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Charles L Francoeur, Stephan A Mayer
For patients who survive the initial bleeding event of a ruptured brain aneurysm, delayed cerebral ischemia (DCI) is one of the most important causes of mortality and poor neurological outcome. New insights in the last decade have led to an important paradigm shift in the understanding of DCI pathogenesis. Large-vessel cerebral vasospasm has been challenged as the sole causal mechanism; new hypotheses now focus on the early brain injury, microcirculatory dysfunction, impaired autoregulation, and spreading depolarization...
October 14, 2016: Critical Care: the Official Journal of the Critical Care Forum
Izaskun Buendia, Giammarco Tenti, Patrycja Michalska, Iago Méndez-López, Enrique Luengo, Michele Satriani, Juan Fernando Padin Nogueira, Manuela G López, María Teresa Ramos, Antonio G García, J Carlos Menéndez, Rafael León
During brain ischemia, oxygen and glucose deprivation induces calcium overload, extensive oxidative stress, neuroinflammation and, finally, massive neuronal loss. In the search of a neuroprotective compound to mitigate this neuronal loss, we have designed and synthesized a new multitarget hybrid (ITH14001) directed at the reduction of calcium overload by acting on two regulators of calcium homeostasis; the mitochondrial Na+/Ca2+ exchanger (mNCX) and L-type voltage dependent calcium channels (VDCCs). This compound is a hybrid of CGP37157 (mNCX inhibitor) and nimodipine (L-type VDCCs blocker), and its pharmacological evaluation revealed a moderate ability to selectively inhibit both targets...
October 12, 2016: ACS Chemical Neuroscience
Elisabeth B Marsh, Wendy C Ziai, Rafael H Llinas
INTRODUCTION: Reversible cerebral vasoconstriction syndrome (RCVS) typically affects young patients and left untreated can result in hemorrhage or ischemic stroke. Though the disorder has been well characterized in the literature, the most appropriate way to diagnose, treat, and evaluate therapeutic response remains unclear. In previous studies, transcranial Doppler ultrasound (TCD) has shown elevated velocities indicative of vasospasm. This imaging modality is noninvasive and inexpensive; an attractive option for diagnosis and therapeutic monitoring if it is sensitive enough to detect changes in the acute setting given that RCVS often affects the distal vessels early in the course of disease...
May 2016: Case Reports in Neurology
Wenli Liu, Xiaona Wang, Ruilian Chen, Kaixuan Zhang, Yao Li, Yi Li, Duanyun Si, Junbo Gong, Dianshu Yin, Yongli Wang, Zhenping Wei, Mingshi Yang
The previous investigation has proved that their existed pharmacokinetic difference between the different crystal forms of the polymorphic drugs after oral administration. However, no systemic investigations have been made on the change of this pharmacokinetic difference, resulted either from the physiological or from the pathological factors. In this paper, we used polymorphic nimodipine (Nim) as a model drug and investigated the effect of age difference (2- and 9-month old) on the pharmacokinetics after oral delivery in rats...
September 2016: Acta Pharmaceutica Sinica. B
Ana B Sanchez, Kathryn E Medders, Ricky Maung, Paloma Sánchez-Pavón, Daniel Ojeda-Juárez, Marcus Kaul
BACKGROUND: The chemokine receptor CXCR4 (CD184) and its natural ligand CXCL12 contribute to many physiological processes, including decisions about cell death and survival in the central nervous system. In addition, CXCR4 is a co-receptor for human immunodeficiency virus (HIV)-1 and mediates the neurotoxicity of the viral envelope protein gp120. However, we previously observed that CXCL12 also causes toxicity in cerebrocortical neurons but the cellular mechanism remained incompletely defined...
2016: Journal of Neuroinflammation
R Loch Macdonald, Tom A Schweizer
Subarachnoid haemorrhage is an uncommon and severe subtype of stroke affecting patients at a mean age of 55 years, leading to loss of many years of productive life. The rupture of an intracranial aneurysm is the underlining cause in 85% of cases. Survival from aneurysmal subarachnoid haemorrhage has increased by 17% in the past few decades, probably because of better diagnosis, early aneurysm repair, prescription of nimodipine, and advanced intensive care support. Nevertheless, survivors commonly have cognitive impairments, which in turn affect patients' daily functionality, working capacity, and quality of life...
September 13, 2016: Lancet
Jinchao Ai, Haitong Wan, Mingchun Shu, Huifen Zhou, Tao Zhao, Wei Fu, Yu He
Guhong injection (GHI), composed of aceglutamide and safflower aqueous extract, has been used clinically for the treatment of cerebrovascular diseases such as cerebral embolism, hemorrhage and mental deterioration. In this paper, we reported the results of the first study on the anti-inflammatory effects of GHI in murine focal cerebral ischemia-reperfusion (I/R) injury. Adult male SD rats were randomly divided into six groups: Sham group, I/R group, GHI-L group (2.5 mL/kg), GHI-M group (5 mL/kg), GHI-H group (10 mL/kg) and Nimodipine group...
September 13, 2016: Archives of Pharmacal Research
Shuhua Wang, Hongling Yang, Jie Zhang, Bin Zhang, Tao Liu, Lu Gan, Jiangang Zheng
BACKGROUND: Cerebral infarction frequently leads to mild cognitive impairment (MCI). Prompt management of MCI can prevent vascular dementia and improve patient outcome. This single center randomized controlled trial aims to investigate the efficacy and safety of acupuncture and nimodipine to treat post-cerebral infarction MCI. METHODS: A total of 126 Chinese patients with post-cerebral infarction MCI recruited from the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine between April 2013 and June 2014 were randomized at 1:1: 1 ratio into nimodipine alone (30 mg/time and 3 times daily), acupuncture alone (30 min/time, 6 times/week), and nimodipine + acupuncture groups...
2016: BMC Complementary and Alternative Medicine
Hasan Emre Aydin, Nuriye Ezgi Bektur, Zuhtu Ozbek, Setenay Oner, Cengiz Baycu, Fatma Sultan Kiliç
AIM: Cerebral vasospasm following subarachnoid hemorrhage (SAH) is the most important complication which effects mortality and morbidity of patients with intracranial aneurysm although effective treatment. Today, the mechanisms of vasospasm is not understood in spite of experimetal and clinical researches. The aim of our study to investigate the effect of curcumin which used in medical treatment of some illness and known antioxidant drug on vasospasm following SAH. MATERIAL AND METHODS: In this study, 200-250 gr weight and 64 rats were divided into 7 groups...
May 25, 2016: Turkish Neurosurgery
Xiaowei Shi, Wenjing Yu, Lixing Liu, Wei Liu, Xiaomeng Zhang, Tiantian Yang, Limin Chai, Lixia Lou, Yonghong Gao, Lingqun Zhu
Ischemic stroke, particularly permanent occlusion, accounts for the overwhelming majority of all strokes. In addition to the occlusion of arteries, the inflammatory response plays a pivotal role in the severity of the cerebral injury and its clinical prognosis. Here, panax notoginseng saponins (PNS) extracted from a traditional Chinese herbal medicine was administered following permanent middle cerebral artery occlusion (MCAO) in rats to explore the neuroprotective mechanisms against ischemic injury. The results showed that MCAO surgery was successful in producing an infarct and that PNS and nimodipine could ameliorate the neurological deficits...
September 2, 2016: Metabolic Brain Disease
Yan Wang, Yingbo Li, Chen Di, Tu Liu, Qianlin Hou, Shali Wang
Hypoxic-ischemic encephalopathy (HIE) is a serious clinical problem, responsible for many cases of motor impairment, cognitive deficits, and mortality. Transient receptor potential canonical (TRPC) channels are nonselective cation channels that play a role in many disorders, including trauma, pulmonary hypertension, and excitotoxicity. However, the properties and underlying mechanisms of TRPC channels in HIE are still controversial. Extracellular signal-regulated kinase (ERK) and mammalian target of rapamycin (mTOR) are central signaling pathways that transmit signals from extracellular to intracellular agents and mediate prosurvival, proliferation, and motility proteins...
September 28, 2016: Neuroreport
Shu Hasegawa, Yu Hasegawa, Masaki Miura
BACKGROUND: Cerebral vasospasm (CVS) is well known as a major complication in subarachnoid hemorrhage (SAH) patients, and research has long been focused on improving morbidity and mortality. As CVS commonly develops from day 4 to day 14 after SAH onset, SAH patients require therapies with drugs for preventing CVS after surgical treatment for the source of hemorrhage, mostly ruptured intracranial aneurysms. It is thought that the pathogenesis of CVS is initiated by prolonged smooth muscle contraction, and the subsequent hypoperfusion and cytotoxic responses induce cerebral ischemia...
August 8, 2016: Current Drug Delivery
Min Deng, Xu-Feng Wang
OBJECTIVE: Mild cognitive impairment (MCI) is a pre-dementia state; 5-10% of cases per year will evolve into dementia. MCI can be amnestic (AMCI) or non-amnestic. AMCI is associated with a higher risk of progression. In recent years, interest in acupuncture as a potential treatment for AMCI has grown. The aim of this meta-analysis was to estimate the clinical effectiveness and safety of acupuncture for AMCI. METHODS: Randomised controlled trials (RCTs) of acupuncture versus medical treatment for AMCI were identified using the following databases from inception to July 2015: PubMed; Medline; CENTRAL; Chinese Scientific Journal Database; The Chinese Acupuncture Trials Register; China National Knowledge Infrastructure (CNKI); and Wanfang database...
October 2016: Acupuncture in Medicine: Journal of the British Medical Acupuncture Society
Pallavi Bhambri, Ali Sarvi, John H Wong, Uttandaraman Sundararaj, Alim P Mitha
OBJECTIVE: The only pharmacologic prophylaxis for cerebral vasospasm after subarachnoid hemorrhage is oral nimodipine. A novel way to mitigate this risk may be to design a drug eluting stent that elutes verapamil over the time period typically associated with vasospasm. In this study, we explore different methods of coating nitinol stents with a bioabsorbable polymer and determine the release profile of various verapamil coated stents for the potential treatment of vasospasm. METHODS: Nitinol stents were coated with different concentrations of poly(lactic acid-co-glycolic acid) (PLGA) in chloroform solution and using three coating techniques: dip coating, spin coating, and electrospinning...
July 29, 2016: Journal of Neurointerventional Surgery
M M Tanashyan, A A Shabalina, E V Gnedovskaya, T S Gan'shina, E V Kurza, D V Maslennikov, R S Mirzoyan
It was investigated the effect of two adamantane derivatives, memantine and 5-hydroxyadamantan-2-one (5-HA), in patients with cerebrovascular disorders. In vitro studies showed that 5-HA, unlike memantine, exhibited antiplatelet activity. Experiments showed that memantine reduced cerebral blood flow in the brain cortex of intact rats and those under conditions of transient global ischemia, whereas 5-HA only selectively improved blood flow in ischemic brain and was superior to the reference drug nimodipine. The obtained data indicate the leading role of the GABA-ergic (rather than glutamatergic mechanisms) in implementation of the anti-ischemic cerebrovascular activity...
2016: Eksperimental'naia i Klinicheskaia Farmakologiia
David Weise, Jakob Mann, Jost-Julian Rumpf, Stefan Hallermann, Joseph Classen
Activity-dependent changes of postsynaptic Ca(2+)-concentration are influenced by a variety of different Ca(2+)-channels and play an important role in synaptic plasticity. Paired associative stimulation (PAS) and theta-burst stimulation (TBS) are noninvasive magnetic stimulation protocols used in human subjects to induce lasting corticospinal excitability changes that have been likened to synaptic long-term potentiation and long-term depression. To better characterize the Ca(2+)-related physiological mechanisms underlying PAS- and TBS-induced plasticity, we examined the impact of different Ca(2+)-sources...
July 11, 2016: Cerebral Cortex
Kevser Erol, Semra Yiğitaslan, Çiğdem Ünel, Bilgin Kaygısız, Engin Yıldırım
BACKGROUND: Calcium homeostasis is considered to be important in antineoplastic as well as in neurotoxic adverse effects of cisplatin. AIMS: This study aimed to investigate the role of Ca(2+) in cisplatin neurotoxicity in cultured rat dorsal root ganglia (DRG) cells. STUDY DESIGN: Cell culture study. METHODS: DRG cells prepared from 1-day old Sprague-Dawley rats were used to determine the role of Ca(2+) in the cisplatin (10-600 μM) neurotoxicity...
March 2016: Balkan Medical Journal
Jun Chen, Michael J Sanderson
Asthma is characterized by airway hyper-responsiveness - the excessive contraction of airway smooth muscle. The extent of this airway contraction is proportional to the frequency of Ca(2+) oscillations within airway smooth muscle cells (ASMCs). Sustained Ca(2+) oscillations require a Ca(2+) influx to replenish Ca(2+) losses across the plasma membrane. Our previous studies implied store-operated calcium entry (SOCE) as the major pathway for this Ca(2+) influx. Here, we explore this hypothesis, by examining the effects of SOCE inhibitors (GSK7975A and GSK5498A) as well as L-type voltage-gated Ca(2+) channel (VGCC) inhibitors (nifedipine and nimodipine) on airway contraction and Ca(2+) oscillations and SOCE-mediated Ca(2+) influx in ASMCs within mouse precision-cut lung slices (PCLS)...
July 11, 2016: Journal of Physiology
Qipeng Zhao, Xiuli Cheng, Xiaobo Wang, Jing Wang, Yafei Zhu, Xueqin Ma
ETHNOPHARMACOLOGICAL RELEVANCE: The present study is to investigate the neuroprotective effect of Mu-Xiang-You-Fang (MXYF), a classic Traditional Chinese Medicine used by Chinese minorities to treat stroke, on cerebral ischemia-reperfusion (I/R) injury and the related signaling pathways. MATERIALS AND METHODS: Male Sprague-Dawley rats were divided into 6 groups: sham group, I/R group, nimodipine and MXYF (58, 116 and 232mg/kg respectively) groups. Cerebral ischemia model was induced by middle cerebral artery occlusion for 2h followed by reperfusion for 48h...
July 7, 2016: Journal of Ethnopharmacology
Alpana Singh, Poonam Verma, Gillela Balaji, Supriti Samantaray, Kochupurackal P Mohanakumar
Parkinson's disease (PD), the most common progressive neurodegenerative movement disorder, results from loss of dopaminergic neurons of substantia nigra pars compacta. These neurons exhibit Cav1.3 channel-dependent pacemaking activity. Epidemiological studies suggest reduced risk for PD in population under long-term antihypertensive therapy with L-type calcium channel antagonists. These prompted us to investigate nimodipine, an L-type calcium channel blocker for neuroprotective effect in cellular and animal models of PD...
October 2016: Neurochemistry International
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