nitrone group, showed potent radical-scavenging activity. Compound 22a had broad neuroprotective effects, including rescuing iodoacetic acid-induced neuronal loss, preventing from t-BHP-induced neuronal injury...
October 14, 2016: Chemical & Pharmaceutical Bulletin
Hao Zhou, Wu-Shuang Yang, Ying Li, Tong Ren, Lu Peng, Han Guo, Jin-Feng Liu, Yu Zhou, Yun Zhao, Li-Chao Yang, Xin Jin
This study was carried out to investigate the exact mechanisms behind the neuroprotective effects of oleoylethanolamide (OEA) after acute cerebral ischemic injury. Transient focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) for 90 min followed by reperfusion. OEA (40 mg/kg, ip) was administered with a single injection upon reperfusion. The number of apoptotic cells was detected by TUNEL staining. The expression of Bax, Bcl-2, and TLR4, as well as the activities of NF-κB, Akt, and ERK1/2 were analyzed by western blot...
October 13, 2016: Naunyn-Schmiedeberg's Archives of Pharmacology
G Wang, P-P Wang, P-P Meng, C Han, S-W Yue
OBJECTIVE: Cerebral ischemia-reperfusion is the major pathophysiological process in stroke and can cause severe and lasting sequel. However, an intensive exercise training can potentially effect a quick and efficient recovery. We used swimming training on rats with cerebral ischemia-reperfusion (CIR) and explore the underlying neuroprotective mechanism(s), including the effects of intensive training on the expression of semaphorin 3A (Sema3A) and its receptor Neuropilin-1 (NRP-1). MATERIALS AND METHODS: The middle cerebral artery occlusion/reperfusion (MCAO/R) model was established by inserting a thread into the middle cerebral artery of Sprague-Dawley (SD) rats, and randomly dividing into the control group and training groups for different training intensities...
September 2016: European Review for Medical and Pharmacological Sciences
Ruihe Lin, Jingli Cai, Eric W Kostuk, Robert Rosenwasser, Lorraine Iacovitti
BACKGROUND: Dimethyl fumarate (DMF), working via its metabolite monomethylfumarate (MMF), acts as a potent antioxidant and immunomodulator in animal models of neurologic disease and in patients with multiple sclerosis. These properties and their translational potential led us to investigate whether DMF/MMF could also protect at-risk and/or dying neurons in models of ischemic stroke in vitro and in vivo. Although the antioxidant effects have been partially addressed, the benefits of DMF immunomodulation after ischemic stroke still need to be explored...
October 13, 2016: Journal of Neuroinflammation
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