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Statins AND brain

Taizen Nakase, Tatsuya Ishikawa, Hajime Miyata
Fragility of atheromatous plaque in the internal carotid artery can be a risk of brain infarction. The activation of macrophages by oxidative stress and the vulnerability of vascular endothelial cells have been reported to participate in the fragility of atheromatous plaque. Therefore, from the view point of prevention of brain infarction, we investigated the pathological factors which may influence the stabilization of atheromatous plaque. Patients undertaking carotid endoarterectomy (CEA) were continuously screened...
October 13, 2016: Neuropathology: Official Journal of the Japanese Society of Neuropathology
Fabiana K Ludka, Maurício P Cunha, Tharine Dal-Cim, Luisa Bandeira Binder, Leandra C Constantino, Caio M Massari, Wagner C Martins, Ana Lúcia S Rodrigues, Carla I Tasca
Intracerebroventricular (icv) amyloid-beta (Aβ)1-40 infusion to mice has been demonstrated to cause neurotoxicty and depressive-like behavior and it can be used to evaluate antidepressant and neuroprotective effect of drugs. Atorvastatin is a widely used statin that has demonstrated antidepressant-like effect in predictable animal behavioral models and neuroprotective effect against Aβ1-40 infusion. The purpose of this study was to determine the effect of in vivo atorvastatin treatment against Aβ1-40-induced changes in mood-related behaviors and biochemical parameters in ex vivo hippocampal slices from mice...
October 5, 2016: Molecular Neurobiology
Mathew J Wong, Crystal Kantores, Julijana Ivanovska, Amish Jain, Robert P Jankov
Chronic neonatal pulmonary hypertension (PHT) frequently results in early death. Systemically administered Rho-kinase (ROCK) inhibitors prevent and reverse chronic PHT in neonatal rats, but at the cost of severe adverse effects, including systemic hypotension and growth restriction. Simvastatin has pleiotropic inhibitory effects on isoprenoid intermediates that may limit activity of RhoA, which signals upstream of ROCK. We therefore hypothesized that statin treatment would safely limit pulmonary vascular RhoA activity and prevent and reverse experimental chronic neonatal PHT via downstream inhibitory effects on pathological ROCK activity...
September 30, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
Soheila Adeli, Maryam Zahmatkesh, Gholamreza Tavoosidana, Morteza Karimian, Gholamreza Hassanzadeh
Brain oxidative status is a crucial factor in the development of sporadic Alzheimer's disease (AD). Klotho, an anti-aging protein, diminishes oxidative stress by the induction of manganese superoxide dismutase (MnSOD). Thus, the substances that increase klotho expression could be considered as a potential treatment for Alzheimer's disease when the oxidative imbalance is present. Statins are suggested to up-regulate klotho expression. We examined the effect of simvastatin (5mg/kg, daily for 3weeks) on hippocampal klotho and MnSOD expression in the cognitive declined animal model induced by intracerebroventricular (ICV)-streptozotocin (STZ) administration...
January 4, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
Caio M Massari, Adalberto A Castro, Tharine Dal-Cim, Débora Lanznaster, Carla I Tasca
Parkinson's disease (PD) involves the loss of striatal dopaminergic neurons, although other neurotransmitters and brain areas are also involved in its pathophysiology. In rodent models to PD it has been shown statins improve cognitive and motor deficits and attenuate inflammatory responses evoked by PD-related toxins. Statins are the drugs most prescribed to hypercholesterolemia, but neuroprotective effects have also been attributed to statins treatment in humans and in animal models. This study aimed to establish an in vitro model of 6-hydroxydopamine (6-OHDA)-induced toxicity, used as an initial screening test to identify effective drugs against neural degeneration related to PD...
December 2016: Toxicology in Vitro: An International Journal Published in Association with BIBRA
Ana Lucía Rodríguez-Perea, Johanna Gutierrez-Vargas, Gloria Patricia Cardona-Gómez, Carlos Julio Montoya Guarin, Mauricio Rojas, Paula Andrea Velilla Hernández
Regulatory T cells (Tregs) inhibit the activation of the immune response which could down-regulate the systemic and focal activation observed during ischemic stroke. In fact, in animal models, Tregs infiltrate the infarcted brain and reduce the pro-inflammatory cytokine production and infarct volume, mainly in late stages of ischemia. Recently, an expansion and greater suppressive capacity of circulating Tregs after treatment with statins was observed, in addition to their cardio- and neuroprotective actions demonstrated previously...
September 10, 2016: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
Chan Zhang, Jian-Min Wu, Min Liao, Jun-Ling Wang, Chao-Jin Xu
Simvastatin, a lipophilic and fermentation-derived natural statin, is reported to treat neurological disorders, such as traumatic brain injury, Parkinson's disease (PD), Alzheimer disease (AD), etc. Recently, research also indicated that simvastatin could promote regeneration in the dentate gyrus of adult mice by Wnt/β-catenin signaling (Robin et al. in Stem Cell Reports 2:9-17, 2014). However, the effect and mechanisms by which simvastatin may affect the neural stem cells (NSCs; from the embryonic day 14...
August 19, 2016: Journal of Molecular Neuroscience: MN
Leila Simani, Nima Naderi, Fariba Khodagholi, Masoud Mehrpour, Sanaz Nasoohi
Statins are widely used in high-risk patients to reduce the stroke incidence. However, little has been investigated about the impact of chronic pretreatment with statins on cerebral ischemic insult following defined arterial occlusion. To address this in experimental rats, in the present work, atorvastatin was orally dosed for 1 month to evaluate the outcomes of the subsequent occlusive stroke induced by middle cerebral artery occlusion (MCAO). Our data was suggestive of potential escalating impact of chronic atorvastatin (Atv; 10 mg/kg) on neurological function, but not infarct volume...
August 19, 2016: Journal of Molecular Neuroscience: MN
Iskra A Signore, Carolina Jerez, Diego Figueroa, José Suazo, Katherine Marcelain, Oscar Cerda, Alicia Colombo Flores
BACKGROUND: Orofacial clefts (OFCs) are common birth defects, which include a range of disorders with a complex etiology affecting formation of craniofacial structures. Some forms of syndromic OFCs are produced by defects in the cholesterol pathway. The principal enzyme of the cholesterol pathway is the 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR). Our aim is to study whether defects of HMGCR function would produce orofacial malformation similar to those found in disorders of cholesterol synthesis...
August 4, 2016: Birth Defects Research. Part A, Clinical and Molecular Teratology
Sally-Ann Cooper, Temitope Ademola, Muriel Caslake, Elizabeth Douglas, Jonathan Evans, Nicola Greenlaw, Caroline Haig, Angela Hassiotis, Andrew Jahoda, Alex McConnachie, Jill Morrison, Howard Ring, John Starr, Ciara Stiles, Chammy Sirisena, Frank Sullivan
BACKGROUND: Dementia is very common in Down syndrome (trisomy 21) adults. Statins may slow brain amyloid β (Aβ, coded on chromosome 21) deposition and, therefore, delay Alzheimer disease onset. One prospective cohort study with Down syndrome adults found participants on statins had reduced risk of incident dementia, but there are no randomised controlled trials (RCTs) on this issue. Evidence is sparse on the best instruments to detect longitudinal cognitive decline in older Down syndrome adults...
2016: Trials
B Samura
to investigate an interrelationship between pre-treatment galcetin-3 (Gal-3) level and one-year survival rate, cardiovascular events in subjects with multiple myeloma. Eighty nine subjects with full or partial remission of multiple myeloma were enrolled in the study. Patients were divided into 2 groups based on whether or not statins were included in their treatment: a statin group (n=43) and a no statin group (n=46). Among the 43 patients in the statin group, 31 patients received 20mg/day atorvastatin and 12 patients received 40-mg/day atorvastatin...
June 2016: Georgian Medical News
Mireia Campos-Martorell, Mary Cano-Sarabia, Alba Simats, Mar Hernández-Guillamon, Anna Rosell, Daniel Maspoch, Joan Montaner
BACKGROUND AND AIMS: Although the beneficial effects of statins on stroke have been widely demonstrated both in experimental studies and in clinical trials, the aim of this study is to prepare and characterize a new liposomal delivery system that encapsulates simvastatin to improve its delivery into the brain. MATERIALS AND METHODS: In order to select the optimal liposome lipid composition with the highest capacity to reach the brain, male Wistar rats were submitted to sham or transitory middle cerebral arterial occlusion (MCAOt) surgery and treated (intravenous [IV]) with fluorescent-labeled liposomes with different net surface charges...
2016: International Journal of Nanomedicine
Barry I Freedman, Crystal A Gadegbeku, R Nick Bryan, Nicholette D Palmer, Pamela J Hicks, Lijun Ma, Michael V Rocco, S Carrie Smith, Jianzhao Xu, Christopher T Whitlow, Benjamin C Wagner, Carl D Langefeld, Amret T Hawfield, Jeffrey T Bates, Alan J Lerner, Dominic S Raj, Mohammad S Sadaghiani, Robert D Toto, Jackson T Wright, Donald W Bowden, Jeff D Williamson, Kaycee M Sink, Joseph A Maldjian, Nicholas M Pajewski, Jasmin Divers
To assess apolipoprotein L1 gene (APOL1) renal-risk-variant effects on the brain, magnetic resonance imaging (MRI)-based cerebral volumes and cognitive function were assessed in 517 African American-Diabetes Heart Study (AA-DHS) Memory IN Diabetes (MIND) and 2568 hypertensive African American Systolic Blood Pressure Intervention Trial (SPRINT) participants without diabetes. Within these cohorts, 483 and 197 had cerebral MRI, respectively. AA-DHS participants were characterized as follows: 60.9% female, mean age of 58...
August 2016: Kidney International
Shaun E Gruenbaum, Alexander Zlotnik, Benjamin F Gruenbaum, Denise Hersey, Federico Bilotta
INTRODUCTION: Traumatic brain injury (TBI) is a major cause of death and disability worldwide. The deleterious effects of secondary brain injury may be attenuated by early pharmacological therapy in the emergency room and intensive care unit (ICU). Current medical management of acute TBI is primarily supportive, aimed at reducing intracranial pressure (ICP) and optimizing cerebral perfusion. There are no pharmacological therapies to date that have been unequivocally demonstrated to improve neurological outcomes after TBI...
September 2016: CNS Drugs
Robert F James, Daniel R Kramer, Zaid S Aljuboori, Gunjan Parikh, Shawn W Adams, Jessica C Eaton, Hussam Abou Al-Shaar, Neeraj Badjatia, William J Mack, J Marc Simard
New neuroprotective treatments aimed at preventing or minimizing "delayed brain injury" are attractive areas of investigation and hold the potential to have substantial beneficial effects on aneurysmal subarachnoid hemorrhage (aSAH) survivors. The underlying mechanisms for this "delayed brain injury" are multi-factorial and not fully understood. The most ideal treatment strategies would have the potential for a pleotropic effect positively modulating multiple implicated pathophysiological mechanisms at once...
August 2016: Current Treatment Options in Neurology
Jarred M Griffin, Dan Kho, E Scott Graham, Louise F B Nicholson, Simon J O'Carroll
BACKGROUND: Astrocytes and cerebral endothelial cells are important components of the blood-brain barrier (BBB). Disruption to this barrier through inflammation is a major contributor to Alzheimer's disease (AD) pathology. The amyloid beta (Aβ) protein is known to exist in several forms and is a key modulator of AD that is known to cause inflammation and changes to BBB function. While one of these forms, fibrillary Aβ (fAβ), is known to cause endothelial cell death at the BBB, no studies have looked specifically at its role on inflammation in a model of the human BBB...
2016: PloS One
Jong-Won Chung, Jaechun Hwang, Mi Ji Lee, Jihoon Cha, Oh Young Bang
BACKGROUND AND PURPOSE: Although statin use has been linked to the stabilization of systemic atherosclerosis, its effect on symptomatic intracranial atherosclerotic plaques has yet to be explored. We hypothesized that premorbid statin use is associated with plaque instability in intracranial arteries and may lead to differential patterns (size and distribution) of ischemic lesions in patients with acute intracranial atherosclerotic stroke. METHODS: One hundred and thirty-six patients with acute infarcts caused by intracranial atherosclerotic stroke underwent high-resolution magnetic resonance imaging...
July 2016: Stroke; a Journal of Cerebral Circulation
M H A Noureldine, G Harifi, A Berjawi, A A Haydar, M Nader, R Elnawar, A Sweid, J Al Saleh, M A Khamashta, I Uthman
Epilepsy and seizures are reported among the neurological manifestations of antiphospholipid syndrome (APS) at a prevalence rate of approximately 8%, which is nearly 10 times the prevalence of epilepsy in the general population. The association of seizures with antiphospholipid antibodies (aPL) is even more significant in the presence of systemic lupus erythematosus (SLE). In this review, we discuss the epidemiological, pathophysiological, laboratory, clinical, and radiological aspects of this association, and derive suggestions on when to consider testing for aPL in epileptic patients and how to manage seizures secondary to APS based on literature data...
May 25, 2016: Lupus
Vicente Cés Souza-Dantas, Pedro Póvoa, Fernando Bozza, Marcio Soares, Jorge Salluh
Delirium is the most frequent and severe clinical presentation of brain dysfunction in critically ill septic patients with an incidence ranging from 9% to 71%. Delirium represents a significant burden for patients and relatives, as well as to the health care system, resulting in higher costs, long-term cognitive impairment and significant risk of death after 6 months. Current interventions for the prevention of delirium typically involve early recognition and amelioration of modifiable risk factors and treatment of underlying conditions that predisposes the individual to delirium...
June 3, 2016: Hospital Practice (Minneapolis)
Fabrizio Sallustio, Valeria Studer
Alzheimer's disease (AD) is the most common cause of dementia among the elderly. It is pathologically characterized by diffused extracellular deposits, senile plaques, and intracellular neurofibrillary tangles in the brain, responsible for neuronal dysfunction and cell death. Memory, language and other cognitive functions can be affected to a limited extent in the initial stage called mild cognitive impairment (MCI) or in a more severe and daily life interfering manner in the later stage called dementia. Currently no effective disease-modifying treatment exists for the majority of neurodegenerative diseases...
2016: CNS & Neurological Disorders Drug Targets
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