Severe hypertriglyceridemia does not protect from ischemic brain injury in gene-modified hypertriglyceridemic mice.

Science.gov (United States)

Chen, Yong; Liu, Ping; Qi, Rong; Wang, Yu-Hui; Liu, George; Wang, Chun

2016-05-15

Hypertriglyceridemia (HTG) is a weak risk factor in primary ischemic stroke prevention. However, clinical studies have found a counterintuitive association between a good prognosis after ischemic stroke and HTG. This "HTG paradox" requires confirmation and further explanation. The aim of this study was to experimentally assess this paradox relationship using the gene-modified mice model of extreme HTG. We first used the human Apolipoprotein CIII transgenic (Tg-ApoCIII) mice and non-transgenic (Non-Tg) littermates to examine the effect of HTG on stroke. To our surprise, infarct size, neurological deficits, brain edema, BBB permeability, neuron density and lipid peroxidation were the same in Tg-ApoCIII mice and Non-Tg mice after temporary middle cerebral artery occlusion (tMCAO). In the late phase (21 days after surgery), no differences were found in brain atrophy, neurological dysfunctions, weight and mortality between the two groups. To confirm the results in Tg-ApoCIII mice, Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1(GPIHBP1) knockout mice, another severe HTG mouse model, were used and yielded similar results. Our study demonstrates for the first time that extreme HTG does not affect ischemic brain injuries in the tMCAO mouse model, indicating that the association between HTG and good outcomes after ischemic stroke probably represents residual unmeasured confounding. Further clinical and prospective population-based studies are needed to explore variables that contribute to the paradox. Copyright © 2016 Elsevier B.V. All rights reserved.

Ischemic conditioning-induced endogenous brain protection: Applications pre-, per- or post-stroke.

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Wang, Yuechun; Reis, Cesar; Applegate, Richard; Stier, Gary; Martin, Robert; Zhang, John H

2015-10-01

In the area of brain injury and neurodegenerative diseases, a plethora of experimental and clinical evidence strongly indicates the promise of therapeutically exploiting the endogenous adaptive system at various levels like triggers, mediators and the end-effectors to stimulate and mobilize intrinsic protective capacities against brain injuries. It is believed that ischemic pre-conditioning and post-conditioning are actually the strongest known interventions to stimulate the innate neuroprotective mechanism to prevent or reverse neurodegenerative diseases including stroke and traumatic brain injury. Recently, studies showed the effectiveness of ischemic per-conditioning in some organs. Therefore the term ischemic conditioning, including all interventions applied pre-, per- and post-ischemia, which spans therapeutic windows in 3 time periods, has recently been broadly accepted by scientific communities. In addition, it is extensively acknowledged that ischemia-mediated protection not only affects the neurons but also all the components of the neurovascular network (consisting of neurons, glial cells, vascular endothelial cells, pericytes, smooth muscle cells, and venule/veins). The concept of cerebroprotection has been widely used in place of neuroprotection. Intensive studies on the cellular signaling pathways involved in ischemic conditioning have improved the mechanistic understanding of tolerance to cerebral ischemia. This has added impetus to exploration for potential pharmacologic mimetics, which could possibly induce and maximize inherent protective capacities. However, most of these studies were performed in rodents, and the efficacy of these mimetics remains to be evaluated in human patients. Several classical signaling pathways involving apoptosis, inflammation, or oxidation have been elaborated in the past decades. Newly characterized mechanisms are emerging with the advances in biotechnology and conceptual renewal. In this review we are going to focus on

Nicotinamide mononucleotide inhibits post-ischemic NAD(+) degradation and dramatically ameliorates brain damage following global cerebral ischemia.

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Park, Ji H; Long, Aaron; Owens, Katrina; Kristian, Tibor

2016-11-01

Nicotinamide adenine dinucleotide (NAD(+)) is an essential cofactor for multiple cellular metabolic reactions and has a central role in energy production. Brain ischemia depletes NAD(+) pools leading to bioenergetics failure and cell death. Nicotinamide mononucleotide (NMN) is utilized by the NAD(+) salvage pathway enzyme, nicotinamide adenylyltransferase (Nmnat) to generate NAD(+). Therefore, we examined whether NMN could protect against ischemic brain damage. Mice were subjected to transient forebrain ischemia and treated with NMN or vehicle at the start of reperfusion or 30min after the ischemic insult. At 2, 4, and 24h of recovery, the proteins poly-ADP-ribosylation (PAR), hippocampal NAD(+) levels, and expression levels of NAD(+) salvage pathway enzymes were determined. Furthermore, animal's neurologic outcome and hippocampal CA1 neuronal death was assessed after six days of reperfusion. NMN (62.5mg/kg) dramatically ameliorated the hippocampal CA1 injury and significantly improved the neurological outcome. Additionally, the post-ischemic NMN treatment prevented the increase in PAR formation and NAD(+) catabolism. Since the NMN administration did not affect animal's temperature, blood gases or regional cerebral blood flow during recovery, the protective effect was not a result of altered reperfusion conditions. These data suggest that administration of NMN at a proper dosage has a strong protective effect against ischemic brain injury. Published by Elsevier Inc.

The distribution of N-isopropyl-p-iodoamphetamine in experimental ischemic brain of the mongolian gerbil

International Nuclear Information System (INIS)

Jinnouchi, Seishi; Hoshi, Hiroaki; Watanabe, Katsushi; Ueda, Takashi; Yamaguchi, Tadatoshi

1988-01-01

We studied the distribution of N-isopropyl-p-[I-131]-iodoamphetamine (IMP) in permanent and temporary ischemic brains of mongolian gerbils. For the permanent ischemic brain model, the right common carotid artery was ligated under ether anesthesia. For the temporary ischemic brain model, the right common carotid artery was clamped by a clip and recirculated at 3 hours thereafter. After given time intervals, 1.35 MBq (50 μCi) of IMP was injected intravenously into 17 gerbils (permanent ischemic brain model), 18 gerbils (temporary ischemic brain model) which had severe neurological symptoms, and 3 normal gerbils for controls. One minute, 10 minutes, 1 hour and 6 hours after the injection, gerbils were sacrified and autoradiography of the brain was performed. The activity of IMP in various parts of the brain was calculated from each autoradiogram. In permanent ischemic brains, low perfusion areas were observed in the right cerebral hemisphere, the brain stem (5 ∼ 20 % of normal value), and in the left hemisphere (40 ∼ 60 % of normal value). In temporary ischemic brains, focal areas of increased activity were observed in the right cerebral hemisphere and the thalamus from 10 minutes to 24 hours after recirculation. The high activity disappeared rapidly at 10 minutes after the injection. It seemed that this high activity represented luxury perfusion in the region with severe tissue damage. In the left hemisphere, almost complete recovery of perfusion occurred at 1 ∼ 3 days after recirculation. These results suggested the possibility of IMP to demonstrate cerebral ischemia, luxury perfusion and diaschisis. (author)

ischemic brain injury in neonatal rats

African Journals Online (AJOL)

Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, ... Methods: Forty-eight rats (P7-pups) were randomly assigned to one of four groups: ... Keywords: Hypoxic–ischemic brain injury, α-Lipoic acid, Cerebral infarct area, Edema, Antioxidants, .... Of the 48 rats initially used in the current study, 5.

Computed microtomography visualization and quantification of mouse ischemic brain lesion by nonionic radio contrast agents.

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Dobrivojević, Marina; Bohaček, Ivan; Erjavec, Igor; Gorup, Dunja; Gajović, Srećko

2013-02-01

To explore the possibility of brain imaging by microcomputed tomography (microCT) using x-ray contrasting methods to visualize mouse brain ischemic lesions after middle cerebral artery occlusion (MCAO). Isolated brains were immersed in ionic or nonionic radio contrast agent (RCA) for 5 days and subsequently scanned using microCT scanner. To verify whether ex-vivo microCT brain images can be used to characterize ischemic lesions, they were compared to Nissl stained serial histological sections of the same brains. To verify if brains immersed in RCA may be used afterwards for other methods, subsequent immunofluorescent labeling with anti-NeuN was performed. Nonionic RCA showed better gray to white matter contrast in the brain, and therefore was selected for further studies. MicroCT measurement of ischemic lesion size and cerebral edema significantly correlated with the values determined by Nissl staining (ischemic lesion size: P=0.0005; cerebral edema: P=0.0002). Brain immersion in nonionic RCA did not affect subsequent immunofluorescent analysis and NeuN immunoreactivity. MicroCT method was proven to be suitable for delineation of the ischemic lesion from the non-infarcted tissue, and quantification of lesion volume and cerebral edema.

Quantification of convection-enhanced delivery to the ischemic brain

International Nuclear Information System (INIS)

Haar, Peter J; Broaddus, William C; Chen, Zhi-jian; Gillies, George T; Fatouros, Panos P; Corwin, Frank D

2010-01-01

Convection-enhanced delivery (CED) could have clinical application in the delivery of neuroprotective agents following ischemic stroke. However, ischemic brain tissue changes such as cytotoxic edema, in which cellular swelling decreases the fractional volume of the extracellular space, would be expected to significantly alter the distribution of neuroprotective agents delivered by CED. We sought to predict and characterize these effects using the magnetic resonance contrast agent gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) as a model therapeutic agent. CED was observed using MRI in a normal rat brain and in a middle cerebral artery (MCA) occlusion rat model of brain ischemia. Gd-DTPA was infused to the caudate putamen in the normal rat (n = 6) and MCA occlusion model (n = 6). In each rat, baseline apparent diffusion coefficient images were acquired prior to infusion, and T1 maps were then acquired 13 times throughout the duration of the experiment. These T1 maps were used to compute Gd-DTPA concentrations throughout each brain. In the MCA occlusion group, CED delivered Gd-DTPA to a comparatively larger volume with lower average tissue concentrations. Following the infusion, the total content of Gd-DTPA decreased more slowly in the MCA occlusion group than in the normal group. This quantitative characterization confirms that edematous ischemic tissue changes alter the distribution of agents by CED. These findings may have important implications for CED in the treatment of brain injury, and will assist in future efforts to model the distribution of therapeutic agents

Perinatal Hypoxic-Ischemic brain injury; MR findings

International Nuclear Information System (INIS)

Park, Dong Woo; Seo, Chang Hye

1994-01-01

To characterize the MR findings of hypoxic-ischemic brain injury and to assess the value of the MR imaging. SE T1-, T2-weighted, and IR brain MR images of 44 infants and children with the past history of perinatal hypoxic insults were reviewed. Abnormal brain MR findings of 8 patients with birth history of prematurity and 36 patients with birth history of full-term/posterm including 7 with severe anoxic insult history, were compared in regard to the location and the character of the lesions. MRI demonstrated the followings; (1)abnormal signal intensity lesions of subcortical and/or deep cerebral white matter, cortex, and deep gray matter, (2)atrophy of the cerebral white matter, cortex and corpus callosum, with/without ventriculomegaly, and (3)delay in myelination. Periventricular and deep white matter lesions were demonstrated in the prematurity, the deep white matter lesions and/ or subcortical white matter lesions in the term/post-term, and deep gray matter lesions in the 7 patients with severe anoxic insults history. MR imaging was useful in the diagnosis of the hypoxic-ischemic brain injury, and the white and gray matter lesions were correlated with the time of the injury and the severity of hypoxic insult

Fetal Stress and Programming of Hypoxic/Ischemic-Sensitive Phenotype in the Neonatal Brain: Mechanisms and Possible Interventions

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Li, Yong; Gonzalez, Pablo; Zhang, Lubo

2012-01-01

Growing evidence of epidemiological, clinical and experimental studies has clearly shown a close link between adverse in utero environment and the increased risk of neurological, psychological and psychiatric disorders in later life. Fetal stresses, such as hypoxia, malnutrition, and fetal exposure to nicotine, alcohol, cocaine and glucocorticoids may directly or indirectly act at cellular and molecular levels to alter the brain development and result in programming of heightened brain vulnerability to hypoxic-ischemic encephalopathy and the development of neurological diseases in the postnatal life. The underlying mechanisms are not well understood. However, glucocorticoids may play a crucial role in epigenetic programming of neurological disorders of fetal origins. This review summarizes the recent studies about the effects of fetal stress on the abnormal brain development, focusing on the cellular, molecular and epigenetic mechanisms and highlighting the central effects of glucocorticoids on programming of hypoxicischemic-sensitive phenotype in the neonatal brain, which may enhance the understanding of brain pathophysiology resulting from fetal stress and help explore potential targets of timely diagnosis, prevention and intervention in neonatal hypoxic-ischemic encephalopathy and other for brain disorders. PMID:22627492

RISK FACTORS AND ETIOLOGY OF TRANSIENT ISCHEMIC ATTACKS IN PATIENTS WITH BRAIN INFARCTION

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Kavian Ghandehari

2010-12-01

Full Text Available   Abstract INTRODUCTION: Transient ischemic attacks (TIA are warnings of future stroke. There is no difference in risk factors, pathophysiology and prevention between TIA and brain infarction. methods: Consecutive patients with brain infarction admitted to Ghaem Hospital, Mashhad, Northeastern Iran, were enrolled in a prospective study during 2006. Diagnosis of ischemic stroke was established by a neurologist who also obtained history of TIA and vascular risk factors. All of the stroke patients underwent a standard battery of diagnostic investigations and etiology of ischemic stroke was determined by the Practical Iranian Criteria classification. Fisher’s exact test was used for statistical analysis. results: 348 stroke patients (186 women, 162 men were studied. History of TIA was present in 42 patients (29 women, 13 men, i.e. 12% of the stroke patients. TIA was more common in women (df=1, P=0.02. The frequency of hypertension, diabetes and ipsilateral carotid stenosis was not significantly different between patients with history of TIA and other stroke patients (P=0.87, P=0.64 and P=0.61, respectively. Hyper-cholesterolemia and smoking were significantly more frequent in stroke patients with history of TIA (P=0.011 and P=0.014, respectively. The frequency of TIA was not significantly different among patients with lacunar, versus large vessel territory infarcts (df=1, P=0.84. There was no significant difference in the frequency of various stroke etiologies in patients with and without history of TIA (df=4, P=0.61. CONCLUSIONS: Stroke patients with history of TIA have vascular risk factors similar to other stroke patients. A positive history of TIA does not affirm any specific etiology of ischemic stroke.     Keywords: Risk factors, etiology, transient ischemic attacks.

Relationships between brain and body temperature, clinical and imaging outcomes after ischemic stroke

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Karaszewski, Bartosz; Carpenter, Trevor K; Thomas, Ralph G R; Armitage, Paul A; Lymer, Georgina Katherine S; Marshall, Ian; Dennis, Martin S; Wardlaw, Joanna M

2013-01-01

Pyrexia soon after stroke is associated with severe stroke and poor functional outcome. Few studies have assessed brain temperature after stroke in patients, so little is known of its associations with body temperature, stroke severity, or outcome. We measured temperatures in ischemic and normal-appearing brain using 1H-magnetic resonance spectroscopy and its correlations with body (tympanic) temperature measured four-hourly, infarct growth by 5 days, early neurologic (National Institute of Health Stroke Scale, NIHSS) and late functional outcome (death or dependency). Among 40 patients (mean age 73 years, median NIHSS 7, imaged at median 17 hours), temperature in ischemic brain was higher than in normal-appearing brain on admission (38.6°C-core, 37.9°C-contralateral hemisphere, P=0.03) but both were equally elevated by 5 days; both were higher than tympanic temperature. Ischemic lesion temperature was not associated with NIHSS or 3-month functional outcome; in contrast, higher contralateral normal-appearing brain temperature was associated with worse NIHSS, infarct expansion and poor functional outcome, similar to associations for tympanic temperature. We conclude that brain temperature is higher than body temperature; that elevated temperature in ischemic brain reflects a local tissue response to ischemia, whereas pyrexia reflects the systemic response to stroke, occurs later, and is associated with adverse outcomes. PMID:23571281

Structural MRI markers of brain aging early after ischemic stroke.

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Werden, Emilio; Cumming, Toby; Li, Qi; Bird, Laura; Veldsman, Michele; Pardoe, Heath R; Jackson, Graeme; Donnan, Geoffrey A; Brodtmann, Amy

2017-07-11

To examine associations between ischemic stroke, vascular risk factors, and MRI markers of brain aging. Eighty-one patients (mean age 67.5 ± 13.1 years, 31 left-sided, 61 men) with confirmed first-ever (n = 66) or recurrent (n = 15) ischemic stroke underwent 3T MRI scanning within 6 weeks of symptom onset (mean 26 ± 9 days). Age-matched controls (n = 40) completed identical testing. Multivariate regression analyses examined associations between group membership and MRI markers of brain aging (cortical thickness, total brain volume, white matter hyperintensity [WMH] volume, hippocampal volume), normalized against intracranial volume, and the effects of vascular risk factors on these relationships. First-ever stroke was associated with smaller hippocampal volume ( p = 0.025) and greater WMH volume ( p = 0.004) relative to controls. Recurrent stroke was in turn associated with smaller hippocampal volume relative to both first-ever stroke ( p = 0.017) and controls ( p = 0.001). These associations remained significant after adjustment for age, sex, education, and, in stroke patients, infarct volume. Total brain volume was not significantly smaller in first-ever stroke patients than in controls ( p = 0.056), but the association became significant after further adjustment for atrial fibrillation ( p = 0.036). Cortical thickness and brain volumes did not differ as a function of stroke type, infarct volume, or etiology. Brain structure is likely to be compromised before ischemic stroke by vascular risk factors. Smaller hippocampal and total brain volumes and increased WMH load represent proxies for underlying vascular brain injury. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Ginsenoside Rg1 improves ischemic brain injury by balancing ...

African Journals Online (AJOL)

Ginsenoside Rg1 improves ischemic brain injury by balancing mitochondrial ... and autophagy-related proteins were determined by reat time-polymerase chain ... Treatment with autophagy inhibitors decreased the mitochondrial protective ...

Dabrafenib, an inhibitor of RIP3 kinase-dependent necroptosis, reduces ischemic brain injury

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Shelly A Cruz

2018-01-01

Full Text Available Ischemic brain injury triggers neuronal cell death by apoptosis via caspase activation and by necroptosis through activation of the receptor-interacting protein kinases (RIPK associated with the tumor necrosis factor-alpha (TNF-α/death receptor. Recent evidence shows RIPK inhibitors are neuroprotective and alleviate ischemic brain injury in a number of animal models, however, most have not yet undergone clinical trials and safety in humans remains in question. Dabrafenib, originally identified as a B-raf inhibitor that is currently used to treat melanoma, was later revealed to be a potent RIPK3 inhibitor at micromolar concentrations. Here, we investigated whether Dabrafenib would show a similar neuroprotective effect in mice subjected to ischemic brain injury by photothrombosis. Dabrafenib administered intraperitoneally at 10 mg/kg one hour after photothrombosis-induced focal ischemic injury significantly reduced infarct lesion size in C57BL6 mice the following day, accompanied by a markedly attenuated upregulation of TNF-α. However, subsequent lower doses (5 mg/kg/day failed to sustain this neuroprotective effect after 4 days. Dabrafenib blocked lipopolysaccharides-induced activation of TNF-α in bone marrow-derived macrophages, suggesting that Dabrafenib may attenuate TNF-α-induced necroptotic pathway after ischemic brain injury. Since Dabrafenib is already in clinical use for the treatment of melanoma, it might be repurposed for stroke therapy.

Differential Temporal Evolution Patterns in Brain Temperature in Different Ischemic Tissues in a Monkey Model of Middle Cerebral Artery Occlusion

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Zhihua Sun

2012-01-01

Full Text Available Brain temperature is elevated in acute ischemic stroke, especially in the ischemic penumbra (IP. We attempted to investigate the dynamic evolution of brain temperature in different ischemic regions in a monkey model of middle cerebral artery occlusion. The brain temperature of different ischemic regions was measured with proton magnetic resonance spectroscopy (1H MRS, and the evolution processes of brain temperature were compared among different ischemic regions. We found that the normal (baseline brain temperature of the monkey brain was 37.16°C. In the artery occlusion stage, the mean brain temperature of ischemic tissue was 1.16°C higher than the baseline; however, this increase was region dependent, with 1.72°C in the IP, 1.08°C in the infarct core, and 0.62°C in the oligemic region. After recanalization, the brain temperature of the infarct core showed a pattern of an initial decrease accompanied by a subsequent increase. However, the brain temperature of the IP and oligemic region showed a monotonously and slowly decreased pattern. Our study suggests that in vivo measurement of brain temperature could help to identify whether ischemic tissue survives.

Hyper-attenuating brain lesions on CT after ischemic stroke and thrombectomy are associated with final brain infarction.

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Cabral, F B; Castro-Afonso, L H; Nakiri, G S; Monsignore, L M; Fábio, Src; Dos Santos, A C; Pontes-Neto, O M; Abud, D G

2017-12-01

Purpose Hyper-attenuating lesions, or contrast staining, on a non-contrast brain computed tomography (NCCT) scan have been investigated as a predictor for hemorrhagic transformation after endovascular treatment of acute ischemic stroke (AIS). However, the association of hyper-attenuating lesions and final ischemic areas are poorly investigated in this setting. The aim of the present study was to assess correlations between hyper-attenuating lesions and final brain infarcted areas after thrombectomy for AIS. Methods Data from patients with AIS of the anterior circulation who underwent endovascular treatment were retrospectively assessed. Images of the brain NCCT scans were analyzed in the first hours and late after treatment. The hyper-attenuating areas were compared to the final ischemic areas using the Alberta Stroke Program Early CT Score (ASPECTS). Results Seventy-one of the 123 patients (65.13%) treated were included. The association between the hyper-attenuating region in the post-thrombectomy CT scan and final brain ischemic area were sensitivity (58.3% to 96.9%), specificity (42.9% to 95.6%), positive predictive values (71.4% to 97.7%), negative predictive values (53.8% to 79.5%), and accuracy values (68% to 91%). The highest sensitivity values were found for the lentiform (96.9%) and caudate nuclei (80.4%) and for the internal capsule (87.5%), and the lowest values were found for the M1 (58.3%) and M6 (66.7%) cortices. Conclusions Hyper-attenuating lesions on head NCCT scans performed after endovascular treatment of AIS may predict final brain infarcted areas. The prediction appears to be higher in the deep brain regions compared with the cortical regions.

Regional brain structural abnormality in ischemic stroke patients: a voxel-based morphometry study

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Ping Wu

2016-01-01

Full Text Available Our previous study used regional homogeneity analysis and found that activity in some brain areas of patients with ischemic stroke changed significantly. In the current study, we examined structural changes in these brain regions by taking structural magnetic resonance imaging scans of 11 ischemic stroke patients and 15 healthy participants, and analyzing the data using voxel-based morphometry. Compared with healthy participants, patients exhibited higher gray matter density in the left inferior occipital gyrus and right anterior white matter tract. In contrast, gray matter density in the right cerebellum, left precentral gyrus, right middle frontal gyrus, and left middle temporal gyrus was less in ischemic stroke patients. The changes of gray matter density in the middle frontal gyrus were negatively associated with the clinical rating scales of the Fugl-Meyer Motor Assessment (r = -0.609, P = 0.047 and the left middle temporal gyrus was negatively correlated with the clinical rating scales of the nervous functional deficiency scale (r = -0.737, P = 0.010. Our findings can objectively identify the functional abnormality in some brain regions of ischemic stroke patients.

Brain metabolism in patients with freezing of gait after hypoxic-ischemic brain injury

OpenAIRE

Yoon, Seo Yeon; Lee, Sang Chul; Kim, Na Young; An, Young-Sil; Kim, Yong Wook

2017-01-01

Abstract Movement disorders are 1 of the long-term neurological complications that can occur after hypoxic-ischemic brain injury (HIBI). However, freezing of gait (FOG) after HIBI is rare. The aim of this study was to examine the brain metabolism of patients with FOG after HIBI using F-18 fluoro-2-deoxy-D-glucose positron emission tomography (F-18 FDG PET). We consecutively enrolled 11 patients with FOG after HIBI. The patients’ overall brain metabolism was measured by F-18 FDG PET, and we co...

Molecular Mechanisms Responsible for Neuron-Derived Conditioned Medium (NCM-Mediated Protection of Ischemic Brain.

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Chi-Hsin Lin

Full Text Available The protective value of neuron-derived conditioned medium (NCM in cerebral ischemia and the underlying mechanism(s responsible for NCM-mediated brain protection against cerebral ischemia were investigated in the study. NCM was first collected from the neuronal culture growing under the in vitro ischemic condition (glucose-, oxygen- and serum-deprivation or GOSD for 2, 4 or 6 h. Through the focal cerebral ischemia (bilateral CCAO/unilateral MCAO animal model, we discovered that ischemia/reperfusion (I/R-induced brain infarction was significantly reduced by NCM, given directly into the cistern magna at the end of 90 min of CCAO/MCAO. Immunoblocking and chemical blocking strategies were applied in the in vitro ischemic studies to show that NCM supplement could protect microglia, astrocytes and neurons from GOSD-induced cell death, in a growth factor (TGFβ1, NT-3 and GDNF and p-ERK dependent manner. Brain injection with TGFβ1, NT3, GDNF and ERK agonist (DADS alone or in combination, therefore also significantly decreased the infarct volume of ischemic brain. Moreover, NCM could inhibit ROS but stimulate IL-1β release from GOSD-treated microglia and limit the infiltration of IL-β-positive microglia into the core area of ischemic brain, revealing the anti-oxidant and anti-inflammatory activities of NCM. In overall, NCM-mediated brain protection against cerebral ischemia has been demonstrated for the first time in S.D. rats, due to its anti-apoptotic, anti-oxidant and potentially anti-glutamate activities (NCM-induced IL-1β can inhibit the glutamate-mediated neurotoxicity and restriction upon the infiltration of inflammatory microglia into the core area of ischemic brain. The therapeutic potentials of NCM, TGFβ1, GDNF, NT-3 and DADS in the control of cerebral ischemia in human therefore have been suggested and require further investigation.

Neuroprotective actions of taurine on hypoxic-ischemic brain damage in neonatal rats.

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Zhu, Xiao-Yun; Ma, Peng-Sheng; Wu, Wei; Zhou, Ru; Hao, Yin-Ju; Niu, Yang; Sun, Tao; Li, Yu-Xiang; Yu, Jian-Qiang

2016-06-01

Taurine is an abundant amino acid in the nervous system, which has been proved to possess antioxidation, osmoregulation and membrane stabilization. Previously it has been demonstrated that taurine exerts ischemic brain injury protective effect. This study was designed to investigate whether the protective effect of taurine has the possibility to be applied to treat neonatal hypoxic-ischemic brain damage. Seven-day-old Sprague-Dawley rats were treated with left carotid artery ligation followed by exposure to 8% oxygen to generate the experimental group. The cerebral damage area was measured after taurine post-treatment with 2,3,5-triphenyltetrazolium chloride (TTC) staining, Hematoxyline-Eosin (HE) staining and Nissl staining. The activities of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), myeloperoxtidase (MPO), ATP and Lactic Acid productions were assayed with ipsilateral hemisphere homogenates. Western-blot and immunofluorescence assay were processed to detect the expressions of AIF, Cyt C, Bax, Bcl-2 in brain. We found that taurine significantly reduced brain infarct volume and ameliorated morphological injury obviously reversed the changes of SOD, MDA, GSH-Px, T-AOC, ATP, MPO, and Lactic Acid levels. Compared with hypoxic-ischemic group, it showed marked reduction of AIF, Cyt C and Bax expressions and increase of Bcl-2 after post-treatment. We conclude that taurine possesses an efficacious neuroprotective effect after cerebral hypoxic-ischemic damage in neonatal rats. Copyright © 2016 Elsevier Inc. All rights reserved.

Type 2 diabetes is not a risk factor for asymptomatic ischemic brain lesion. The Funagata study

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Saitoh, Tamotsu; Daimon, Makoto; Eguchi, Hideyuki; Hosoya, Takaaki; Kawanami, Toru; Kurita, Keiji; Tominaga, Makoto; Kato, Takeo [Yamagata Univ. (Japan). School of Medicine

2002-05-01

The purpose of this study is to clarify whether type 2 diabetes (DM) is a risk factor for asymptomatic (silent) ischemic brain lesion, which is controversial at present. The subjects (n=187), who showed normal results on both neurological and neuropsychological examinations, underwent a 75-g OGTT and were examined by brain MRI on T1-weighted, T2-weighted, and FLAIR (fluid-attenuated inversion recovery) images. Their brain MRIs were evaluated quantitatively with the ischemia rating scale defined here. The subjects were grouped based on their glucose tolerance: normal glucose tolerance (NGT) (n=48), impaired glucose tolerance (IGT) (n=62), and DM (n=65). The subjects with DM were further divided based on their duration of illness: 20 with short duration (short DM: 1.3{+-}0.8 years) and 45 with long duration (long DM; 8.9{+-}5.4 years). Ages were matched among the groups. The percentages of individuals with asymptomatic ischemic brain lesion were 81% in NGT, 74% in IGT, 65% in short DM, and 78% in long DM. No significant difference was observed among the groups in terms of the percentage. Namely, even in individuals with a long history of DM without clinical stroke, the prevalence of asymptomatic ischemic brain lesion was not different from that of the other groups. Multiple regression and multiple logistic regression analyses showed that age and hypertension were significant independent risk factors for asymptomatic ischemic brain lesion, whereas hypercholesterolemia, smoking, and glucose intolerance, including IGT, short DM and long DM, were not. DM is not a risk factor for asymptomatic ischemic brain lesion. (author)

Modeling the ischemic blood-brain barrier; the effects of oxygen-glucose deprivation (OGD) on endothelial cells in culture

DEFF Research Database (Denmark)

Tornabene, Erica; Helms, Hans Christian Cederberg; Berndt, Philipp

Introduction - The blood-brain barrier (BBB) is a physical, transport and metabolic barrier which plays a key role in preventing uncontrolled exchanges between blood and brain, ensuring an optimal environment for neurons activity. This extent interface is created by the endothelial cells forming...... pathways across the barrier in ischemic and postischemic brain endothelium is important for developing new medical therapies capable to exploit the barrier changes occurring during/after ischemia to permeate in the brain and treat this devastating disease. Materials and Methods - Primary cultures...... the wall of brain capillaries. The restrictive nature of the BBB is due to the tight junctions (TJs), which seal the intercellular clefts, limiting the paracellular diffusion, efflux transporters, which extrude xenobiotics, and metabolizing enzymes, which may break down or convert molecules during...

Type 2 diabetes is not a risk factor for asymptomatic ischemic brain lesion. The Funagata study

International Nuclear Information System (INIS)

Saitoh, Tamotsu; Daimon, Makoto; Eguchi, Hideyuki; Hosoya, Takaaki; Kawanami, Toru; Kurita, Keiji; Tominaga, Makoto; Kato, Takeo

2002-01-01

The purpose of this study is to clarify whether type 2 diabetes (DM) is a risk factor for asymptomatic (silent) ischemic brain lesion, which is controversial at present. The subjects (n=187), who showed normal results on both neurological and neuropsychological examinations, underwent a 75-g OGTT and were examined by brain MRI on T1-weighted, T2-weighted, and FLAIR (fluid-attenuated inversion recovery) images. Their brain MRIs were evaluated quantitatively with the ischemia rating scale defined here. The subjects were grouped based on their glucose tolerance: normal glucose tolerance (NGT) (n=48), impaired glucose tolerance (IGT) (n=62), and DM (n=65). The subjects with DM were further divided based on their duration of illness: 20 with short duration (short DM: 1.3±0.8 years) and 45 with long duration (long DM; 8.9±5.4 years). Ages were matched among the groups. The percentages of individuals with asymptomatic ischemic brain lesion were 81% in NGT, 74% in IGT, 65% in short DM, and 78% in long DM. No significant difference was observed among the groups in terms of the percentage. Namely, even in individuals with a long history of DM without clinical stroke, the prevalence of asymptomatic ischemic brain lesion was not different from that of the other groups. Multiple regression and multiple logistic regression analyses showed that age and hypertension were significant independent risk factors for asymptomatic ischemic brain lesion, whereas hypercholesterolemia, smoking, and glucose intolerance, including IGT, short DM and long DM, were not. DM is not a risk factor for asymptomatic ischemic brain lesion. (author)

Blood-brain barrier alterations provide evidence of subacute diaschisis in an ischemic stroke rat model.

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Svitlana Garbuzova-Davis

Full Text Available Comprehensive stroke studies reveal diaschisis, a loss of function due to pathological deficits in brain areas remote from initial ischemic lesion. However, blood-brain barrier (BBB competence in subacute diaschisis is uncertain. The present study investigated subacute diaschisis in a focal ischemic stroke rat model. Specific focuses were BBB integrity and related pathogenic processes in contralateral brain areas.In ipsilateral hemisphere 7 days after transient middle cerebral artery occlusion (tMCAO, significant BBB alterations characterized by large Evans Blue (EB parenchymal extravasation, autophagosome accumulation, increased reactive astrocytes and activated microglia, demyelinization, and neuronal damage were detected in the striatum, motor and somatosensory cortices. Vascular damage identified by ultrastuctural and immunohistochemical analyses also occurred in the contralateral hemisphere. In contralateral striatum and motor cortex, major ultrastructural BBB changes included: swollen and vacuolated endothelial cells containing numerous autophagosomes, pericyte degeneration, and perivascular edema. Additionally, prominent EB extravasation, increased endothelial autophagosome formation, rampant astrogliosis, activated microglia, widespread neuronal pyknosis and decreased myelin were observed in contralateral striatum, and motor and somatosensory cortices.These results demonstrate focal ischemic stroke-induced pathological disturbances in ipsilateral, as well as in contralateral brain areas, which were shown to be closely associated with BBB breakdown in remote brain microvessels and endothelial autophagosome accumulation. This microvascular damage in subacute phase likely revealed ischemic diaschisis and should be considered in development of treatment strategies for stroke.

Sodium Pyruvate Reduced Hypoxic-Ischemic Injury to Neonatal Rat Brain

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Pan, Rui; Rong, Zhihui; She, Yun; Cao, Yuan; Chang, Li-Wen; Lee, Wei-Hua

2012-01-01

Background Neonatal hypoxia-ischemia (HI) remains a major cause of severe brain damage and is often associated with high mortality and lifelong disability. Immature brains are extremely sensitive to hypoxia-ischemia, shown as prolonged mitochondrial neuronal death. Sodium pyruvate (SP), a substrate of the tricarboxylic acid cycle and an extracellular antioxidant, has been considered as a potential treatment for hypoxic-ischemic encephalopathy (HIE), but its effects have not been evaluated in ...

Relationship between hypertensive cerebral hemorrhage and ischemic lesions

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Yamaguchi, Shinya; Tsuchiya, Takashi; Yamaguchi, Takenori

1991-01-01

Patchy parenchymal lesions of increased intensity were frequently identified in patients with cerebral hemorrhage in T2-weighted image of high-fields MR imaging. We studied 64 patients with brain hemorrhage to determine the frequency and distribution of those lesions. We defined an area with high intensity in T2 weighted and low or iso-intensity area in T1 weighted images smaller than 1.5 cm in diameter to be 'ischemic lesion'. Ishemic lesions were found in 48 (75%) of all cases; in 25 (75%) of 32 patients with putaminal hemorrhage, in 15 (100%) of 15 with thalamic hemorrhage, in 3 (33%) of 9 with subcortical hemorrhage. Multiple ischemic lesions were more frequently seen in thalamic hemorrhage than in putaminal hemorrhage. Only 5 (10%) of 48 cases with associated ischemic lesions had a previous history related to those lesions. Multivariable regression analysis identified hypertension as the major predictor of the presence of ischemic lesions. Patients with brain hemorrhage frequently accompanied with incidental ischemic lesions, making it difficult to establish a guideline of blood pressure control for prevention of recurrent stroke. (author)

Transcriptomics and proteomics analyses of the PACAP38 influenced ischemic brain in permanent middle cerebral artery occlusion model mice

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Hori Motohide

2012-11-01

Full Text Available Abstract Introduction The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP is considered to be a potential therapeutic agent for prevention of cerebral ischemia. Ischemia is a most common cause of death after heart attack and cancer causing major negative social and economic consequences. This study was designed to investigate the effect of PACAP38 injection intracerebroventrically in a mouse model of permanent middle cerebral artery occlusion (PMCAO along with corresponding SHAM control that used 0.9% saline injection. Methods Ischemic and non-ischemic brain tissues were sampled at 6 and 24 hours post-treatment. Following behavioral analyses to confirm whether the ischemia has occurred, we investigated the genome-wide changes in gene and protein expression using DNA microarray chip (4x44K, Agilent and two-dimensional gel electrophoresis (2-DGE coupled with matrix assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS, respectively. Western blotting and immunofluorescent staining were also used to further examine the identified protein factor. Results Our results revealed numerous changes in the transcriptome of ischemic hemisphere (ipsilateral treated with PACAP38 compared to the saline-injected SHAM control hemisphere (contralateral. Previously known (such as the interleukin family and novel (Gabra6, Crtam genes were identified under PACAP influence. In parallel, 2-DGE analysis revealed a highly expressed protein spot in the ischemic hemisphere that was identified as dihydropyrimidinase-related protein 2 (DPYL2. The DPYL2, also known as Crmp2, is a marker for the axonal growth and nerve development. Interestingly, PACAP treatment slightly increased its abundance (by 2-DGE and immunostaining at 6 h but not at 24 h in the ischemic hemisphere, suggesting PACAP activates neuronal defense mechanism early on. Conclusions This study provides a detailed inventory of PACAP influenced gene expressions

NOX4-dependent neuronal autotoxicity and BBB breakdown explain the superior sensitivity of the brain to ischemic damage.

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Casas, Ana I; Geuss, Eva; Kleikers, Pamela W M; Mencl, Stine; Herrmann, Alexander M; Buendia, Izaskun; Egea, Javier; Meuth, Sven G; Lopez, Manuela G; Kleinschnitz, Christoph; Schmidt, Harald H H W

2017-11-14

Ischemic injury represents the most frequent cause of death and disability, and it remains unclear why, of all body organs, the brain is most sensitive to hypoxia. In many tissues, type 4 NADPH oxidase is induced upon ischemia or hypoxia, converting oxygen to reactive oxygen species. Here, we show in mouse models of ischemia in the heart, brain, and hindlimb that only in the brain does NADPH oxidase 4 (NOX4) lead to ischemic damage. We explain this distinct cellular distribution pattern through cell-specific knockouts. Endothelial NOX4 breaks down the BBB, while neuronal NOX4 leads to neuronal autotoxicity. Vascular smooth muscle NOX4, the common denominator of ischemia within all ischemic organs, played no apparent role. The direct neuroprotective potential of pharmacological NOX4 inhibition was confirmed in an ex vivo model, free of vascular and BBB components. Our results demonstrate that the heightened sensitivity of the brain to ischemic damage is due to an organ-specific role of NOX4 in blood-brain-barrier endothelial cells and neurons. This mechanism is conserved in at least two rodents and humans, making NOX4 a prime target for a first-in-class mechanism-based, cytoprotective therapy in the unmet high medical need indication of ischemic stroke. Copyright © 2017 the Author(s). Published by PNAS.

Behavior outcome after ischemic and hemorrhagic stroke, with similar brain damage, in rats.

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Mestriner, Régis Gemerasca; Miguel, Patrícia Maidana; Bagatini, Pamela Brambilla; Saur, Lisiani; Boisserand, Lígia Simões Braga; Baptista, Pedro Porto Alegre; Xavier, Léder Leal; Netto, Carlos Alexandre

2013-05-01

Stroke causes disability and mortality worldwide and is divided into ischemic and hemorrhagic subtypes. Although clinical trials suggest distinct recovery profiles for ischemic and hemorrhagic events, this is not conclusive due to stroke heterogeneity. The aim of this study was to produce similar brain damage, using experimental models of ischemic (IS) and hemorrhagic (HS) stroke and evaluate the motor spontaneous recovery profile. We used 31 Wistar rats divided into the following groups: Sham (n=7), ischemic (IS) (n=12) or hemorrhagic (HS) (n=12). Brain ischemia or hemorrhage was induced by endotelin-1 (ET-1) and collagenase type IV-S (collagenase) microinjections, respectively. All groups were evaluated in the open field, cylinder and ladder walk behavioral tests at distinct time points as from baseline to 30 days post-surgery (30 PS). Histological and morphometric analyses were used to assess the volume of lost tissue and lesion length. Present results reveal that both forms of experimental stroke had a comparable long-term pattern of damage, since no differences were found in volume of tissue lost or lesion size 30 days after surgery. However, behavioral data showed that hemorrhagic rats were less impaired at skilled walking than ischemic ones at 15 and 30 days post-surgery. We suggest that experimentally comparable stroke design is useful because it reduces heterogeneity and facilitates the assessment of neurobiological differences related to stroke subtypes; and that spontaneous skilled walking recovery differs between experimental ischemic and hemorrhagic insults. Copyright © 2013 Elsevier B.V. All rights reserved.

Evidence that the EphA2 receptor exacerbates ischemic brain injury.

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John Thundyil

Full Text Available Ephrin (Eph signaling within the central nervous system is known to modulate axon guidance, synaptic plasticity, and to promote long-term potentiation. We investigated the potential involvement of EphA2 receptors in ischemic stroke-induced brain inflammation in a mouse model of focal stroke. Cerebral ischemia was induced in male C57Bl6/J wild-type (WT and EphA2-deficient (EphA2(-/- mice by middle cerebral artery occlusion (MCAO; 60 min, followed by reperfusion (24 or 72 h. Brain infarction was measured using triphenyltetrazolium chloride staining. Neurological deficit scores and brain infarct volumes were significantly less in EphA2(-/- mice compared with WT controls. This protection by EphA2 deletion was associated with a comparative decrease in brain edema, blood-brain barrier damage, MMP-9 expression and leukocyte infiltration, and higher expression levels of the tight junction protein, zona occludens-1. Moreover, EphA2(-/- brains had significantly lower levels of the pro-apoptotic proteins, cleaved caspase-3 and BAX, and higher levels of the anti-apoptotic protein, Bcl-2 as compared to WT group. We confirmed that isolated WT cortical neurons express the EphA2 receptor and its ligands (ephrin-A1-A3. Furthermore, expression of all four proteins was increased in WT primary cortical neurons following 24 h of glucose deprivation, and in the brains of WT mice following stroke. Glucose deprivation induced less cell death in primary neurons from EphA2(-/- compared with WT mice. In conclusion, our data provide the first evidence that the EphA2 receptor directly contributes to blood-brain barrier damage and neuronal death following ischemic stroke.

Objective Ventricle Segmentation in Brain CT with Ischemic Stroke Based on Anatomical Knowledge

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Xiaohua Qian

2017-01-01

Full Text Available Ventricle segmentation is a challenging technique for the development of detection system of ischemic stroke in computed tomography (CT, as ischemic stroke regions are adjacent to the brain ventricle with similar intensity. To address this problem, we developed an objective segmentation system of brain ventricle in CT. The intensity distribution of the ventricle was estimated based on clustering technique, connectivity, and domain knowledge, and the initial ventricle segmentation results were then obtained. To exclude the stroke regions from initial segmentation, a combined segmentation strategy was proposed, which is composed of three different schemes: (1 the largest three-dimensional (3D connected component was considered as the ventricular region; (2 the big stroke areas were removed by the image difference methods based on searching optimal threshold values; (3 the small stroke regions were excluded by the adaptive template algorithm. The proposed method was evaluated on 50 cases of patients with ischemic stroke. The mean Dice, sensitivity, specificity, and root mean squared error were 0.9447, 0.969, 0.998, and 0.219 mm, respectively. This system can offer a desirable performance. Therefore, the proposed system is expected to bring insights into clinic research and the development of detection system of ischemic stroke in CT.

[Secondary prevention of ischemic non cardioembolic stroke].

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Armario, Pedro; Pinto, Xavier; Soler, Cristina; Cardona, Pere

2015-01-01

Stroke patients are at high risk for recurrence or new occurrence of other cardiovascular events or cardiovascular mortality. It is estimated that a high percentage of non-cardioembolic ischemic stroke can be prevented by a suitable modification of lifestyle (diet and exercise), reducing blood pressure (BP) with antihypertensive medication, platelet aggregation inhibitors, statins and high intake reducing consumption of. Unfortunately the degree of control of the different risk factors in secondary prevention of stroke is low. The clinical practice guidelines show clear recommendations with corresponding levels of evidence, but only if implemented in a general way they will get a better primary and secondary stroke prevention. Copyright © 2014 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

Neural precursor cells in the ischemic brain - integration, cellular crosstalk and consequences for stroke recovery

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Dirk M. Hermann

2014-09-01

Full Text Available After an ischemic stroke, neural precursor cells (NPCs proliferate within major germinal niches of the brain. Endogenous NPCs subsequently migrate towards the ischemic lesion where they promote tissue remodelling and neural repair. Unfortunately, this restorative process is generally insufficient and thus unable to support a full recovery of lost neurological functions. Supported by solid experimental and preclinical data, the transplantation of exogenous NPCs has emerged as a potential tool for stroke treatment. Transplanted NPCs are thought to act mainly via trophic and immune modulatory effects, thereby complementing the restorative responses initially executed by the endogenous NPC population. Recent studies have attempted to elucidate how the therapeutic properties of transplanted NPCs vary depending on the route of transplantation. Systemic NPC delivery leads to potent immune modulatory actions, which prevent secondary neuronal degeneration, reduces glial scar formation, diminishes oxidative stress and stabilizes blood-brain barrier integrity. On the contrary, local stem cell delivery, allows for the accumulation of large numbers of transplanted NPCs in the brain, thus achieving high levels of locally available tissue trophic factors, which may better induce a strong endogenous NPC proliferative response.Herein we describe the diverse capabilities of exogenous (systemically vs locally transplanted NPCs in enhancing the endogenous neurogenic response after stroke, and how the route of transplantation may affect migration, survival, bystander effects and integration of the cellular graft. It is the authors’ claim that understanding these aspects will be of pivotal importance in discerning how transplanted NPCs exert their therapeutic effects in stroke.

How study patients who receive fluo pyrimidines to prevent ischemic events

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Saldombide, L.

2010-01-01

Introduction: Ischemic heart disease is the main cause of death in Uruguay and cancer is the second. The pillar of the systemic treatment of colorectal cancer are fluo pyrimidines and cause acute ischemic events in 3-8% of t rated patients. The 5 fluorouracil is the third anticancer drug most used Objective: Due to the high incidence of the two diseases and the risk of death caused by the ischemic treatment complications, the literature is analyzed to define how to study patients who receive fluo pyrimidines as a medium of preventing the same. Development: fluo pyrimidines cardio-toxicity can occur by myocardial toxicity, vasospasm, dihydropyrimidine dehydrogenase deficiency, autoimmune phenomena, platelet hyper aggregability, etc. The clinic is varied and underestimated: angina, abnormal ST silent and reversible, arrhythmias, heart failure, hypertension and heart failure. It is the most common complication with continuous infusion of 5 Fu and its equivalent capecitabine with bolus f lou pyrimidines. It is common that ischemic heart disease prioritises the risk increase of complications, but their absence does not exist. Without ischemic heart disease it is difficult to prevent ischemic events, however proposes that the older higher risk. Results: No uniform guidelines is advised: detailed history, determine if risk factors such as smoking, hypertension, diabetes and dyslipidemia and They are present electrocardiogram and cardiac evaluation. Warn the patient about angina l pain as early symptom and monitor symptoms during chemotherapy including cardio-vascular hypotension. Discontinue the medication and perform classic anti-angina l symptoms and / or signs of ischemia. Not reintroduce unless it is the only therapeutic option, since mortality may exceed

Presumptive Ischemic Brain Infarction in a Dog with Evans’ Syndrome

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Angelo Pasquale Giannuzzi

2014-01-01

Full Text Available A ten-year-old neutered female mixed breed dog was referred for pale mucous membrane and acute onset of right prosencephalic clinical signs. Brain magnetic resonance imaging was suggestive for right middle cerebral artery ischemic stroke. Based on cell blood count, serum biochemistry and serologic tests and flow cytometric detection of anti-platelets and anti-red blood cells antibodies, a diagnosis of immunomediated haemolytic anemia associated with thrombocytopenia of suspected immunomediated origin was done. Immunosuppresive therapy with prednisone was started and the dog clinically recovered. Two months later complete normalization of CBC and serum biochemistry was documented. The dog remained stable for 7 months without therapy; then she relapsed. CBC revealed mild regenerative anemia with spherocytosis and thrombocytopenia. A conclusive Evans’ syndrome diagnosis was done and prednisone and cyclosporine treatment led to normalization of physical and CBC parameters. The dog is still alive at the time the paper submitted. Possible thrombotic etiopathogenetic mechanisms are illustrated in the paper and the authors suggest introducing Evans’ syndrome in the differential diagnosis list for brain ischemic stroke in dogs.

The influence of general anesthesia on the brain in aged patients with previous ischemic cerebrovascular disease

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Kokubo, Yasuaki; Kayama, Takamasa; Kondo, Rei; Oki, Masato; Takaoka, Seiji

2008-01-01

Whenever we discuss the overall results of surgical treatment for unruptured cerebral aneurysms, especially in aged patients, we tend to consider advanced age or general anesthesia as causes for unfavorable results. There are no reports concerning ischemic stroke events following general anesthesia in aged patients with a prior history of cerebrovascular disease. The purpose of this study is to clarify the influence of general anesthesia on the brats in aged patients with a previous history of ischemic cerebrovascular disease. The subjects were 30 consecutive patients over 70 years of age with previous ischemic cerebrovascular disease who underwent various surgeries except brain and cardiac surgery under general anesthesia. The patients were 70 to 85 years old, with a mean age of 76. Twenty-three were men and 7 were women. Surgical procedures were 12 gastrointestinal, 6 orthopedic and 4 urogenital and others. The type of cerebrovascular disease evaluated by neuroradiologist and anesthesiologist based on MR imaging was devided as follows: 16 patients had minor stroke, 7 had transient ischemic attack/reversible ischemic neurological deficit (TIA/RIND) and 7 had asymptomatic cerebral infarction. MR angiography was also assessed to evaluate the main artery in the brain. Blood pressure and arterial blood gas (PaCO 2 ) during general anesthesia were analyzed, and the rate of systemic and neurological complications following general anesthesia were evaluated. MR angiography revealed no occlusion or severe stenosis of the main artery in the brain of any of the patients. The minimum systolic blood pressure showed less than 100 mmHg transiently for 5-20 minutes in 28 of 30 patients during general anesthesia. The minimum value was 65 mmHg maintained for 5 minutes. The minimum PaCO 2 during general anesthesia was as follows: 1 case 36 mmHg. There were no neurological complications following general anesthesia in this study. One of 30 patients (3.3%) had suffered from pneumonia

Quantification of ante-mortem hypoxic ischemic brain injury by post-mortem cerebral magnetic resonance imaging in neonatal encephalopathy.

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Montaldo, Paolo; Chaban, Badr; Lally, Peter J; Sebire, Neil J; Taylor, Andrew M; Thayyil, Sudhin

2015-11-01

Post-mortem (PM) magnetic resonance imaging (MRI) is increasingly used as an alternative to conventional autopsy in babies dying from neonatal encephalopathy. However, the confounding effect of post-mortem changes on the detection of ante-mortem ischemic injury is unclear. We examined whether quantitative MR measurements can accurately distinguish ante-mortem ischemic brain injury from artifacts using post-mortem MRI. We compared PM brain MRI (1.5 T Siemens, Avanto) in 7 infants who died with neonatal encephalopathy (NE) of presumed hypoxic-ischemic origin with 7 newborn infants who had sudden unexplained neonatal death (SUND controls) without evidence of hypoxic-ischemic brain injury at autopsy. We measured apparent diffusion coefficients (ADCs), T1-weighted signal intensity ratios (SIRs) compared to vitreous humor and T2 relaxation times from 19 predefined brain areas typically involved in neonatal encephalopathy. There were no differences in mean ADC values, SIRs on T1-weighted images or T2 relaxation times in any of the 19 predefined brain areas between NE and SUND infants. All MRI images showed loss of cortical gray/white matter differentiation, loss of the normal high signal intensity (SI) in the posterior limb of the internal capsule on T1-weighted images, and high white matter SI on T2-weighted images. Normal post-mortem changes may be easily mistaken for ante-mortem ischemic injury, and current PM MRI quantitative assessment cannot reliably distinguish these. These findings may have important implications for appropriate interpretation of PM imaging findings, especially in medico-legal practice. Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Right-to-left shunt and subclinical ischemic brain lesions in Chinese migraineurs: a multicentre MRI study.

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Jiang, Xiao-Han; Wang, Si-Bo; Tian, Qian; Zhong, Chi; Zhang, Guan-Ling; Li, Ya-Jie; Lin, Pan; You, Yong; Guo, Rong; Cui, Ying-Hua; Xing, Ying-Qi

2018-02-14

Migraine is considered as a risk factor for subclinical brain ischemic lesions, and right-to-left shunt (RLS) is more common among migraineurs. This cross-sectional study assessed the association of RLS with the increased prevalence of subclinical ischemic brain lesions in migraineurs. We enrolled 334 migraineurs from a multicentre study from June 2015 to August 2016. Participants were all evaluated using contrast-enhanced transcranial Doppler, magnetic resonance imaging (MRI), and completed a questionnaire covering demographics, the main risk factors of vascular disease, and migraine status. RLS was classified into four grades (Grade 0 = Negative; Grade I = 1 ≤ microbubbles (MBs) ≤ 10; Grade II = MBs > 10 and no curtain; Grade III = curtain). Silent brain ischemic infarctions (SBI) and white matter hyperintensities (WMHs) were evaluated on MRI. We found no significant differences between migraineurs with RLS and migraineurs without RLS in subclinical ischemic brain lesions.SBI and WMHs did not increase with the size of the RLS(p for trend for SBI = 0.066, p for trend for WMHs = 0.543). Furthermore, curtain RLS in migraineurs was a risk factor for the presence of SBI (p = 0.032, OR = 3.47; 95%CI: 1.12-10.76). There was no association between RLS and the presence of WMHs. Overall, RLS is not associated with increased SBI or WMHs in migraineurs. However, when RLS is present as a curtain pattern, it is likely to be a risk factor for SBIs in migraineurs. No. NCT02425696 ; registered on April 21, 2015.

Rationale for ischemic conditioning to prevent stroke in patients with intracranial arterial stenosis

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Sami Al Kasab

2016-01-01

Full Text Available Intracranial atherosclerotic arterial stenosis (ICAS is one of the most common causes of stroke worldwide and is associated with particularly a high risk of recurrent stroke. Although aggressive medical management, consisting of dual antiplatelet therapy and intensive control of vascular risk factors, has improved the prognosis of patients with ICAS, subgroups of patients remain at very high risk of stroke. More effective therapies for these high-risk patients are urgently needed. One promising treatment is remote limb ischemic conditioning, which involves producing repetitive, transient ischemia of a limb by inflating a blood pressure cuff with the intention of protecting the brain from subsequent ischemia. In this study, we review the limitations of currently available treatments, discuss the potential mechanisms of action of ischemic conditioning, describe the preclinical and clinical data suggesting a possible role of ischemic conditioning in treating patients with ICAS, and outline the questions that still need to be answered in future studies of ischemic conditioning in subjects with ICAS.

USE OF DIFFUSION-WEIGHTED MAGNETIC RESONANCE IMAGING FOR REVEALING HYPOXIC-ISCHEMIC BRAIN LESIONS IN NEONATES

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E. V. Shimchenko

2014-01-01

Full Text Available The article presents advantages of use of diffusion-weighted magnetic resonance imaging (DW MRI for revealing hypoxic-ischemic brain lesions in neonates. The trial included 97 neonates with perinatal brain lesion who had been undergoing treatment at a resuscitation department or neonatal pathology department in the first month of life. The article shows high information value of diffusion-weighted images (DWI for diagnostics of hypoxic-ischemic lesions in comparison with regular standard modes. In the event of no structural brain lesions of neonates, pronounced increase in signal characteristics revealed by DWI indicated considerable pathophysiological alterations. Subsequently, children developed structural alterations in the form of cystic encephalomalacia with expansion of cerebrospinal fluid spaces manifested with pronounced neurological deficit. DW MRI has been offered as a method of prognosticating further neurological development of children on early stages. 

MRI in ischemic brain diseases

International Nuclear Information System (INIS)

Steinbrich, W.; Friedmann, G.; Pawlik, G.; Boecher-Schwarz, H.G.; Heiss, W.D.

1986-01-01

The results of MRI and CT in 55 patients with brain infarcts were compared; in 26 of these cases an additional PET examination was obtained in order to study the regional glucose utilisation. MRI was superior to CT, demonstrating 11% more of the infarcts, particularly during the first 24 hours, in small lesions confined to the grey or subcortical white matter and in infratentorial ischemic lesion. On the other hand, only CT was able to show fresh hemorrhage, although MRI was the method of choice to demonstrate old blood collections. To characterise the follow up of an infarct, CT and MRI were similar, except the marginal contrast enhancement sometimes demonstrated by CT studies between the 2nd and 4th week after stroke event. PET was inferior to show details because of its poorer spatial resolution, but anyhow had a high sensitivity and provided additional informations concerning secondary inactivations of brain areas not directly damaged. Additionally PET was able to demonstrate areas of anaerobic glycolysis and lesions of diminished glucose utilisation in TIAs. Small areas of gliosis in the white matter of the cerebral hemispheres were frequently found in patients with cerebro-vascular diseases; they were best shown by MRI, but do not correlate with the extent of vascular stenoses or occlusions, shown by angiography. (orig) [de

Endothelium-targeted overexpression of heat shock protein 27 ameliorates blood–brain barrier disruption after ischemic brain injury

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Jiang, Xiaoyan; Zhang, Lili; Pu, Hongjian; Hu, Xiaoming; Zhang, Wenting; Cai, Wei; Gao, Yanqin; Leak, Rehana K.; Keep, Richard F.; Bennett, Michael V. L.; Chen, Jun

2017-01-01

The damage borne by the endothelial cells (ECs) forming the blood–brain barrier (BBB) during ischemic stroke and other neurological conditions disrupts the structure and function of the neurovascular unit and contributes to poor patient outcomes. We recently reported that structural aberrations in brain microvascular ECs—namely, uncontrolled actin polymerization and subsequent disassembly of junctional proteins, are a possible cause of the early onset BBB breach that arises within 30–60 min of reperfusion after transient focal ischemia. Here, we investigated the role of heat shock protein 27 (HSP27) as a direct inhibitor of actin polymerization and protectant against BBB disruption after ischemia/reperfusion (I/R). Using in vivo and in vitro models, we found that targeted overexpression of HSP27 specifically within ECs—but not within neurons—ameliorated BBB impairment 1–24 h after I/R. Mechanistically, HSP27 suppressed I/R-induced aberrant actin polymerization, stress fiber formation, and junctional protein translocation in brain microvascular ECs, independent of its protective actions against cell death. By preserving BBB integrity after I/R, EC-targeted HSP27 overexpression attenuated the infiltration of potentially destructive neutrophils and macrophages into brain parenchyma, thereby improving long-term stroke outcome. Notably, early poststroke administration of HSP27 attached to a cell-penetrating transduction domain (TAT-HSP27) rapidly elevated HSP27 levels in brain microvessels and ameliorated I/R-induced BBB disruption and subsequent neurological deficits. Thus, the present study demonstrates that HSP27 can function at the EC level to preserve BBB integrity after I/R brain injury. HSP27 may be a therapeutic agent for ischemic stroke and other neurological conditions involving BBB breakdown. PMID:28137866

Parameterized entropy analysis of EEG following hypoxic-ischemic brain injury

International Nuclear Information System (INIS)

Tong Shanbao; Bezerianos, Anastasios; Malhotra, Amit; Zhu Yisheng; Thakor, Nitish

2003-01-01

In the present study Tsallis and Renyi entropy methods were used to study the electric activity of brain following hypoxic-ischemic (HI) injury. We investigated the performances of these parameterized information measures in describing the electroencephalogram (EEG) signal of controlled experimental animal HI injury. The results show that (a): compared with Shannon and Renyi entropy, the parameterized Tsallis entropy acts like a spatial filter and the information rate can either tune to long range rhythms or to short abrupt changes, such as bursts or spikes during the beginning of recovery, by the entropic index q; (b): Renyi entropy is a compact and predictive indicator for monitoring the physiological changes during the recovery of brain injury. There is a reduction in the Renyi entropy after brain injury followed by a gradual recovery upon resuscitation

Progressively Disrupted Brain Functional Connectivity Network in Subcortical Ischemic Vascular Cognitive Impairment Patients.

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Sang, Linqiong; Chen, Lin; Wang, Li; Zhang, Jingna; Zhang, Ye; Li, Pengyue; Li, Chuanming; Qiu, Mingguo

2018-01-01

Cognitive impairment caused by subcortical ischemic vascular disease (SIVD) has been elucidated by many neuroimaging studies. However, little is known regarding the changes in brain functional connectivity networks in relation to the severity of cognitive impairment in SIVD. In the present study, 20 subcortical ischemic vascular cognitive impairment no dementia patients (SIVCIND) and 20 dementia patients (SIVaD) were enrolled; additionally, 19 normal controls were recruited. Each participant underwent a resting-state functional MRI scan. Whole-brain functional networks were analyzed with graph theory and network-based statistics (NBS) to study the functional organization of networks and find alterations in functional connectivity among brain regions. After adjustments for age, gender, and duration of formal education, there were significant group differences for two network functional organization indices, global efficiency and local efficiency, which decreased (NC > SIVCIND > SIVaD) as cognitive impairment worsened. Between-group differences in functional connectivity (NBS corrected, p  impairment worsened, with an increased number of decreased connections between brain regions. We also observed more reductions in nodal efficiency in the prefrontal and temporal cortices for SIVaD than for SIVCIND. These findings indicated a progressively disrupted pattern of the brain functional connectivity network with increased cognitive impairment and showed promise for the development of reliable biomarkers of network metric changes related to cognitive impairment caused by SIVD.

Potential roles of cell-derived microparticles in ischemic brain disease.

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Horstman, Lawrence L; Jy, Wenche; Bidot, Carlos J; Nordberg, Mary L; Minagar, Alireza; Alexander, J Steven; Kelley, Roger E; Ahn, Yeon S

2009-10-01

The objective of this study is to review the role of cell-derived microparticles in ischemic cerebrovascular diseases. An extensive PubMed search of literature pertaining to this study was performed in April 2009 using specific keyword search terms related to cell-derived microparticles and ischemic stroke. Some references are not cited here as it is not possible to be all inclusive or due to space limitation. Cell-derived microparticles are small membranous vesicles released from the plasma membranes of platelets, leukocytes, red cells and endothelial cells in response to diverse biochemical agents or mechanical stresses. They are the main carriers of circulating tissue factor, the principal initiator of intravascular thrombosis, and are implicated in a variety of thrombotic and inflammatory disorders. This review outlines evidence suggesting that cell-derived microparticles are involved predominantly with microvascular, as opposed to macrovascular, thrombosis. More specifically, cell-derived microparticles may substantially contribute to ischemic brain disease in several settings, as well as to neuroinflammatory conditions. If further work confirms this hypothesis, novel therapeutic strategies for minimizing cell-derived microparticles-mediated ischemia are available or can be developed, as discussed.

Complement inhibition by hydroxychloroquine prevents placental and fetal brain abnormalities in antiphospholipid syndrome.

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Bertolaccini, Maria Laura; Contento, Gregorio; Lennen, Ross; Sanna, Giovanni; Blower, Philip J; Ma, Michelle T; Sunassee, Kavitha; Girardi, Guillermina

2016-12-01

Placental ischemic disease and adverse pregnancy outcomes are frequently observed in patients with antiphospholipid syndrome (APS). Despite the administration of conventional antithrombotic treatment a significant number of women continue to experience adverse pregnancy outcomes, with uncertain prevention and management. Efforts to develop effective pharmacological strategies for refractory obstetric APS cases will be of significant clinical benefit for both mothers and fetuses. Although the antimalarial drug, hydroxychloroquine (HCQ) is increasingly used to treat pregnant women with APS, little is known about its efficacy and mechanism of action of HCQ. Because complement activation plays a crucial and causative role in placental ischemia and abnormal fetal brain development in APS we hypothesised that HCQ prevents these pregnancy complications through inhibition of complement activation. Using a mouse model of obstetric APS that closely resembles the clinical condition, we found that HCQ prevented fetal death and the placental metabolic changes -measured by proton magnetic resonance spectroscopy in APS-mice. Using 111 In labelled antiphospholipid antibodies (aPL) we identified the placenta and the fetal brain as the main organ targets in APS-mice. Using this same method, we found that HCQ does not inhibit aPL binding to tissues as was previously suggested from in vitro studies. While HCQ did not affect aPL binding to fetal brain it prevented fetal brain abnormal cortical development. HCQ prevented complement activation in vivo and in vitro. Complement C5a levels in serum samples from APS patients and APS-mice were lower after treatment with HCQ while the antibodies titres remained unchanged. HCQ prevented not only placental insufficiency but also abnormal fetal brain development in APS. By inhibiting complement activation, HCQ might also be an effective antithrombotic therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cardiorespiratory fitness, cognition and brain structure after TIA or minor ischemic stroke.

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Boss, H Myrthe; Van Schaik, Sander M; Witkamp, Theo D; Geerlings, Mirjam I; Weinstein, Henry C; Van den Berg-Vos, Renske M

2017-10-01

Background It is not known whether cardiorespiratory fitness is associated with better cognitive performance and brain structure in patients with a TIA or minor ischemic stroke. Aims To examine the association between cardiorespiratory fitness, cognition and brain structure in patients with a TIA and minor stroke. Methods The study population consisted of patients with a TIA or minor stroke with a baseline measurement of the peak oxygen consumption, a MRI scan of brain and neuropsychological assessment. Composite z-scores were calculated for the cognitive domains attention, memory and executive functioning. White matter hyperintensities, microbleeds and lacunes were rated visually. The mean apparent diffusion coefficient was measured in regions of interest in frontal and occipital white matter and in the centrum semiovale as a marker of white matter structure. Normalized brain volumes were estimated by use of Statistical Parametric Mapping. Results In 84 included patients, linear regression analysis adjusted for age, sex and education showed that a higher peak oxygen consumption was associated with higher cognitive z-scores, a larger grey matter volume (B = 0.15 (95% CI 0.05; 0.26)) and a lower mean apparent diffusion coefficient (B = -.004 (95% CI -.007; -.001)). We found no association between the peak oxygen consumption and severe white matter hyperintensities, microbleeds, lacunes and total brain volume. Conclusions These data suggest that cardiorespiratory fitness is associated with better cognitive performance, greater grey matter volume and greater integrity of the white matter in patients with a TIA or minor ischemic stroke. Further prospective trials are necessary to define the effect of cardiorespiratory fitness on cognition and brain structure in patients with TIA or minor stroke.

Correlation between Nerve Growth Factor (NGF with Brain Derived Neurotropic Factor (BDNF in Ischemic Stroke Patient

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Joko Widodo

2016-05-01

Full Text Available Background: The neurotrophins nerve growth factor (NGF and brain-derived neurotrophic factor (BDNF is a family of polypeptides that play critical role during neuronal development, appear to mediate protective role on neurorepair in ischemic stroke. Naturally in adult brain neurorepair process consist of: angiogenesis, neurogenesis, and neuronal plasticity, it can also be stimulated by endogenous neurorepair. In this study we observed correlation between NGF and BDNF ischemic stroke patient’s onset: 7-30 and over 30 days. Methods: This is cross sectional study on 46 subjects aged 38 – 74 years old with ischemic stroke from The Indonesian Central Hospital of Army Gatot Subroto Jakarta. Diagnosis of ischemic stroke was made using clinical examination and magnetic resonance imaging (MRI by neurologist. Subjects were divided into 2 groups based on stroke onset: 7 – 30 days (Group A: 19 subjects and > 30 days (Group B: 27 Subjects. Serum NGF levels were measured with ELISA method and BDNF levels were measured using multiplex method with Luminex Magpix. Results: Levels of NGF and BDNF were significantly different between onset group A and B (NGF p= 0.022, and BDNF p=0.008, with mean levels NGF in group A higher than group B, indicating that BDNF levels is lower in group A than group B. There was no significant correlation between NGF and BDNF levels in all groups. Conclusion: The variations in neurotrophic factor levels reflect an endogenous attempt at neuroprotection against biochemical and molecular changes after ischemic stroke. NGF represents an early marker of brain injury while BDNF recovery is most prominent during the first 14 days after onsite but continuous for more than 30 days. There is no significant correlation between NGF and BDNF in each group.  

Edaravone Enhances Brain-Derived Neurotrophic Factor Production in the Ischemic Mouse Brain

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Satoshi Okuyama

2015-04-01

Full Text Available Edaravone, a clinical drug used to treat strokes, protects against neuronal cell death and memory loss in the ischemic brains of animal models through its antioxidant activity. In the present study, we subcutaneously administrated edaravone to mice (3 mg/kg/day for three days immediately after bilateral common carotid artery occlusion, and revealed through an immunohistochemical analysis that edaravone (1 accelerated increases in the production of brain-derived neurotrophic factor (BDNF in the hippocampus; (2 increased the number of doublecortin-positive neuronal precursor cells in the dentate gyrus subgranular zone; and (3 suppressed the ischemia-induced inactivation of calcium-calmodulin-dependent protein kinase II in the hippocampus. We also revealed through a Western blotting analysis that edaravone (4 induced the phosphorylation of cAMP response element-binding (CREB, a transcription factor that regulates BDNF gene expression; and (5 induced the phosphorylation of extracellular signal-regulated kinases 1/2, an upstream signal factor of CREB. These results suggest that the neuroprotective effects of edaravone following brain ischemia were mediated not only by the elimination of oxidative stress, but also by the induction of BDNF production.

Molecular dialogues between the ischemic brain and the peripheral immune system: Dualistic roles in injury and repair

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An, Chengrui; Shi, Yejie; Li, Peiying; Hu, Xiaoming; Gan, Yu; Stetler, Ruth A.; Leak, Rehana K.; Gao, Yanqin; Sun, Bao-Liang; Zheng, Ping; Chen, Jun

2014-01-01

Immune and inflammatory responses actively modulate the pathophysiological processes of acute brain injuries such as stroke. Soon after the onset of stroke, signals such as brain-derived antigens, danger-associated molecular patterns (DAMPs), cytokines, and chemokines are released from the injured brain into the systemic circulation. The injured brain also communicates with peripheral organs through the parasympathetic and sympathetic branches of the autonomic nervous system. Many of these diverse signals not only activate resident immune cells in the brain, but also trigger robust immune responses in the periphery. Peripheral immune cells then migrate toward the site of injury and release additional cytokines, chemokines, and other molecules, causing further disruptive or protective effects in the ischemic brain. Bidirectional communication between the injured brain and the peripheral immune system is now known to regulate the progression of stroke pathology as well as tissue repair. In the end, this exquisitely coordinated crosstalk helps determine the fate of animals after stroke. This article reviews the literature on ischemic brain-derived signals through which peripheral immune responses are triggered, and the potential impact of these peripheral responses on brain injury and repair. Pharmacological strategies and cell-based therapies that target the dialogue between the brain and peripheral immune system show promise as potential novel treatments for stroke. PMID:24374228

Glucocorticoids Protect Neonatal Rat Brain in Model of Hypoxic-Ischemic Encephalopathy (HIE

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Benjamin Harding

2016-12-01

Full Text Available Hypoxic-ischemic encephalopathy (HIE resulting from asphyxia in the peripartum period is the most common cause of neonatal brain damage and can result in significant neurologic sequelae, including cerebral palsy. Currently therapeutic hypothermia is the only accepted treatment in addition to supportive care for infants with HIE, however, many additional neuroprotective therapies have been investigated. Of these, glucocorticoids have previously been shown to have neuroprotective effects. HIE is also frequently compounded by infectious inflammatory processes (sepsis and as such, the infants may be more amenable to treatment with an anti-inflammatory agent. Thus, the present study investigated dexamethasone and hydrocortisone treatment given after hypoxic-ischemic (HI insult in neonatal rats via intracerebroventricular (ICV injection and intranasal administration. In addition, we examined the effects of hydrocortisone treatment in HIE after lipopolysaccharide (LPS sensitization in a model of HIE and sepsis. We found that dexamethasone significantly reduced rat brain infarction size when given after HI treatment via ICV injection; however it did not demonstrate any neuroprotective effects when given intranasally. Hydrocortisone after HI insult also significantly reduced brain infarction size when given via ICV injection; and the intranasal administration showed to be protective of brain injury in male rats at a dose of 300 µg. LPS sensitization did significantly increase the brain infarction size compared to controls, and hydrocortisone treatment after LPS sensitization showed a significant decrease in brain infarction size when given via ICV injection, as well as intranasal administration in both genders at a dose of 300 µg. To conclude, these results show that glucocorticoids have significant neuroprotective effects when given after HI injury and that these effects may be even more pronounced when given in circumstances of additional

Edaravone attenuates neuronal apoptosis in hypoxic-ischemic brain damage rat model via suppression of TRAIL signaling pathway.

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Li, Chunyi; Mo, Zhihuai; Lei, Junjie; Li, Huiqing; Fu, Ruying; Huang, Yanxia; Luo, Shijian; Zhang, Lei

2018-06-01

Edaravone is a new type of oxygen free radical scavenger and able to attenuate various brain damage including hypoxic-ischemic brain damage (HIBD). This study was aimed at investigating the neuroprotective mechanism of edaravone in rat hypoxic-ischemic brain damage model and its correlation with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) signaling pathway. 75 seven-day-old Sprague-Dawley neonatal rats were equally divided into three groups: sham-operated group (sham), HIBD group and HIBD rats injected with edaravone (HIBD + EDA) group. Neurological severity and space cognitive ability of rats in each group were evaluated using Longa neurological severity score and Morris water maze testing. TUNEL assay and flow cytometry were used to determine brain cell apoptosis. Western blot was used to estimate the expression level of death receptor-5 (DR5), Fas-associated protein with death domain (FADD), caspase 8, B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax). In addition, immunofluorescence was performed to detect caspase 3. Edaravone reduced neurofunctional damage caused by HIBD and improved the cognitive capability of rats. The above experiment results suggested that edaravone could down-regulate the expression of active caspase 3 protein, thereby relieving neuronal apoptosis. Taken together, edaravone could attenuate neuronal apoptosis in rat hypoxic-ischemic brain damage model via suppression of TRAIL signaling pathway, which also suggested that edaravone might be an effective therapeutic strategy for HIBD clinical treatment. Copyright © 2018 Elsevier Ltd. All rights reserved.

Nutrition for brain recovery after ischemic stroke: an added value to rehabilitation.

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Aquilani, Roberto; Sessarego, Paolo; Iadarola, Paolo; Barbieri, Annalisa; Boschi, Federica

2011-06-01

In patients who undergo rehabilitation after ischemic stroke, nutrition strategies are adopted to provide tube-fed individuals with adequate nutrition and/or to avoid the body wasting responsible for poor functional outcome and prolonged stay in the hospital. Investigations have documented that nutrition interventions can enhance the recovery of neurocognitive function in individuals with ischemic stroke. Experimental studies have shown that protein synthesis is suppressed in the ischemic penumbra. In clinical studies on rehabilitation patients designed to study the effects of counteracting or limiting this reduction of protein synthesis by providing protein supplementation, patients receiving such supplementation had enhanced recovery of neurocognitive function. Cellular damage in cerebral ischemia is also partly caused by oxidative damage secondary to free radical formation and lipid peroxidation. Increased oxidative stress negatively affects a patient's life and functional prognosis. Some studies have documented that nutrition supplementation with B-group vitamins may mitigate oxidative damage after acute ischemic stroke. Experimental investigations have also shown that cerebral ischemia changes synaptic zinc release and that acute ischemia increases zinc release, aggravating neuronal injury. In clinical practice, patients with ischemic stroke were found to have a lower than recommended dietary intake of zinc. Patients in whom daily zinc intake was normalized had better recovery of neurological deficits than subjects given a placebo. The aim of this review is to highlight those brain metabolic alterations susceptible to nutrition correction in clinical practice. The mechanisms underlying the relationship between cerebral ischemia and nutrition metabolic conditions are discussed.

MRI patterns of hypoxic-ischemic brain injury in preterm and full term infants – classical and less common MR findings

International Nuclear Information System (INIS)

Cabaj, Astra; Bekiesińska-Figatowska, Monika; Mądzik, Jaroslaw

2012-01-01

Hypoxic-ischemic brain injury occurring in antenatal, perinatal or early postnatal period constitutes an important diagnostic problem in both term and prematurely born neonates. Over the past several years magnetic resonance imaging (MRI) has become relatively easily accessible in Poland. On the basis of the central nervous system MRI, the experienced radiologist are able to determine the location of the hypoxic-ischemic lesions, their extent and evolution. Therefore he can help clinicians to answer the question whether the brain damage of the newborn is responsible for its clinical condition and he can contribute to determining the prognosis of the infant’s future development. The aim of this study is to present the current knowledge of different types of hypoxic-ischemic brain lesions based on our personal experience and MR images from the archives of the Department of Diagnostic Imaging at the Institute of Mother and Child

Computerized tomography of the brain and associated risk factors in 240 patients iwth reversible cerebral ischemic attacks (RIAs)

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Bozzao, L.; Fantozzi, L.M.; Carolei, A.; Pappata, S.; Vesentini, G.; Allori, L.; Rasura, M.; Fieschi, C.

1985-01-01

The frequency and distribution of focal low density cerebral ischemic lesions in RIA patients with regard to factors as age at onset, number and temporal profile of the reversible cerebral ischemic events on admission, presence of associated medical conditions such as hypertension and diabetes mellitus, have been investigated with computerized tomography of the brain. (author). 7 refs.; 1 tab

Ketogenic Diet Improves Brain Ischemic Tolerance and Inhibits NLRP3 Inflammasome Activation by Preventing Drp1-Mediated Mitochondrial Fission and Endoplasmic Reticulum Stress

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Min Guo

2018-03-01

Full Text Available Background: Neuroprotective effects of ketogenic diets (KD have been reported in stroke models, and nucleotide-binding domain (NOD-like receptor protein 3 (NLRP3 inflammasome has also been implicated in the pathogenesis of stroke. This study aimed to investigate the effects of KD on NLRP3 inflammasome and explore the potential molecular mechanisms.Methods: In in vivo study, mice were fed with KD for 3 weeks and then subjected to middle cerebral artery occlusion/reperfusion (MCAO/R-injury. In in vitro study, SH-SY-5Y cells were treated with β-hydroxybutyrate (BHB followed by oxygen–glucose deprivation/reoxygenation (OGD/R. NLRP3 inflammasome activation and related regulatory mechanisms were evaluated.Results: Mice fed with KD had increased tolerance to MCAO/R. KD inhibited endoplasmic reticulum (ER stress and suppressed TXNIP/NLRP3 inflammasome activation in the brain. The in vitro study showed BHB (10 mM prevented the mitochondrial translocation of dynamin-related protein 1 (Drp1 to inhibit mitochondrial fission. Furthermore, BHB decreased reactive oxygen species (ROS generation, inhibited ROS-NLRP3 pathway in OGD/R-treated cells, and suppressed ER stress-induced NLRP3 inflammasome activation.Conclusions: KD may suppress ER stress and protect mitochondrial integrity by suppressing the mitochondrial translocation of Drp1 to inhibit NLRP3 inflammasome activation, thus exerting neuroprotective effects. Our findings provide evidence for the potential application of KD in the prevention of ischemic stroke.

An emboligenic pulmonary abscess leading to ischemic stroke and secondary brain abscess

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Albrecht Philipp

2012-11-01

Full Text Available Abstract Background Ischemic stroke by septic embolism occurs primarily in the context of infective endocarditis or in patients with a right-to-left shunt and formation of a secondary cerebral abscess is a rare event. Erosion of pulmonary veins by a pulmonary abscess can lead to transcardiac septic embolism but to our knowledge no case of septic embolic ischemic stroke from a pulmonary abscess with secondary transformation into a brain abscess has been reported to date. Case presentation We report the case of a patient with a pulmonary abscess causing a septic embolic cerebral infarction which then transformed into a cerebral abscess. After antibiotic therapy and drainage of the abscess the patient could be rehabilitated and presented an impressive improvement of symptoms. Conclusion Septic embolism should be considered as cause of ischemic stroke in patients with pulmonary abscess and can be followed by formation of a secondary cerebral abscess. Early antibiotic treatment and repeated cranial CT-scans for detection of a secondary abscess should be performed.

Molecular dialogs between the ischemic brain and the peripheral immune system: dualistic roles in injury and repair.

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An, Chengrui; Shi, Yejie; Li, Peiying; Hu, Xiaoming; Gan, Yu; Stetler, Ruth A; Leak, Rehana K; Gao, Yanqin; Sun, Bao-Liang; Zheng, Ping; Chen, Jun

2014-04-01

Immune and inflammatory responses actively modulate the pathophysiological processes of acute brain injuries such as stroke. Soon after the onset of stroke, signals such as brain-derived antigens, danger-associated molecular patterns (DAMPs), cytokines, and chemokines are released from the injured brain into the systemic circulation. The injured brain also communicates with peripheral organs through the parasympathetic and sympathetic branches of the autonomic nervous system. Many of these diverse signals not only activate resident immune cells in the brain, but also trigger robust immune responses in the periphery. Peripheral immune cells then migrate toward the site of injury and release additional cytokines, chemokines, and other molecules, causing further disruptive or protective effects in the ischemic brain. Bidirectional communication between the injured brain and the peripheral immune system is now known to regulate the progression of stroke pathology as well as tissue repair. In the end, this exquisitely coordinated crosstalk helps determine the fate of animals after stroke. This article reviews the literature on ischemic brain-derived signals through which peripheral immune responses are triggered, and the potential impact of these peripheral responses on brain injury and repair. Pharmacological strategies and cell-based therapies that target the dialog between the brain and peripheral immune system show promise as potential novel treatments for stroke. Published by Elsevier Ltd.

Adenosine A1 receptors contribute to immune regulation after neonatal hypoxic ischemic brain injury

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Winerdal, Max; Winerdal, Malin E.; Wang, Ying-Qing; Fredholm, Bertil B.; Winqvist, Ola; Ådén, Ulrika

2015-01-01

Neonatal brain hypoxic ischemia (HI) often results in long-term motor and cognitive impairments. Post-ischemic inflammation greatly effects outcome and adenosine receptor signaling modulates both HI and immune cell function. Here, we investigated the influence of adenosine A1 receptor deficiency (A1R−/−) on key immune cell populations in a neonatal brain HI model. Ten-day-old mice were subjected to HI. Functional outcome was assessed by open locomotion and beam walking test and infarction siz...

Imaging of cerebral ischemic edema and neuronal death

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Kummer, Ruediger von [Universitaetsklinikum Carl Gustav Carus, Institut fuer Diagnostische und Interventionelle Neuroradiologie, Dresden (Germany); Dzialowski, Imanuel [Elblandklinikum Meissen, Neurologische Rehabilitationsklinik Grossenhain, Meissen (Germany)

2017-06-15

In acute cerebral ischemia, the assessment of irreversible injury is crucial for treatment decisions and the patient's prognosis. There is still uncertainty how imaging can safely differentiate reversible from irreversible ischemic brain tissue in the acute phase of stroke. We have searched PubMed and Google Scholar for experimental and clinical papers describing the pathology and pathophysiology of cerebral ischemia under controlled conditions. Within the first 6 h of stroke onset, ischemic cell injury is subtle and hard to recognize under the microscope. Functional impairment is obvious, but can be induced by ischemic blood flow allowing recovery with flow restoration. The critical cerebral blood flow (CBF) threshold for irreversible injury is ∝15 ml/100 g x min. Below this threshold, ischemic brain tissue takes up water in case of any residual capillary flow (ionic edema). Because tissue water content is linearly related to X-ray attenuation, computed tomography (CT) can detect and measure ionic edema and, thus, determine ischemic brain infarction. In contrast, diffusion-weighted magnetic resonance imaging (DWI) detects cytotoxic edema that develops at higher thresholds of ischemic CBF and is thus highly sensitive for milder levels of brain ischemia, but not specific for irreversible brain tissue injury. CT and MRI are complimentary in the detection of ischemic stroke pathology and are valuable for treatment decisions. (orig.)

Brain metabolism in patients with freezing of gait after hypoxic-ischemic brain injury: A pilot study.

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Yoon, Seo Yeon; Lee, Sang Chul; Kim, Na Young; An, Young-Sil; Kim, Yong Wook

2017-11-01

Movement disorders are 1 of the long-term neurological complications that can occur after hypoxic-ischemic brain injury (HIBI). However, freezing of gait (FOG) after HIBI is rare. The aim of this study was to examine the brain metabolism of patients with FOG after HIBI using F-18 fluoro-2-deoxy-D-glucose positron emission tomography (F-18 FDG PET).We consecutively enrolled 11 patients with FOG after HIBI. The patients' overall brain metabolism was measured by F-18 FDG PET, and we compared their regional brain metabolic activity with that from 15 healthy controls using a voxel-by-voxel-based statistical mapping analysis. Additionally, we correlated each patient's FOG severity with the brain metabolism using a covariance analysis.Patients with FOG had significantly decreased brain glucose metabolism in the midbrain, bilateral thalamus, bilateral cingulate gyri, right supramarginal gyrus, right angular gyrus, right paracentral lobule, and left precentral gyrus (PFDR-corrected brain metabolism were noted in patients with FOG. The covariance analysis identified significant correlations between the FOG severity and the brain metabolism in the right lingual gyrus, left fusiform gyrus, and bilateral cerebellar crus I (Puncorrected brain regions in the gait-related neural network, including the cerebral cortex, subcortical structures, brainstem, and cerebellum, may significantly contribute to the development of FOG in HIBI. Moreover, the FOG severity may be associated with the visual cortex and cerebellar regions.

Inhibition of CD147 (Cluster of Differentiation 147) Ameliorates Acute Ischemic Stroke in Mice by Reducing Thromboinflammation.

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Jin, Rong; Xiao, Adam Y; Chen, Rui; Granger, D Neil; Li, Guohong

2017-12-01

Inflammation and thrombosis currently are recognized as critical contributors to the pathogenesis of ischemic stroke. CD147 (cluster of differentiation 147), also known as extracellular matrix metalloproteinase inducer, can function as a key mediator of inflammatory and immune responses. CD147 expression is increased in the brain after cerebral ischemia, but its role in the pathogenesis of ischemic stroke remains unknown. In this study, we show that CD147 acts as a key player in ischemic stroke by driving thrombotic and inflammatory responses. Focal cerebral ischemia was induced in C57BL/6 mice by a 60-minute transient middle cerebral artery occlusion. Animals were treated with anti-CD147 function-blocking antibody (αCD147) or isotype control antibody. Blood-brain barrier permeability, thrombus formation, and microvascular patency were assessed 24 hours after ischemia. Infarct size, neurological deficits, and inflammatory cells invaded in the brain were assessed 72 hours after ischemia. CD147 expression was rapidly increased in ischemic brain endothelium after transient middle cerebral artery occlusion. Inhibition of CD147 reduced infarct size and improved functional outcome on day 3 after transient middle cerebral artery occlusion. The neuroprotective effects were associated with (1) prevented blood-brain barrier damage, (2) decreased intravascular fibrin and platelet deposition, which in turn reduced thrombosis and increased cerebral perfusion, and (3) reduced brain inflammatory cell infiltration. The underlying mechanism may include reduced NF-κB (nuclear factor κB) activation, MMP-9 (matrix metalloproteinase-9) activity, and PAI-1 (plasminogen activator inhibitor-1) expression in brain microvascular endothelial cells. Inhibition of CD147 ameliorates acute ischemic stroke by reducing thromboinflammation. CD147 might represent a novel and promising therapeutic target for ischemic stroke and possibly other thromboinflammatory disorders. © 2017 American Heart

Early VEGF inhibition attenuates blood-brain barrier disruption in ischemic rat brains by regulating the expression of MMPs.

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Zhang, Hai-Tao; Zhang, Ping; Gao, Yi; Li, Chen-Long; Wang, Hong-Jun; Chen, Ling-Chao; Feng, Yan; Li, Rui-Yan; Li, Yong-Li; Jiang, Chuan-Lu

2017-01-01

Vascular endothelial growth factor (VEGF) inhibition has been demonstrated to be an effective strategy in preserving the integrity of the blood-brain barrier (BBB) in patients with acute ischemic stroke. Loss of the BBB is the key event associated with morbidity and mortality in these patients. However, the underlying mechanisms remain poorly understood. In the present study, the effects of VEGF inhibition and the possible mechanism that underlies acute cerebral ischemia in rats was investigated. Following the induction of transient middle cerebral artery occlusion for a 90‑min period, either an anti‑VEGF neutralizing antibody (RB‑222; 5 or 10 µg), or IgG (control), was administered by intracerebroventricular injection at 1 h following reperfusion. Functional outcomes, BBB leakage, brain edema, microvessel numbers and the relative protein levels of VEGF, matrix metalloproteinase (MMP)-2, MMP-9, occludin and collagen-IV were then determined using neurological assessments, Evans Blue staining, brain water content, CD31 staining and western blotting. Treatment with RB‑222 at a dose of 5 and 10 µg significantly improved neurological functional outcomes and diminished infarct size, BBB leakage and brain edema compared with the MCAO and IgG groups at 24 h following reperfusion; 10 µg RB‑222 was more effective than a 5 µg dose of the antibody. In addition, RB‑222 reduced the number of immature microvessels, which subsequently attenuated BBB permeability. RB‑222 significantly repressed VEGF expression as well as decreased MMP‑2 and MMP‑9 expression. However, it enhanced occludin and collagen‑IV levels in the ischemic rat brain compared with the MCAO and IgG groups. Taken together, the results indicate that early inhibition of VEGF may have significant potential against cerebral ischemia, partly by regulating the expression of MMPs.

Ceftriaxone attenuates hypoxic-ischemic brain injury in neonatal rats

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Huang Yen

2011-09-01

Full Text Available Abstract Background Perinatal brain injury is the leading cause of subsequent neurological disability in both term and preterm baby. Glutamate excitotoxicity is one of the major factors involved in perinatal hypoxic-ischemic encephalopathy (HIE. Glutamate transporter GLT1, expressed mainly in mature astrocytes, is the major glutamate transporter in the brain. HIE induced excessive glutamate release which is not reuptaked by immature astrocytes may induce neuronal damage. Compounds, such as ceftriaxone, that enhance the expression of GLT1 may exert neuroprotective effect in HIE. Methods We used a neonatal rat model of HIE by unilateral ligation of carotid artery and subsequent exposure to 8% oxygen for 2 hrs on postnatal day 7 (P7 rats. Neonatal rats were administered three dosages of an antibiotic, ceftriaxone, 48 hrs prior to experimental HIE. Neurobehavioral tests of treated rats were assessed. Brain sections from P14 rats were examined with Nissl and immunohistochemical stain, and TUNEL assay. GLT1 protein expression was evaluated by Western blot and immunohistochemistry. Results Pre-treatment with 200 mg/kg ceftriaxone significantly reduced the brain injury scores and apoptotic cells in the hippocampus, restored myelination in the external capsule of P14 rats, and improved the hypoxia-ischemia induced learning and memory deficit of P23-24 rats. GLT1 expression was observed in the cortical neurons of ceftriaxone treated rats. Conclusion These results suggest that pre-treatment of infants at risk for HIE with ceftriaxone may reduce subsequent brain injury.

Systematic Analysis of RNA Regulatory Network in Rat Brain after Ischemic Stroke

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Juan Liu

2018-01-01

Full Text Available Although extensive studies have identified large number of microRNAs (miRNAs and long noncoding RNAs (lncRNAs in ischemic stroke, the RNA regulation network response to focal ischemia remains poorly understood. In this study, we simultaneously interrogate the expression profiles of lncRNAs, miRNAs, and mRNAs changes during focal ischemia induced by transient middle cerebral artery occlusion. A set of 1924 novel lncRNAs were identified and may involve brain injury and DNA repair as revealed by coexpression network analysis. Furthermore, many short interspersed elements (SINE mediated lncRNA:mRNA duplexes were identified, implying that lncRNAs mediate Staufen1-mediated mRNA decay (SMD which may play a role during focal ischemia. Moreover, based on the competitive endogenous RNA (ceRNA hypothesis, a stroke regulatory ceRNA network which reveals functional lncRNA:miRNA:mRNA interactions was revealed in ischemic stroke. In brief, this work reports a large number of novel lncRNAs responding to focal ischemia and constructs a systematic RNA regulation network which highlighted the role of ncRNAs in ischemic stroke.

Chemical exchange-sensitive spin-lock MRI of glucose analog 3-O-methyl-d-glucose in normal and ischemic brain.

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Jin, Tao; Mehrens, Hunter; Wang, Ping; Kim, Seong-Gi

2018-05-01

Glucose transport is important for understanding brain glucose metabolism. We studied glucose transport with a presumably non-toxic and non-metabolizable glucose analog, 3-O-methyl-d-glucose, using a chemical exchange-sensitive spin-lock MRI technique at 9.4 Tesla. 3-O-methyl-d-glucose showed comparable chemical exchange properties with d-glucose and 2-deoxy-d-glucose in phantoms, and higher and lower chemical exchange-sensitive spin-lock sensitivity than Glc and 2-deoxy-d-glucose in in vivo experiments, respectively. The changes of the spin-lattice relaxation rate in the rotating frame (Δ R 1 ρ) in normal rat brain peaked at ∼15 min after the intravenous injection of 1 g/kg 3-O-methyl-d-glucose and almost maintained a plateau for >1 h. Doses up to 4 g/kg 3-O-methyl-d-glucose were linearly correlated with Δ R 1 ρ. In rats with focal ischemic stroke, chemical exchange-sensitive spin-lock with 3-O-methyl-d-glucose injection at 1 h after stroke onset showed reduced Δ R 1 ρ in the ischemic core but higher Δ R 1 ρ in the peri-core region compared to normal tissue, which progressed into the ischemic core at 3 h after stroke onset. This suggests that the hyper-chemical exchange-sensitive spin-lock region observed at 1 h is the ischemic penumbra at-risk of infarct. In summary, 3-O-methyl-d-glucose-chemical exchange-sensitive spin-lock can be a sensitive MRI technique to probe the glucose transport in normal and ischemic brains.

Application of diffusion-weighted echo planar imaging for diagnosis of small acute and subacute brain ischemic lesions

International Nuclear Information System (INIS)

Enomoto, Kyoko; Watanabe, Tsuneya; Amanuma, Makoto; Heshiki, Atsuko

1997-01-01

The aim of this study was to determine the utility of diffusion-weighted echo planar imaging (DW-EPI) for detecting acute and subacute brain ischemic foci less than 2 cm in size. Thirty patients underwent DW-EPI on a 1.5 T super-conducting unit using a SE-EPI sequence with an arbitrary pair of Stejskal-Tanner gradients applied along the imaging axes. DW-EPI demonstrated all the mast recent ischemic lesions as areas of decreased diffusion, providing greater conspicuity and larger size than conventional spin-echo imaging. DW-EPI is a promising method to detect within a subsecond early ischemia and reversible ischemic changes that are not demonstrate on routine spin-echo images. (author)

Protective effect of Kombucha tea on brain damage induced by transient cerebral ischemia and reperfusion in rat

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Najmeh Kabiri

2016-09-01

Full Text Available The aim of study was to investigate the potential neuroprotective effects of Kombucha on cerebral damage induced by ischemia in rats (n=99. Cerebral infarct volume in the ischemic rats received Kombucha solution showed no significance alteration. However, the permeability of blood-brain barrier significantly decreased in both ischemic rats received 15 mg/kg Kombucha tea and Sham group. In addition, brain water content in the ischemic groups treated with Kombucha solution was significantly higher than the Sham group, although right hemispheres in all of the treated groups illustrated higher brain water content than the left ones. Brain anti-oxidant capacity elevated in the ischemic rats treated with Kombucha and in the Sham group. Brain and plasma malondialdehyde concentrations significantly decreased in both of the ischemic groups injected with Kombucha. The findings suggest that Kombucha tea could be useful for the prevention of cerebral damage.

S100B protein in serum is elevated after global cerebral ischemic injury

Institute of Scientific and Technical Information of China (English)

Bao-di Sun; Hong-mei Liu; Shi-nan Nie

2013-01-01

BACKGROUND:S100B protein in patients with cardiac arrest,hemorrhagic shock and other causes of global cerebral ischemic injury will be dramatically increased.Ischemic brain injury may elevate the level of serum S100 B protein and the severity of brain damage.METHODS:This article is a critical and descriptive review on S100 B protein in serum after ischemic brain injury.We searched Pubmed database with key words or terms such as 'S100B protein', 'cardiac arrest', 'hemorrhagic shock' and 'ischemia reperfusion injury' appeared in the last five years.RESULTS:S100B protein in patients with cardiac arrest,hemorrhagic shock and other causes of ischemic brain injury will be dramatically increased.Ischemic brain injury elevated the level of serum S100 B protein,and the severity of brain damage.CONCLUSION:The level of S100 B protein in serum is elevated after ischemic brain injury,but its mechanism is unclear.

Pharmacokinetic Study of Piracetam in Focal Cerebral Ischemic Rats.

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Paliwal, Pankaj; Dash, Debabrata; Krishnamurthy, Sairam

2018-04-01

Cerebral ischemia affects hepatic enzymes and brain permeability extensively. Piracetam was investigated up to phase III of clinical trials and there is lack of data on brain penetration in cerebral ischemic condition. Thus, knowledge of the pharmacokinetics and brain penetration of piracetam during ischemic condition would aid to improve pharmacotherapeutics in ischemic stroke. Focal cerebral ischemia was induced by middle cerebral artery occlusion for 2 h in male Wistar rats followed by reperfusion. After 24 h of middle cerebral artery occlusion or 22 h of reperfusion, piracetam was administered for pharmacokinetic, brain penetration, and pharmacological experiments. In pharmacokinetic study, blood samples were collected at different time points after 200-mg/kg (oral) and 75-mg/kg (intravenous) administration of piracetam through right external jugular vein cannulation. In brain penetration study, the cerebrospinal fluid, systemic blood, portal blood, and brain samples were collected at pre-designated time points after 200-mg/kg oral administration of piracetam. In a separate experiment, the pharmacological effect of the single oral dose of piracetam in middle cerebral artery occlusion was assessed at a dose of 200 mg/kg. All the pharmacokinetic parameters of piracetam including area under curve (AUC 0-24 ), maximum plasma concentration (C max ), time to reach the maximum plasma concentration (t max ), elimination half-life (t 1/2 ), volume of distribution (V z ), total body clearance, mean residence time, and bioavailability were found to be similar in ischemic stroke condition except for brain penetration. Piracetam exposure (AUC 0-2 ) in brain and CSF were found to be 2.4- and 3.1-fold higher, respectively, in ischemic stroke compared to control rats. Piracetam significantly reduced infarct volume by 35.77% caused by middle cerebral artery occlusion. There was no change in the pharmacokinetic parameters of piracetam in the ischemic stroke model except for

Impact of Secondary Prevention on Mortality after a First Ischemic Stroke in Puerto Rico.

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Rojas, Maria E; Marsh, Wallace; Felici-Giovanini, Marcos E; Rodríguez-Benitez, Rosa J; Zevallos, Juan C

2017-03-01

The objective of this study was to evaluate the impact of the prescription of secondary prevention therapies on mortality in Puerto Rican patients hospitalized with a first ischemic stroke. This was a retrospective secondary data analysis of the 2007 and 2009 Puerto Rico Stroke Registry electronic database. Information was obtained from the medical charts of patients discharged with ICD-9 codes 434 and 436 from 20 hospitals located in Puerto Rico. Descriptive analyses were conducted for demographics and comorbidities. Chi2 statistics compared the proportion of patients prescribed secondary prevention therapy and the proportion of patients not prescribed secondary prevention therapy. Lastly, survival rates were calculated from 2007 up to and including December 2010. The mean age of the 3,965 patients was 70 (±14) years. Secondary prevention therapy was prescribed to only 1% of the patients. The most frequent comorbidities were hypertension (85%), diabetes (52%), and hyperlipidemia (25%). The case fatality rate for patients prescribed secondary prevention therapy was 16%, compared to 26% for patients not prescribed secondary prevention therapy (p<0.01). The mean survival for stroke patients prescribed secondary preventions was 450 days (95% CI;182−718), compared to 266 days (95% CI; 244−287) for those not prescribed secondary prevention therapy (p = 0.175). A low percentage of patients with a first ischemic stroke were prescribed secondary prevention therapy. While not statistically significant, survival analysis suggests that secondary prevention therapy decreased mortality in patients with a stroke.

Sensorimotor Functional and Structural Networks after Intracerebral Stem Cell Grafts in the Ischemic Mouse Brain.

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Green, Claudia; Minassian, Anuka; Vogel, Stefanie; Diedenhofen, Michael; Beyrau, Andreas; Wiedermann, Dirk; Hoehn, Mathias

2018-02-14

Past investigations on stem cell-mediated recovery after stroke have limited their focus on the extent and morphological development of the ischemic lesion itself over time or on the integration capacity of the stem cell graft ex vivo However, an assessment of the long-term functional and structural improvement in vivo is essential to reliably quantify the regenerative capacity of cell implantation after stroke. We induced ischemic stroke in nude mice and implanted human neural stem cells (H9 derived) into the ipsilateral cortex in the acute phase. Functional and structural connectivity changes of the sensorimotor network were noninvasively monitored using magnetic resonance imaging for 3 months after stem cell implantation. A sharp decrease of the functional sensorimotor network extended even to the contralateral hemisphere, persisting for the whole 12 weeks of observation. In mice with stem cell implantation, functional networks were stabilized early on, pointing to a paracrine effect as an early supportive mechanism of the graft. This stabilization required the persistent vitality of the stem cells, monitored by bioluminescence imaging. Thus, we also observed deterioration of the early network stabilization upon vitality loss of the graft after a few weeks. Structural connectivity analysis showed fiber-density increases between the cortex and white matter regions occurring predominantly on the ischemic hemisphere. These fiber-density changes were nearly the same for both study groups. This motivated us to hypothesize that the stem cells can influence, via early paracrine effect, the functional networks, while observed structural changes are mainly stimulated by the ischemic event. SIGNIFICANCE STATEMENT In recent years, research on strokes has made a shift away from a focus on immediate ischemic effects and towards an emphasis on the long-range effects of the lesion on the whole brain. Outcome improvements in stem cell therapies also require the understanding of

Intranasal Delivery of Granulocyte Colony-Stimulating Factor Enhances Its Neuroprotective Effects Against Ischemic Brain Injury in Rats.

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Sun, Bao-Liang; He, Mei-Qing; Han, Xiang-Yu; Sun, Jing-Yi; Yang, Ming-Feng; Yuan, Hui; Fan, Cun-Dong; Zhang, Shuai; Mao, Lei-Lei; Li, Da-Wei; Zhang, Zong-Yong; Zheng, Cheng-Bi; Yang, Xiao-Yi; Li, Yang V; Stetler, R Anne; Chen, Jun; Zhang, Feng

2016-01-01

Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic growth factor with strong neuroprotective properties. However, it has limited capacity to cross the blood-brain barrier and thus potentially limiting its protective capacity. Recent studies demonstrated that intranasal drug administration is a promising way in delivering neuroprotective agents to the central nervous system. The current study therefore aimed at determining whether intranasal administration of G-CSF increases its delivery to the brain and its neuroprotective effect against ischemic brain injury. Transient focal cerebral ischemia in rat was induced with middle cerebral artery occlusion. Our resulted showed that intranasal administration is 8-12 times more effective than subcutaneous injection in delivering G-CSF to cerebrospinal fluid and brain parenchyma. Intranasal delivery enhanced the protective effects of G-CSF against ischemic injury in rats, indicated by decreased infarct volume and increased recovery of neurological function. The neuroprotective mechanisms of G-CSF involved enhanced upregulation of HO-1 and reduced calcium overload following ischemia. Intranasal G-CSF application also promoted angiogenesis and neurogenesis following brain ischemia. Taken together, G-CSF is a legitimate neuroprotective agent and intranasal administration of G-CSF is more effective in delivery and neuroprotection and could be a practical approach in clinic.

Effect of alternate energy substrates on mammalian brain metabolism during ischemic events.

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Koppaka, S S; Puchowicz; LaManna, J C; Gatica, J E

2008-01-01

Regulation of brain metabolism and cerebral blood flow involves complex control systems with several interacting variables at both cellular and organ levels. Quantitative understanding of the spatially and temporally heterogeneous brain control mechanisms during internal and external stimuli requires the development and validation of a computational (mathematical) model of metabolic processes in brain. This paper describes a computational model of cellular metabolism in blood-perfused brain tissue, which considers the astrocyte-neuron lactate-shuttle (ANLS) hypothesis. The model structure consists of neurons, astrocytes, extra-cellular space, and a surrounding capillary network. Each cell is further compartmentalized into cytosol and mitochondria. Inter-compartment interaction is accounted in the form of passive and carrier-mediated transport. Our model was validated against experimental data reported by Crumrine and LaManna, who studied the effect of ischemia and its recovery on various intra-cellular tissue substrates under standard diet conditions. The effect of ketone bodies on brain metabolism was also examined under ischemic conditions following cardiac resuscitation through our model simulations. The influence of ketone bodies on lactate dynamics on mammalian brain following ischemia is studied incorporating experimental data.

The neuroprotective effects of intramuscular insulin-like growth factor-I treatment in brain ischemic rats.

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Heng-Chih Chang

Full Text Available Brain ischemia leads to muscle inactivity-induced atrophy and may exacerbate motor function deficits. Intramuscular insulin-like growth factor I (IGF-I injection has been shown to alleviate the brain ischemia-induced muscle atrophy and thus improve the motor function. Motor function is normally gauged by the integrity and coordination of the central nervous system and peripheral muscles. Whether brain ischemic regions are adaptively changed by the intramuscular IGF-I injection is not well understood. In this study, the effect of intramuscular IGF-I injection was examined on the central nervous system of brain ischemic rats. Rats were divided into 4 groups: sham control, brain ischemia control, brain ischemia with IGF-I treatment, and brain ischemia with IGF-I plus IGF-I receptor inhibitor treatment. Brain ischemia was induced by right middle cerebral artery occlusion. IGF-I and an IGF-1 receptor inhibitor were injected into the affected calf and anterior tibialis muscles of the treated rats for 4 times. There was an interval of 2 days between each injection. Motor function was examined and measured at the 24 hours and 7 days following a brain ischemia. The affected hind-limb muscles, sciatic nerve, lumbar spinal cord, and motor cortex were collected for examination after euthanizing the rats. IGF-I expression in the central nervous system and affected muscles were significantly decreased after brain ischemia. Intramuscular IGF-I injection increased the IGF-I expression in the affected muscles, sciatic nerve, lumbar spinal cord, and motor cortex. It also increased the p-Akt expression in the affected motor cortex. Furthermore, intramuscular IGF-I injection decreased the neuronal apoptosis and improved the motor function. However, co-administration of the IGF-I receptor inhibitor eliminated these effects. Intramuscular IGF-I injection after brain ischemia attenuated or reversed the decrease of IGF-I in both central and peripheral tissues, and

Synthetic Oligodeoxynucleotides Containing Multiple Telemeric TTAGGG Motifs Suppress Inflammasome Activity in Macrophages Subjected to Oxygen and Glucose Deprivation and Reduce Ischemic Brain Injury in Stroke-Prone Spontaneously Hypertensive Rats.

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Jing Zhao

Full Text Available The immune system plays a fundamental role in both the development and pathobiology of stroke. Inflammasomes are multiprotein complexes that have come to be recognized as critical players in the inflammation that ultimately contributes to stroke severity. Inflammasomes recognize microbial and host-derived danger signals and activate caspase-1, which in turn controls the production of the pro-inflammatory cytokine IL-1β. We have shown that A151, a synthetic oligodeoxynucleotide containing multiple telemeric TTAGGG motifs, reduces IL-1β production by activated bone marrow derived macrophages that have been subjected to oxygen-glucose deprivation and LPS stimulation. Further, we demonstrate that A151 reduces the maturation of caspase-1 and IL-1β, the levels of both the iNOS and NLRP3 proteins, and the depolarization of mitochondrial membrane potential within such cells. In addition, we have demonstrated that A151 reduces ischemic brain damage and NLRP3 mRNA levels in SHR-SP rats that have undergone permanent middle cerebral artery occlusion. These findings clearly suggest that the modulation of inflammasome activity via A151 may contribute to a reduction in pro-inflammatory cytokine production by macrophages subjected to conditions that model brain ischemia and modulate ischemic brain damage in an animal model of stroke. Therefore, modulation of ischemic pathobiology by A151 may have a role in the development of novel stroke prevention and therapeutic strategies.

Pharmacoepidemiological analysis of the drugs used for secondary prevention of brain infarction on dispensary stage

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Miheyeva N.V.

2014-03-01

Full Text Available Aim. The secondary prevention of cerebral infarction on dispensary stage to current clinical guidelines was analyzed. Adherence of patients to prescribe medications was evaluated. Material and methods. 106 patients of hospital neurologic department with brain infarction were included in prospective pharmacoepidemiological study of the drugs used for secondary prevention of brain infarction on dispensary stage since 1 January 2009 to 31 December 2009. Duration of outpatient observation was 3 years. Results. All of the patients were of 64,9 ± 10,3 years old. Hypertension was diagnosed in 102 of them (96.2%, atrial fibrillation — in 33 (31.1% patients. 39 (36.8% patients died during 3 years after discharge from the hospital. ACE inhibitors/angiotensin II receptor antagonist were prescribed for 83 (78.3% patients, antiplatelet- 76 (71,7%, statins — 16 (15,1% patients in discharge from hospital. Warfarin was prescribed only for 1 (3.05% patient with atrial fibrillation and ischemic stroke.consumption of drugs with evidence efficiency were diminished already after one year of observation in outpatient clinics. Conclusion.Therapy for secondary stroke prevention is not fully comply with current clinical guidelines

How to minimize ischemic complication related to swollen temporalis muscle following indirect revascularization surgery in moyamoya disease: a technical report.

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Joo, Sung Pil; Kim, Tae Sun; Moon, Hyung Sik

2014-05-01

There are several reports in the literature of postoperative ischemic events due to swelling of the temporalis muscle after indirect revascularization surgery. Here, we report our surgical technique for preventing ischemic events during the acute postoperative recovery period in moyamoya patients. We used various types of titanium mesh to cover the bony defect area in 8 patients (10 operations) with moyamoya disease. The mesh was cut and manipulated according to the shape of the bony defect. Surgical results were favorable, with no newly developed ischemic event or infarction in the acute recovery period. The mesh formed an outer table of skull, so there was no compressive effect on the temporalis muscle and no cosmetic defects. The titanium mesh appears to be effective and useful for prevention of ischemic insult in the treatment of moyamoya disease. The choice of this procedure depends on both the operative findings of temporalis muscle thickness and the status of ischemic vulnerability of moyamoya brain. Georg Thieme Verlag KG Stuttgart · New York.

Temporal delta wave and ischemic lesions on MRI

International Nuclear Information System (INIS)

Inui, Koji; Kawamoto, Hozumi; Kawakita, Masahiko; Wako, Kazuhisa; Nakashima, Hiromichi; Kamihara, Masanori; Nomura, Junichi

1994-01-01

The present study was designed to determine the clinical significance of a temporal low-voltage irregular delta wave (TLID) on EEG. Among 808 EEG records examined during one year at our hospital, the TLID was commonly detected in patients with clinically diagnosed ischemic brain diseases such as multiple infarction. Subsequently, a relation of the TLID to ischemic lesions on MRI was examined in 50 elderly depressive patients. It was found that there was a close correlation between the occurrence of the TLID and small ischemic lesions on MRI (p<0.001). These results suggest that the TLID is a valuable indicator of minor ischemic changes of the brain. (author)

Neuroprotective Role of Nerve Growth Factor in Hypoxic-Ischemic Brain Injury

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Antonio Chiaretti

2013-06-01

Full Text Available Hypoxic-ischemic brain injuries (HIBI in childhood are frequently associated with poor clinical and neurological outcome. Unfortunately, there is currently no effective therapy to restore neuronal loss and to determine substantial clinical improvement. Several neurotrophins, such as Nerve Growth Factor (NGF, Brain-Derived Neurotrophic Factor (BDNF, and Glial Derived Neurotrophic Factor (GDNF, play a key role in the development, differentiation, and survival of the neurons of the peripheral and central nervous system. Experimental animal studies demonstrated their neuroprotective role in HIBI, while only a few studies examined the neuroprotective mechanisms in patients with severe HIBI. We report two cases of children with HIBI and prolonged comatose state who showed a significant improvement after intraventricular NGF administration characterized by amelioration of electroencephalogram (EEG and cerebral perfusion at single-photon emission computed tomography (SPECT. The improvement in motor and cognitive functions of these children could be related to the neuroprotective role exerted by NGF in residual viable cholinergic neurons, leading to the restoration of neuronal networks in the damaged brain.

Detection of hypoxic-ischemic brain injury with 3D-enhanced T2* weighted angiography (ESWAN) imaging

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Gang, QiangQiang, E-mail: rousikang@163.com; Zhang, Jianing, E-mail: 1325916060@qq.com; Hao, Peng, E-mail: 1043600590@qq.com; Xu, Yikai, E-mail: yikaivip@163.com

2013-11-01

Objective: To demonstrate the use of 3D-enhanced T2* weighted angiography (ESWAN) imaging for the observation and quantification of the evolution of brain injury induced by a recently developed model of hypoxic-ischemic brain injury (HI/R) in neonatal piglets. Methods: For these experiments, newborn piglets were subjected to HI/R injury, during which ESWAN scanning was performed, followed by H and E staining and immunohistochemistry of AQP-4 expression. Results: In the striatum, values from T2* weighted magnetic resonance imaging (MRI) increased and reached their highest level at 3 days post injury, whereas T2* values increased and peaked at 24 h in the subcortical region. The change in T2* values was concordant with brain edema. Phase values in the subcortical border region were not dependent on time post-injury. Magnitude values were significantly different from the control group, and increased gradually over time in the subcortical border region. Susceptibility-weighted images (SWI) indicated small petechial hemorrhages in the striatum and thalamus, as well as dilated intramedullary veins. Conclusion: SWI images can be used to detect white and gray matter microhemorrhages and dilated intramedullary veins. The T2*, phase, and magnitude map can also reflect the development of brain injury. Our data illustrate that ESWAN imaging can increase the diagnostic sensitivity and specificity of MRI in neonatal hypoxic-ischemic encephalopathy.

Detection of hypoxic-ischemic brain injury with 3D-enhanced T2* weighted angiography (ESWAN) imaging

International Nuclear Information System (INIS)

Gang, QiangQiang; Zhang, Jianing; Hao, Peng; Xu, Yikai

2013-01-01

Objective: To demonstrate the use of 3D-enhanced T2* weighted angiography (ESWAN) imaging for the observation and quantification of the evolution of brain injury induced by a recently developed model of hypoxic-ischemic brain injury (HI/R) in neonatal piglets. Methods: For these experiments, newborn piglets were subjected to HI/R injury, during which ESWAN scanning was performed, followed by H and E staining and immunohistochemistry of AQP-4 expression. Results: In the striatum, values from T2* weighted magnetic resonance imaging (MRI) increased and reached their highest level at 3 days post injury, whereas T2* values increased and peaked at 24 h in the subcortical region. The change in T2* values was concordant with brain edema. Phase values in the subcortical border region were not dependent on time post-injury. Magnitude values were significantly different from the control group, and increased gradually over time in the subcortical border region. Susceptibility-weighted images (SWI) indicated small petechial hemorrhages in the striatum and thalamus, as well as dilated intramedullary veins. Conclusion: SWI images can be used to detect white and gray matter microhemorrhages and dilated intramedullary veins. The T2*, phase, and magnitude map can also reflect the development of brain injury. Our data illustrate that ESWAN imaging can increase the diagnostic sensitivity and specificity of MRI in neonatal hypoxic-ischemic encephalopathy

The role in thanatogenesis of generalized brain edema in ischemic cerebral infarction (computer-morphometric research

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E. A. Dyadyk

2012-12-01

Full Text Available This work presents the results of computer-morphometric study of perivascular and pericellular free (oedematous spaces in brain cortex at death from the ischemic cerebral infarction and from reasons unconnected directly with cerebral pathology. It was revealed, that the mean area of perivascular spaces (vasogenic edema index at brain infarction in 13 times exceeds such at extracerebral pathology, and mean area of pericellular spaces (cytotoxic edema index – almost in 12 times, but also it substantially differs on the degree of variation (in 2,5 times higher, than area of perivascular spaces.

Deficiency of vasodilator-stimulated phosphoprotein (VASP increases blood-brain-barrier damage and edema formation after ischemic stroke in mice.

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Peter Kraft

2010-12-01

Full Text Available Stroke-induced brain edema formation is a frequent cause of secondary infarct growth and deterioration of neurological function. The molecular mechanisms underlying edema formation after stroke are largely unknown. Vasodilator-stimulated phosphoprotein (VASP is an important regulator of actin dynamics and stabilizes endothelial barriers through interaction with cell-cell contacts and focal adhesion sites. Hypoxia has been shown to foster vascular leakage by downregulation of VASP in vitro but the significance of VASP for regulating vascular permeability in the hypoxic brain in vivo awaits clarification.Focal cerebral ischemia was induced in Vasp(-/- mice and wild-type (WT littermates by transient middle cerebral artery occlusion (tMCAO. Evan's Blue tracer was applied to visualize the extent of blood-brain-barrier (BBB damage. Brain edema formation and infarct volumes were calculated from 2,3,5-triphenyltetrazolium chloride (TTC-stained brain slices. Both mouse groups were carefully controlled for anatomical and physiological parameters relevant for edema formation and stroke outcome. BBB damage (p0.05 towards worse neurological outcomes.Our study identifies VASP as critical regulator of BBB maintenance during acute ischemic stroke. Therapeutic modulation of VASP or VASP-dependent signalling pathways could become a novel strategy to combat excessive edema formation in ischemic brain damage.

Dual Antiplatelet Therapy in Secondary Prevention of Ischemic Stroke: A Ghost from the Past or a New Frontier?

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Clotilde Balucani

2010-01-01

Full Text Available With majority of ischemic strokes attributable to atherothrombosis and many being predictable after transient ischemic attacks (TIA, the role of early secondary prevention with antiplatelet agents is under renewed investigation. Prior major clinical trials of various secondary stroke prevention regimens pointed to a greater efficacy of dual antiplatelet agents if initiated early from symptom onset. This paper examines data and rationale behind dual antiplatelet regimens across the completed clinical trials. The safety of dual antiplatelets approach is of concern, but it could be outweighed, at least in early management, by a greater reduction in recurrence of ischemic events since this risk is “front loaded” after minor stroke or TIA. Aspirin monotherapy, though considered standard of care, is compared to aspirin-extended release dipiridamole and its combination with clopidogrel in early-phase completed and efficacy-phase ongoing clinical trials.

Brain Injury Safety Tips and Prevention

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... submit" name="commit" type="submit" value="Submit" /> Brain Injury Safety Tips and Prevention Recommend on Facebook ... not grass or dirt. More HEADS UP Video: Brain Injury Safety and Prevention frame support disabled and/ ...

Rehabilitation Outcomes: Ischemic versus Hemorrhagic Strokes

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Perna, Robert; Temple, Jessica

2015-01-01

Background. Ischemic and hemorrhagic strokes have different pathophysiologies and possibly different long-term cerebral and functional implications. Hemorrhagic strokes expose the brain to irritating effects of blood and ischemic strokes reflect localized or diffuse cerebral vascular pathology. Methods. Participants were individuals who suffered either an ischemic (n = 172) or hemorrhagic stroke (n = 112) within the past six months and were involved in a postacute neurorehabilitation program....

Role of neuroinflammation in ischemic stroke

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Rui Liu; Meng-Xian Pan; Jun-Chun Tang; Ya Zhang; Hua-Bao Liao; Yang Zhuang; Dan Zhao; Qi Wan

2017-01-01

Ischemic stroke causes the depletion of energy and induce excitotoxicity and neuroinflammation in the brain that results from thrombotic blockage. Neuroinflammation occurs initially depending on activated resident microglia that has the same function as the macrophage. Activated microglia participates in the neuroinflammatory process by phagocytosing the injured brain cells and producing the pro- and anti-inflammatory mediators. In this review, the authors present an overview of the role of microglia in mediating neuroinflammation in ischemic stroke.

Prevention of ischemic stroke in clinical practice: a role of internists and general practitioners.

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Niewada, Maciej; Członkowska, Anna

2014-01-01

Stroke constitutes a substantial clinical and socio-economic burden. It is currently the third cause of death worldwide and results in mortality or disability in every third patient at the end of the first year following an acute cerebrovascular event. Although in-hospital mortality rates in stroke patients have decreased, prevention and cardiovascular risk control remain critical for improving the prognosis and reducing stroke burden worldwide. The definitions of stroke and transient ischemic attack (TIA) have been recently modified following the findings from neuroimaging and thrombolysis research. Both stroke and TIA are recurrent and preventable disorders. Both patients with stroke and those with TIA require prompt clinical workup, risk assessment, and appropriate management because the risk of recurrence, stroke, and coronary events is significant. The 5 most common cardiovascular risk factors (high blood pressure, smoking, abdominal obesity, diet, and lack of physical activity) are responsible for 80% of the cases. Stroke prevention involves lifestyle modification and specific treatment. Secondary prevention of ischemic stroke involves early treatment (antiplatelets and carotid interventions) and long-term management including lifestyle changes, antihypertensive therapy, antiplatelets, antithrombotic drugs in patients with atrial fibrillation, and the use of statins and other lipid-lowering drugs. Stroke patients are at risk of depression, dementia, epilepsy, and other complications that also require targeted treatment.

RESVERATROL PRECONDITIONING INDUCES A NOVEL EXTENDED WINDOW OF ISCHEMIC TOLERANCE IN THE MOUSE BRAIN

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Koronowski, Kevin B.; Dave, Kunjan R.; Saul, Isabel; Camarena, Vladimir; Thompson, John W.; Neumann, Jake T.; Young, Juan I.; Perez-Pinzon, Miguel A.

2015-01-01

Background and Purpose Prophylactic treatments that afford neuroprotection against stroke may emerge from the field of preconditioning. Resveratrol mimics ischemic preconditioning, reducing ischemic brain injury when administered two days prior to global ischemia in rats. This protection is linked to Sirt1 and enhanced mitochondrial function possibly through its repression of UCP2. BDNF is another neuroprotective protein associated with Sirt1. In this study we sought to identify the conditions of resveratrol preconditioning (RPC) that most robustly induce neuroprotection against focal ischemia in mice. Methods We tested four different RPC paradigms against a middle cerebral artery occlusion (MCAo) model of stroke. Infarct volume and neurological score were calculated 24 hours following MCAo. Sirt1-chromatin binding was evaluated by ChIP-qPCR. Percoll gradients were used to isolate synaptic fractions and changes in protein expression were determined via Western blot analysis. BDNF concentration was measured using a BDNF-specific ELISA assay. Results While repetitive RPC induced neuroprotection from MCAo, strikingly one application of RPC 14 days prior to MCAo showed the most robust protection, reducing infarct volume by 33% and improving neurological score by 28%. Fourteen days following RPC, Sirt1 protein was increased 1.5 fold and differentially bound to the UCP2 and BDNF promoter regions. Accordingly, synaptic UCP2 protein decreased by 23% and cortical BDNF concentration increased 26%. Conclusions RPC induces a novel extended window of ischemic tolerance in the brain that lasts for at least 14 days. Our data suggest that this tolerance may be mediated by Sirt1, through upregulation of BDNF and downregulation of UCP2. PMID:26159789

NeuroSPECT assessment of ischemic penumbra in acute brain infarct: control of intra-arterial thrombolysis

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Mena, F.J.; Mena, I.; Contreras, I.; Soto, F.; Ducci, H.; Fruns, M.

2002-01-01

Introduction: Brain infarct is the most common cause of incapacity in adults, the second cause of dementia and the 2nd or 3rd cause of death. Acute brain infarct is a medical emergency potentially reversible if treated with thrombolysis in the first hours of evolution. Thrombolysis is now an approved and efficacious method of treatment for acute ischemic stroke. During the first 3 hours of evolution, intravenous administration of plasminogen activator (tPA) can be performed. The window of time of treatment is expanded to 6 hours with the intra-arterial super selective route for thrombolysis. Aim: The aim of this study was to define levels of reversible ischemia (penumbra) demonstrated by statistically evaluated HMPAO Tc99m NeuroSPECT performed before and after intra-arterial thrombolysis in the treatment of acute infarct. Materials and Methods: 21 patients were treated during the first 6 hours of evolution of an acute ischemic stroke with the following protocol. 1) Admission, and complete neurological evaluation. 2) Brain CT scan to rule hemorrhage or established infarct. 3) I.V injection of 1100MBq Tc99m HMPAO (Ceretec tm) 4) Conventional cerebral angiography and intra-arterial thrombolysis and/or angioplasty/stenting if necessary. 5) NeuroSPECT assessment of ischemic penumbra. 6) Control at 24 hrs with NeuroSPECT. NeuroSPECT image acquisition is performed immediately following arterial thrombolysis with a dual Head Camera, SHR collimators and conventional protocol. Image processing was performed using the Segami Software, as previously reported in Alasbimn Journal2 (7): April 2000. http://www.alasbimnjournal.cl. The analysis consists of 1) Tallairach brain volume normalization. 2) Voxel by voxel comparison of the individual brain cortex uptake normalized to the maximum in the cortex with a normal database of 24 age-matched controls. Results: The results are expressed in standard deviations (S.D.) below the normal mean. Normal mean is 72% + 6. Only voxels between

Lack of TAFI increases brain damage and microparticle generation after thrombolytic therapy in ischemic stroke.

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Orbe, J; Alexandru, N; Roncal, C; Belzunce, M; Bibiot, P; Rodriguez, J A; Meijers, J C M; Georgescu, A; Paramo, J A

2015-08-01

Thrombin-activatable fibrinolysis inhibitor (TAFI) plays an important role in coagulation and fibrinolysis. Whereas TAFI deficiency may lead to a haemorrhagic tendency, data from TAFI knockout mice (TAFI-/-) are controversial and no differences have been reported in these animals after ischemic stroke. There are also no data regarding the role of circulating microparticles (MPs) in TAFI-/-. to examine the effect of tPA on the rate of intracranial haemorrhage (ICH) and on MPs generated in a model of ischemic stroke in TAFI-/- mice. Thrombin was injected into the middle cerebral artery (MCA) to analyse the effect of tPA (10mg/Kg) on the infarct size and haemorrhage in the absence of TAFI. Immunofluorescence for Fluoro-Jade C was performed on frozen brain slides to analyse neuronal degeneration after ischemia. MPs were isolated from mouse blood and their concentrations calculated by flow cytometry. Compared with saline, tPA significantly increased the infarct size in TAFI-/- mice (p<0.05). Although plasma fibrinolytic activity (fibrin plate assay) was higher in these animals, no macroscopic or microscopic ICH was detected. A positive signal for apoptosis and degenerating neurons was observed in the infarct area, being significantly higher in tPA treated TAFI-/- mice (p<0.05). Interestingly, higher numbers of MPs were found in TAFI-/- plasma as compared to wild type, after stroke (p<0.05). TAFI deficiency results in increased brain damage in a model of thrombolysis after ischemic stroke, which was not associated with bleeding but with neuronal degeneration and MP production. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cerebral ischemic injury decreases α-synuclein expression in brain tissue and glutamate-exposed HT22 cells.

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Koh, Phil-Ok

2017-09-01

α-Synuclein is abundantly expressed in neuronal tissue, plays an essential role in the pathogenesis of neurodegenerative disorders, and exerts a neuroprotective effect against oxidative stress. Cerebral ischemia causes severe neurological disorders and neuronal dysfunction. In this study, we examined α-synuclein expression in middle cerebral artery occlusion (MCAO)-induced cerebral ischemic injury and neuronal cells damaged by glutamate treatment. MCAO surgical operation was performed on male Sprague-Dawley rats, and brain samples were isolated 24 hours after MCAO. We confirmed neurological behavior deficit, infarction area, and histopathological changes following MCAO injury. A proteomic approach and Western blot analysis demonstrated a decrease in α-synuclein in the cerebral cortices after MCAO injury. Moreover, glutamate treatment induced neuronal cell death and decreased α-synuclein expression in a hippocampal-derived cell line in a dose-dependent manner. It is known that α-synuclein regulates neuronal survival, and low levels of α-synuclein expression result in cytotoxicity. Thus, these results suggest that cerebral ischemic injury leads to a reduction in α-synuclein and consequently causes serious brain damage.

Real-time monitoring of ischemic and contralateral brain pO2 during stroke by variable length multisite resonators.

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Hou, Huagang; Li, Hongbin; Dong, Ruhong; Khan, Nadeem; Swartz, Harold

2014-06-01

Electron paramagnetic resonance (EPR) oximetry using variable length multi-probe implantable resonator (IR), was used to investigate the temporal changes in the ischemic and contralateral brain pO2 during stroke in rats. The EPR signal to noise ratio (S/N) of the IR with four sensor loops at a depth of up to 11 mm were compared with direct implantation of lithium phthalocyanine (LiPc, oximetry probe) deposits in vitro. These IRs were used to follow the temporal changes in pO2 at two sites in each hemisphere during ischemia induced by left middle cerebral artery occlusion (MCAO) in rats breathing 30% O2 or 100% O2. The S/N ratios of the IRs were significantly greater than the LiPc deposits. A similar pO2 at two sites in each hemisphere prior to the onset of ischemia was observed in rats breathing 30% O2. However, a significant decline in the pO2 of the left cortex and striatum occurred during ischemia, but no change in the pO2 of the contralateral brain was observed. A significant increase in the pO2 of only the contralateral non-ischemic brain was observed in the rats breathing 100% O2. No significant difference in the infarct volume was evident between the animals breathing 30% O2 or 100% O2 during ischemia. EPR oximetry with IRs can repeatedly assess temporal changes in the brain pO2 at four sites simultaneously during stroke. This oximetry approach can be used to test and develop interventions to rescue ischemic tissue by modulating cerebral pO2 during stroke. Copyright © 2014 Elsevier Inc. All rights reserved.

Disturbed oscillatory brain dynamics in subcortical ischemic vascular dementia

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van Straaten Elisabeth CW

2012-07-01

Full Text Available Abstract Background White matter hyperintensities (WMH can lead to dementia but the underlying physiological mechanisms are unclear. We compared relative oscillatory power from electroencephalographic studies (EEGs of 17 patients with subcortical ischemic vascular dementia, based on extensive white matter hyperintensities (SIVD-WMH with 17 controls to investigate physiological changes underlying this diagnosis. Results Differences between the groups were large, with a decrease of relative power of fast activity in patients (alpha power 0.25 ± 0.12 versus 0.38 ± 0.13, p = 0.01; beta power 0.08 ± 0.04 versus 0.19 ± 0.07; p Conclusions This pattern of disturbance in oscillatory brain activity indicate loss of connections between neurons, providing a first step in the understanding of cognitive dysfunction in SIVD-WMH.

Measurement of Lactate Content and Amide Proton Transfer Values in the Basal Ganglia of a Neonatal Piglet Hypoxic-Ischemic Brain Injury Model Using MRI.

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Zheng, Y; Wang, X-M

2017-04-01

As amide proton transfer imaging is sensitive to protein content and intracellular pH, it has been widely used in the nervous system, including brain tumors and stroke. This work aimed to measure the lactate content and amide proton transfer values in the basal ganglia of a neonatal piglet hypoxic-ischemic brain injury model by using MR spectroscopy and amide proton transfer imaging. From 58 healthy neonatal piglets (3-5 days after birth; weight, 1-1.5 kg) selected initially, 9 piglets remained in the control group and 43 piglets, in the hypoxic-ischemic brain injury group. Single-section amide proton transfer imaging was performed at the coronal level of the basal ganglia. Amide proton transfer values of the bilateral basal ganglia were measured in all piglets. The ROI of MR spectroscopy imaging was the right basal ganglia, and the postprocessing was completed with LCModel software. After hypoxic-ischemic insult, the amide proton transfer values immediately decreased, and at 0-2 hours, they remained at their lowest level. Thereafter, they gradually increased and finally exceeded those of the control group at 48-72 hours. After hypoxic-ischemic insult, the lactate content increased immediately, was maximal at 2-6 hours, and then gradually decreased to the level of the control group. The amide proton transfer values were negatively correlated with lactate content ( r = -0.79, P < .05). This observation suggests that after hypoxic-ischemic insult, the recovery of pH was faster than that of lactate homeostasis. © 2017 by American Journal of Neuroradiology.

Chronic Exposure to Subtherapeutic Antibiotics Aggravates Ischemic Stroke Outcome in Mice

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Xiao-Hui Dong

2017-10-01

Full Text Available Subtherapeutic antibiotics have been widely used in agriculture since the 1950s, which can be accumulated in human body through various approaches and may have long-term consequences. However, there is limited information about the link between chronic subtherapeutic antibiotic exposure and the outcome of ischemic brain injury. Here we showed that long-term treatment with subtherapeutic chlortetracycline, penicillin or vancomycin, which were widely used in agriculture approved by US Food and Drug Administration (FDA, could impair EPC functions, reduce ischemic brain angiogenesis and aggravate cerebral ischemic injury and long-term stroke outcomes in mice. In addition, transplantated EPCs from chronic antibiotic-treated mice showed a lower therapeutic effect on cerebral ischemic injury reduction and local angiogenesis promotion compared to those from control mice, and EPCs from the donor animals could integrate into the recipient ischemic brain in mice. Furthermore, transplanted EPCs might exert paracrine effects on cerebral ischemic injury reduction in mice, which could be impaired by chronic antibiotic exposure. In conclusion, chronic subtherapeutic antibiotic exposure aggravated cerebral ischemic injury in mice, which might be partly attributed to the impairment of both EPC-mediated angiogenesis and EPCs' paracrine effects. These findings reveal a previously unrecognized impact of chronic subtherapeutic antibiotic exposure on ischemic injury.

METABOLIC THERAPY IN PATIENTS WITH ISCHEMIC STROKE

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L. B. Zavaliy

2018-01-01

cognitive function in patients who had experienced a stroke,. The drug does not significantly improve the neurological status of patients after a stroke, but it reduces the risk of the stroke development in the next 10 years. Thus, we analyzed mechanisms of medical substances action and data of experimental and clinical studies, including ones after thrombolytic therapy and with inclusion of drugs for primary and secondary prevention of ischemic stroke. The reasonability and effectiveness of prescribing a combination of drugs of different pharmacological groups affecting brain metabolism remains controversial, since the excessive drug treatment may have complications. The safety of metabolic therapy is in doubt, and some of authors views presented confirm the need for additional large independent studies.

Experimental model considerations for the study of protein-energy malnutrition co-existing with ischemic brain injury.

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Prosser-Loose, Erin J; Smith, Shari E; Paterson, Phyllis G

2011-05-01

Protein-energy malnutrition (PEM) affects ~16% of patients at admission for stroke. We previously modeled this in a gerbil global cerebral ischemia model and found that PEM impairs functional outcome and influences mechanisms of ischemic brain injury and recovery. Since this model is no longer reliable, we investigated the utility of the rat 2-vessel occlusion (2-VO) with hypotension model of global ischemia for further study of this clinical problem. Male, Sprague-Dawley rats were exposed to either control diet (18% protein) or PEM induced by feeding a low protein diet (2% protein) for 7d prior to either global ischemia or sham surgery. PEM did not significantly alter the hippocampal CA1 neuron death (p = 0.195 by 2-factor ANOVA) or the increase in dendritic injury caused by exposure to global ischemia. Unexpectedly, however, a strong trend was evident for PEM to decrease the consistency of hippocampal damage, as shown by an increased incidence of unilateral or no hippocampal damage (p=0.069 by chi-square analysis). Although PEM caused significant changes to baseline arterial blood pH, pO(2), pCO(2), and fasting glucose (p0.269). Intra-ischemic tympanic temperature and blood pressure were strictly and equally controlled between ischemic groups. We conclude that co-existing PEM confounded the consistency of hippocampal injury in the 2-VO model. Although the mechanisms responsible were not identified, this model of brain ischemia should not be used for studying this co-morbidity factor. © 2011 Bentham Science Publishers Ltd.

Klotho upregulation contributes to the neuroprotection of ligustilide against cerebral ischemic injury in mice.

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Long, Fang-Yi; Shi, Meng-Qi; Zhou, Hong-Jing; Liu, Dong-Ling; Sang, Na; Du, Jun-Rong

2018-02-05

Klotho, an aging-suppressor gene, encodes a protein that potentially acts as a neuroprotective factor. Our previous studies showed that ligustilide minimizes the cognitive dysfunction and brain damage induced by cerebral ischemia; however, the underlying mechanisms remain unclear. This study aims to investigate whether klotho is involved in the protective effects of ligustilide against cerebral ischemic injury in mice. Cerebral ischemia was induced by bilateral common carotid arterial occlusion. Neurobehavioral tests as well as Nissl and Fluoro-Jade B staining were used to evaluate the protective effects of ligustilide in cerebral ischemia, and Western blotting and ELISA approaches were used to investigate the underlying mechanisms. Administration of ligustilide prevented the development of neurological deficits and reduced neuronal loss in the hippocampal CA1 region and the caudate putamen after cerebral ischemia. The protective effects were associated with inhibition of the RIG-I/NF-κB p65 and Akt/FoxO1 pathways and with prevention of inflammation and oxidative stress in the brain. Further, downregulation of klotho could attenuate the neuroprotection of ligustilide against cerebral ischemic injury. Ligustilide exerted neuroprotective effects in mice after cerebral ischemia by regulating anti-inflammatory and anti-oxidant signaling pathways. Furthermore, klotho upregulation contributes to the neuroprotection of LIG against cerebral ischemic injury. These results indicated that ligustilide may be a promising therapeutic agent for the treatment of cerebral ischemia. Copyright © 2017 Elsevier B.V. All rights reserved.

Neuroprotective effects of scutellarin against hypoxic-ischemic-induced cerebral injury via augmentation of antioxidant defense capacity.

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Guo, Hong; Hu, Li-Min; Wang, Shao-Xia; Wang, Yu-Lin; Shi, Fang; Li, Hui; Liu, Yang; Kang, Li-Yuan; Gao, Xiu-Mei

2011-12-31

An increasing number of studies has indicated that hypoxic-ischemic-induced cerebral injury is partly mediated via oxidative stress. Recent researches have focused on searching for drug and herbal manipulations to protect against hypoxic-ischemic-induced oxidative cell damage. Scutellarin is a flavonoid derived from the Erigeron breviscapus (vant.) and has been reported to exhibit neuroprotective properties. However, its precise mechanism, particularly its antioxidation mechanism, remains elusive. In the present study, we investigated the neuroprotective effects of scutellarin on middle cerebral artery occlusion (MCAO)-induced brain damage in rats, and oxygen-glucose deprivation (OGD)-induced toxicity in primary culture of rat cortical neurons. In vivo, intraperitoneal injections of scutellarin (20 and 60 mg/kg) improved the neurological score and diminished the percentage of brain infarct volume. At the same time, scutellarin significantly increased superoxide dismutase (SOD), catalase (CAT) activities and glutathione (GSH) level in ischemic brain tissues, enhancing endogenous antioxidant activity. Moreover, pretreatment of scutellarin (25, 50 and 100 μM) protected neurons against lethal stimuli, decreased the percentage of apoptotic cells and inhibited reactive oxygen species (ROS) generation in OGD-induced primary cortical neurons in vitro. These results suggest that the preventive and therapeutic potential of scutellarin in cerebral injury patients is, at least in part, ascribed to augmentation of cellular antioxidant defense capacity.

Impact of perinatal systemic hypoxic-ischemic injury on the brain of male offspring rats: an improved model of neonatal hypoxic-ischemic encephalopathy in early preterm newborns.

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Yuejun Huang

Full Text Available In this study, we attempted to design a model using Sprague-Dawley rats to better reproduce perinatal systemic hypoxic-ischemic encephalopathy (HIE in early preterm newborns. On day 21 of gestation, the uterus of pregnant rats were exposed and the blood supply to the fetuses of neonatal HIE groups were thoroughly abscised by hemostatic clamp for 5, 10 or 15 min. Thereafter, fetuses were moved from the uterus and manually stimulated to initiate breathing in an incubator at 37 °C for 1 hr in air. We showed that survival rates of offspring rats were decreased with longer hypoxic time. TUNEL staining showed that apoptotic cells were significant increased in the brains of offspring rats from the 10 min and 15 min HIE groups as compared to the offspring rats in the control group at postnatal day (PND 1, but there was no statistical difference between the offspring rats in the 5 min HIE and control groups. The perinatal hypoxic treatment resulted in decreased neurons and increased cleaved caspase-3 protein levels in the offspring rats from all HIE groups at PND 1. Platform crossing times and the percentage of the time spent in the target quadrant of Morris Water Maze test were significantly reduced in the offspring rats of all HIE groups at PND 30, which were associated with decreased brain-derived neurotrophic factor levels and neuronal cells in the hippocampus of offspring rats at PND 35. These data demonstrated that perinatal ischemic injury led to the death of neuronal cells and long-lasting impairment of memory. This model reproduced hypoxic ischemic encephalopathy in early preterm newborns and may be appropriate for investigating therapeutic interventions.

Impact of Perinatal Systemic Hypoxic–Ischemic Injury on the Brain of Male Offspring Rats: An Improved Model of Neonatal Hypoxic–Ischemic Encephalopathy in Early Preterm Newborns

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Xu, Hongwu; Wu, Weizhao; Lai, Xiulan; Ho, Guyu; Ma, Lian; Chen, Yunbin

2013-01-01

In this study, we attempted to design a model using Sprague-Dawley rats to better reproduce perinatal systemic hypoxic-ischemic encephalopathy (HIE) in early preterm newborns. On day 21 of gestation, the uterus of pregnant rats were exposed and the blood supply to the fetuses of neonatal HIE groups were thoroughly abscised by hemostatic clamp for 5, 10 or 15 min. Thereafter, fetuses were moved from the uterus and manually stimulated to initiate breathing in an incubator at 37 °C for 1 hr in air. We showed that survival rates of offspring rats were decreased with longer hypoxic time. TUNEL staining showed that apoptotic cells were significant increased in the brains of offspring rats from the 10 min and 15 min HIE groups as compared to the offspring rats in the control group at postnatal day (PND) 1, but there was no statistical difference between the offspring rats in the 5 min HIE and control groups. The perinatal hypoxic treatment resulted in decreased neurons and increased cleaved caspase-3 protein levels in the offspring rats from all HIE groups at PND 1. Platform crossing times and the percentage of the time spent in the target quadrant of Morris Water Maze test were significantly reduced in the offspring rats of all HIE groups at PND 30, which were associated with decreased brain-derived neurotrophic factor levels and neuronal cells in the hippocampus of offspring rats at PND 35. These data demonstrated that perinatal ischemic injury led to the death of neuronal cells and long-lasting impairment of memory. This model reproduced hypoxic ischemic encephalopathy in early preterm newborns and may be appropriate for investigating therapeutic interventions. PMID:24324800

[Revelation of the circumstances of the accident vascular arterial ischemic brain in at term or near-term and referral].

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Cneude, F; Diependaele, J-F; Chabernaud, J-L

2017-09-01

The neonatal arterial ischemic stroke is an emergency. Recurrent focal seizures, generally occurring in the first 24-72 hours after birth, are the commonest first clinical signs. When neonatal arterial ischemic stroke is suspected, optimal initial management involves careful supportive care including treatment of clinical and frequent or prolonged subclinical seizures, correction of the possible metabolic disorders and their prevention. Contrary to hypoxic ischemic encephalopathy, therapeutic hypothermia is not indicated. This newborn requires emergent transfer to a neonatal intensive care unit for the confirmation of the diagnosis by means of a specialized neonatal transport team. © 2017 Elsevier Masson SAS. Tous droits réservés.

Smoking Cessation Intervention After Ischemic Stroke or Transient Ischemic Attack. A Randomized Controlled Pilot Trial

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Brunner Frandsen, Nicole; Sørensen, Margit; Hyldahl, Tanja Kirstine

2012-01-01

BACKGROUND: Smoking cessation is widely recommended for secondary stroke prevention. However, little is known about the efficacy of smoking cessation intervention after stroke or transient ischemic attack (TIA). METHODS: Ninety-four smokers under age 76, admitted with ischemic stroke or TIA were ...

Tissue hypoxia during ischemic stroke: adaptive clues from hypoxia-tolerant animal models.

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Nathaniel, Thomas I; Williams-Hernandez, Ashley; Hunter, Anan L; Liddy, Caroline; Peffley, Dennis M; Umesiri, Francis E; Imeh-Nathaniel, Adebobola

2015-05-01

The treatment and prevention of hypoxic/ischemic brain injury in stroke patients remain a severe and global medical issue. Numerous clinical studies have resulted in a failure to develop chemical neuroprotection for acute, ischemic stroke. Over 150 estimated clinical trials of ischemic stroke treatments have been done, and more than 200 drugs and combinations of drugs for ischemic and hemorrhagic strokes have been developed. Billions of dollars have been invested for new scientific breakthroughs with only limited success. The revascularization of occluded cerebral arteries such as anti-clot treatments of thrombolysis has proven effective, but it can only be used in a 3-4.5h time frame after the onset of a stroke, and not for every patient. This review is about novel insights on how to resist tissue hypoxia from unconventional animal models. Ability to resist tissue hypoxia is an extraordinary ability that is not common in many laboratory animals such as rat and mouse models. For example, we can learn from a naked mole-rat, Chrysemys picta, how to actively regulate brain metabolic activity to defend the brain against fluctuating oxygen tension and acute bouts of oxidative stress following the onset of a stroke. Additionally, a euthermic arctic ground squirrel can teach us how the brain of a stroke patient can remain well oxygenated during tissue hypoxia with no evidence of cellular stress. In this review, we discuss how these animals provide us with a system to gain insight into the possible mechanisms of tissue hypoxia/ischemia. This issue is of clinical significance to stroke patients. We describe specific physiological and molecular adaptations employed by different animals' models of hypoxia tolerance in aquatic and terrestrial environments. We highlight how these adaptations might provide potential clues on strategies to adapt for the clinical management of tissue hypoxia during conditions such as stroke where oxygen demand fails to match the supply. Copyright

Cortical hypoxic-ischemic brain damage in shaken-baby (shaken impact) syndrome: value of diffusion-weighted MRI

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Parizel, Paul M.; Oezsarlak, Oezkan; Goethem, Johan W. van; Ceulemans, Berten; Laridon, Annick; Jorens, Philippe G.

2003-01-01

Shaken-baby syndrome (SBS) is a type of child abuse caused by violent shaking of an infant, with or without impact, and characterized by subdural hematomas, retinal hemorrhages, and occult bone fractures. Parenchymal brain lesions in SBS may be missed or underestimated on CT scans, but can be detected at an earlier stage with diffusion-weighted MRI (DW-MRI) as areas of restricted diffusion. We demonstrate the value of DW-MRI in a 2-month-old baby boy with suspected SBS. The pattern of diffusion abnormalities indicates that the neuropathology of parenchymal lesions in SBS is due to hypoxic-ischemic brain injuries, and not to diffuse axonal injury. (orig.)

Cortical hypoxic-ischemic brain damage in shaken-baby (shaken impact) syndrome: value of diffusion-weighted MRI

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Parizel, Paul M.; Oezsarlak, Oezkan; Goethem, Johan W. van [Department of Radiology, University of Antwerp, Wilrijkstraat 10, 2650, Edegem (Belgium); Ceulemans, Berten; Laridon, Annick [Department of Pediatric Neurology, University of Antwerp, Wilrijkstraat 10, 2650, Edegem (Belgium); Jorens, Philippe G. [Department of Pediatric Intensive Care Medicine, University of Antwerp, Wilrijkstraat 10, 2650, Edegem (Belgium)

2003-12-01

Shaken-baby syndrome (SBS) is a type of child abuse caused by violent shaking of an infant, with or without impact, and characterized by subdural hematomas, retinal hemorrhages, and occult bone fractures. Parenchymal brain lesions in SBS may be missed or underestimated on CT scans, but can be detected at an earlier stage with diffusion-weighted MRI (DW-MRI) as areas of restricted diffusion. We demonstrate the value of DW-MRI in a 2-month-old baby boy with suspected SBS. The pattern of diffusion abnormalities indicates that the neuropathology of parenchymal lesions in SBS is due to hypoxic-ischemic brain injuries, and not to diffuse axonal injury. (orig.)

Regional cerebral blood flow in patients with transient ischemic attacks studied by Xenon-133 inhalation and emission tomography

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Vorstrup, S; Hemmingsen, R; Henriksen, L

1983-01-01

Cerebral blood flow CBF was studied in 14 patients with transient ischemic attacks TIA and arteriosclerotic neck vessel disease. CBF was measured by a rapidly rotating single photon emission computerized tomograph using Xenon-133 inhalation. This method yields images of 3 brain slices depicting CBF...... with no abnormality on the CT-scan. The abnormal blood flow pattern was found to be unchanged after clinically successful reconstructive vascular surgery. This suggests the presence of irreversible ischemic tissue damage without gross emollition (incomplete infarction). It is concluded, that TIAs are often harmful...... events, as no less than 9 of the 14 patients studied had evidence of complete and/or incomplete infarction. Thorough examination and rational therapy should be instituted as soon as possible to prevent further ischemic lesions....

Multiple Silent Lacunes Are Associated with Recurrent Ischemic Stroke

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Andersen, Søren Due; Skjøth, Flemming; Yavarian, Yousef

2016-01-01

ackground: Silent lacunes are a common finding on brain imaging in ischemic stroke patients, but the prognostic significance of these lesions is uncertain. We aimed at investigating the association of silent lacunes and the risk of ischemic stroke recurrence, death, and cardiovascular events...... in a cohort of patients with incident ischemic stroke and no atrial fibrillation (AF). Methods: We included 786 patients (mean age 59.5 (SD 14.0); 42.9% females) in a registry-based, observational cohort study on patients with first-ever ischemic stroke. On brain MRI we assessed the number of silent lacunes...... as none, single, or multiple and we calculated stratified incidence rates of the outcomes. Cox proportional hazard ratios (HRs) adjusted for age, gender, congestive heart failure, hypertension, diabetes, and vascular disease were calculated with no silent lacunes as reference. In additional analyses, we...

Characteristics of Misclassified CT Perfusion Ischemic Core in Patients with Acute Ischemic Stroke.

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Ralph R E G Geuskens

Full Text Available CT perfusion (CTP is used to estimate the extent of ischemic core and penumbra in patients with acute ischemic stroke. CTP reliability, however, is limited. This study aims to identify regions misclassified as ischemic core on CTP, using infarct on follow-up noncontrast CT. We aim to assess differences in volumetric and perfusion characteristics in these regions compared to areas that ended up as infarct on follow-up.This study included 35 patients with >100 mm brain coverage CTP. CTP processing was performed using Philips software (IntelliSpace 7.0. Final infarct was automatically segmented on follow-up noncontrast CT and used as reference. CTP and follow-up noncontrast CT image data were registered. This allowed classification of ischemic lesion agreement (core on CTP: rMTT≥145%, aCBV<2.0 ml/100g and infarct on follow-up noncontrast CT and misclassified ischemic core (core on CTP, not identified on follow-up noncontrast CT regions. False discovery ratio (FDR, defined as misclassified ischemic core volume divided by total CTP ischemic core volume, was calculated. Absolute and relative CTP parameters (CBV, CBF, and MTT were calculated for both misclassified CTP ischemic core and ischemic lesion agreement regions and compared using paired rank-sum tests.Median total CTP ischemic core volume was 49.7ml (IQR:29.9ml-132ml; median misclassified ischemic core volume was 30.4ml (IQR:20.9ml-77.0ml. Median FDR between patients was 62% (IQR:49%-80%. Median relative mean transit time was 243% (IQR:198%-289% and 342% (IQR:249%-432% for misclassified and ischemic lesion agreement regions, respectively. Median absolute cerebral blood volume was 1.59 (IQR:1.43-1.79 ml/100g (P<0.01 and 1.38 (IQR:1.15-1.49 ml/100g (P<0.01 for misclassified ischemic core and ischemic lesion agreement, respectively. All CTP parameter values differed significantly.For all patients a considerable region of the CTP ischemic core is misclassified. CTP parameters significantly

The Neuronal Ischemic Tolerance Is Conditioned by the Tp53 Arg72Pro Polymorphism.

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Ramos-Araque, Maria E; Rodriguez, Cristina; Vecino, Rebeca; Cortijo Garcia, Elisa; de Lera Alfonso, Mercedes; Sanchez Barba, Mercedes; Colàs-Campàs, Laura; Purroy, Francisco; Arenillas, Juan F; Almeida, Angeles; Delgado-Esteban, Maria

2018-04-23

Cerebral preconditioning (PC) confers endogenous brain protection after stroke. Ischemic stroke patients with a prior transient ischemic attack (TIA) may potentially be in a preconditioned state. Although PC has been associated with the activation of pro-survival signals, the mechanism by which preconditioning confers neuroprotection is not yet fully clarified. Recently, we have described that PC-mediated neuroprotection against ischemic insult is promoted by p53 destabilization, which is mediated by its main regulator MDM2. Moreover, we have previously described that the human Tp53 Arg72Pro single nucleotide polymorphism (SNP) controls susceptibility to ischemia-induced neuronal apoptosis and governs the functional outcome of patients after stroke. Here, we studied the contribution of the human Tp53 Arg72Pro SNP on PC-induced neuroprotection after ischemia. Our results showed that cortical neurons expressing the Pro72-p53 variant exhibited higher PC-mediated neuroprotection as compared with Arg72-p53 neurons. PC prevented ischemia-induced nuclear and cytosolic p53 stabilization in Pro72-p53 neurons. However, PC failed to prevent mitochondrial p53 stabilization, which occurs in Arg72-p53 neurons after ischemia. Furthermore, PC promoted neuroprotection against ischemia by controlling the p53/active caspase-3 pathway in Pro72-p53, but not in Arg72-p53 neurons. Finally, we found that good prognosis associated to TIA within 1 month prior to ischemic stroke was restricted to patients harboring the Pro72 allele. Our findings demonstrate that the Tp53 Arg72Pro SNP controls PC-promoted neuroprotection against a subsequent ischemic insult by modulating mitochondrial p53 stabilization and then modulates TIA-induced ischemic tolerance.

Dibucaine mitigates spreading depolarization in human neocortical slices and prevents acute dendritic injury in the ischemic rodent neocortex.

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W Christopher Risher

Full Text Available Spreading depolarizations that occur in patients with malignant stroke, subarachnoid/intracranial hemorrhage, and traumatic brain injury are known to facilitate neuronal damage in metabolically compromised brain tissue. The dramatic failure of brain ion homeostasis caused by propagating spreading depolarizations results in neuronal and astroglial swelling. In essence, swelling is the initial response and a sign of the acute neuronal injury that follows if energy deprivation is maintained. Choosing spreading depolarizations as a target for therapeutic intervention, we have used human brain slices and in vivo real-time two-photon laser scanning microscopy in the mouse neocortex to study potentially useful therapeutics against spreading depolarization-induced injury.We have shown that anoxic or terminal depolarization, a spreading depolarization wave ignited in the ischemic core where neurons cannot repolarize, can be evoked in human slices from pediatric brains during simulated ischemia induced by oxygen/glucose deprivation or by exposure to ouabain. Changes in light transmittance (LT tracked terminal depolarization in time and space. Though spreading depolarizations are notoriously difficult to block, terminal depolarization onset was delayed by dibucaine, a local amide anesthetic and sodium channel blocker. Remarkably, the occurrence of ouabain-induced terminal depolarization was delayed at a concentration of 1 µM that preserves synaptic function. Moreover, in vivo two-photon imaging in the penumbra revealed that, though spreading depolarizations did still occur, spreading depolarization-induced dendritic injury was inhibited by dibucaine administered intravenously at 2.5 mg/kg in a mouse stroke model.Dibucaine mitigated the effects of spreading depolarization at a concentration that could be well-tolerated therapeutically. Hence, dibucaine is a promising candidate to protect the brain from ischemic injury with an approach that does not rely on

Pattern of brain injury and depressed heart rate variability in newborns with hypoxic ischemic encephalopathy.

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Metzler, Marina; Govindan, Rathinaswamy; Al-Shargabi, Tareq; Vezina, Gilbert; Andescavage, Nickie; Wang, Yunfei; du Plessis, Adre; Massaro, An N

2017-09-01

BackgroundDecreased heart rate variability (HRV) is a measure of autonomic dysfunction and brain injury in newborns with hypoxic ischemic encephalopathy (HIE). This study aimed to characterize the relationship between HRV and brain injury pattern using magnetic resonance imaging (MRI) in newborns with HIE undergoing therapeutic hypothermia.MethodsHRV metrics were quantified in the time domain (α S , α L , and root mean square at short (RMS S ) and long (RMS L ) timescales) and frequency domain (relative low-(LF) and high-frequency (HF) power) over 24-27 h of life. The brain injury pattern shown by MRI was classified as no injury, pure cortical/white matter injury, mixed watershed/mild basal ganglia injury, predominant basal ganglia or global injury, and death. HRV metrics were compared across brain injury pattern groups using a random-effects mixed model.ResultsData from 74 infants were analyzed. Brain injury pattern was significantly associated with the degree of HRV suppression. Specifically, negative associations were observed between the pattern of brain injury and RMS S (estimate -0.224, SE 0.082, P=0.006), RMS L (estimate -0.189, SE 0.082, P=0.021), and LF power (estimate -0.044, SE 0.016, P=0.006).ConclusionDegree of HRV depression is related to the pattern of brain injury. HRV monitoring may provide insights into the pattern of brain injury at the bedside.

Arterially perfused neurosphere-derived cells distribute outside the ischemic core in a model of transient focal ischemia and reperfusion in vitro.

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Chiara Pastori

Full Text Available BACKGROUND: Treatment with neural stem cells represents a potential strategy to improve functional recovery of post-ischemic cerebral injury. The potential benefit of such treatment in acute phases of human ischemic stroke depends on the therapeutic viability of a systemic vascular delivery route. In spite of the large number of reports on the beneficial effects of intracerebral stem cells injection in experimental stroke, very few studies demonstrated the effectiveness of the systemic intravenous delivery approach. METODOLOGY/PRINCIPAL FINDINGS: We utilized a novel in vitro model of transient focal ischemia to analyze the brain distribution of neurosphere-derived cells (NCs in the early 3 hours that follow transient occlusion of the medial cerebral artery (MCA. NCs obtained from newborn C57/BL6 mice are immature cells with self-renewal properties that could differentiate into neurons, astrocytes and oligodendrocytes. MCA occlusion for 30 minutes in the in vitro isolated guinea pig brain preparation was followed by arterial perfusion with 1x10(6 NCs charged with a green fluorescent dye, either immediately or 60 minutes after reperfusion onset. Changes in extracellular pH and K(+ concentration during and after MCAO were measured through ion-sensitive electrodes. CONCLUSION/SIGNIFICANCE: It is demonstrated that NCs injected through the vascular system do not accumulate in the ischemic core and preferentially distribute in non-ischemic areas, identified by combined electrophysiological and morphological techniques. Direct measurements of extracellular brain ions during and after MCA occlusion suggest that anoxia-induced tissue changes, such as extracellular acidosis, may prevent NCs from entering the ischemic area in our in vitro model of transitory focal ischemia and reperfusion suggesting a role played by the surrounding microenviroment in driving NCs outside the ischemic core. These findings strongly suggest that the potential beneficial effect

Neuroprotection of lamotrigine on hypoxic-ischemic brain damage in neonatal rats: Relations to administration time and doses

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Yong-Hong Yi

2008-06-01

Full Text Available Yong-Hong Yi1, Wen-Chao Guo1, Wei-Wen Sun1, Tao Su1, Han Lin1, Sheng-Qiang Chen1, Wen-Yi Deng1, Wei Zhou2, Wei-Ping Liao11Department of Neurology, Institute of Neurosciences and the Second Affiliated Hospital, 2Department of Neonatology, Affiliated Guangzhou Children’s Hospital, Guangzhou Medical College, Guangzhou, Guangdong Province, P.R. ChinaAbstract: Lamotrigine (LTG, an antiepileptic drug, has been shown to be able to improve cerebral ischemic damage by limiting the presynaptic release of glutamate. The present study investigated further the neuroprotective effect of LTG on hypoxic-ischemic brain damage (HIBD in neonatal rats and its relations to administration time and doses. The HIBD model was produced in 7-days old SD rats by left common carotid artery ligation followed by 2 h hypoxic exposure (8% oxygen. LTG was administered intraperitoneally with the doses of 5, 10, 20, and 40 mg/kg 3 h after operation and the dose of 20 mg/kg 1 h before and 3 h, 6 h after operation. Blood and brain were sampled 24 h after operation. Nissl staining, terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL, and neuron-specific enolase (NSE immunohistochemical staining were used for morphological studies. Water content in left cortex and NSE concentration in serum were determined. LTG significantly reduced water content in the cerebral cortex, as well as the number of TUNEL staining neurons in the dentate gyrus and cortex in hypoxic-ischemia (HI model. Furthermore, LTG significantly decreased the NSE level in serum and increased the number of NSE staining neurons in the cortex. These effects, except that on water content, were dose-dependent and were more remarkable in the pre-treated group than in the post-treated groups. These results demonstrate that LTG may have a neuroprotective effect on acute HIBD in neonates. The effect is more prominent when administrated with higher doses and before HI.Keywords: hypoxic-ischemic brain

Sevoflurane postconditioning against cerebral ischemic neuronal injury is abolished in diet-induced obesity: role of brain mitochondrial KATP channels.

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Yang, Zecheng; Chen, Yunbo; Zhang, Yan; Jiang, Yi; Fang, Xuedong; Xu, Jingwei

2014-03-01

Obesity is associated with increased infarct volumes and adverse outcomes following ischemic stroke. However, its effect on anesthetic postconditioning‑induced neuroprotection has not been investigated. The present study examined the effect of sevoflurane postconditioning on focal ischemic brain injury in diet‑induced obesity. Sprague‑Dawley rats were fed a high‑fat diet (HF; 45% kcal as fat) for 12 weeks to develop obesity syndrome. Rats fed a low‑fat diet (LF; 10% kcal as fat) served as controls. The HF or LF‑fed rats were subjected to focal cerebral ischemia for 60 min, followed by 24 h of reperfusion. Postconditioning was performed by exposure to sevoflurane for 15 min immediately at the onset of reperfusion. The involvement of the mitochondrial KATP (mitoKATP) channel was analyzed by the administration of a selective inhibitor of 5‑hydroxydecanoate (5‑HD) prior to sevoflurane postconditioning or by administration of diazoxide (DZX), a mitoKATP channel opener, instead of sevoflurane. The cerebral infarct volume, neurological score and motor coordination were evaluated 24 h after reperfusion. The HF‑fed rats had larger infarct volumes, and lower neurological scores than the LF‑fed rats and also failed to respond to neuroprotection by sevoflurane or DZX. By contrast, sevoflurane and DZX reduced the infarct volumes and improved the neurological scores and motor coordination in the LF‑fed rats. Pretreatment with 5‑HD inhibited sevoflurane‑induced neuroprotection in the LF‑fed rats, whereas it had no effect in the HF‑fed rats. Molecular studies demonstrated that the expression of Kir6.2, a significant mitoKATP channel component, was reduced in the brains of the HF‑fed rats compared with the LF‑fed rats. The results of this study indicate that diet‑induced obesity eliminates the ability of anesthetic sevoflurane postconditioning to protect the brain against cerebral ischemic neuronal injury, most likely due to an impaired brain

Observation of the relationship between regional cerebral blood flow and brain functional changes in the patients with ischemic cerebrovascular diseases

International Nuclear Information System (INIS)

Guan Yihui; Lin Xiangtong; Liu Yongchang

1994-01-01

The brain perfusion SPECT imaging and functional changes in 27 patients with ischemic cerebrovascular diseases and 20 controls were investigated. Correlated with the clinical findings and MRI study, we discovered the lowered perfusion of Broca and Wernicke area is closely related with the aphasia caused by left basal ganglia infarction. In hemianopia group, as the visual function improved after the light stimulation treatment, the blood perfusion increased in occipital lobe. The lowered perfusion in vestibular center can be observed in vertigo group. From these studies, we concluded that 99m Tc-HMPAO brain SPECT imaging can partly reflect the brain functions

FLAIR lesion segmentation: Application in patients with brain tumors and acute ischemic stroke

International Nuclear Information System (INIS)

Artzi, Moran; Aizenstein, Orna; Jonas-Kimchi, Tali; Myers, Vicki; Hallevi, Hen; Ben Bashat, Dafna

2013-01-01

Background: Lesion size in fluid attenuation inversion recovery (FLAIR) images is an important clinical parameter for patient assessment and follow-up. Although manual delineation of lesion areas considered as ground truth, it is time-consuming, highly user-dependent and difficult to perform in areas of indistinct borders. In this study, an automatic methodology for FLAIR lesion segmentation is proposed, and its application in patients with brain tumors undergoing therapy; and in patients following stroke is demonstrated. Materials and methods: FLAIR lesion segmentation was performed in 57 magnetic resonance imaging (MRI) data sets obtained from 44 patients: 28 patients with primary brain tumors; 5 patients with recurrent-progressive glioblastoma (rGB) who were scanned longitudinally during anti-angiogenic therapy (18 MRI scans); and 11 patients following ischemic stroke. Results: FLAIR lesion segmentation was obtained in all patients. When compared to manual delineation, a high visual similarity was observed, with an absolute relative volume difference of 16.80% and 20.96% and a volumetric overlap error of 24.87% and 27.50% obtained for two raters: accepted values for automatic methods. Quantitative measurements of the segmented lesion volumes were in line with qualitative radiological assessment in four patients who received anti-anogiogenic drugs. In stroke patients the proposed methodology enabled identification of the ischemic lesion and differentiation from other FLAIR hyperintense areas, such as pre-existing disease. Conclusion: This study proposed a replicable methodology for FLAIR lesion detection and quantification and for discrimination between lesion of interest and pre-existing disease. Results from this study show the wide clinical applications of this methodology in research and clinical practice

FLAIR lesion segmentation: Application in patients with brain tumors and acute ischemic stroke

Energy Technology Data Exchange (ETDEWEB)

Artzi, Moran, E-mail: artzimy@gmail.com [The Functional Brain Center, The Wohl Institute for Advanced Imaging, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel); Aizenstein, Orna, E-mail: ornaaize@gmail.com [The Functional Brain Center, The Wohl Institute for Advanced Imaging, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Jonas-Kimchi, Tali, E-mail: talijk@tlvmc.gov.il [Radiology Department, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Myers, Vicki, E-mail: vicki_myers@hotmail.com [The Functional Brain Center, The Wohl Institute for Advanced Imaging, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Hallevi, Hen, E-mail: hen.hallevi@gmail.com [Neurology Department, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Ben Bashat, Dafna, E-mail: dafnab@tlvmc.gov.il [The Functional Brain Center, The Wohl Institute for Advanced Imaging, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel)

2013-09-15

Background: Lesion size in fluid attenuation inversion recovery (FLAIR) images is an important clinical parameter for patient assessment and follow-up. Although manual delineation of lesion areas considered as ground truth, it is time-consuming, highly user-dependent and difficult to perform in areas of indistinct borders. In this study, an automatic methodology for FLAIR lesion segmentation is proposed, and its application in patients with brain tumors undergoing therapy; and in patients following stroke is demonstrated. Materials and methods: FLAIR lesion segmentation was performed in 57 magnetic resonance imaging (MRI) data sets obtained from 44 patients: 28 patients with primary brain tumors; 5 patients with recurrent-progressive glioblastoma (rGB) who were scanned longitudinally during anti-angiogenic therapy (18 MRI scans); and 11 patients following ischemic stroke. Results: FLAIR lesion segmentation was obtained in all patients. When compared to manual delineation, a high visual similarity was observed, with an absolute relative volume difference of 16.80% and 20.96% and a volumetric overlap error of 24.87% and 27.50% obtained for two raters: accepted values for automatic methods. Quantitative measurements of the segmented lesion volumes were in line with qualitative radiological assessment in four patients who received anti-anogiogenic drugs. In stroke patients the proposed methodology enabled identification of the ischemic lesion and differentiation from other FLAIR hyperintense areas, such as pre-existing disease. Conclusion: This study proposed a replicable methodology for FLAIR lesion detection and quantification and for discrimination between lesion of interest and pre-existing disease. Results from this study show the wide clinical applications of this methodology in research and clinical practice.

Ischemic stroke in combined cerebrovascular abnormalities - aneurysm of the right internal carotid artery and arteriovenous malformation temporo occipital in the right hemisphere

International Nuclear Information System (INIS)

Manolova, T.; Naydenov, K.; Manchev, I.; Manchev, L.

2016-01-01

A case of combined vascular abnormalities is presented- an aneurysm of the internal carotid artery and arterio-venous malformation temporooccipitally on the right, clinically presented by an ischemic brain stroke in the territory supplied by the right middle cerebral artery. Treatment included - hypo-tensive drugs, antiplatelet (antiaggregants) agents and vasodilators, which lead to significant improvement of the general and focal neurological symptoms. Neurosurgical intervention is been discussed, in order to remove the vascular malformation and to prevent future vascular events. Key words: Aneurysm. Arteriovenous Malformation. Ischemic Stroke

The Correlation Between a Short-term Conventional Electroencephalography in the First Day of Life and Brain Magnetic Resonance Imaging in Newborns Undergoing Hypothermia for Hypoxic-Ischemic Encephalopathy.

Science.gov (United States)

Obeid, Rawad; Sogawa, Yoshimi; Gedela, Satyanarayana; Naik, Monica; Lee, Vince; Telesco, Richard; Wisnowski, Jessica; Magill, Christine; Painter, Michael J; Panigrahy, Ashok

2017-02-01

Electroencephalograph recorded in the first day of life in newborns treated with hypothermia for hypoxic-ischemic encephalopathy could be utilized as a predictive tool for the severity of brain injury on magnetic resonance imaging and mortality. We analyzed newborns who were admitted for therapeutic hypothermia due to hypoxic-ischemic encephalopathy. All enrolled infants underwent encephalography within the first 24 hours of life and underwent brain magnetic resonance imaging after rewarming. All encephalographs were independently reviewed for background amplitude, continuity, and variability. Brain injury determined by magnetic resonance imaging was scored using methods described by Bonifacio et al. Forty-one newborns were included in the study. Each encephalograph variable correlated significantly with the severity of injury on brain magnetic resonance imaging (P encephalopathy correlated with the extent of injury on brain magnetic resonance imaging. This information may be useful for families and aid guide clinical decision making. Copyright © 2017 Elsevier Inc. All rights reserved.

Protective effects of angiopoietin-like 4 on the blood-brain barrier in acute ischemic stroke treated with thrombolysis in mice.

Science.gov (United States)

Zhang, Bin; Xu, Xiaofeng; Chu, Xiuli; Yu, Xiaoyang; Zhao, Yuwu

2017-04-03

Given the risk of blood-brain barrier damage (BBB) caused by ischemic and tissue plasminogen activator thrombolysis, the preservation of vascular integrity is important. Angiopoietin-like 4 (ANGPTL4), a protein secreted in hypoxia, is involved in the regulation of vascular permeability. We hypothesized that Angptl4 might exert a protective effect in thrombolysis through stabilizing blood-brain barrier and inhibit hyper-permeability. We investigated the role of Angptl4 in stroke using a transient focal cerebral ischemia mouse model. The treated mice were administered Angptl4 1h after the ischemic event upon reperfusion. Our results showed that Angptl4 combined with thrombolysis greatly reduced the infarct volume and consequent neurological deficit. Western blot analyses and gelatin zymography revealed that Angptl4 protected the integrity of the endothelium damaged by thrombolysis. Angptl4 inhibited the up-regulation of vascular endothelial growth factor (VEGF) in the vascular endothelium after stroke, which was suppressed by counteracting VEGFR signaling and diminishing downstream Src signaling, and led to the increased stability of junctions and improved endothelial cell barrier integrity. These findings demonstrated that Angptl4 protects the permeability of the BBB damaged by ischemic and thrombolysis. Suggested that Angptl4 might be a promising target molecule in therapies for vasoprotection after thrombolysis treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

A report on results of brain checkup (Brain Dock) in Hiroshima General Hospital of West Japan Railway Company

International Nuclear Information System (INIS)

Kouno, Yuko; Miyamoto, Haruko; Asaoku, Yoshiko; Sakuma, Kazuyo; Takata, Kohki

2008-01-01

The brain checkup system (Brain Dock) employing head magnetic resonance imaging (MRI) and angiography (MRA) has been prevailing only in Japan. Although detection of cerebral and cerebrovascular disorders in the early stage by MR may be expected to prevent their sequelae, the significance and the management of the abnormalities observed on MR images have not been sufficiently established. We investigated whether several medical risk factors might influence the occurrence of early ischemic cerebrovascular changes such as lacuna stroke. From April 2004 to August 2006, in our hospital, we examined 281 cases undergoing head MRI and MRA in addition to ordinary medical checkups. Of those, 159 cases (56.6%) were found normal, and 122 cases (43.4%) were observed to have some abnormalities on the MR images. The most common abnormality was sinusitis (n=41, 14.6%) and the second was ischemic cerebrovascular changes (n=38, 13.5%). The third was unidentified bright objects (UBOs) (n=30, 10.7%), the pathological significance of which is unclear. Ischemic cerebrovascular changes and UBOs tended to increase with age. The medical checkup data were compared between two groups. One group consisted of 38 cases having ischemic cerebrovascular changes on the MR images. The other, normal, group consisted of 195 cases with no notable cerebral or vascular abnormalities. The level of age, systolic and diastolic blood pressure, fasting plasma glucose (FPG) and HbA1c were significantly higher in the cerebral ischemia group as compared to those in the normal group. By logistic regression analysis, the increases of age, blood pressure and FPG were related respectively to the incidence of ischemic cerebrovascular changes, whereas the increase of HbA1c did not reach statistical significance. The results indicate that increase in age, blood pressure or FPG is an independent risk factor of ischemic cerebrovascular changes. We suggest that strict control of blood pressure and plasma glucose level may

Regional cerebral blood flow before and after vascular surgery in patients with transient ischemic attacks with 133-xenon inhalation tomography

DEFF Research Database (Denmark)

Vorstrup, S; Hemmingsen, Ralf; Lindewald, H

1982-01-01

Cerebral blood flow CBF was studied in 14 patients with transient ischemic attacks TIA and arteriosclerotic neck vessel disease. CBF was measured by a rapidly rotating single photon emission computerized tomograph using Xenon-133 inhalation. This method yields images of 3 brain slices depicting CBF...... with no abnormality on the CT-scan. The abnormal blood flow pattern was found to be unchanged after clinically successful reconstructive vascular surgery. This suggests the presence of irreversible ischemic tissue damage without gross emollition (incomplete infarction). It is concluded, that TIAs are often harmful...... events, as no less than 9 of the 14 patients studied had evidence of complete and/or incomplete infarction. Thorough examination and rational therapy should be instituted as soon as possible to prevent further ischemic lesions....

Cortical neurogenesis in adult rats after ischemic brain injury: most new neurons fail to mature

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Qing-quan Li

2015-01-01

Full Text Available The present study examines the hypothesis that endogenous neural progenitor cells isolated from the neocortex of ischemic brain can differentiate into neurons or glial cells and contribute to neural regeneration. We performed middle cerebral artery occlusion to establish a model of cerebral ischemia/reperfusion injury in adult rats. Immunohistochemical staining of the cortex 1, 3, 7, 14 or 28 days after injury revealed that neural progenitor cells double-positive for nestin and sox-2 appeared in the injured cortex 1 and 3 days post-injury, and were also positive for glial fibrillary acidic protein. New neurons were labeled using bromodeoxyuridine and different stages of maturity were identified using doublecortin, microtubule-associated protein 2 and neuronal nuclei antigen immunohistochemistry. Immature new neurons coexpressing doublecortin and bromodeoxyuridine were observed in the cortex at 3 and 7 days post-injury, and semi-mature and mature new neurons double-positive for microtubule-associated protein 2 and bromodeoxyuridine were found at 14 days post-injury. A few mature new neurons coexpressing neuronal nuclei antigen and bromodeoxyuridine were observed in the injured cortex 28 days post-injury. Glial fibrillary acidic protein/bromodeoxyuridine double-positive astrocytes were also found in the injured cortex. Our findings suggest that neural progenitor cells are present in the damaged cortex of adult rats with cerebral ischemic brain injury, and that they differentiate into astrocytes and immature neurons, but most neurons fail to reach the mature stage.

Exploratory Use of Decision Tree Analysis in Classification of Outcome in Hypoxic–Ischemic Brain Injury

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Thanh G. Phan

2018-03-01

Full Text Available BackgroundPrognostication following hypoxic ischemic encephalopathy (brain injury is important for clinical management. The aim of this exploratory study is to use a decision tree model to find clinical and MRI associates of severe disability and death in this condition. We evaluate clinical model and then the added value of MRI data.MethodThe inclusion criteria were as follows: age ≥17 years, cardio-respiratory arrest, and coma on admission (2003–2011. Decision tree analysis was used to find clinical [Glasgow Coma Score (GCS, features about cardiac arrest, therapeutic hypothermia, age, and sex] and MRI (infarct volume associates of severe disability and death. We used the area under the ROC (auROC to determine accuracy of model. There were 41 (63.7% males patients having MRI imaging with the average age 51.5 ± 18.9 years old. The decision trees showed that infarct volume and age were important factors for discrimination between mild to moderate disability and severe disability and death at day 0 and day 2. The auROC for this model was 0.94 (95% CI 0.82–1.00. At day 7, GCS value was the only predictor; the auROC was 0.96 (95% CI 0.86–1.00.ConclusionOur findings provide proof of concept for further exploration of the role of MR imaging and decision tree analysis in the early prognostication of hypoxic ischemic brain injury.

Exploratory Use of Decision Tree Analysis in Classification of Outcome in Hypoxic-Ischemic Brain Injury.

Science.gov (United States)

Phan, Thanh G; Chen, Jian; Singhal, Shaloo; Ma, Henry; Clissold, Benjamin B; Ly, John; Beare, Richard

2018-01-01

Prognostication following hypoxic ischemic encephalopathy (brain injury) is important for clinical management. The aim of this exploratory study is to use a decision tree model to find clinical and MRI associates of severe disability and death in this condition. We evaluate clinical model and then the added value of MRI data. The inclusion criteria were as follows: age ≥17 years, cardio-respiratory arrest, and coma on admission (2003-2011). Decision tree analysis was used to find clinical [Glasgow Coma Score (GCS), features about cardiac arrest, therapeutic hypothermia, age, and sex] and MRI (infarct volume) associates of severe disability and death. We used the area under the ROC (auROC) to determine accuracy of model. There were 41 (63.7% males) patients having MRI imaging with the average age 51.5 ± 18.9 years old. The decision trees showed that infarct volume and age were important factors for discrimination between mild to moderate disability and severe disability and death at day 0 and day 2. The auROC for this model was 0.94 (95% CI 0.82-1.00). At day 7, GCS value was the only predictor; the auROC was 0.96 (95% CI 0.86-1.00). Our findings provide proof of concept for further exploration of the role of MR imaging and decision tree analysis in the early prognostication of hypoxic ischemic brain injury.

Early Blood-Brain Barrier Disruption after Mechanical Thrombectomy in Acute Ischemic Stroke.

Science.gov (United States)

Shi, Zhong-Song; Duckwiler, Gary R; Jahan, Reza; Tateshima, Satoshi; Szeder, Viktor; Saver, Jeffrey L; Kim, Doojin; Sharma, Latisha K; Vespa, Paul M; Salamon, Noriko; Villablanca, J Pablo; Viñuela, Fernando; Feng, Lei; Loh, Yince; Liebeskind, David S

2018-05-01

The impact of blood-brain barrier (BBB) disruption can be detected by intraparenchymal hyperdense lesion on the computed tomography (CT) scan after endovascular stroke therapy. The purpose of this study was to determine whether early BBB disruption predicts intracranial hemorrhage and poor outcome in patients with acute ischemic stroke treated with mechanical thrombectomy. We analyzed patients with anterior circulation stroke treated with mechanical thrombectomy and identified BBB disruption on the noncontrast CT images immediately after endovascular treatment. Follow-up CT or magnetic resonance imaging scan was performed at 24 hours to assess intracranial hemorrhage. We dichotomized patients into those with moderate BBB disruption versus those with minor BBB disruption and no BBB disruption. We evaluated the association of moderate BBB disruption after mechanical thrombectomy with intracranial hemorrhage and clinical outcomes. Moderate BBB disruption after mechanical thrombectomy was found in 56 of 210 patients (26.7%). Moderate BBB disruption was independently associated with higher rates of hemorrhagic transformation (OR 25.33; 95% CI 9.93-64.65; P disruption with intracranial hemorrhage remained in patients with successful reperfusion after mechanical thrombectomy. The location of BBB disruption was not associated with intracranial hemorrhage and poor outcome. Moderate BBB disruption is common after mechanical thrombectomy in a quarter of patients with acute ischemic stroke and increases the risk of intracranial hemorrhage and poor outcome. Copyright © 2018 by the American Society of Neuroimaging.

Serum Markers of Apoptosis in Traumatic and Ischemic Brain Injury

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N. N. Yepifantseva

2009-01-01

Full Text Available Objective: to study the time course of changes and relationship of the serum indicators of apoptotic processes in neurore-suscitation patients. Subjects and methods. Thirty-eight neuroresuscitation patients, including 14 patients with severe brain injury (SBI (mean age 41.4±4.3 years and 24 patients with strokes (mean age 53.8±2.5 years, were examined. The group of patients with strokes was divided into 2 subroups: 1 11 patients with ischemic strokes (IS and 2 13 with hemorrhagic strokes (HS. The Glasgow coma scores for admission consciousness loss were 7.6±0.8 in the SBI group and 9.5±0.7 in the stroke group; mortality was 28.6 and 37.5%, respectively. A control group included 16 subjects (mean age 47.9±3.8 years. The investigators measured the serum levels of FAS antigen and its ligand (sAPO-I/FAS and sFAS-L, cas-pase-1/ICE, sCD40 (Bender MedSystem, Austria and hTRAIL (Biosource, Belgium by solid-phase immunoassay in neuroresuscitation patients on days 1, 7, and 14 of the acute period of diseases. They used statistical methods, such as Wilcoxon-Mann-Whitney U-test, Spearman’s rank correlation test. Results. A reduction in hTRAIL was observed in all the groups. There was a decrease in serum sCD40 in strokes on days 1 to 14 and in SBI on days 7 to 14. An increase in caspase 1/ICE was seen in HS in the first 24 hours, in IS on days 1 to 7, and in SBI on days 1 to 14. The most pronounced rise in caspase-1/ICE was induced by ischemic brain lesion within the first week of disease. A prolonged increase up to 2 weeks was noted in SBI. No rise in serum FAS-L was found in the examinees. The time course of changes in sAPO-I/FAS was different in all the groups. The most marked, moderate, and none reductions were revealed in HS, IS, and SBI, respectively. There was a pronounced serum sAPO-I/FAS increase in SBI within the first 24 hours. Assessment of correlations between the serum indicators of apoptosis revealed that there were differences in the

MRI at 3 Tesla detects no evidence for ischemic brain damage in intensively treated patients with homozygous familial hypercholesterolemia

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Schmitz, Stephan A.; O' Regan, Declan P.; Fitzpatrick, Julie; Hajnal, Joseph V. [Hammersmith Hospital Campus, Imaging Sciences Department, MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, London (United Kingdom); Neuwirth, Clare; Potter, Elizabeth; Tosi, Isabella; Naoumova, Rossi P. [MRC Clinical Sciences Centre, Clinical Research Facility, London (United Kingdom); Hammersmith Hospital, Lipid Clinic, London (United Kingdom)

2007-11-15

Homozygous familial hypercholesterolemia (FH) is considered a model disease for excessive plasma cholesterol levels. Patients with untreated homozygous FH have a markedly increased risk for premature atherosclerosis. The frequency and extent of ischemic brain damage detectable by high-field magnetic resonance imaging (MRI) after long-term intensive treatment are unknown. In a case control study, five patients with homozygous FH (one male and four females; mean age: 23.6 {+-} 9.2, range: 12-36 years; mean pre-treatment serum total cholesterol level: 26.9 {+-} 3.24 mmol/L; all patients with documented atherosclerotic plaques in the carotid arteries) and five age- and sex-matched healthy controls were studied. All patients had been on maximal lipid-lowering medication since early childhood, and four of them were also on treatment with low-density lipoprotein (LDL) apheresis at bi-weekly intervals. Brain MRI was performed at 3 Tesla field strength with fluid-attenuated T2-weighted inversion recovery and T1-weighted spin-echo MR pulse sequences and subsequently evaluated by two independent readers. The maximal lipid-lowering treatment reduced the total serum cholesterol by more than 50% in the patients, but their serum concentrations were still 3.6-fold higher than those found in the controls (11.9 {+-} 4.2 vs. 4.5 {+-} 0.5 mmol/L; p < 0.0047). No brain abnormality was observed in any of the patients with homozygous FH. Homozygous FH patients on intensive cholesterol-lowering therapy have no evidence of ischemic brain damage at 3 Tesla MRI despite the remaining high cholesterol levels. (orig.)

MRI at 3 Tesla detects no evidence for ischemic brain damage in intensively treated patients with homozygous familial hypercholesterolemia

International Nuclear Information System (INIS)

Schmitz, Stephan A.; O'Regan, Declan P.; Fitzpatrick, Julie; Hajnal, Joseph V.; Neuwirth, Clare; Potter, Elizabeth; Tosi, Isabella; Naoumova, Rossi P.

2007-01-01

Homozygous familial hypercholesterolemia (FH) is considered a model disease for excessive plasma cholesterol levels. Patients with untreated homozygous FH have a markedly increased risk for premature atherosclerosis. The frequency and extent of ischemic brain damage detectable by high-field magnetic resonance imaging (MRI) after long-term intensive treatment are unknown. In a case control study, five patients with homozygous FH (one male and four females; mean age: 23.6 ± 9.2, range: 12-36 years; mean pre-treatment serum total cholesterol level: 26.9 ± 3.24 mmol/L; all patients with documented atherosclerotic plaques in the carotid arteries) and five age- and sex-matched healthy controls were studied. All patients had been on maximal lipid-lowering medication since early childhood, and four of them were also on treatment with low-density lipoprotein (LDL) apheresis at bi-weekly intervals. Brain MRI was performed at 3 Tesla field strength with fluid-attenuated T2-weighted inversion recovery and T1-weighted spin-echo MR pulse sequences and subsequently evaluated by two independent readers. The maximal lipid-lowering treatment reduced the total serum cholesterol by more than 50% in the patients, but their serum concentrations were still 3.6-fold higher than those found in the controls (11.9 ± 4.2 vs. 4.5 ± 0.5 mmol/L; p < 0.0047). No brain abnormality was observed in any of the patients with homozygous FH. Homozygous FH patients on intensive cholesterol-lowering therapy have no evidence of ischemic brain damage at 3 Tesla MRI despite the remaining high cholesterol levels. (orig.)

Apparent diffusion coefficient histogram analysis of neonatal hypoxic-ischemic encephalopathy

International Nuclear Information System (INIS)

Cauley, Keith A.; Filippi, Christopher G.

2014-01-01

Diffusion-weighted imaging is a valuable tool in the assessment of the neonatal brain, and changes in diffusion are seen in normal development as well as in pathological states such as hypoxic-ischemic encephalopathy (HIE). Various methods of quantitative assessment of diffusion values have been reported. Global ischemic injury occurring during the time of rapid developmental changes in brain myelination can complicate the imaging diagnosis of neonatal HIE. To compare a quantitative method of histographic analysis of brain apparent coefficient (ADC) maps to the qualitative interpretation of routine brain MR imaging studies. We correlate changes in diffusion values with gestational age in radiographically normal neonates, and we investigate the sensitivity of the method as a quantitative measure of hypoxic-ischemic encephalopathy. We reviewed all brain MRI studies from the neonatal intensive care unit (NICU) at our university medical center over a 4-year period to identify cases that were radiographically normal (23 cases) and those with diffuse, global hypoxic-ischemic encephalopathy (12 cases). We histographically displayed ADC values of a single brain slice at the level of the basal ganglia and correlated peak (s-sD av ) and lowest histogram values (s-sD lowest ) with gestational age. Normative s-sD av values correlated significantly with gestational age and declined linearly through the neonatal period (r 2 = 0.477, P av and s-sD lowest ADC values than were reflected in the normative distribution; several cases of HIE fell within a 95% confidence interval for normative studies, and one case demonstrated higher-than-normal s-sD av . Single-slice histographic display of ADC values is a rapid and clinically feasible method of quantitative analysis of diffusion. In this study normative values derived from consecutive neonates without radiographic evidence of ischemic injury are correlated with gestational age, declining linearly throughout the perinatal period. This

Transient central diabetes insipidus following ischemic stroke

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Muthukrishnan Jayaraman

2013-01-01

Full Text Available Central Diabetes Insipidus (CDI following ischemic infarction of the brain has been described as a rare presentation. Posterior pituitary ischemia has also been postulated as a possible cause of idiopathic CDI. We encountered a young male with bilateral extensive ischemic infarction sustained at high altitude, who had transient polyuria due to central diabetes insipidus, requiring desmopressin therapy. DI completely resolved during the course of his neurological recovery.

How study patients who receive fluo pyrimidines to prevent ischemic events; Como estudiar los pacientes que recibiran fluopirimidinas para prevenir eventos isquemicos

Energy Technology Data Exchange (ETDEWEB)

Saldombide, L. [Hospital de Clinicas. Montevideo (Uruguay)

2010-11-15

Introduction: Ischemic heart disease is the main cause of death in Uruguay and cancer is the second. The pillar of the systemic treatment of colorectal cancer are fluo pyrimidines and cause acute ischemic events in 3-8% of t rated patients. The 5 fluorouracil is the third anticancer drug most used Objective: Due to the high incidence of the two diseases and the risk of death caused by the ischemic treatment complications, the literature is analyzed to define how to study patients who receive fluo pyrimidines as a medium of preventing the same. Development: fluo pyrimidines cardio-toxicity can occur by myocardial toxicity, vasospasm, dihydropyrimidine dehydrogenase deficiency, autoimmune phenomena, platelet hyper aggregability, etc. The clinic is varied and underestimated: angina, abnormal ST silent and reversible, arrhythmias, heart failure, hypertension and heart failure. It is the most common complication with continuous infusion of 5 Fu and its equivalent capecitabine with bolus f lou pyrimidines. It is common that ischemic heart disease prioritises the risk increase of complications, but their absence does not exist. Without ischemic heart disease it is difficult to prevent ischemic events, however proposes that the older higher risk. Results: No uniform guidelines is advised: detailed history, determine if risk factors such as smoking, hypertension, diabetes and dyslipidemia and They are present electrocardiogram and cardiac evaluation. Warn the patient about angina l pain as early symptom and monitor symptoms during chemotherapy including cardio-vascular hypotension. Discontinue the medication and perform classic anti-angina l symptoms and / or signs of ischemia. Not reintroduce unless it is the only therapeutic option, since mortality may exceed.

Role of brain natriuretic peptide as a novel prognostic biomarker in acute ischemic stroke

Directory of Open Access Journals (Sweden)

Bindu Menon

2016-01-01

Full Text Available Aim: We investigated to study the prognostic importance of brain natriuretic peptide (BNP in ischemic stroke. Materials and Methods: We prospectively enrolled 100 patients with acute ischemic stroke and measured plasma BNP levels and compared with age- and sex-matched healthy controls. Risk factors, biochemical parameters, lipid profile, carotid and vertebral Doppler, imaging, and cardiac evaluation were done. Stroke severity was assessed by the National Institutes of Health Stroke Scale (NIHSS score on admission and functional disability by Barthel Index (BI at 3 months. Ischemic stroke subtype was classified according to the Oxfordshire Community Stroke Project (OCSP. Data were entered in MS Excel, and appropriate statistical analysis was done using the SPSS software version 21.0. A P = 0.05 was considered as significant. Results: Mean age of patients was 55.17 ± 11.37 years with a male:female ratio 3:1. OCSP showed total anterior circulation infarct (TACI 35, partial anterior circulation infarct 9, lacunar infarct 12, and posterior circulation infarct 44. NIHSS on admission was average 10 ± 7 and BI was 57 ± 30. BNP in patients (435 ng/ml was very high as compared to controls (<60 ng/ml (P < 0.001. There was a positive correlation between age and BNP (R2 = 0.34; P < 0.00; NIHSS and BNP (R2 = 0.255; P < 0.01, negative correlation between BI and BNP (R2 = −0.064; P < 0.01. Mean BNP levels across the OCSP showed higher values in TACI (F = 4.609 P = 0.005. Regression analysis showed that BNP can predict BI which was statistically significant. Conclusion: Plasma BNP levels was significantly elevated in patients with ischemic stroke. Our study concludes that high BNP levels are seen in large anterior circulation stroke and is a predictor for the poor functional outcome at 3 months. Determination of BNP levels as a biomarker could be helpful in predicting the outcome in stroke patients.

Neurological outcomes in patients with ischemic stroke receiving enoxaparin or heparin for venous thromboembolism prophylaxis: subanalysis of the Prevention of VTE after Acute Ischemic Stroke with LMWH (PREVAIL) study.

Science.gov (United States)

Kase, Carlos S; Albers, Gregory W; Bladin, Christopher; Fieschi, Cesare; Gabbai, Alberto A; O'Riordan, William; Pineo, Graham F

2009-11-01

The Prevention of VTE after Acute Ischemic Stroke with LMWH (PREVAIL) study demonstrated that enoxaparin was superior to unfractionated heparin (UFH) in preventing venous thromboembolism in patients with ischemic stroke and was associated with a small but statistically significant increase in extracranial hemorrhage rates. In this PREVAIL subanalysis, we evaluate the long-term neurological outcomes associated with the use of enoxaparin compared with UFH. We also determine predictors of stroke progression. Acute ischemic stroke patients aged >or=18 years, who could not walk unassisted, were randomized to receive enoxaparin (40 mg once daily) or UFH (5000 U every 12 hours) for 10 days. Patients were stratified according to baseline stroke severity using the National Institutes of Health Stroke Scale score. End points for this analysis included stroke progression (>or=4-point increase in National Institutes of Health Stroke Scale score), neurological outcomes up to 3 months postrandomization (assessed using National Institutes of Health Stroke Scale score and modified Rankin Scale score), and incidence of intracranial hemorrhage. Stroke progression occurred in 45 of 877 (5.1%) patients in the enoxaparin group and 42 of 872 (4.8%) of those receiving UFH. Similar improvements in National Institutes of Health Stroke Scale and modified Rankin Scale scores were observed in both groups over the 90-day follow-up period. Incidence of intracranial hemorrhage was comparable between groups (20 of 877 [2.3%] and 22 of 872 [2.5%] in enoxaparin and UFH groups, respectively). Baseline National Institutes of Health Stroke Scale score, hyperlipidemia, and Hispanic ethnicity were independent predictors of stroke progression. The clinical benefits associated with use of enoxaparin for venous thromboembolism prophylaxis in patients with acute ischemic stroke are not associated with poorer long-term neurological outcomes or increased rates of symptomatic intracranial hemorrhage compared

Early MEK1/2 Inhibition after Global Cerebral Ischemia in Rats Reduces Brain Damage and Improves Outcome by Preventing Delayed Vasoconstrictor Receptor Upregulation

DEFF Research Database (Denmark)

Johansson, Sara Ellinor; Larsen, Stine Schmidt; Povlsen, Gro Klitgaard

2014-01-01

BACKGROUND: Global cerebral ischemia following cardiac arrest is associated with increased cerebral vasoconstriction and decreased cerebral blood flow, contributing to delayed neuronal cell death and neurological detriments in affected patients. We hypothesize that upregulation of contractile ETB...... and 5-HT1B receptors, previously demonstrated in cerebral arteries after experimental global ischemia, are a key mechanism behind insufficient perfusion of the post-ischemic brain, proposing blockade of this receptor upregulation as a novel target for prevention of cerebral hypoperfusion and delayed...... neuronal cell death after global cerebral ischemia. The aim was to characterize the time-course of receptor upregulation and associated neuronal damage after global ischemia and investigate whether treatment with the MEK1/2 inhibitor U0126 can prevent cerebrovascular receptor upregulation and thereby...

Cardiovascular risk factors cause premature rarefaction of the collateral circulation and greater ischemic tissue injury.

Science.gov (United States)

Moore, Scott M; Zhang, Hua; Maeda, Nobuyo; Doerschuk, Claire M; Faber, James E

2015-07-01

Collaterals lessen tissue injury in occlusive disease. However, aging causes progressive decline in their number and smaller diameters in those that remain (collateral rarefaction), beginning at 16 months of age in mice (i.e., middle age), and worse ischemic injury-effects that are accelerated in even 3-month-old eNOS(-/-) mice. These findings have found indirect support in recent human studies. We sought to determine whether other cardiovascular risk factors (CVRFs) associated with endothelial dysfunction cause collateral rarefaction, investigate possible mechanisms, and test strategies for prevention. Mice with nine different models of CVRFs of 4-12 months of age were assessed for number and diameter of native collaterals in skeletal muscle and brain and for collateral-dependent perfusion and ischemic injury after arterial occlusion. Hypertension caused collateral rarefaction whose severity increased with duration and level of hypertension, accompanied by greater hindlimb ischemia and cerebral infarct volume. Chronic treatment of wild-type mice with L-N (G)-nitro-arginine methylester caused similar rarefaction and worse ischemic injury which were not prevented by lowering arterial pressure with hydralazine. Metabolic syndrome, hypercholesterolemia, diabetes mellitus, and obesity also caused collateral rarefaction. Neither chronic statin treatment nor exercise training lessened hypertension-induced rarefaction. Chronic CVRF presence caused collateral rarefaction and worse ischemic injury, even at relatively young ages. Rarefaction was associated with increased proliferation rate of collateral endothelial cells, effects that may promote accelerated endothelial cell senescence.

Brain hypoxia imaging

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Song, Ho Chun [Chonnam National University Medical School, Gwangju (Korea, Republic of)

2007-04-15

The measurement of pathologically low levels of tissue pO{sub 2} is an important diagnostic goal for determining the prognosis of many clinically important diseases including cardiovascular insufficiency, stroke and cancer. The target tissues nowadays have mostly been tumors or the myocardium, with less attention centered on the brain. Radiolabelled nitroimidazole or derivatives may be useful in identifying the hypoxic cells in cerebrovascular disease or traumatic brain injury, and hypoxic-ischemic encephalopathy. In acute stroke, the target of therapy is the severely hypoxic but salvageable tissue. {sup 18}F-MISO PET and {sup 99m}Tc-EC-metronidazole SPECT in patients with acute ischemic stroke identified hypoxic tissues and ischemic penumbra, and predicted its outcome. A study using {sup 123}I-IAZA in patient with closed head injury detected the hypoxic tissues after head injury. Up till now these radiopharmaceuticals have drawbacks due to its relatively low concentration with hypoxic tissues associated with/without low blood-brain barrier permeability and the necessity to wait a long time to achieve acceptable target to background ratios for imaging in acute ischemic stroke. It is needed to develop new hypoxic marker exhibiting more rapid localization in the hypoxic region in the brain. And then, the hypoxic brain imaging with imidazoles or non-imidazoles may be very useful in detecting the hypoxic tissues, determining therapeutic strategies and developing therapeutic drugs in several neurological disease, especially, in acute ischemic stroke.

Effects of Ischemic Preconditioning of Different Intraoperative Ischemic Times of Vascularized Bone Graft Rabbit Models

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Ahmad Sukari Halim

2013-11-01

Full Text Available BackgroundIschemic preconditioning has been shown to improve the outcomes of hypoxic tolerance of the heart, brain, lung, liver, jejunum, skin, and muscle tissues. However, to date, no report of ischemic preconditioning on vascularized bone grafts has been published.MethodsSixteen rabbits were divided into four groups with ischemic times of 2, 6, 14, and 18 hours. Half of the rabbits in each group underwent ischemic preconditioning. The osteomyocutaneous flaps consisted of the tibia bone, from which the overlying muscle and skin were raised. The technique of ischemic preconditioning involved applying a vascular clamp to the pedicle for 3 cycles of 10 minutes each. The rabbits then underwent serial plain radiography and computed tomography imaging on the first, second, fourth, and sixth postoperative weeks. Following this, all of the rabbits were sacrificed and histological examinations were performed.ResultsThe results showed that for clinical analysis of the skin flaps and bone grafts, the preconditioned groups showed better survivability. In the plain radiographs, except for two non-preconditioned rabbits with intraoperative ischemic times of 6 hours, all began to show early callus formation at the fourth week. The computed tomography findings showed more callus formation in the preconditioned groups for all of the ischemic times except for the 18-hour group. The histological findings correlated with the radiological findings. There was no statistical significance in the difference between the two groups.ConclusionsIn conclusion, ischemic preconditioning improved the survivability of skin flaps and increased callus formation during the healing process of vascularized bone grafts.

Safety and feasibility of post-stroke care and exercise after minor ischemic stroke or transient ischemic attack: MotiveS & MoveIT

NARCIS (Netherlands)

Boss, H.M.; Van Schaik, S.M.; Deijle, I.A.; de Melker, E.C.; van den Berg, B.M.; Scherder, E.J.A.; Bosboom, W.M.J.; Weinstein, H.C.; van den Berg-Vos, R.M.

2014-01-01

Background: Despite the beneficial effect of cardiac rehabilitation after myocardial infarction, a rehabilitation program to improve cardiorespiratory fitness and influence secondary prevention has not been implemented for ischemic stroke and transient ischemic attack (TIA). Objective: To

Effects of hyperbaric oxygen and nerve growth factor on the long-term neural behavior of neonatal rats with hypoxic ischemic brain damage.

Science.gov (United States)

Wei, Lixia; Ren, Qing; Zhang, Yongjun; Wang, Jiwen

2017-04-01

To evaluate the effects of HBO (Hyperbaric oxygen) and NGF (Nerve growth factor) on the long-term neural behavior of neonatal rats with HIBD (Neonatal hypoxic ischemic brain damage). The HIBD model was produced by ligating the right common carotid artery of 7 days old SD (Sprague-Dawley) rats followed by 8% O2 + 92% N2 for 2h. Totally 40 rats were randomly divided into 5 groups including sham-operated group, HIBD control group, HBO treated group, NGF treated group and NGF + HBO treated group. The learning and memory ability of these rats was evaluated by Morris water maze at 30 days after birth, and sensory motor function was assessed by experiments of foot error and limb placement at 42 days after birth. The escape latency of HBO treated group, NGF treated group and NGF + HBO treated group was shorter than that of HIBD control group (pmemory ability and sensory motor function in neonatal rats after hypoxic ischemic brain damage.

Computed tomography and brain scintigraphy in ischemic stroke

International Nuclear Information System (INIS)

Chiu, L.C.; Fodor, L.B.; Cornell, S.H.; Christie, J.H.

1976-01-01

Radionuclide and computed tomographic (CT) scans were reviewed in 215 patients with ischemic stroke. The findings vary depending on the site of vascular occlusion. In middle cerebral artery occlusion, four distinct patterns may be seen on the scintigrams. The CT scans show little variation in appearance. The tentorial confluence sign is an important finding on scintigrams of patients with occipital infarction; the absence of this sign should suggest another diagnosis. During the first week and after the fourth week following an ischemic stroke, the scintigram is usually negative, whereas the lesion is visible by CT. However, there are a significant number of false negative CT scans; therefore, both examinations are advocated in difficult cases

Rational modulation of the innate immune system for neuroprotection in ischemic stroke

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Diana eAmantea

2015-04-01

Full Text Available The innate immune system plays a dualistic role in the evolution of ischemic brain damage and has also been implicated in ischemic tolerance produced by different conditioning stimuli. Early after ischemia, perivascular astrocytes release cytokines and activate metalloproteases (MMPs that contribute to blood–brain barrier (BBB disruption and vasogenic oedema; whereas at later stages, they provide extracellular glutamate uptake, BBB regeneration and neurotrophic factors release. Similarly, early activation of microglia contributes to ischemic brain injury via the production of inflammatory cytokines, including tumor necrosis factor (TNF and interleukin (IL-1, reactive oxygen and nitrogen species and proteases. Nevertheless, microglia also contributes to the resolution of inflammation, by releasing IL-10 and tumor growth factor (TGF-beta, and to the late reparative processes by phagocytic activity and growth factors production. Indeed, after ischemia, microglia/macrophages differentiate towards several phenotypes: the M1 pro-inflammatory phenotype is classically activated via toll-like receptors or interferon-γ, whereas M2 phenotypes are alternatively activated by regulatory mediators, such as ILs 4, 10, 13 or TGF-beta. Thus, immune cells exert a dualistic role on the evolution of ischemic brain damage, since the classic phenotypes promote injury, whereas alternatively activated M2 macrophages or N2 neutrophils prompt tissue remodeling and repair.Moreover, a subdued activation of the immune system has been involved in ischemic tolerance, since different preconditioning stimuli act via modulation of inflammatory mediators, including toll-like receptors and cytokine signaling pathways. This further underscores that the immuno-modulatory approach for the treatment of ischemic stroke should be aimed at blocking the detrimental effects, while promoting the beneficial responses of the immune reaction.

Migraine, the heart and the brain

NARCIS (Netherlands)

Koppen, H.

2018-01-01

The association between migraine and silent ischemic brain lesions was investigated. Also the occurence of right-to-left shunts in different migraine groups and controls. The functional consequences of silent ischemic brain lesions were investigated.

Melatonin and Ischemic Stroke: Mechanistic Roles and Action.

Science.gov (United States)

Andrabi, Syed Suhail; Parvez, Suhel; Tabassum, Heena

2015-01-01

Stroke is one of the most devastating neurological disabilities and brain's vulnerability towards it proves to be fatal and socio-economic loss of millions of people worldwide. Ischemic stroke remains at the center stage of it, because of its prevalence amongst the several other types attacking the brain. The various cascades of events that have been associated with stroke involve oxidative stress, excitotoxicity, mitochondrial dysfunction, upregulation of Ca(2+) level, and so forth. Melatonin is a neurohormone secreted by pineal and extra pineal tissues responsible for various physiological processes like sleep and mood behaviour. Melatonin has been implicated in various neurological diseases because of its antioxidative, antiapoptotic, and anti-inflammatory properties. We have previously reviewed the neuroprotective effect of melatonin in various models of brain injury like traumatic brain injury and spinal cord injury. In this review, we have put together the various causes and consequence of stroke and protective role of melatonin in ischemic stroke.

Impaired cerebral autoregulation and brain injury in newborns with hypoxic-ischemic encephalopathy treated with hypothermia.

Science.gov (United States)

Massaro, An N; Govindan, R B; Vezina, Gilbert; Chang, Taeun; Andescavage, Nickie N; Wang, Yunfei; Al-Shargabi, Tareq; Metzler, Marina; Harris, Kari; du Plessis, Adre J

2015-08-01

Impaired cerebral autoregulation may contribute to secondary injury in newborns with hypoxic-ischemic encephalopathy (HIE). Continuous, noninvasive assessment of cerebral pressure autoregulation can be achieved with bedside near-infrared spectroscopy (NIRS) and systemic mean arterial blood pressure (MAP) monitoring. This study aimed to evaluate whether impaired cerebral autoregulation measured by NIRS-MAP monitoring during therapeutic hypothermia and rewarming relates to outcome in 36 newborns with HIE. Spectral coherence analysis between NIRS and MAP was used to quantify changes in the duration [pressure passivity index (PPI)] and magnitude (gain) of cerebral autoregulatory impairment. Higher PPI in both cerebral hemispheres and gain in the right hemisphere were associated with neonatal adverse outcomes [death or detectable brain injury by magnetic resonance imaging (MRI), P < 0.001]. NIRS-MAP monitoring of cerebral autoregulation can provide an ongoing physiological biomarker that may help direct care in perinatal brain injury. Copyright © 2015 the American Physiological Society.

Intermittent fasting attenuates inflammasome activity in ischemic stroke.

Science.gov (United States)

Fann, David Yang-Wei; Santro, Tomislav; Manzanero, Silvia; Widiapradja, Alexander; Cheng, Yi-Lin; Lee, Seung-Yoon; Chunduri, Prasad; Jo, Dong-Gyu; Stranahan, Alexis M; Mattson, Mark P; Arumugam, Thiruma V

2014-07-01

Recent findings have revealed a novel inflammatory mechanism that contributes to tissue injury in cerebral ischemia mediated by multi-protein complexes termed inflammasomes. Intermittent fasting (IF) can decrease the levels of pro-inflammatory cytokines in the periphery and brain. Here we investigated the impact of IF (16h of food deprivation daily) for 4months on NLRP1 and NLRP3 inflammasome activities following cerebral ischemia. Ischemic stroke was induced in C57BL/6J mice by middle cerebral artery occlusion, followed by reperfusion (I/R). IF decreased the activation of NF-κB and MAPK signaling pathways, the expression of NLRP1 and NLRP3 inflammasome proteins, and both IL-1β and IL-18 in the ischemic brain tissue. These findings demonstrate that IF can attenuate the inflammatory response and tissue damage following ischemic stroke by a mechanism involving suppression of NLRP1 and NLRP3 inflammasome activity. Copyright © 2014 Elsevier Inc. All rights reserved.

NEUROGENETIC ASPECTS OF PERINATAL HYPOXIC-ISCHEMIC AFFECTIONS OF THE CENTRAL NERVOUS SYSTEM

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George A. Karkashadze

2016-01-01

Full Text Available Neurogenetics is a thriving young science greatly contributing to the generally accepted concept of the brain development in health and disease. Thereby; scientists are not only able to highlight new key points in traditional ideas about the origin of diseases; but also to completely rethink their view on the problem of pathology development. In particular; new data on neurogenetics of perinatal affections of the central nervous system (CNS has appeared. Genetic factors in varying degrees affect perinatal hypoxic-ischemic CNS affections. Prematurity determination stays the most studied among them. Nevertheless; there is increasing evidence of significant epigenetic regulations of neuro-expression caused by hypoxia; malnutrition of a pregnant woman; stress; smoking; alcohol; drugs that either directly pathologically affect the developing brain; or form a brain phenotype sensitive to a perinatal CNS affection. New data obliges to change the approaches to prevention of perinatal CNS affections.

Diffusion-weighted MR imaging in animal modil with acute ischemic brain infarction : evaluation of reversible brain injury

International Nuclear Information System (INIS)

Byun, Woo Mok; Chang, Han Won; Cho, Inn Ho; Hah, Jung Sang; Sung, Eon Gi

2001-01-01

To determine whether the analysis of abnormally high signal intensities in ischemic tissue, as revealed by diffusion-weighted MR imaging (DWI) can be used to evaluate reversible brain lesions in a cat model of acute ischemia. Ten cats were divided into two groups of five (Group I and Group II), and in all animals the middle cerebral artery was temporarily occluded. Group I underwent T2-DWI 30 minutes after occlusion, and Group II 120 minutes after occlusion. In both groups, DWI was performed one hour and 24 hours after reperfusion (at one hour, non-T2-weighted; at 24 hours, T2-weighted). Both occlusion and reperfusion were monitored by 99m TC-ECD brain perfusion SPECT. All animals were sacrificed 24 hours later and their brain tissue was stained with TTC. Signal intensity ratios (SIR, signifying average signal intensity within the region of interest divided by that in the contralateral, nonischemic, homologous region) of the two groups, as seen on DWI were compared. The percentage of hemispheric lesions occurring in the two groups was also compared. SIR after occlusion of the middle cerebral artery was 1.29 in Group I and 1.59 in Group II. Twenty-four hours after reperfusion, SIR in Group I was higher than in Group II (p<0.01). After occlusion and reperfusion, the percentage of hemispheric lesions in Group I was less than in Group II. For the latter, the percentage of these lesions revealed by TTC staining and T2-weighted imaging was 48% and 59%, respectively, findings distinctly different from those for Group I. In addition, in group I, infarction was revealed by neither TTC staining nor T2-weighted imaging (p<0.01). The use of DWI to evaluate signal intensity ratios can help determine whether or not brain injury after temporary cerebral ischemia is reversible

Acute ischemic stroke prognostication, comparison between ...

African Journals Online (AJOL)

Ossama Y. Mansour

2014-11-20

Nov 20, 2014 ... patients with acute ischemic stroke in comparison with the NIHSS and the GCS. Methods: .... All patients received a CT scan of the brain on admission. Diagnostic ... adjusted for age, sex, Charlson Index and Oxfordshire. 248.

Brain parenchyma PO2, PCO2, and pH during and after hypoxic, ischemic brain insult in dogs.

Science.gov (United States)

McKinley, B A; Morris, W P; Parmley, C L; Butler, B D

1996-11-01

1) The investigation of fiberoptic PO2, PCO2, and pH sensor technology as a monitor of brain parenchyma during and after brain injury, and 2) the comparison of brain parenchyma PO2, PCO2, and pH with intracranial pressure during and after hypoxic, ischemic brain insult. Prospective, controlled, animal study in an acute experimental preparation. Physiology laboratory in a university medical school. Fourteen mongrel dogs (20 to 35 kg), anesthetized, room-air ventilated. Anesthesia was induced with thiopental and maintained after intubation using 1% to 1.5% halothane in room air (FiO2 0.21). Mechanical ventilation was established to maintain end-tidal PCO2 approximately 35 torr (-4.7 kPa). Intravenous, femoral artery, and pulmonary artery catheters were placed. The common carotid arteries were surgically exposed, and ultrasonic blood flow probes were applied. A calibrated intracranial pressure probe was placed through a right-side transcranial bolt, and a calibrated intracranial chemistry probe with optical sensors for PO2, PCO2, and pH was placed through a left-side bolt into brain parenchyma. Brain insult was induced in the experimental group (n = 6) by hypoxia (FiO2 0.1), ischemia (bilateral carotid artery occlusion), and hypotension (mean arterial pressure [MAP] approximately 40 mm Hg produced with isoflurane approximately 4%). After 45 mins, carotid artery occlusion was released, FiO2 was reset to 0.21, and anesthetic was returned to halothane (approximately 1.25%). The control group (n = 5) had the same surgical preparation and sequence of anesthetic agent exposure but no brain insult. Monitored variables included brain parenchyma PO2, PCO2, and pH, which were monitored at 1-min intervals, and intracranial pressure, MAP, arterial hemoglobin oxygen saturation (by pulse oximetry), end-tidal PCO2, and carotid artery blood flow rate, for which data were collected at 15-min intervals for 7 hrs. Arterial and mixed venous blood gas analyses were done at approximately 1

Apparent diffusion coefficient histogram analysis of neonatal hypoxic-ischemic encephalopathy

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Cauley, Keith A. [University of Massachusetts Medical School, Department of Radiology, Worcester, MA (United States); New York Presbyterian Hospital, Columbia University Medical Center, Department of Radiology, New York, NY (United States); Filippi, Christopher G. [New York Presbyterian Hospital, Columbia University Medical Center, Department of Radiology, New York, NY (United States)

2014-06-15

Diffusion-weighted imaging is a valuable tool in the assessment of the neonatal brain, and changes in diffusion are seen in normal development as well as in pathological states such as hypoxic-ischemic encephalopathy (HIE). Various methods of quantitative assessment of diffusion values have been reported. Global ischemic injury occurring during the time of rapid developmental changes in brain myelination can complicate the imaging diagnosis of neonatal HIE. To compare a quantitative method of histographic analysis of brain apparent coefficient (ADC) maps to the qualitative interpretation of routine brain MR imaging studies. We correlate changes in diffusion values with gestational age in radiographically normal neonates, and we investigate the sensitivity of the method as a quantitative measure of hypoxic-ischemic encephalopathy. We reviewed all brain MRI studies from the neonatal intensive care unit (NICU) at our university medical center over a 4-year period to identify cases that were radiographically normal (23 cases) and those with diffuse, global hypoxic-ischemic encephalopathy (12 cases). We histographically displayed ADC values of a single brain slice at the level of the basal ganglia and correlated peak (s-sD{sub av}) and lowest histogram values (s-sD{sub lowest}) with gestational age. Normative s-sD{sub av} values correlated significantly with gestational age and declined linearly through the neonatal period (r {sup 2} = 0.477, P < 0.01). Six of 12 cases of known HIE demonstrated significantly lower s-sD{sub av} and s-sD{sub lowest} ADC values than were reflected in the normative distribution; several cases of HIE fell within a 95% confidence interval for normative studies, and one case demonstrated higher-than-normal s-sD{sub av}. Single-slice histographic display of ADC values is a rapid and clinically feasible method of quantitative analysis of diffusion. In this study normative values derived from consecutive neonates without radiographic evidence of

Comprehensive cardiac rehabilitation for secondary prevention after transient ischemic attack or mild stroke: I: feasibility and risk factors.

Science.gov (United States)

Prior, Peter L; Hachinski, Vladimir; Unsworth, Karen; Chan, Richard; Mytka, Sharon; O'Callaghan, Christina; Suskin, Neville

2011-11-01

Comprehensive cardiac rehabilitation (CCR), which integrates structured lifestyle interventions and medications, reduces morbidity and mortality among cardiac patients. CCR has not typically been used with cerebrovascular populations, despite important commonalities with heart patients. We tested feasibility and effectiveness of 6-month outpatient CCR for secondary prevention after transient ischemic attack or mild, nondisabling stroke. This article presents risk factors. A future article will discuss psychological outcomes. Consecutive consenting subjects having sustained a transient ischemic attack or mild, nondisabling stroke within the previous 12 months (mean, 11.5 weeks; event-to-CCR entry) with ≥1 vascular risk factor, were recruited from a stroke prevention clinic providing usual care. We measured 6-month CCR outcomes following a prospective cohort design. Of 110 subjects recruited from January 2005 to April 2006, 100 subjects (mean age, 64.9 years; 46 women) entered and 80 subjects completed CCR. We obtained favorable, significant intake-to-exit changes in: aerobic capacity (+31.4%; Pstroke, offering a promising model for vascular protection across chronic disease entities. We know of no similar previous investigation, and are now conducting a randomized trial.

Neuronal Rho GTPase Rac1 elimination confers neuroprotection in a mouse model of permanent ischemic stroke.

Science.gov (United States)

Karabiyik, Cansu; Fernandes, Rui; Figueiredo, Francisco Rosário; Socodato, Renato; Brakebusch, Cord; Lambertsen, Kate Lykke; Relvas, João Bettencourt; Santos, Sofia Duque

2017-09-28

The Rho GTPase Rac1 is a multifunctional protein involved in distinct pathways ranging from development to pathology. The aim of the present study was to unravel the contribution of neuronal Rac1 in regulating the response to brain injury induced by permanent focal cerebral ischemia (pMCAO). Our results show that pMCAO significantly increased total Rac1 levels in wild type mice, mainly through rising nuclear Rac1, while a reduction in Rac1 activation was observed. Such changes preceded cell death induced by excitotoxic stress. Pharmacological inhibition of Rac1 in primary neuronal cortical cells prevented the increase in oxidative stress induced after overactivation of glutamate receptors. However, this was not sufficient to prevent the associated neuronal cell death. In contrast, RNAi-mediated knock down of Rac1 in primary cortical neurons prevented cell death elicited by glutamate excitotoxicity and decreased the activity of NADPH oxidase. To test whether in vivo down regulation of neuronal Rac1 was neuroprotective after pMCAO, we used tamoxifen-inducible neuron-specific conditional Rac1-knockout mice. We observed a significant 50% decrease in brain infarct volume of knockout mice and a concomitant increase in HIF-1α expression compared to littermate control mice, demonstrating that ablation of Rac1 in neurons is neuroprotective. Transmission electron microscopy performed in the ischemic brain showed that lysosomes in the infarct of Rac1- knockout mice were preserved at similar levels to those of non-infarcted tissue, while littermate mice displayed a decrease in the number of lysosomes, further corroborating the notion that Rac1 ablation in neurons is neuroprotective. Our results demonstrate that Rac1 plays important roles in the ischemic pathological cascade and that modulation of its levels is of therapeutic interest. © 2017 International Society of Neuropathology.

Association of NOS3 gene variants and clinical contributors of hypoxic-ischemic encephalopathy

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Kuzmanić Šamija, R. [Department of Pediatrics, University Hospital Split, Split (Croatia); Primorac, D. [School of Medicine Split, University of Split, Split (Croatia); Department of Pediatrics, School of Medicine, University of Osijek, Osijek (Croatia); Eberly College of Science, Penn State University, University Park, PA (United States); St. Catherine Speciality Hospital, Zabok (Croatia); Rešić, B. [School of Medicine Split, University of Split, Split (Croatia); Pavlov, V. [Department of Neonatology, University Hospital Split, Split (Croatia); Čapkun, V. [Department of Nuclear Medicine, University Hospital Split, Split (Croatia); Punda, H. [School of Medicine Split, University of Split, Split (Croatia); Lozić, B. [Department of Pediatrics, University Hospital Split, Split (Croatia); Zemunik, T. [Department of Medical Biology, School of Medicine Split, University of Split, Split (Croatia)

2014-08-15

The aim of this study was to analyze the association of different clinical contributors of hypoxic-ischemic encephalopathy with NOS3 gene polymorphisms. A total of 110 children with hypoxic-ischemic encephalopathy and 128 control children were selected for this study. Association of gender, gestational age, birth weight, Apgar score, cranial ultrasonography, and magnetic resonance imaging findings with genotypic data of six haplotype-tagging single nucleotide polymorphisms and the most commonly investigated rs1800779 and rs2070744 polymorphisms was analyzed. The TGT haplotype of rs1800783, rs1800779, and rs2070744 polymorphisms was associated with hypoxic-ischemic encephalopathy. Children with the TGT haplotype were infants below 32 weeks of gestation and they had the most severe brain damage. Increased incidence of the TT genotype of the NOS3 rs1808593 SNP was found in the group of hypoxic-ischemic encephalopathy patients with medium and severe brain damage. The probability of brain damage was twice as high in children with the TT genotype than in children with the TG genotype of the same polymorphism. Furthermore, the T allele of the same polymorphism was twice as frequent in children with lower Apgar scores. This study strongly suggests associations of NOS3 gene polymorphism with intensity of brain damage and severity of the clinical picture in affected children.

Association of NOS3 gene variants and clinical contributors of hypoxic-ischemic encephalopathy

International Nuclear Information System (INIS)

Kuzmanić Šamija, R.; Primorac, D.; Rešić, B.; Pavlov, V.; Čapkun, V.; Punda, H.; Lozić, B.; Zemunik, T.

2014-01-01

The aim of this study was to analyze the association of different clinical contributors of hypoxic-ischemic encephalopathy with NOS3 gene polymorphisms. A total of 110 children with hypoxic-ischemic encephalopathy and 128 control children were selected for this study. Association of gender, gestational age, birth weight, Apgar score, cranial ultrasonography, and magnetic resonance imaging findings with genotypic data of six haplotype-tagging single nucleotide polymorphisms and the most commonly investigated rs1800779 and rs2070744 polymorphisms was analyzed. The TGT haplotype of rs1800783, rs1800779, and rs2070744 polymorphisms was associated with hypoxic-ischemic encephalopathy. Children with the TGT haplotype were infants below 32 weeks of gestation and they had the most severe brain damage. Increased incidence of the TT genotype of the NOS3 rs1808593 SNP was found in the group of hypoxic-ischemic encephalopathy patients with medium and severe brain damage. The probability of brain damage was twice as high in children with the TT genotype than in children with the TG genotype of the same polymorphism. Furthermore, the T allele of the same polymorphism was twice as frequent in children with lower Apgar scores. This study strongly suggests associations of NOS3 gene polymorphism with intensity of brain damage and severity of the clinical picture in affected children

Multiplex Brain Proteomic Analysis Revealed the Molecular Therapeutic Effects of Buyang Huanwu Decoction on Cerebral Ischemic Stroke Mice.

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Hong-Jhang Chen

Full Text Available Stroke is the second-leading cause of death worldwide, and tissue plasminogen activator (TPA is the only drug used for a limited group of stroke patients in the acute phase. Buyang Huanwu Decoction (BHD, a traditional Chinese medicine prescription, has long been used for improving neurological functional recovery in stroke. In this study, we characterized the therapeutic effect of TPA and BHD in a cerebral ischemia/reperfusion (CIR injury mouse model using multiplex proteomics approach. After the iTRAQ-based proteomics analysis, 1310 proteins were identified from the mouse brain with <1% false discovery rate. Among them, 877 quantitative proteins, 10.26% (90/877, 1.71% (15/877, and 2.62% (23/877 of the proteins was significantly changed in the CIR, BHD treatment, and TPA treatment, respectively. Functional categorization analysis showed that BHD treatment preserved the integrity of the blood-brain barrier (BBB (Alb, Fga, and Trf, suppressed excitotoxicity (Grm5, Gnai, and Gdi, and enhanced energy metabolism (Bdh, thereby revealing its multiple effects on ischemic stroke mice. Moreover, the neurogenesis marker doublecortin was upregulated, and the activity of glycogen synthase kinase 3 (GSK-3 and Tau was inhibited, which represented the neuroprotective effects. However, TPA treatment deteriorated BBB breakdown. This study highlights the potential of BHD in clinical applications for ischemic stroke.

Biomarkers of Hypoxic Ischemic Encephalopathy in Newborns

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Martha V. Douglas-Escobar

2012-11-01

Full Text Available As neonatal intensive care has evolved, the focus has shifted from improving mortality alone to an effort to improve both mortality and morbidity. The most frequent source of neonatal brain injury occurs as a result of hypoxic-ischemic injury. Hypoxic-ischemic injury occurs in about 2 of 1,000 full-term infants and severe injured infants will have lifetime disabilities and neurodevelopmental delays. Most recently, remarkable efforts toward neuroprotection have been started with the advent of therapeutic hypothermia and a key step in the evolution of neonatal neuroprotection is the discovery of biomarkers that enable the clinician-scientist to screen infants for brain injury, monitor progression of disease, identify injured brain regions, and assess efficacy of neuroprotective clinical trials. Lastly, biomarkers offer great hope identifying when an injury occurred shedding light on the potential pathophysiology and the most effective therapy. In this article, we will review biomarkers of HIE including S100b, neuron specific enolase, umbilical cord IL-6, CK-BB, GFAP, myelin basic protein, UCHL-1, and pNF-H. We hope to contribute to the awareness, validation and clinical use of established as well as novel neonatal brain injury biomarkers.

Long-Term Functional and Psychosocial Outcomes After Hypoxic-Ischemic Brain Injury: A Case-Controlled Comparison to Traumatic Brain Injury.

Science.gov (United States)

Harbinson, Meredith; Zarshenas, Sareh; Cullen, Nora K

2017-12-01

Despite the increasing rate of survival from hypoxic-ischemic brain injury (HIBI), there is a paucity of evidence on the long-term functional outcomes after inpatient rehabilitation among these nontrauma patients compared to patients with traumatic brain injury (TBI). To compare functional and psychosocial outcomes of patients with HIBI to those of case-matched patients with TBI 4-11 years after brain insult. Retrospective, matched case-controlled study. Data at the time of rehabilitation admission and discharge were collected as part of a larger acquired brain injury (ABI) database at Toronto Rehabilitation Institute (TRI) between 1999 and 2009. This study consisted of 11 patients with HIBI and 11 patients with TBI that attended the neuro-rehabilitation day program at TRI during a similar time frame and were matched on age, admission Functional Independence Measure (FIM) scores, and acute care length of stay (ALOS). At 4-11 years following brain insult, patients were reassessed using the FIM, Disability Rating Scale (DRS), Personal Health Questionnaire Depression Scale (PHQ-9), and the Mayo-Portland Adaptability Inventory 4 (MPAI-4). At follow-up, patients with HIBI had significantly lower FIM motor and cognitive scores than patients with TBI (75.3 ± 20.6 versus 88.1 ± 4.78, P MPAI-4 at follow-up (P < .05). The study results suggest that patients with HIBI achieve less long-term functional improvements compared to patients with TBI. Further research is warranted to compare the components of inpatient rehabilitation while adjusting for demographics and clinical characteristics between these 2 groups of patients. III. Copyright © 2017 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Aging alters the immunological response to ischemic stroke.

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Ritzel, Rodney M; Lai, Yun-Ju; Crapser, Joshua D; Patel, Anita R; Schrecengost, Anna; Grenier, Jeremy M; Mancini, Nickolas S; Patrizz, Anthony; Jellison, Evan R; Morales-Scheihing, Diego; Venna, Venugopal R; Kofler, Julia K; Liu, Fudong; Verma, Rajkumar; McCullough, Louise D

2018-05-11

The peripheral immune system plays a critical role in aging and in the response to brain injury. Emerging data suggest inflammatory responses are exacerbated in older animals following ischemic stroke; however, our understanding of these age-related changes is poor. In this work, we demonstrate marked differences in the composition of circulating and infiltrating leukocytes recruited to the ischemic brain of old male mice after stroke compared to young male mice. Blood neutrophilia and neutrophil invasion into the brain were increased in aged animals. Relative to infiltrating monocyte populations, brain-invading neutrophils had reduced phagocytic potential, and produced higher levels of reactive oxygen species and extracellular matrix-degrading enzymes (i.e., MMP-9), which were further exacerbated with age. Hemorrhagic transformation was more pronounced in aged versus young mice relative to infarct size. High numbers of myeloperoxidase-positive neutrophils were found in postmortem human brain samples of old (> 71 years) acute ischemic stroke subjects compared to non-ischemic controls. Many of these neutrophils were found in the brain parenchyma. A large proportion of these neutrophils expressed MMP-9 and positively correlated with hemorrhage and hyperemia. MMP-9 expression and hemorrhagic transformation after stroke increased with age. These changes in the myeloid response to stroke with age led us to hypothesize that the bone marrow response to stroke is altered with age, which could be important for the development of effective therapies targeting the immune response. We generated heterochronic bone marrow chimeras as a tool to determine the contribution of peripheral immune senescence to age- and stroke-induced inflammation. Old hosts that received young bone marrow (i.e., Young → Old) had attenuation of age-related reductions in bFGF and VEGF and showed improved locomotor activity and gait dynamics compared to isochronic (Old → Old) controls

Targeted Temperature Management at 33°C or 36°C Produces Equivalent Neuroprotective Effects in the Middle Cerebral Artery Occlusion Rat Model of Ischemic Stroke.

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Lee, Jung Ho; Lim, Jisoo; Chung, Yong Eun; Chung, Sung Phil; Park, Incheol; Kim, Chul Hoon; You, Je Sung

2018-01-15

Targeted temperature management (TTM, 32°C to 36°C) is one of the most successful achievements in modern resuscitation medicine. It has become standard treatment for survivors of sudden cardiac arrest to minimize secondary brain damage. TTM at 36°C is just as effective as TTM at 33°C and is actually preferred because it reduces adverse TTM-associated effects. TTM also likely has direct neuroprotective effects in ischemic brains in danger of stroke. It remains unclear, however, whether higher temperature TTM is equally effective in protecting the brain from the effects of stroke. Here, we asked whether TTM at 36°C is as effective as TTM at 33°C in improving outcomes in a middle cerebral artery occlusion (MCAO) model of ischemic stroke. After dividing rats randomly into MCAO, MCAO+33°C TTM, MCAO+36°C TTM and sham groups, we subjected all of them except for the sham group to MCAO for 3 h (for the behavioral tests) or 4 h (for all other biochemical analyses). We found TTM protocols at both 33°C and 36°C produce comparable reductions of infarct volumes in the MCAO territory and equally attenuate the extracellular release of high mobility group box 1 (HMGB1) in post-ischemic brains. Both TTM conditions prevent the mRNA induction of a major pro-inflammatory cytokine, TNF-α, in the ischemic penumbra region. Finally, both TTM protocols produce similar improvements in neurological outcomes in rats, as measured by a battery of behavior tests 21 h after the start of reperfusion. These data acquired in a rat MCAO model suggest TTM at 36°C has excellent therapeutic potential for improving clinical outcomes for patients with acute ischemic stroke.

Effect of Ischemic Postconditioning and Atorvastatin in the Prevention of Remote Lung Reperfusion Injury

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Carlos Henrique Marques dos Santos

Full Text Available Abstract Objective: The aim of the present study was to evaluate the ability of ischemic postconditioning, atorvastatin and both associated to prevent or minimize reperfusion injury in the lung of rats subjected to ischemia and reperfusion by abdominal aortic clamping. Methods: We used 41 Wistar norvegic rats, which were distributed into 5 groups: ischemia and reperfusion (I/R, ischemic postcondictioning (IPC, postconditioning + atorvastatin (IPC+A, atorvastatin (A and SHAM. It was performed a medium laparotomy, dissection and isolation of the infra-renal abdominal aorta; except for the SHAM group, all the others were submitted to the aortic clamping for 70 minutes (ischemia and posterior clamp removal (reperfusion, 70 minutes. In the IPC and IPC+A groups, postconditioning was performed between the ischemia and reperfusion phases by four cycles of reperfusion and ischemia lasting 30 seconds each. In the IPC+A and A groups, preceding the surgical procedure, administration of 3.4 mg/day of atorvastatin was performed for seven days by gavage. After the surgical procedure, the right caudal lobe was removed from the lung for histological study, using tissue injury score ranging from grade 1 (normal tissue to grade 4 (intense lesion. Results: The mean lung injury was 3.6 in the I/R group, 1.6 in the IPC group, 1.2 in the IPC+A group, 1.2 in the A group, and 1 in the SHAM group (P<0.01. Conclusion: Ischemic postconditioning and atorvastatin were able to minimize lung reperfusion injury, alone or in combination.

Probucol plus cilostazol attenuate hypercholesterolemia‑induced exacerbation in ischemic brain injury via anti-inflammatory effects.

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Kim, Ji Hyun; Hong, Ki Whan; Bae, Sun Sik; Shin, Yong-Il; Choi, Byung Tae; Shin, Hwa Kyoung

2014-09-01

Probucol, a lipid-lowering agent with anti-oxidant properties, is involved in protection against atherosclerosis, while cilostazol, an antiplatelet agent, has diverse neuroprotective properties. In this study, we investigated the anti-inflammatory effects of probucol and cilostazol on focal cerebral ischemia with hypercholesterolemia. Apolipoprotein E (ApoE) knockout (KO) mice were fed a high-fat diet (HFD) with or without 0.3% probucol and/or 0.2% cilostazol for 10 weeks. To assess the protective effects of the combined therapy of probucol and cilostazol on ischemic injury, the mice received 40 min of middle cerebral artery occlusion (MCAO). Infarct volumes, neurobehavioral deficits and neuroinflammatory mediators were subsequently evaluated 48 h after reperfusion. Probucol alone and probucol plus cilostazol significantly decreased total- and low-density lipoprotein (LDL)-cholesterol in ApoE KO with HFD. MCAO resulted in significantly larger infarct volumes in ApoE KO mice provided with HFD compared to those fed a regular diet, although these volumes were significantly reduced in the probucol plus cilostazol group. Consistent with a smaller infarct size, probucol alone and the combined treatment of probucol and cilostazol improved neurological and motor function. In addition, probucol alone and probucol plus cilostazol decreased MCP-1 expression and CD11b and GFAP immuno-reactivity in the ischemic cortex. These findings suggested that the inhibitory effects of probucol plus cilostazol in MCP-1 expression in the ischemic brain with hypercholesterolemia allowed the identification of one of the mechanisms responsible for anti-inflammatory action. Probucol plus cilostazol may therefore serve as a therapeutic strategy for reducing the impact of stroke in hypercholesterolemic subjects.

The role of angiogenesis in damage and recovery from ischemic stroke.

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Arenillas, Juan F; Sobrino, Tomás; Castillo, José; Dávalos, Antoni

2007-06-01

Ischemic stroke is burdened with a high morbidity and mortality in our society. However, there are few effective and largely available therapies for this devastating disease. In additon to advancing acute reperfusion therapies, there is a need to develop treatments aimed to promote repair and regeneration of brain tissue damaged by ischemia (neurorecovery). Therapeutic angiogenesis and vasculogenesis represent novel approaches of regenerative medicine that may help in the cure of patients with acute ischemic stroke. Translation of our knowledge about these processes from the bench to bedside is still underway. Although angiogenesis (the sprouting of new blood vessels from pre-existing vascular structures) is likely to contribute to neurorepair, the finality of the angiogenic response in acute ischemic stroke has not been fully elucidated. The first therapeutic approach to angiogenesis after ischemic stroke would be the modulation of the endogenous angiogenic response. In this setting, early instauration of physical activity, statins, and peroxisome proliferator-activated receptor-gamma agonists may enhance angiogenesis and neuroregeneration. Gene therapy with vascular growth factors has been successfully tested in patients affected by chronic myocardial and peripheral ischemia. Regarding brain ischemia, experiments in animal models have shown that the effect of these growth factors is critically affected by the dosage, route of delivery, and time of administration in relation to stroke onset. In addition, the optimal angiogenic substance is unknown. Finally, vectors for gene transfer should be further optimized. Therapeutic vasculogenesis consists of the administration of exogenous endothelial progenitor cells in order to enhance brain repair processes. Endothelial progenitor cells may be recruited in response to cerebral ischemia and participate in reparative vasculogenesis after acute ischemic stroke. Further research is needed to clarify their role and

Adenosine A1 receptors contribute to immune regulation after neonatal hypoxic ischemic brain injury.

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Winerdal, Max; Winerdal, Malin E; Wang, Ying-Qing; Fredholm, Bertil B; Winqvist, Ola; Ådén, Ulrika

2016-03-01

Neonatal brain hypoxic ischemia (HI) often results in long-term motor and cognitive impairments. Post-ischemic inflammation greatly effects outcome and adenosine receptor signaling modulates both HI and immune cell function. Here, we investigated the influence of adenosine A1 receptor deficiency (A1R(-/-)) on key immune cell populations in a neonatal brain HI model. Ten-day-old mice were subjected to HI. Functional outcome was assessed by open locomotion and beam walking test and infarction size evaluated. Flow cytometry was performed on brain-infiltrating cells, and semi-automated analysis of flow cytometric data was applied. A1R(-/-) mice displayed larger infarctions (+33%, p beam walking tests (44% more mistakes, p < 0.05) than wild-type (WT) mice. Myeloid cell activation after injury was enhanced in A1R(-/-) versus WT brains. Activated B lymphocytes expressing IL-10 infiltrated the brain after HI in WT, but were less activated and did not increase in relative frequency in A1R(-/-). Also, A1R(-/-) B lymphocytes expressed less IL-10 than their WT counterparts, the A1R antagonist DPCPX decreased IL-10 expression whereas the A1R agonist CPA increased it. CD4(+) T lymphocytes including FoxP3(+) T regulatory cells, were unaffected by genotype, whereas CD8(+) T lymphocyte responses were smaller in A1R(-/-) mice. Using PCA to characterize the immune profile, we could discriminate the A1R(-/-) and WT genotypes as well as sham operated from HI-subjected animals. We conclude that A1R signaling modulates IL-10 expression by immune cells, influences the activation of these cells in vivo, and affects outcome after HI.

Pharmacological targeting of secondary brain damage following ischemic or hemorrhagic stroke, traumatic brain injury, and bacterial meningitis - a systematic review and meta-analysis.

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Beez, Thomas; Steiger, Hans-Jakob; Etminan, Nima

2017-12-07

The effectiveness of pharmacological strategies exclusively targeting secondary brain damage (SBD) following ischemic stroke, aneurysmal subarachnoid hemorrhage, aSAH, intracerebral hemorrhage (ICH), traumatic brain injury (TBI) and bacterial meningitis is unclear. This meta-analysis studied the effect of SBD targeted treatment on clinical outcome across the pathological entities. Randomized, controlled, double-blinded trials on aforementioned entities with 'death' as endpoint were identified. Effect sizes were analyzed and expressed as pooled risk ratio (RR) estimates with 95% confidence intervals (CI). 123 studies fulfilled the criteria, with data on 66,561 patients. In the pooled analysis, there was a minor reduction of mortality for aSAH [RR 0.93 (95% CI:0.85-1.02)], ICH [RR 0.92 (95% CI:0.82-1.03)] and bacterial meningitis [RR 0.86 (95% CI:0.68-1.09)]. No reduction of mortality was found for ischemic stroke [RR 1.05 (95% CI:1.00-1.11)] and TBI [RR 1.03 (95% CI:0.93-1.15)]. Additional analysis of "poor outcome" as endpoint gave similar results. Subgroup analysis with respect to effector mechanisms showed a tendency towards a reduced mortality for the effector mechanism category "oxidative metabolism/stress" for aSAH with a risk ratio of 0.86 [95% CI: 0.73-1.00]. Regarding specific medications, a statistically significant reduction of mortality and poor outcome was confirmed only for nimodipine for aSAH and dexamethasone for bacterial meningitis. Our results show that only a few selected SBD directed medications are likely to reduce the rate of death and poor outcome following aSAH, and bacterial meningitis, while no convincing evidence could be found for the usefulness of SBD directed medications in ischemic stroke, ICH and TBI. However, a subtle effect on good or excellent outcome might remain undetected. These results should lead to a new perspective of secondary reactions following cerebral injury. These processes should not be seen as suicide mechanisms

[Human umbilical cord blood mononuclear cell transplantation promotes long-term neurobehavioral functional development of newborn SD rats with hypoxic ischemic brain injury].

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Huang, Hui-zhi; Wen, Xiao-hong; Liu, Hui; Huang, Jin-hua; Liu, Shang-quan; Ren, Wei-hua; Fang, Wen-xiang; Qian, Yin-feng; Hou, Wei-zhu; Yan, Ming-jie; Yao, You-heng; Li, Wei-Zu; Li, Qian-Jin

2013-06-01

To explore the effect of human umbilical cord blood mononuclear cells (UCBMC) promoting nerve behavior function and brain tissue recovery of neonatal SD rat with hypoxic ischemic brain injury (HIBI). A modified newborn rat model that had a combined hypoxic and ischemic brain injury as described by Rice-Vannucci was used, early nervous reflex, the Morris water maze and walking track analysis were used to evaluate nervous behavioral function, and brain MRI, HE staining to evaluate brain damage recovery. Newborn rat Rice-Vannucci model showed significant brain atrophy, obvious hemiplegia of contralateral limbs,e.g right step length [(7.67 ± 0.46) cm vs. (8.22 ± 0.50) cm, F = 1.494] and toe distance [(0.93 ± 0.06) cm vs. (1.12 ± 0.55) cm, F = 0.186] were significantly reduced compared with left side, learning and memory ability was significantly impaired compared with normal control group (P vs.(14.22 ± 5.07) s, t = 4.618] and negative geotaxis reflex time [(7.26 ± 2.00) s vs. (11.76 ± 3.73) s, t = 4.755] on postnatal 14 days of HIBI+ transplantation group were significantly reduced compared with HIBI+NaCl group (P vs. (34.04 ± 12.95) s, t = 3.356] and swimming distance [ (9.12 ± 1.21) cm vs.(12.70 ± 1.53) cm, t = 17.095] of HIBI+transplantation group were significantly reduced compared with those of HIBI+NaCl group (P brain volume on postnatal 10 d [ (75.37 ± 4.53)% vs. (67.17 ± 4.08)%, t = -6.017] and 67 d [ (69.05 ± 3.58)% vs.(60.83 ± 3.69)%, t = -7.148]of HIBI+ transplantation group were significantly larger than those of HIBI+NaCl group (P left cortical edema significantly reduced and nerve cell necrosis of HIBI+ transplantation group is not obvious compared with HIBI+NaCl group. Human UCBMC intraperitoneal transplantation significantly promoted recovery of injured brain cells and neurobehavioral function development.

Sodium Valproate, a Histone Deacetylase Inhibitor, Is Associated With Reduced Stroke Risk After Previous Ischemic Stroke or Transient Ischemic Attack

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Brookes, Rebecca L.; Crichton, Siobhan; Wolfe, Charles D.A.; Yi, Qilong; Li, Linxin; Hankey, Graeme J.; Rothwell, Peter M.

2018-01-01

Background and Purpose— A variant in the histone deacetylase 9 (HDAC9) gene is associated with large artery stroke. Therefore, inhibiting HDAC9 might offer a novel secondary preventative treatment for ischemic stroke. The antiepileptic drug sodium valproate (SVA) is a nonspecific inhibitor of HDAC9. We tested whether SVA therapy given after ischemic stroke was associated with reduced recurrent stroke rate. Methods— Data were pooled from 3 prospective studies recruiting patients with previous stroke or transient ischemic attack and long-term follow-up: the South London Stroke Register, The Vitamins to Prevent Stroke Study, and the Oxford Vascular Study. Patients receiving SVA were compared with patients who received antiepileptic drugs other than SVA using survival analysis and Cox Regression. Results— A total of 11 949 patients with confirmed ischemic event were included. Recurrent stroke rate was lower in patient taking SVA (17 of 168) than other antiepileptic drugs (105 of 530; log-rank survival analysis P=0.002). On Cox regression, controlling for potential cofounders, SVA remained associated with reduced stroke (hazard ratio=0.44; 95% confidence interval: 0.3–0.7; P=0.002). A similar result was obtained when patients taking SVA were compared with all cases not taking SVA (Cox regression, hazard ratio=0.47; 95% confidence interval: 0.29–0.77; P=0.003). Conclusions— These results suggest that exposure to SVA, an inhibitor of HDAC, may be associated with a lower recurrent stroke risk although we cannot exclude residual confounding in this study design. This supports the hypothesis that HDAC9 is important in the ischemic stroke pathogenesis and that its inhibition, by SVA or a more specific HDAC9 inhibitor, is worthy of evaluation as a treatment to prevent recurrent ischemic stroke. PMID:29247141

No improvement of neuronal metabolism in the reperfusion phase with melatonin treatment after hypoxic-ischemic brain injury in the neonatal rat.

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Berger, Hester R; Morken, Tora Sund; Vettukattil, Riyas; Brubakk, Ann-Mari; Sonnewald, Ursula; Widerøe, Marius

2016-01-01

Mitochondrial impairment is a key feature underlying neonatal hypoxic-ischemic (HI) brain injury and melatonin is potentially neuroprotective through its effects on mitochondria. In this study, we have used (1) H and (13) C NMR spectroscopy after injection of [1-(13) C]glucose and [1,2-(13) C]acetate to examine neuronal and astrocytic metabolism in the early reperfusion phase after unilateral HI brain injury in 7-day-old rat pups, exploring the effects of HI on mitochondrial function and the potential protective effects of melatonin on brain metabolism. One hour after hypoxia-ischemia, astrocytic metabolism was recovered and glycolysis was normalized, whereas mitochondrial metabolism in neurons was clearly impaired. Pyruvate carboxylation was also lower in both hemispheres after HI. The transfer of glutamate from neurons to astrocytes was higher whereas the transfer of glutamine from astrocytes to neurons was lower 1 h after HI in the contralateral hemisphere. Neuronal metabolism was equally affected in pups treated with melatonin (10 mg/kg) immediately after HI as in vehicle treated pups indicating that the given dose of melatonin was not capable of protecting the neuronal mitochondria in this early phase after HI brain injury. However, any beneficial effects of melatonin might have been masked by modulatory effects of the solvent dimethyl sulfoxide on cerebral metabolism. Neuronal and astrocytic metabolism was examined by (13) C and (1) H NMR spectroscopy in the early reperfusion phase after unilateral hypoxic-ischemic brain injury and melatonin treatment in neonatal rats. One hour after hypoxia-ischemia astrocytic mitochondrial metabolism had recovered and glycolysis was normalized, whereas mitochondrial metabolism in neurons was impaired. Melatonin treatment did not show a protective effect on neuronal metabolism. © 2015 International Society for Neurochemistry.

Melatonin and Ischemic Stroke: Mechanistic Roles and Action

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Syed Suhail Andrabi

2015-01-01

Full Text Available Stroke is one of the most devastating neurological disabilities and brain’s vulnerability towards it proves to be fatal and socio-economic loss of millions of people worldwide. Ischemic stroke remains at the center stage of it, because of its prevalence amongst the several other types attacking the brain. The various cascades of events that have been associated with stroke involve oxidative stress, excitotoxicity, mitochondrial dysfunction, upregulation of Ca2+ level, and so forth. Melatonin is a neurohormone secreted by pineal and extra pineal tissues responsible for various physiological processes like sleep and mood behaviour. Melatonin has been implicated in various neurological diseases because of its antioxidative, antiapoptotic, and anti-inflammatory properties. We have previously reviewed the neuroprotective effect of melatonin in various models of brain injury like traumatic brain injury and spinal cord injury. In this review, we have put together the various causes and consequence of stroke and protective role of melatonin in ischemic stroke.

GSK-3β inhibitor TWS119 attenuates rtPA-induced hemorrhagic transformation and activates the Wnt/β-catenin signaling pathway after acute ischemic stroke in rats.

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Wang, Wei; Li, Mingchang; Wang, Yuefei; Li, Qian; Deng, Gang; Wan, Jieru; Yang, Qingwu; Chen, Qianxue; Wang, Jian

2016-12-01

Hemorrhagic transformation (HT) is a devastating complication for patients with acute ischemic stroke who are treated with tissue plasminogen activator (tPA). It is associated with high morbidity and mortality, but no effective treatments are currently available to reduce HT risk. Therefore, methods to prevent HT are urgently needed. In this study, we used TWS119, an inhibitor of glycogen synthase kinase 3β (GSK-3β), to evaluate the role of the Wnt/β-catenin signaling pathway in recombinant tPA (rtPA)-induced HT. Sprague-Dawley rats were subjected to a middle cerebral artery occlusion (MCAO) model of ischemic stroke and then were administered rtPA, rtPA combined with TWS119, or vehicle at 4 h. The animals were sacrificed 24 h after infarct induction. Rats treated with rtPA showed evident HT, had more severe neurologic deficit, brain edema, and blood-brain barrier breakdown, and had larger infarction volume than did the vehicle group. Rats treated with TWS119 had significantly improved outcomes compared with those of rats treated with rtPA alone. In addition, Western blot analysis showed that TWS119 increased the protein expression of β-catenin, claudin-3, and ZO-1 while suppressing the expression of GSK-3β. These results suggest that TWS119 reduces rtPA-induced HT and attenuates blood-brain barrier disruption, possibly through activation of the Wnt/β-catenin signaling pathway. This study provides a potential therapeutic strategy to prevent tPA-induced HT after acute ischemic stroke.

Paraneoplastic Ischemic Stroke: Case Report and Review

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Murat Sumer

2008-10-01

Full Text Available OBJECTIVE: Paraneoplastic etiology is not frequent among cerebrovascular disorders. This rare disorder is interesting with different mechanisms, clinical manifestations and treatment options. Diagnosis may be overlooked for its rarity. We present a paraneoplastic ischemic stroke patient with its clinical and imaging characteristics for recalling this rare disease. CASE: A sixty years old woman with a history of ovarian and colon cancer and liver metastasis admitted with acute left sided hemiplegia. Brain magnetic resonance imaging showed multiple ischemic lesions at the same age. Laboratory findings were compatible with chronic disseminated intravascular coagulopathy. She was anticoagulated but the clinical findings were not changed. She died one month after her discharge from the hospital. CONCLUSIONS: Paraneoplastic ischemic stroke is rare and it should be recognized by the clinician to differentiate from other ischemic strokes by its different mechanisms, imaging characteristics and treatment modalities. Prognosis depends on the characteristics of the primary tumor

The Potential of Tetrandrine as a Protective Agent for Ischemic Stroke

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Sheng-Hong Tseng

2011-09-01

Full Text Available Stroke is one of the leading causes of mortality, with a high incidence of severe morbidity in survivors. The treatment to minimize tissue injury after stroke is still unsatisfactory and it is mandatory to develop effective treatment strategies for stroke. The pathophysiology of ischemic stroke is complex and involves many processes including energy failure, loss of ion homeostasis, increased intracellular calcium level, platelet aggregation, production of reactive oxygen species, disruption of blood brain barrier, and inflammation and leukocyte infiltration, etc. Tetrandrine, a bisbenzylisoquinoline alkaloid, has many pharmacologic effects including anti-inflammatory and cytoprotective effects. In addition, tetrandrine has been found to protect the liver, heart, small bowel and brain from ischemia/reperfusion injury. It is a calcium channel blocker, and can inhibit lipid peroxidation, reduce generation of reactive oxygen species, suppress the production of cytokines and inflammatory mediators, inhibit neutrophil recruitment and platelet aggregation, which are all devastating factors during ischemia/reperfusion injury of the brain. Because tetrandrine can counteract these important pathophysiological processes of ischemic stroke, it has the potential to be a protective agent for ischemic stroke.

Integrity of Cerebellar Fastigial Nucleus Intrinsic Neurons Is Critical for the Global Ischemic Preconditioning

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Eugene V. Golanov

2017-09-01

Full Text Available Excitation of intrinsic neurons of cerebellar fastigial nucleus (FN renders brain tolerant to local and global ischemia. This effect reaches a maximum 72 h after the stimulation and lasts over 10 days. Comparable neuroprotection is observed following sublethal global brain ischemia, a phenomenon known as preconditioning. We hypothesized that FN may participate in the mechanisms of ischemic preconditioning as a part of the intrinsic neuroprotective mechanism. To explore potential significance of FN neurons in brain ischemic tolerance we lesioned intrinsic FN neurons with excitotoxin ibotenic acid five days before exposure to 20 min four-vessel occlusion (4-VO global ischemia while analyzing neuronal damage in Cornu Ammoni area 1 (CA1 hippocampal area one week later. In FN-lesioned animals, loss of CA1 cells was higher by 22% compared to control (phosphate buffered saline (PBS-injected animals. Moreover, lesion of FN neurons increased morbidity following global ischemia by 50%. Ablation of FN neurons also reversed salvaging effects of five-minute ischemic preconditioning on CA1 neurons and morbidity, while ablation of cerebellar dentate nucleus neurons did not change effect of ischemic preconditioning. We conclude that FN is an important part of intrinsic neuroprotective system, which participates in ischemic preconditioning and may participate in naturally occurring neuroprotection, such as “diving response”.

Lifestyle interventions to prevent cardiovascular events after stroke and transient ischemic attack

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Deijle, Inger A.; Van Schaik, Sander M.; Van Wegen, Erwin E.H.; Weinstein, Henry C.; Kwakkel, Gert; Van Den Berg-Vos, Renske M.

2017-01-01

Background and Purpose - Patients with a transient ischemic attack or ischemic stroke have an increased risk of subsequent cardiovascular events. The purpose of this systematic review and meta-analysis was to determine whether lifestyle interventions focusing on behaviorally modifiable risk factors

AceDoPC, a structured phospholipid to target the brain with docosahexaenoic acid

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Lagarde Michel

2016-01-01

Full Text Available AceDoPC® is a structured phospholipid or acetyl-LysoPC-DHA made to prevent docosahexaenoic acyl migrating from the sn-2 to sn-1 position of the phospholipid, however keeping the main physical-chemical properties of LysoPC-DHA. As previously shown for LysoPC-DHA, AceDoPC® allows DHA crossing a re-constituted blood-brain barrier with higher efficiency than non-esterified DHA or PC-DHA. When injected to blood of rats, AceDoPC® is processed within the brain to deliver DHA to phosphatidyl-choline and -ethanolamine. When injected to rats following the induction of an ischemic stroke, AceDoPC® prevents the extension of brain lesions more efficiently than DHA. Overall, these properties make AceDoPC® a promising phospholipid carrier of DHA to the brain.

Stachys sieboldii (Labiatae, Chorogi) Protects against Learning and Memory Dysfunction Associated with Ischemic Brain Injury.

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Harada, Shinichi; Tsujita, Tsukasa; Ono, Akiko; Miyagi, Kei; Mori, Takaharu; Tokuyama, Shogo

2015-01-01

Stachys sieboldii (Labiatae; Chinese artichoke, a tuber), "chorogi" in Japanese, has been extensively used in folk medicine, and has a number of pharmacological properties, including antioxidative activity. However, few studies have examined the neuroprotective effects of S. sieboldii tuber extract (chorogi extract), and it remains unknown whether the extract can alleviate learning and memory dysfunction associated with vascular dementia or Alzheimer's disease. Therefore, in this study, we investigated the neuroprotective effects of chorogi extract, and examined its protection against learning and memory dysfunction using Ginkgo biloba leaf extract (ginkgo extract) as a positive control. Mice were subjected to bilateral carotid artery occlusion (BCAO) for 30 min. Oral administration of chorogi extract or ginkgo extract significantly reduced post-ischemic glucose intolerance on day 1 and neuronal damage including memory impairment on day 3 after BCAO, compared with the vehicle-treated group. Neither herbal medicine affected locomotor activity. Furthermore, neither significantly alleviated scopolamine-induced learning and memory impairment. In primary neurons, neuronal survival rate was significantly reduced by hydrogen peroxide treatment. This hydrogen peroxide-induced neurotoxicity was significantly suppressed by chorogi extract and ginkgo extract. Taken together, our findings suggest that chorogi extract as well as ginkgo extract can protect against learning and memory dysfunction associated with ischemic brain injury through an antioxidative mechanism.

Adding left atrial appendage closure to open heart surgery provides protection from ischemic brain injury six years after surgery independently of atrial fibrillation history: the LAACS randomized study.

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Park-Hansen, Jesper; Holme, Susanne J V; Irmukhamedov, Akhmadjon; Carranza, Christian L; Greve, Anders M; Al-Farra, Gina; Riis, Robert G C; Nilsson, Brian; Clausen, Johan S R; Nørskov, Anne S; Kruuse, Christina R; Rostrup, Egill; Dominguez, Helena

2018-05-23

Open heart surgery is associated with high occurrence of atrial fibrillation (AF), subsequently increasing the risk of post-operative ischemic stroke. Concomitant with open heart surgery, a cardiac ablation procedure is commonly performed in patients with known AF, often followed by left atrial appendage closure with surgery (LAACS). However, the protective effect of LAACS on the risk of cerebral ischemia following cardiac surgery remains controversial. We have studied whether LAACS in addition to open heart surgery protects against post-operative ischemic brain injury regardless of a previous AF diagnosis. One hundred eighty-seven patients scheduled for open heart surgery were enrolled in a prospective, open-label clinical trial and randomized to concomitant LAACS vs. standard care. Randomization was stratified by usage of oral anticoagulation (OAC) planned to last at least 3 months after surgery. The primary endpoint was a composite of post-operative symptomatic ischemic stroke, transient ischemic attack or imaging findings of silent cerebral ischemic (SCI) lesions. During a mean follow-up of 3.7 years, 14 (16%) primary events occurred among patients receiving standard surgery vs. 5 (5%) in the group randomized to additional LAACS (hazard ratio 0.3; 95% CI: 0.1-0.8, p = 0.02). In per protocol analysis (n = 141), 14 (18%) primary events occurred in the control group vs. 4 (6%) in the LAACS group (hazard ratio 0.3; 95% CI: 0.1-1.0, p = 0.05). In a real-world setting, LAACS in addition to elective open-heart surgery was associated with lower risk of post-operative ischemic brain injury. The protective effect was not conditional on AF/OAC status at baseline. LAACS study, clinicaltrials.gov NCT02378116 , March 4th 2015, retrospectively registered.

Free radical scavenger, edaravone, reduces the lesion size of lacunar infarction in human brain ischemic stroke

Science.gov (United States)

2011-01-01

Background Although free radicals have been reported to play a role in the expansion of ischemic brain lesions, the effect of free radical scavengers is still under debate. In this study, the temporal profile of ischemic stroke lesion sizes was assessed for more than one year to evaluate the effect of edaravone which might reduce ischemic damage. Methods We sequentially enrolled acute ischemic stroke patients, who admitted between April 2003 and March 2004, into the edaravone(-) group (n = 83) and, who admitted between April 2004 and March 2005, into the edaravone(+) group (n = 93). Because, edaravone has been used as the standard treatment after April 2004 in our hospital. To assess the temporal profile of the stroke lesion size, the ratio of the area [T2-weighted magnetic resonance images (T2WI)/iffusion-weighted magnetic resonance images (DWI)] were calculated. Observations on T2WI were continued beyond one year, and observational times were classified into subacute (1-2 months after the onset), early chronic (3-6 month), late chronic (7-12 months) and old (≥13 months) stages. Neurological deficits were assessed by the National Institutes of Health Stroke Scale upon admission and at discharge and by the modified Rankin Scale at 1 year following stroke onset. Results Stroke lesion size was significantly attenuated in the edaravone(+) group compared with the edaravone(-) group in the period of early and late chronic observational stages. However, this reduction in lesion size was significant within a year and only for the small-vessel occlusion stroke patients treated with edaravone. Moreover, patients with small-vessel occlusion strokes that were treated with edaravone showed significant neurological improvement during their hospital stay, although there were no significant differences in outcome one year after the stroke. Conclusion Edaravone treatment reduced the volume of the infarct and improved neurological deficits during the subacute period, especially

Free radical scavenger, edaravone, reduces the lesion size of lacunar infarction in human brain ischemic stroke

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Suzuki Akifumi

2011-03-01

Full Text Available Abstract Background Although free radicals have been reported to play a role in the expansion of ischemic brain lesions, the effect of free radical scavengers is still under debate. In this study, the temporal profile of ischemic stroke lesion sizes was assessed for more than one year to evaluate the effect of edaravone which might reduce ischemic damage. Methods We sequentially enrolled acute ischemic stroke patients, who admitted between April 2003 and March 2004, into the edaravone(- group (n = 83 and, who admitted between April 2004 and March 2005, into the edaravone(+ group (n = 93. Because, edaravone has been used as the standard treatment after April 2004 in our hospital. To assess the temporal profile of the stroke lesion size, the ratio of the area [T2-weighted magnetic resonance images (T2WI/iffusion-weighted magnetic resonance images (DWI] were calculated. Observations on T2WI were continued beyond one year, and observational times were classified into subacute (1-2 months after the onset, early chronic (3-6 month, late chronic (7-12 months and old (≥13 months stages. Neurological deficits were assessed by the National Institutes of Health Stroke Scale upon admission and at discharge and by the modified Rankin Scale at 1 year following stroke onset. Results Stroke lesion size was significantly attenuated in the edaravone(+ group compared with the edaravone(- group in the period of early and late chronic observational stages. However, this reduction in lesion size was significant within a year and only for the small-vessel occlusion stroke patients treated with edaravone. Moreover, patients with small-vessel occlusion strokes that were treated with edaravone showed significant neurological improvement during their hospital stay, although there were no significant differences in outcome one year after the stroke. Conclusion Edaravone treatment reduced the volume of the infarct and improved neurological deficits during the subacute

Computerized detection of acute ischemic stroke in brain computed tomography images

International Nuclear Information System (INIS)

Nagashima, Hiroyuki; Shiraishi, Akihisa; Harakawa, Tetsumi; Shiraishi, Junji; Doi, Kunio; Sunaga, Shinichi

2009-01-01

The interpretation of acute ischemic stroke (AIS) in computed tomography (CT) images is a very difficult challenge for radiologists. To assist radiologists in CT image interpretation, we have developed a computerized method for the detection of AIS using 100 training cases and 60 testing cases. In our computerized method, the inclination of the isotropic brain CT volume data is corrected by rotation and shifting. The subtraction data for the contralateral volume is then derived by subtraction from the mirrored (right-left reversed) volume data. Initial candidates suspected to have experienced AIS were identified using multiple-thresholding and filtering techniques. Twenty-one image features of these candidates were extracted and applied to a rule-based test to identify final candidates for AIS. The detection sensitivity values for the training cases and for the testing cases were 95.0% with 3.1 false positives per case and 85.7% with 3.4 false positives per case, respectively. Our computerized method showed good performance in the detection of AIS by CT and is expected to be useful in decision-making by radiologists. (author)

Supplementation with different teas from Camellia sinensis prevents memory deficits and hippocampus oxidative stress in ischemia-reperfusion.

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Martins, Alexandre; Schimidt, Helen L; Garcia, Alexandre; Colletta Altermann, Caroline Dalla; Santos, Francielli W; Carpes, Felipe P; da Silva, Weber Cláudio; Mello-Carpes, Pâmela B

2017-09-01

Memory and cognition impairments resultant of ischemic stroke could be minimized or avoided by antioxidant supplementation. In this regard, the neuroprotective potential of Green tea from Camellia sinensis has been investigated. However, there is a lack of information regarding the neuroprotective potential of others teas processed from the Camellia sinensis. Here we investigate the neuroprotective role of green, red, white and black tea on memory deficits and brain oxidative stress in a model of ischemic stroke in rats. Our findings show that green and red teas prevent deficits in object and social recognition memories, but only green tea protects against deficits in spatial memory and avoids hippocampal oxidative status and intense necrosis and others alterations in the brain tissue. In summary, green tea shows better neuroprotection in ischemic stroke than the others teas from Camellia sinensis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Computerized tomographic evaluation of chronic ischemic lesions in cerebral white matter

International Nuclear Information System (INIS)

Yamanouchi, Hiroshi; Tohgi, Hideo; Iio, Masahiro; Tomonaga, Masanori.

1981-01-01

The purpose of this study is to clarify the correlation between the low density areas and periventricular lucency (PVL) on CT and the histopathologic changes of chronic ischemic lesions in cerebral white matter. Thirty seven brains from chronic cases with stroke and 17 brains from patients who showed PVLs on CT were examined histologically. CT scans were performed using GE CT/T. Chronic ischemic lesions with severe demyelination or diffuse cavitation were detected as low density areas on CT. But if associated with severe gliosis, those lesions could not be detected on CT. Areas with myelin pallor could not be detected on CT. In some cases diffuse ischemic lesions as demyelination and cavitation were found in the areas corresponding to PVLs on CT. However, they were not always expressed on CT. Other cases with PVL had no histological changes in the frontal white matter. In conclusion, chronic ischemic lesions in the cerebral white matter could not always be detected as low density areas on CT. This may be partly because decreased density due to demyelination and cavitation was counterbalanced by severe gliosis which tends to increase the density. In some cases PVLs were related to diffuse ischemic lesions in the frontal white matter, but this was not always the case. (author)

Anti-Inflammatory Effects of Traditional Chinese Medicines against Ischemic Injury in In Vivo Models of Cerebral Ischemia

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Chin-Yi Cheng

2016-01-01

Full Text Available Inflammation plays a crucial role in the pathophysiology of acute ischemic stroke. In the ischemic cascade, resident microglia are rapidly activated in the brain parenchyma and subsequently trigger inflammatory mediator release, which facilitates leukocyte-endothelial cell interactions in inflammation. Activated leukocytes invade the endothelial cell junctions and destroy the blood-brain barrier integrity, leading to brain edema. Toll-like receptors (TLRs stimulation in microglia/macrophages through the activation of intercellular signaling pathways secretes various proinflammatory cytokines and enzymes and then aggravates cerebral ischemic injury. The secreted cytokines activate the proinflammatory transcription factors, which subsequently regulate cytokine expression, leading to the amplification of the inflammatory response and exacerbation of the secondary brain injury. Traditional Chinese medicines (TCMs, including TCM-derived active compounds, Chinese herbs, and TCM formulations, exert neuroprotective effects against inflammatory responses by downregulating the following: ischemia-induced microglial activation, microglia/macrophage-mediated cytokine production, proinflammatory enzyme production, intercellular adhesion molecule-1, matrix metalloproteinases, TLR expression, and deleterious transcription factor activation. TCMs also aid in upregulating anti-inflammatory cytokine expression and neuroprotective transcription factor activation in the ischemic lesion in the inflammatory cascade during the acute phase of cerebral ischemia. Thus, TCMs exert potent anti-inflammatory properties in ischemic stroke and warrant further investigation.

Increased serum neuron specific enolase concentrations in patients with hyperglycemic cortical ischemic stroke

NARCIS (Netherlands)

Elting, JW; De Keyser, J; Sulter, G.

1998-01-01

A detrimental effect of hyperglycemia in ischemic brain has been demonstrated in laboratory experiments and it has been found that hyperglycemia in ischemic stroke is a predictor of poor outcome. We determined serum neuron specific enolase (NSE) concentrations in 41 consecutive patients with a

Hot topics in research: Preventive neuroradiology in brain aging and cognitive decline

NARCIS (Netherlands)

C.A. Raji; H. Eyre; S.H. Wei; D.E. Bredesen; S. Moylan (Steven); M. Law; G. Small; P.M. Thompson (Paul); R.M. Friedlander; D.H. Silverman; B.T. Baune; T.A. Hoang; N. Salamon; A.W. Toga (Arthur); M.W. Vernooij (Meike)

2015-01-01

textabstractPreventive neuroradiology is a new concept supported by growing literature. The main rationale of preventive neuroradiology is the application of multimodal brain imaging toward early and subclinical detection of brain disease and subsequent preventive actions through identification of

Perturbation of Brain Oscillations after Ischemic Stroke: A Potential Biomarker for Post-Stroke Function and Therapy

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Gratianne Rabiller

2015-10-01

Full Text Available Brain waves resonate from the generators of electrical current and propagate across brain regions with oscillation frequencies ranging from 0.05 to 500 Hz. The commonly observed oscillatory waves recorded by an electroencephalogram (EEG in normal adult humans can be grouped into five main categories according to the frequency and amplitude, namely δ (1–4 Hz, 20–200 μV, θ (4–8 Hz, 10 μV, α (8–12 Hz, 20–200 μV, β (12–30 Hz, 5–10 μV, and γ (30–80 Hz, low amplitude. Emerging evidence from experimental and human studies suggests that groups of function and behavior seem to be specifically associated with the presence of each oscillation band, although the complex relationship between oscillation frequency and function, as well as the interaction between brain oscillations, are far from clear. Changes of brain oscillation patterns have long been implicated in the diseases of the central nervous system including ischemic stroke, in which the reduction of cerebral blood flow as well as the progression of tissue damage have direct spatiotemporal effects on the power of several oscillatory bands and their interactions. This review summarizes the current knowledge in behavior and function associated with each brain oscillation, and also in the specific changes in brain electrical activities that correspond to the molecular events and functional alterations observed after experimental and human stroke. We provide the basis of the generations of brain oscillations and potential cellular and molecular mechanisms underlying stroke-induced perturbation. We will also discuss the implications of using brain oscillation patterns as biomarkers for the prediction of stroke outcome and therapeutic efficacy.

Ischemic tolerance modulates TRAIL expression and its receptors and generates a neuroprotected phenotype.

Science.gov (United States)

Cantarella, G; Pignataro, G; Di Benedetto, G; Anzilotti, S; Vinciguerra, A; Cuomo, O; Di Renzo, G F; Parenti, C; Annunziato, L; Bernardini, R

2014-07-17

TNF-related apoptosis inducing ligand (TRAIL), a member of the TNF superfamily released by microglia, appears to be involved in the induction of apoptosis following focal brain ischemia. Indeed, brain ischemia is associated with progressive enlargement of damaged areas and prominent inflammation. As ischemic preconditioning reduces inflammatory response to brain ischemia and ameliorates brain damage, the purpose of the present study was to evaluate the role of TRAIL and its receptors in stroke and ischemic preconditioning and to propose, by modulating TRAIL pathway, a new therapeutic strategy in stroke. In order to achieve this aim a rat model of harmful focal ischemia, obtained by subjecting animals to 100 min of transient occlusion of middle cerebral artery followed by 24 h of reperfusion and a rat model of ischemic preconditioning in which the harmful ischemia was preceded by 30 mins of tMCAO, which represents the preconditioning protective stimulus, were used. Results show that the neuroprotection elicited by ischemic preconditioning occurs through both upregulation of TRAIL decoy receptors and downregulation of TRAIL itself and of its death receptors. As a counterproof, immunoneutralization of TRAIL in tMCAO animals resulted in significant restraint of tissue damage and in a marked functional recovery. Our data shed new light on the mechanisms that propagate ongoing neuronal damage after ischemia in the adult mammalian brain and provide new molecular targets for therapeutic intervention. Strategies aimed to repress the death-inducing ligands TRAIL, to antagonize the death receptors, or to activate the decoy receptors open new perspectives for the treatment of stroke.

Hypoxic-ischemic encefalopathy: Clinical course and prognosis

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Ćosić-Cerovac Nataša

2003-01-01

Full Text Available Background. Establishing the value of neurological examination, and additional diagnostic methods (ultrasonography and magnetic resonance imaging of the brain in the diagnosis and prognosis of hypoxic-ischemic encephalopathy and its treatment, tracking the clinical course, and making the prognosis of neurological development in newborn infants with hypoxic-ischemic encefalopathy. Methods. The group of 40 term newborn infants with suspected intrauterine asphyxia was examined. All the infants were prospectivelly followed untill the 3rd year of age at the Clinic for Neurology and Psychiatry for Children and Youth in order to estimate their neurological development and to diagnose the occurence of persistent neurological disorders. All the infants were analyzed by their gestational age and Apgar score in the 1st and the 5th minute of life. They were all examined neurologically and by ultrasonography in the first week of life and, repeatedly, at the age of 1, 3, 6, 9, 12, 18, as well as in the 24th month of life. They were treated by the standard methods for this disease. Finally, all the infants were examined neurologically and by magnetic resonance imaging of the brain in their 3rd year of age. On the basis of neurological finding infants were devided into 3 groups: infants with normal neurological finding, infants with mild neurological symptomatology, and infants with severe neurological disorders. Results. It was shown that neurological finding, ultrasonography and magnetic resonance imaging of the brain positively correlated with the later neurological development of the infants with hypoxic-ischemic encephalopathy. Conclusion. Only the combined use of these techniques had full diagnostic and prognostic significance emphasizing that the integrative approach was very important in the diagnosis of brain lesions in infants.

Early predictors of brain damage in full-term newborns with hypoxic ischemic encephalopathy

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Alkholy UM

2017-08-01

Full Text Available Usama M Alkholy,1 Nermin Abdalmonem,1 Ahmed Zaki,2 Yasser F Ali,1 Soma Abdalla Mohamed,3 Nasser I Abdelsalam,1 Mustafa Ismail Abu Hashim,1 Mohamed Abou Sekkien,3 Yasser Makram Elsherbiny4 1Pediatric Department, Zagazig University, Egypt; 2Pediatric Department, Mansoura University, Egypt; 3Pediatric Department, Al Azhar University, Egypt; 4Clinical Pathology Department, Menoufia University, Egypt Objective of the study: To evaluate the value of serum creatine phosphokinase-brain specific (CK-BB and urinary lactate/creatinine (L/C ratio as early indicators of brain damage in full-term newborns with hypoxic ischemic encephalopathy (HIE.Patients and methods: A case–control study including 25 full-term new-born infants with perinatal asphyxia who were admitted to neonatal intensive care unit (NICU with a proven diagnosis of HIE, compared to 20 healthy age- and sex-matched full-term newborns. All newborn infants were subjected to full history taking, clinical examination, routine investigations (cord blood gases and complete blood picture, and assessment of serum CK-BB (cord blood, 6 and 24 hours after birth and urinary L/C ratio (collected within the first 6 hours, on the 2nd and 3rd day after birth.Results: The serum CK-BB and urinary L/C ratio in infants with HIE were significantly higher in samples collected throughout the monitoring period when compared with the control group (all P<0.001. The cord CK-BB and urinary L/C ratio within the first 6 hours were significantly higher in infants with severe HIE than in infants with mild and moderate HIE (P<0.001. Cord CK-BB level at 12.5 U/L had 100% sensitivity and 84% specificity in the detection of severe HIE infants. Urinary L/C ratio of more than 10.5 collected within the first 6 hours after birth had 100% sensitivity and 78% specificity for the detection of severe HIE infants.Conclusion: The serum CK-BB and urinary L/C ratio in HIE infants were significantly increased early in the course of the

Health behavior of patients with ischemic heart disease

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Paweł Węgorowski

2017-06-01

Full Text Available Admission By analyzing the available scientific literature, it is possible to define ischemic heart disease as a set of disease symptoms that are a consequence of a chronic state of imbalance between the ability to supply nutrients and oxygen and the real need of myocardial cells for these substances. Adapting life-style behaviors to healthy living is a priority to prevent the onset and development of cardiovascular disease, especially ischemic heart disease, Purpose of research The aim of the study is to determine the health behavior of patients with ischemic heart disease. Materials and methods The study was conducted from 01.08.2015 to 28.12.2015 in a group of 35 people (15 women and 20 men. The research method used in the work is a diagnostic survey, the research technique used was a survey of its own author. Conclusions By analyzing the data collected, it is important to note that patients with coronary heart disease are often associated with health problems such as hypertension, diabetes and abnormal weight. The nutritional habits of the subjects studied can be described as abnormal, particularly the excessive intake of oily meat and too little fish intake. It has also been observed that most of the patients studied have familial predisposition to ischemic heart disease. Discussion Heart attacks occur mostly in people with obesity, diabetes and atherosclerosis. It is also closely related to ischemic heart disease. The health behaviors of patients suffering from Ischemic Heart Disease are moderately satisfactory and therefore the role of a nurse practitioner as a health educator is very difficult but essential in the prevention of ischemic heart disease.

Rehabilitation Outcomes: Ischemic versus Hemorrhagic Strokes.

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Perna, Robert; Temple, Jessica

2015-01-01

Background. Ischemic and hemorrhagic strokes have different pathophysiologies and possibly different long-term cerebral and functional implications. Hemorrhagic strokes expose the brain to irritating effects of blood and ischemic strokes reflect localized or diffuse cerebral vascular pathology. Methods. Participants were individuals who suffered either an ischemic (n = 172) or hemorrhagic stroke (n = 112) within the past six months and were involved in a postacute neurorehabilitation program. Participants completed three months of postacute neurorehabilitation and the Mayo Portland Adaptability Inventory-4 (MPAI-4) at admission and discharge. Admission MPAI-4 scores and level of functioning were comparable. Results. Group ANOVA comparisons show no significant group differences at admission or discharge or difference in change scores. Both groups showed considerably reduced levels of productivity/employment after discharge as compared to preinjury levels. Conclusions. Though the pathophysiology of these types of strokes is different, both ultimately result in ischemic injuries, possibly accounting for lack of findings of differences between groups. In the present study, participants in both groups experienced similar functional levels across all three MPAI-4 domains both at admission and discharge. Limitations of this study include a highly educated sample and few outcome measures.

Rehabilitation Outcomes: Ischemic versus Hemorrhagic Strokes

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Robert Perna

2015-01-01

Full Text Available Background. Ischemic and hemorrhagic strokes have different pathophysiologies and possibly different long-term cerebral and functional implications. Hemorrhagic strokes expose the brain to irritating effects of blood and ischemic strokes reflect localized or diffuse cerebral vascular pathology. Methods. Participants were individuals who suffered either an ischemic (n=172 or hemorrhagic stroke (n=112 within the past six months and were involved in a postacute neurorehabilitation program. Participants completed three months of postacute neurorehabilitation and the Mayo Portland Adaptability Inventory-4 (MPAI-4 at admission and discharge. Admission MPAI-4 scores and level of functioning were comparable. Results. Group ANOVA comparisons show no significant group differences at admission or discharge or difference in change scores. Both groups showed considerably reduced levels of productivity/employment after discharge as compared to preinjury levels. Conclusions. Though the pathophysiology of these types of strokes is different, both ultimately result in ischemic injuries, possibly accounting for lack of findings of differences between groups. In the present study, participants in both groups experienced similar functional levels across all three MPAI-4 domains both at admission and discharge. Limitations of this study include a highly educated sample and few outcome measures.

Perioperative erythropoietin protects the CNS against ischemic lesions in patients after open heart surgery.

Science.gov (United States)

Lakič, Nikola; Mrak, Miha; Šušteršič, Miha; Rakovec, Peter; Bunc, Matjaž

2016-12-01

The aim of this study was to establish erythropoietin as a protective factor against brain ischemia during open heart surgery. A total of 36 consecutive patients scheduled for revascularization heart surgery were included in the study. Of the patients 18 received 3 intravenous doses of recombinant human erythropoietin (rHuEpo, 24,000 IU) and 18 patients received a placebo. Magnetic resonance imaging (MRI) to detect new brain ischemic lesions was performed. Additionally, S100A, S100B, neuron-specific enolase A and B (NSE-A and B) and the concentration of antibodies against N‑methyl-D-aspartate receptors (NMDAR) to identify new neurological complications were determined. Patients who received rHuEpo showed no postoperative ischemic changes in the brain on MRI images. In the control group 5 (27.8 %) new ischemic lesions were found. The NMDAR antibody concentration, S100A, S100B and NSE showed no significant differences between the groups for new cerebral ischemia. High levels of lactate before and after external aortic compression (p = 0.022 and p = 0.048, respectively) and duration of operation could predict new ischemic lesions (p = 0.009). The addition of rHuEpo reduced the formation of lesions detectable by MRI in the brain and could be used clinically as neuroprotection in cardiac surgery.

Peculiarities of reaction of HIF-1α protein of the hippocampus neurons in rats with experimental diabetes mellitus in the dynamics of ischemic-reperfusion damage of the brain

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T. M. Boychuk

2016-12-01

Higher State Educational Establishment of Ukraine “Bukovinian State medical University”, Chernivtsi, Ukraine   Abstract Introduction. The role of the transcriptional factor Hif-1α in pathogenesis of hypoxic damages and diabetes mellitus (DM is proved, although molecular mechanisms underlying the basis of this factor dysfunction in association with DM with ischemic-reperfusion damage of the brain remain unknown. Objective. The objective of this investigation was to study the content of Hif-1α protein in the hippocampus neurons of rats with experimental DM in the dynamics of ischemic-reperfusion damage of the brain. Results. In rats without DM 20 minute ischemia with one hour reperfusion increases the content of Hif-1α protein in all the fields of the hippocampus. On the 12th day of ischemic-reperfusion period in the hippocampus CA2-CA4 fields the values of certain examined indices of the activity of Hif-1α transcriptional factor continue to increase, and in СА1field they normalize or approach to the values of animals in the control group.  In rats with DM during early post-ischemic period there are no changes of Hif-1α protein content in CA1 field, in CA2 field there are signs of its reduced activity, in CA3 field they are limited by the reaction of one index, in CA4 field they are of a similar character with those of the control rats under experimental conditions.  On the 12th day of ischemic-reperfusion period in CA1 field all the indices of activity of Hif-1α transcriptional factor increase exceeding corresponding indices by absolute values in animals of the control group under the same experimental conditions, in СА2 and СА3 fields changes of the examined parameters are limited as compared to the same ones in animals from the control group, in CA4 field values that were increased in the control group decrease. Conclusions. Diabetes mellitus restricts reaction of Hif-1α protein on ischemia-reperfusion inn the neurons of СА1-СА3 fields in

Risk of stroke and cardiovascular events after ischemic stroke or transient ischemic attack in patients with type 2 diabetes or metabolic syndrome: secondary analysis of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial

DEFF Research Database (Denmark)

Callahan, Alfred; Amarenco, Pierre; Goldstein, Larry B

2011-01-01

To perform a secondary analysis of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial, which tested the effect of treatment with atorvastatin in reducing stroke in subjects with a recent stroke or transient ischemic attack, to explore the effects of treatment...

Seizure Severity Is Correlated With Severity of Hypoxic-Ischemic Injury in Abusive Head Trauma.

Science.gov (United States)

Dingman, Andra L; Stence, Nicholas V; O'Neill, Brent R; Sillau, Stefan H; Chapman, Kevin E

2017-12-12

The objective of this study was to characterize hypoxic-ischemic injury and seizures in abusive head trauma. We performed a retrospective study of 58 children with moderate or severe traumatic brain injury due to abusive head trauma. Continuous electroencephalograms and magnetic resonance images were scored. Electrographic seizures (51.2%) and hypoxic-ischemic injury (77.4%) were common in our cohort. Younger age was associated with electrographic seizures (no seizures: median age 13.5 months, interquartile range five to 25 months, versus seizures: 4.5 months, interquartile range 3 to 9.5 months; P = 0.001). Severity of hypoxic-ischemic injury was also associated with seizures (no seizures: median injury score 1.0, interquartile range 0 to 3, versus seizures: 4.5, interquartile range 3 to 8; P = 0.01), but traumatic injury severity was not associated with seizures (no seizures: mean injury score 3.78 ± 1.68 versus seizures: mean injury score 3.83 ± 0.95, P = 0.89). There was a correlation between hypoxic-ischemic injury severity and seizure burden when controlling for patient age (r s =0.61, P interquartile range 0 to 0.23 on magnetic resonance imaging done within two days versus median restricted diffusion ratio 0.13, interquartile range 0.01 to 0.43 on magnetic resonance imaging done after two days, P = 0.03). Electrographic seizures are common in children with moderate to severe traumatic brain injury from abusive head trauma, and therefore children with suspected abusive head trauma should be monitored with continuous electroencephalogram. Severity of hypoxic-ischemic brain injury is correlated with severity of seizures, and evidence of hypoxic-ischemic injury on magnetic resonance imaging may evolve over time. Therefore children with a high seizure burden should be reimaged to evaluate for evolving hypoxic-ischemic injury. Published by Elsevier Inc.

Netrin-1 Ameliorates Blood-Brain Barrier Impairment Secondary to Ischemic Stroke via the Activation of PI3K Pathway

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Jian Yu

2017-12-01

Full Text Available Secondary impairment of blood-brain barrier (BBB occurs in the remote thalamus after ischemic stroke. Netrin-1, an axonal guidance molecule, presents bifunctional effects on blood vessels through receptor-dependent pathways. This study investigates whether netrin-1 protects BBB against secondary injury. Netrin-1 (600 ng/d for 7 days was intracerebroventricularly infused 24 h after middle cerebral artery occlusion (MCAO in hypertensive rats. Neurological function was assessed 8 and 14 days after MCAO, and the permeability of BBB in the ipsilateral thalamus was detected. The viability of brain microvascular endothelial cells was determined after being disposed with netrin-1 (50 ng/mL before oxygen-glucose deprivation (OGD. The role of netrin-1 was further explored by examining its receptors and their function. We found that netrin-1 infusion improved neurological function, attenuated secondary impairment of BBB by up-regulating the levels of tight junction proteins and diminishing extravasation of albumin, with autophagy activation 14 days after MCAO. Netrin-1 also enhanced cell survival and autophagy activity in OGD-treated cells, inhibited by UNC5H2 siRNA transfection. Furthermore, the beneficial effects of netrin-1 were suppressed by PI3K inhibitors 3-Methyladenine and LY294002. Our results showed that netrin-1 ameliorated BBB impairment secondary to ischemic stroke by promoting tight junction function and endothelial survival. PI3K-mediated autophagy activation depending on UNC5H2 receptor could be an underlying mechanism.

Relationship between vascular dysfunction in peripheral arteries and ischemic episodes during daily life in patients with ischemic heart disease and hypercholesterolemia

DEFF Research Database (Denmark)

Søndergaard, Eva; Møller, Jacob E; Egstrup, Kenneth

2002-01-01

cardiovascular risk factors. CONCLUSIONS: These results indicate a significant relationship between ischemic episodes and vascular dysfunction in patients with ischemic heart disease and hypercholesterolemia and may justify an aggressive preventive therapy targeted directly at the endothelium.......BACKGROUND: It is well established that endothelial dysfunction is present in patients with ischemic heart disease and hypercholesterolemia. Some of these patients will have signs of transient myocardial ischemia during Holter monitoring. We sought to describe the correlation between daily life...... ischemia and signs of endothelial dysfunction as assessed by means of brachial vasoreactivity. METHODS: We included in the study 131 patients with documented ischemic heart disease and a serum cholesterol level of > or =5 mmol/L before the institution of lipid-lowering treatment and dietary intervention...

Can induced hypothermia be assured during brain MRI in neonates with hypoxic-ischemic encephalopathy?

International Nuclear Information System (INIS)

Wintermark, Pia; Labrecque, Michelle; Hansen, Anne; Warfield, Simon K.; DeHart, Stephanie

2010-01-01

Until now, brain MRIs in asphyxiated neonates who are receiving therapeutic hypothermia have been performed after treatment is complete. However, there is increasing interest in utilizing early brain MRI while hypothermia is still being provided to rapidly understand the degree of brain injury and possibly refine neuroprotective strategies. This study was designed to assess whether therapeutic hypothermia can be maintained while performing a brain MRI. Twenty MRI scans were obtained in 12 asphyxiated neonates while they were treated with hypothermia. The median difference between esophageal temperature on NICU departure and return was 0.1 C (range: -0.8 to 0.8 C). We found that therapeutic hypothermia can be safely and reproducibly maintained during a brain MRI. Hypothermia treatment should not prevent obtaining an early brain MRI if clinically indicated. (orig.)

Can induced hypothermia be assured during brain MRI in neonates with hypoxic-ischemic encephalopathy?

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Wintermark, Pia [Children' s Hospital Boston, Division of Newborn Medicine, Boston, MA (United States); Children' s Hospital Boston, Department of Radiology, Boston, MA (United States); Montreal Children' s Hospital, Division of Newborn Medicine, Montreal, QC (Canada); Labrecque, Michelle; Hansen, Anne [Children' s Hospital Boston, Division of Newborn Medicine, Boston, MA (United States); Warfield, Simon K.; DeHart, Stephanie [Children' s Hospital Boston, Department of Radiology, Boston, MA (United States)

2010-12-15

Until now, brain MRIs in asphyxiated neonates who are receiving therapeutic hypothermia have been performed after treatment is complete. However, there is increasing interest in utilizing early brain MRI while hypothermia is still being provided to rapidly understand the degree of brain injury and possibly refine neuroprotective strategies. This study was designed to assess whether therapeutic hypothermia can be maintained while performing a brain MRI. Twenty MRI scans were obtained in 12 asphyxiated neonates while they were treated with hypothermia. The median difference between esophageal temperature on NICU departure and return was 0.1 C (range: -0.8 to 0.8 C). We found that therapeutic hypothermia can be safely and reproducibly maintained during a brain MRI. Hypothermia treatment should not prevent obtaining an early brain MRI if clinically indicated. (orig.)

Novel Therapeutic Effects of Leonurine On Ischemic Stroke: New Mechanisms of BBB Integrity

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Qiu-Yan Zhang

2017-01-01

Full Text Available Stroke is a leading cause of morbidity and mortality globally. Leonurine (also named SCM-198, a compound extracted from Herba leonuri, was effective on the prevention of various cardiovascular and brain diseases. The purpose of this study was to explore the possible therapeutic potential of SCM-198 against ischemia reperfusion injury and underlying mechanisms. In the in vivo transient middle cerebral artery occlusion (tMCAO rat model, we found that treatment with SCM-198 could decrease infarct volume and improve neurological deficit by protecting against blood-brain barrier (BBB breakdown. In the in vitro model of cell oxygen-glucose deprivation and reoxygenation (OGD/R, consistent results were obtained with decreased reactive oxygen species (ROS production and maintained the BBB integrity. Further study demonstrated that SCM-198 increased the expression of histone deacetylase- (HDAC- 4 which could inhibit NADPH oxidase- (NOX- 4 and matrix metalloproteinase- (MMP- 9 expression, resulting in the elevation of tight junction proteins, including claudin-5, occludin, and zonula occluden- (ZO- 1. These results indicated SCM-198 protected BBB integrity by regulating the HDAC4/NOX4/MMP-9 tight junction pathway. Our findings provided novel insights into the protective effects and mechanisms of SCM-198 on ischemic stroke, indicating SCM-198 as a new class of potential drug against acute onset of ischemic stroke.

Discovery of 3-n-butyl-2,3-dihydro-1H-isoindol-1-one as a potential anti-ischemic stroke agent

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Lan Z

2015-06-01

Full Text Available Zujian Lan, Xiaoyu Xu, Wenkai Xu, Jin Li, Zengrong Liang, Xuefei Zhang, Ming Lei, Chunshun Zhao School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, People’s Republic of China Abstract: To develop novel anti-ischemic stroke agents with better therapeutic efficacy and bioavailability, we designed and synthesized a series of 3-alkyl-2,3-dihydro-1H-isoindol-1-ones compounds (3a–i derivatives, one of which (3d exhibited the strongest inhibitory activity for the adenosine diphosphate-induced and arachidonic acid-induced platelet aggregation. This activity is superior to that of 3-n-butylphthalide and comparable with aspirin and edaravone. Meanwhile, 3d not only exhibited a potent activity in scavenging free radicals and improving the survival of HT22 cells against the reactive oxygen species-mediated cytotoxicity in vitro but also significantly attenuated the ischemia/reperfusion-induced oxidative stress in ischemic rat brains. Results from transient middle cerebral artery occlusion and permanent middle cerebral artery occlusion model, indicated that 3d could significantly reduce infarct size, improve neurobehavioral deficits, and prominently decrease attenuation of cerebral damage. Most importantly, 3d possessed a very high absolute bioavailability and was rapidly distributed in brain tissue to keep high plasma drug concentration for the treatment of ischemic strokes. In conclusion, our findings suggest that 3-alkyl-2,3-dihydro-1H-isoindol-1-ones, a novel series of compounds, might be candidate drugs for the treatment of acute ischemic strokes, and 3d may be a promising therapeutic agent for the primary and secondary prevention of ischemic stroke. Keywords: stroke, platelet aggregation, ischemia/reperfusion, middle cerebral artery occlusion, 3-alkyl-2,3-dihydro-1H-isoindol-1-ones

Absent collateral function of the circle of Willis as risk factor for ischemic stroke

NARCIS (Netherlands)

Hoksbergen, A. W. J.; Legemate, D. A.; Csiba, L.; Csáti, G.; Síró, P.; Fülesdi, B.

2003-01-01

Background. Autopsy studies show a higher prevalence of circle of Willis anomalies in brains with signs of ischemic infarction. Our goal was to examine the collateral function of the circle of Willis in ischemic stroke patients and to assess in a case-control study if a collateral deficient circle

Tc99m-HMPAO Neuro--SPECT Assessment of Ischemic Penumbra in Acute Brain Infarct: Control of Intra-arterial Thrombolysis Treatment

International Nuclear Information System (INIS)

Mena, Francisco; Mena, Ismael; Ducci, Hector; Soto, Francisco; Pedraza, Luis; Contreras, Andrea; Miranda, Marcelo; Basaez, Esteban; Fruns, Manuel

2004-01-01

Acute brain infarct is a medical emergency potentially reversible if treated with thrombolysis, an approved therapy, if performed in the first 3 to 6 hours of evolution. Thrombolysis has many benefits, but it also has associated risks, mainly development of intracranial hemorrhage. The selection of which patient should receive this type of treatment had been an important research topic over the last decade. As a consequence neuroimaging of brain infarct has significantly improved during the last few years. A variety of diagnostic studies are now available in the evaluation of brain infarct and in particular of potentially reversible brain ischemia, including magnetic resonance imaging (MRI) diffusion-perfusion, perfusion computed tomography (CT) and functional neuroimaging techniques includes positron emission tomography (PET) and single-photon emission tomography (SPECT). The aim of this study is to present our experience with a group of patients that presented with acute brain ischemia and had a NeuroSPECT evaluation before and after intra-arterial thrombolysis and/or possible stent placement, in the treatment of acute brain infarct. Methods: 16 patients were treated acutely for a significant ischemic stroke with the following protocol. 1) Admission, and complete neurological evaluation. 2) Brain CT scan performed to rule out hemorrhage or established infarct. 3) IV injection of 1100MBq Tc 99m HMPAO (Ceretec tm ) 4) Conventional cerebral angiography and intra-arterial thrombolysis with tPA and /or angioplasty/stent if necessary. 5) NeuroSPECT assessment of ischemic penumbra (Pre-therapy results). 6) 14 of 16 patients received a NeuroSPECT (Post-therapy results) control at 24 hours. NeuroSPECT image acquisition was performed immediately following arterial thrombolysis with a dual Head Camera, Siemens ECAM, SHR collimators and conventional protocol. Image processing was performed using the Neurogam, Segami Corp. Software as previously reported in Alasbimn Journal 2

Hyperintense Acute Reperfusion Marker on FLAIR in a Patient with Transient Ischemic Attack

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Alex Förster

2016-01-01

Full Text Available The hyperintense acute reperfusion marker (HARM has initially been described in acute ischemic stroke. The phenomenon is caused by blood-brain barrier disruption following acute reperfusion and consecutive delayed gadolinium enhancement in the subarachnoid space on fluid attenuated inversion recovery (FLAIR images. Here we report the case of an 80-year-old man who presented with transient paresis and sensory loss in the right arm. Initial routine stroke MRI including diffusion- and perfusion-weighted imaging demonstrated no acute pathology. Follow-up MRI after three hours demonstrated subarachnoid gadolinium enhancement in the left middle cerebral artery territory consistent with HARM that completely resolved on follow-up MRI three days later. This case illustrates that even in transient ischemic attack patients disturbances of the blood-brain barrier may be present which significantly exceed the extent of acute ischemic lesions on diffusion-weighted imaging. Inclusion of FLAIR images with delayed acquisition after intravenous contrast agent application in MRI stroke protocols might facilitate the diagnosis of a recent acute ischemic stroke.

RELATIONSHIP BETWEEN LESION LOCATION AND COGNITIVE DOMAINS IN ACUTE ISCHEMIC STROKE PATIENTS

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Vojislava Bugarski

2009-09-01

Full Text Available Localization of brain lesions in acute ischemic stroke has a significant effect on performance in various cognitive domains. The aim of the study was to determine whether there is association between different locations of ischemic brain lesions and different cognitive domains. The study included 40 acute ischemic stroke pati-ents (26 male and 14 female, aged 45-78 years, with 8-16 years of education. Lesi-on location was visualized using brain computerized tomography, whereas perfor-mance in different cognitive domains was assessed using an extensive neuropsychological test battery. The following domains were evaluated: executive function, language, immediate recall, delayed recall, attention, divergent reasoning, and visual-constructive performance in two dimensions. A series of categorical re-gression analyses were applied. The results showed a significant association between the domains of executive function and language and a set of predictors rela-ted to lesion location. Global brain atrophy was found to be a significant partial pre-dictor of performance in all cognitive domains, with higher degrees of global brain atrophy correlating with poorer performance in each of the studied domains. Combi-ned (cortical-subcortical lesions and unilateral lesions were both found to be signi-ficant partial predictors for language, with a higher lesion load being associated with poorer language performance. Combined lesions were also a significant partial pre-dictor for delayed recall, with a higher lesion load correlating with poorer perfor-mance in the delayed recall domain.

Dynamin-Related Protein 1 Inhibitors Protect against Ischemic Toxicity through Attenuating Mitochondrial Ca2+ Uptake from Endoplasmic Reticulum Store in PC12 Cells

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Ye Tian

2014-02-01

Full Text Available Intracellular calcium homeostasis disorder and mitochondrial dysfunction are involved in many acute and chronic brain diseases, including ischemic brain injury. An imbalance in mitochondrial fission and fusion is one of the most important structural abnormalities found in a large number of mitochondrial dysfunction related diseases. Here, we investigated the effects of mitochondrial division inhibitor A (mdivi A and mdivi B, two small molecule inhibitors of mitochondrial fission protein dunamin-related protein 1 (Drp-1, in neuronal injury induced by oxygen-glucose deprivation (OGD in PC12 cells. We found that mdivi A and mdivi B inhibited OGD-induced neuronal injury through attenuating apoptotic cell death. These two inhibitors also preserved mitochondrial function, as evidenced by reduced reactive oxygen species (ROS generation and cytochrome c release, as well as prevented loss of mitochondrial membrane potential (MMP. Moreover, mdivi A and mdivi B significantly suppressed mitochondrial Ca2+ uptake, but had no effect on cytoplasmic Ca2+ after OGD injury. The results of calcium imaging and immunofluorescence staining showed that Drp-1 inhibitors attenuated endoplasmic reticulum (ER Ca2+ release and prevented ER morphological changes induced by OGD. These results demonstrate that Drp-1 inhibitors protect against ischemic neuronal injury through inhibiting mitochondrial Ca2+ uptake from the ER store and attenuating mitochondrial dysfunction.

Risk reduction of brain infarction during carotid endarterectomy or stenting using sonolysis - Prospective randomized study pilot data

Science.gov (United States)

Kuliha, Martin; Školoudík, David; Martin Roubec, Martin; Herzig, Roman; Procházka, Václav; Jonszta, Tomáš; Krajča, Jan; Czerný, Dan; Hrbáč, Tomáš; Otáhal, David; Langová, Kateřina

2012-11-01

Sonolysis is a new therapeutic option for the acceleration of arterial recanalization. The aim of this study was to confirm risk reduction of brain infarction during endarterectomy (CEA) and stenting (CAS) of the internal carotid artery (ICA) using sonolysis with continuous transcranial Doppler (TCD) monitoring by diagnostic 2 MHz probe, additional interest was to assess impact of new brain ischemic lesions on cognitive functions. Methods: All consecutive patients 1/ with ICA stenosis >70%, 2/ indicated to CEA or CAS, 3/ with signed informed consent, were enrolled to the prospective study during 17 months. Patients were randomized into 2 groups: Group 1 with sonolysis during intervention and Group 2 without sonolysis. Neurological examination, assessment of cognitive functions and brain magnetic resonance imaging (MRI) were performed before and 24 hours after intervention in all patients. Occurrence of new brain infarctions (including infarctions >0.5 cm3), and the results of Mini-Mental State Examination, Clock Drawing and Verbal Fluency tests were statistically evaluated using T-test. Results: 97 patients were included into the study. Out of the 47 patients randomized to sonolysis group (Group 1) 25 underwent CEA (Group 1a) and 22 CAS (Group 1b). Out of the 50 patients randomized to control group (Group 2), 22 underwent CEA (Group 2a) and 28 CAS (Group 2b). New ischemic brain infarctions on follow up MRI were found in 14 (29.8%) patients in Group 1-4 (16.0%) in Group 1a and 10 (45.5%) in Group 1b. In Group 2, new ischemic brain infarctions were found in 18 (36.0%) patients-6 (27.3%) in Group 2a and 12 (42.9%) in Group 2b (p>0.05 in all cases). New ischemic brain infarctions >0.5 cm3 were found in 4 (8.5 %) patients in Group 1 and in 11 (22.0 %) patients in Group 2 (p= 0.017). No significant differences were found in cognitive tests results between subgroups (p>0.05 in all tests). Conclusion: Sonolysis seems to be effective in the prevention of large ischemic

Non invasive brain stimulation to enhance post-stroke recovery

OpenAIRE

Nathalie Kubis; Nathalie Kubis

2016-01-01

Brain plasticity after stroke remains poorly understood. Patients may improve spontaneously within the first 3 months and then more slowly in the coming year. The first days, decreased edema and reperfusion of the ischemic penumbra may possibly account for these phenomena, but the improvement during the next weeks suggests plasticity phenomena and cortical reorganization of the brain ischemic areas and of more remote areas. Indeed, the injured ischemic motor cortex has a reduced cortical exci...

Non-Invasive Brain Stimulation to Enhance Post-Stroke Recovery

OpenAIRE

Kubis, Nathalie

2016-01-01

Brain plasticity after stroke remains poorly understood. Patients may improve spontaneously within the first 3 months and then more slowly in the coming year. The first day, decreased edema and reperfusion of the ischemic penumbra may possibly account for these phenomena, but the improvement during the next weeks suggests plasticity phenomena and cortical reorganization of the brain ischemic areas and of more remote areas. Indeed, the injured ischemic motor cortex has a reduced cortical excit...

The diagnostic value of 13N-ammonia PET in ischemic cerebrovascular disorders

International Nuclear Information System (INIS)

Qiao Shuixian; Tang Anwu; Wang Lijuan; Liu Xintong; Yuan Yanbo; Chen Liguang; Luo Yaowu; Zhang Xiangsong; Wang Shuxia; Liu Bin; Xu Weiping

2002-01-01

Objective: To evaluate the feasibility of 13 N-ammonia PET in diagnosing ischemic cerebrovascular disorders. Methods: A total of 25 subjects were investigated. Five healthy volunteers served as normal control. Twenty patients included 13 with transient ischemic attack (TIA), 6 with brain infarction and 1 with moyamoya disease. 740-925 MBq of 13 N-ammonia was injected intravenously, 3-5 min later, PET imaging was performed with T + E 2D acquisition with Siemens ECAT EXACT HR + PET scanner. Image analysis was done by visual and semiquantitative estimating. Standardized uptake value (SUV) was measured in mirror regions of cerebrum with autocopy methods. Nine patients underwent drug stress with oral acetazolamide (ACZ). Images were compared before and after oral ACZ intervention. Results: Physiological brain uptake with SUV ratio of 0.99 +- 0.15 (n=5, left/right) was observed in healthy volunteers. L/N 13 N-ammonia as radioactive tracer was a safe and noninvasive, sensitive and accurate functional imaging modality for brain perfusion. The oral ACZ stress is a safe, simple and reliable diagnostic method for ischemic cerebrovascular disorders. It is of important uses in detecting the potential reserve of cerebral blood flow

A Case Of Transient Ischemic Attack Presenting As Hemichroea

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Hasan Hüseyin Özdemir

2013-12-01

Full Text Available Chorea is defined as; involuntary movements of the distal parts of limbs which have arrhythmic, rapid, bouncing or smooth, simple or complex properties. Choreiform movements occur when putamen, globus pallidus and subthalamic nucleus are affected. Chorea can be observed during the course of metabolic and vascular diseases, neurodegenerative or hereditary diseases. Chorea may be a rare symptom of cerebral hypoperfusion. Transient ischemic attack is an event that occurs in short term characterized by a temporary ischemia of brain. A wide variety of symptoms can be seen depending on the localization of cerebral hypoperfusion. Hemichorea is a very rare finding observed during transient ischemic attacks. In this article hemichorea in a case of symptomatic transient ischemic attack is discussed with relevant literature.

Effect of 3-aminobenzamide, PARP inhibitor, on matrix metalloproteinase-9 level in plasma and brain of ischemic stroke model

International Nuclear Information System (INIS)

Koh, Seong-Ho; Chang, Dae-Il; Kim, Hee-Tae; Kim, Juhan; Kim, Myung-Ho; Kim, Kyung Suk; Bae, Inhee; Kim, Haekwon; Kim, Dong Won; Kim, Seung Hyun

2005-01-01

We investigated the effect of poly(ADP-ribose) polymerase (PARP) inhibitor on the levels of plasma and brain matrix metalloproteinase-9 (MMP-9) and the expression of nuclear factor kappa B (NF-κB) during experimental focal cerebral ischemia. The 3-aminobenzamide (3-AB), a PARP inhibitor, and saline were administered to 80 Sprague-Dawley rats [3-AB group; 5 rats for plasma sampling, 35 for brain sampling, and 40 for TTC staining] and to 85 rats (10, 35, and 40, respectively), respectively, 10 min before the occlusion of the left middle cerebral artery (MCAo) for 2 h. Infarct volume was measured by TTC staining, the serial levels of plasma and brain MMP-9 were measured by zymography just before and 2, 4, 8, 24, 48, and 72 h after MCAo, brain NF-κB activity was determined by Western blotting, and neutrophil infiltration was evaluated by assessing myeloperoxidase activity. Compared with control group, the levels of plasma and brain MMP-9, brain NF-κB, and MPO activities were significantly reduced in 3-AB group at each time point (p < 0.05). Plasma MMP-9 increased maximally at 4 h and then decreased rapidly, brain MMP-9 increased maximally at 24 h and persisted until 72 h, and NF-κB increased maximally at 24 h and then decreased slowly in both groups. Therefore, the PARP inhibitor reduces the expression of MMP-9 and NF-κB and the infiltration of neutrophils in ischemic stroke

PET/CT imaging of striatal dopamine transporters in a newborn piglet model of hypoxic-ischemic brain injury

International Nuclear Information System (INIS)

Zhang Yanfen; Wang Xiaoming; Wang Xiaoyu; Cao Li; Guo Qiyong

2013-01-01

Objective: To investigate changes of striatal DAT following hypoxic ischemic (HI) brain injury in newborn piglets using 11 C-N-2-carbomethoxy-3-(4-fluorophenyl)-tropane (CFT) PET/CT, and to evaluate the value of 11 C-CFT PET/CT in brain injury. Methods: Newborn piglets with HI brain injury (n=20) were taken as a model group,and five piglets were used as a control group. Radioligand 11 C-CFT (55.5-74.0 MBq) was injected through the jugular vein, and PET/CT imaging was performed to observe the changes of striatal DAT in newborn piglets. The ST/occipital lobe (OC) ratio was calculated. Model group was divided into 0-6 h, 20-24 h, 44-48 h and 68-72 h sub-groups after HI in accordance with the imaging time. The piglets were sacrificed immediately after 11 C-CFT PET/CT scanning, and then the brains were removed for pathological analysis. Data analysis was performed with one-way analysis of variance and Pearson linear correlation analysis. Results: After intravenous injection of 11 C-CFT, the radioactivity accumulation in cortical, striatum, and cerebellum was shown clearly in the control and model groups. The radioactivity accumulation was lower in the white matter. The radioactivity in cortical and cerebellum exhibited decreased with time, while the striatum was still clear. After HI, the ST/OC activity ratio in the striatum was initially increased, and the ratio of 0-6 h group (1.34 ± 0.04) was statistically significant compared with that of the control group (1.18 ± 0.06; F=4.658, P<0.05), followed by a gradual decrease. ST/OC ratios of other HI subgroups were 1.27 ±0.01, 1.27 ±0.10 and 1.18 ±0.05, respectively. There was a positive correlation between the number of DAT positive neurons ((13 ± 3), (13 ± 4), (8 ±3) and (4 ±4)/high power field) and 11 C-CFT ST/OC activity ratios (r=0.844, P<0.05). Conclusion: 11 C-CFT PET/CT study can accurately reflect the changes of DAT in the striatum, and the amount of DAT is related to the severity of the ischemic insult

A high-affinity, dimeric inhibitor of PSD-95 bivalently interacts with PDZ1-2 and protects against ischemic brain damage

DEFF Research Database (Denmark)

Bach, Anders*; Clausen, Bettina H; Møller, Magda

2012-01-01

Inhibition of the ternary protein complex of the synaptic scaffolding protein postsynaptic density protein-95 (PSD-95), neuronal nitric oxide synthase (nNOS), and the N-methyl-d-aspartate (NMDA) receptor is a potential strategy for treating ischemic brain damage, but high-affinity inhibitors are ...... of Tat-N-dimer (3 nmol/g) to mice subjected to focal cerebral ischemia reduces infarct volume with 40% and restores motor functions. Thus, Tat-N-dimer is a highly efficacious neuroprotective agent with therapeutic potential in stroke....

[Mechanism of potassium channel in hypoxia-ischemic brain edema: experiment with neonatal rat astrocyte].

Science.gov (United States)

Fu, Xue-mei; Xiang, Long; Liao, Da-qing; Feng, Zhi-chun; Mu, De-zhi

2008-11-04

To investigate the mechanism of potassium channel in brain edema caused by hypoxia-ischemia (HI). Astrocytes were obtained from 3-day-old SD rats, cultured, and randomly divided into 2 groups: normoxia group, cultured under normoxic condition, and hypoxic-ischemic group, cultured under hypoxic-ischemic condition. The cell volume was measured by radiologic method. Patch-clamp technique was used to observe the electric physiological properties of the voltage-gated potassium channels (Kv) in a whole cell configuration, and the change of voltage-gated potassium channel current (IKv) was recorded in cultured neonatal rat astrocyte during HI. Aquaporin 4 (AQP4) expression vector was constructed from pSUPER vector and transfected into the astrocytes (AQP4 RNAi) to construct AQP4 knockdown (AQP4-/-) cells. cellular volume was determined using [3H]-3-O-methyl-D-glucose uptake in both AQP4-/- and AQP4+/+ cells under the condition of HI. Real time PCR and Western blotting were used to detect the mRNA and protein expression of AQP4. The percentages of the AQP4+/+ and AQP4-/- astrocyte volumes in the condition of HI for 0.5, 1, 2, and 4 h were 104+/-7, 109+/-6, 126+/-12, and 152+/-9 times, and 97+/-7, 105+/-9, 109+/-7, and 132+/-6 times as those of their corresponding control groups (all Pastrocytes significantly increased during HI and the degrees of edema mediated by AQP4 knockdown at different time points were all significantly milder (all Pastrocytes via aquaporin-4 and then cell swelling.

Piroxicam-mediated modulatory action of 5-hydroxytryptamine serves as a "brake" on neuronal excitability in ischemic stroke

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Pallab Bhattacharya

2015-01-01

Full Text Available Our previous studies indicated an increase in extracellular γ-aminobutyric acid (GABA in rodent′s ischemic brain after Piroxicam administration, leading to alleviation of glutamate mediated excitotoxicity through activation of type A GABA receptor (GABAA. This study was to investigate if GABAA activation by Piroxicam affects extracellular 5-hydroxytryptamine or not. High performance liquid chromatography revealed that there was a significant decrease in extracellular 5-hydroxytryptamine release in ischemic cerebral cortex and striatum in Piroxicam pre-treated rat brains. This suggests a probable role of Piroxicam in reducing extracellular 5-hydroxytryptamine release in ischemic cerebral cortex and striatum possibly due to the GABAA activation by Piroxicam.

Adherence to treatment of patients with past ischemic stroke.

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V. Je. Azarenko

2018-05-01

Full Text Available The main task of the general practitioner is managing patients with the effects of ischemic stroke. The improvement of patients adherence to treatment in a significant way contributes to successful secondary prevention of ischemic stroke. Adherence to treatment can be determined through various questionnaires, including Morissky-Green. Currently, the adherence to a long-term drug therapy remains insufficient.

The effects of citicoline on acute ischemic stroke

DEFF Research Database (Denmark)

Overgaard, Karsten

2014-01-01

Early reopening of the occluded artery is, thus, important in ischemic stroke, and it has been calculated that 2 million neurons die every minute in an ischemic stroke if no effective therapy is given; therefore, "Time is Brain." In massive hemispheric infarction and edema, surgical decompression...... lowers the risk of death or severe disability defined as a modified Rankin Scale score greater than 4 in selected patients. The majority, around 80%-85% of all ischemic stroke victims, does not fulfill the criteria for revascularization therapy, and also for these patients, there is no effective acute...... therapy. Also there is no established effective acute treatment of spontaneous intracerebral bleeding. Therefore, an effective therapy applicable to all stroke victims is needed. The neuroprotective drug citicoline has been extensively studied in clinical trials with volunteers and more than 11...

3H-1,2-Dithiole-3-thione as a novel therapeutic agent for the treatment of ischemic stroke through Nrf2 defense pathway.

Science.gov (United States)

Kuo, Ping-Chang; Yu, I-Chen; Scofield, Barbara A; Brown, Dennis A; Curfman, Eric T; Paraiso, Hallel C; Chang, Fen-Lei; Yen, Jui-Hung

2017-05-01

Cerebral ischemic stroke accounts for more than 80% of all stroke cases. During cerebral ischemia, reactive oxygen species produced in brain tissue induce oxidative stress and inflammatory responses. D3T, the simplest compound of the cyclic, sulfur-containing dithiolethiones, is found in cruciferous vegetables and has been reported to induce antioxidant genes and glutathione biosynthesis through activation of Nrf2. In addition to antioxidant activity, D3T was also reported to possess anti-inflammatory effects. In this study, we evaluated the therapeutic potential of D3T for the treatment of ischemic stroke and investigated the mechanisms underlying the protective effects of D3T in ischemic stroke. Mice subjected to transient middle cerebral artery occlusion/reperfusion (tMCAO/R) were administered with vehicle or D3T to evaluate the effect of D3T in cerebral brain injury. We observed D3T reduced infarct size, decreased brain edema, lessened blood-brain barrier disruption, and ameliorated neurological deficits. Further investigation revealed D3T suppressed microglia (MG) activation and inhibited peripheral inflammatory immune cell infiltration of CNS in the ischemic brain. The protective effect of D3T in ischemic stroke is mediated through Nrf2 induction as D3T-attenuated brain injury was abolished in Nrf2 deficient mice subjected to tMCAO/R. In addition, in vitro results indicate the induction of Nrf2 by D3T is required for its suppressive effect on MG activation and cytokine production. In summary, we demonstrate for the first time that D3T confers protection against ischemic stroke, which is mediated through suppression of MG activation and inhibition of CNS peripheral cell infiltration, and that the protective effect of D3T in ischemic stroke is dependent on the activation of Nrf2. Copyright © 2017 Elsevier Inc. All rights reserved.

Neurovascular Regulation in the Ischemic Brain

OpenAIRE

Jackman, Katherine; Iadecola, Costantino

2015-01-01

Significance: The brain has high energetic requirements and is therefore highly dependent on adequate cerebral blood supply. To compensate for dangerous fluctuations in cerebral perfusion, the circulation of the brain has evolved intrinsic safeguarding measures. Recent Advances and Critical Issues: The vascular network of the brain incorporates a high degree of redundancy, allowing the redirection and redistribution of blood flow in the event of vascular occlusion. Furthermore, active respons...

Causes and Treatment of Acute Ischemic Stroke During Pregnancy.

Science.gov (United States)

Terón, Ina; Eng, Melissa S; Katz, Jeffrey M

2018-05-21

Treatment recommendations for pregnancy associated ischemic stroke are scarce. This may be due to the fact that, in general, obstetricians tend not to make recommendations for stroke patients and neurologists are not commonly involved in the care of pregnant women. Herein, we review the multiple etiologies of ischemic stroke during pregnancy, considerations for diagnostic testing, and acute treatment and prevention options, including associated risks specific to the pregnant and puerperal state. Intravenous tissue plasminogen activator (tPA) and endovascular thrombectomy have been used successfully to treat pregnant women with acute ischemic stroke. Recent national guidelines recommend considering tPA use during pregnancy for moderate and severe strokes if the potential benefits offset the risks of uterine hemorrhage. Pregnancy-associated ischemic stroke is rare, but can be devastating, and recanalization therapy should not be systematically withheld. Women who are at risk for stroke should be followed carefully, and providers caring for pregnant women should be educated regarding stroke signs and symptoms. Many of the standard post stroke diagnostic modalities may be used safely in pregnancy, and primary and secondary stroke prevention therapy must be tailored to avoid fetal toxicity.

The Traditional Herbal Medicine, Dangkwisoo-San, Prevents Cerebral Ischemic Injury through Nitric Oxide-Dependent Mechanisms

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Ji Hyun Kim

2011-01-01

Full Text Available Dangkwisoo-San (DS is an herbal extract that is widely used in traditional Korean medicine to treat traumatic ecchymosis and pain by promoting blood circulation and relieving blood stasis. However, the effect of DS in cerebrovascular disease has not been examined experimentally. The protective effects of DS on focal ischemic brain were investigated in a mouse model. DS stimulated nitric oxide (NO production in human brain microvascular endothelial cells (HBMECs. DS (10–300 μg/mL produced a concentration-dependent relaxation in mouse aorta, which was significantly attenuated by the nitric oxide synthase (NOS inhibitor L-NAME, suggesting that DS causes vasodilation via a NO-dependent mechanism. DS increased resting cerebral blood flow (CBF, although it caused mild hypotension. To investigate the effect of DS on the acute cerebral injury, C57/BL6J mice received 90 min of middle cerebral artery occlusion followed by 22.5 h of reperfusion. DS administered 3 days before arterial occlusion significantly reduced cerebral infarct size by 53.7% compared with vehicle treatment. However, DS did not reduce brain infarction in mice treated with the relatively specific endothelial NOS (eNOS inhibitor, N5-(1-iminoethyl-L-ornithine, suggesting that the neuroprotective effect of DS is primarily endothelium-dependent. This correlated with increased phosphorylation of eNOS in the brains of DS-treated mice. DS acutely improves CBF in eNOS-dependent vasodilation and reduces infarct size in focal cerebral ischemia. These data provide causal evidence that DS is cerebroprotective via the eNOS-dependent production of NO, which ameliorates blood circulation.

Increased Brain-Specific MiR-9 and MiR-124 in the Serum Exosomes of Acute Ischemic Stroke Patients.

Directory of Open Access Journals (Sweden)

Qiuhong Ji

Full Text Available The aims of this study were to examine the alternation in serum exosome concentrations and the levels of serum exosomal miR-9 and miR-124, two brain-specific miRNAs, in acute ischemic stroke (AIS patients and to explore the predictive values of these miRNAs for AIS diagnosis and damage evaluation. Sixty-five patients with AIS at the acute stage were enrolled and 66 non-stroke volunteers served as controls. Serum exosomes isolated by ExoQuick precipitations were characterized by transmission electron microscopy, nanoparticle-tracking analysis and western blotting. The levels of exosomal miR-9 and miR-124 were determined by real-time quantitative PCR. Compared with controls, the concentration of serum exosomes and the median levels of serum exosomal miR-9 and miR-124 were significantly higher in AIS patients (p<0.01. The levels of both miR-9 and miR-124 were positively correlated with National Institutes of Health Stroke Scale (NIHSS scores, infarct volumes and serum concentrations of IL-6. The areas under the curve for exosomal miR-9 and miR-124 were 0.8026 and 0.6976, respectively. This proof of concept study suggests that serum exosomal miR-9 and miR-124 are promising biomarkers for diagnosing AIS and evaluating the degree of damage caused by ischemic injury. However, further studies are needed to explore the potential roles of the exosomes released from brain tissues in post stroke complications.

[Primary emergencies: management of acute ischemic stroke].

Science.gov (United States)

Leys, Didier; Goldstein, Patrick

2012-01-01

The emergency diagnostic strategy for acute ischemic stroke consists of:--identification of stroke, based on clinical examination (sudden onset of a focal neurological deficit);--identification of the ischemic or hemorrhagic nature by MRI or CT;--determination of the early time-course (clinical examination) and the cause. In all strokes (ischemic or hemorrhagic), treatment consists of:--the same general management (treatment of a life-threatening emergency, ensuring normal biological parameters except for blood pressure, and prevention of complications);--decompressive surgery in the rare cases of intracranial hypertension. For proven ischemic stroke, other therapies consist of: rt-PA for patients admitted with 4.5 hours of stroke onset who have no contraindications, and aspirin (160 to 300 mg) for patients who are not eligible for rt-PA. These treatments should be administered within a few hours. A centralized emergency call system (phone number 15 in France) is the most effective way of achieving this objective.

Neuronal SIRT1 (Silent Information Regulator 2 Homologue 1) Regulates Glycolysis and Mediates Resveratrol-Induced Ischemic Tolerance.

Science.gov (United States)

Koronowski, Kevin B; Khoury, Nathalie; Saul, Isabel; Loris, Zachary B; Cohan, Charles H; Stradecki-Cohan, Holly M; Dave, Kunjan R; Young, Juan I; Perez-Pinzon, Miguel A

2017-11-01

Resveratrol, at least in part via SIRT1 (silent information regulator 2 homologue 1) activation, protects against cerebral ischemia when administered 2 days before injury. However, it remains unclear if SIRT1 activation must occur, and in which brain cell types, for the induction of neuroprotection. We hypothesized that neuronal SIRT1 is essential for resveratrol-induced ischemic tolerance and sought to characterize the metabolic pathways regulated by neuronal Sirt1 at the cellular level in the brain. We assessed infarct size and functional outcome after transient 60 minute middle cerebral artery occlusion in control and inducible, neuronal-specific SIRT1 knockout mice. Nontargeted primary metabolomics analysis identified putative SIRT1-regulated pathways in brain. Glycolytic function was evaluated in acute brain slices from adult mice and primary neuronal-enriched cultures under ischemic penumbra-like conditions. Resveratrol-induced neuroprotection from stroke was lost in neuronal Sirt1 knockout mice. Metabolomics analysis revealed alterations in glucose metabolism on deletion of neuronal Sirt1 , accompanied by transcriptional changes in glucose metabolism machinery. Furthermore, glycolytic ATP production was impaired in acute brain slices from neuronal Sirt1 knockout mice. Conversely, resveratrol increased glycolytic rate in a SIRT1-dependent manner and under ischemic penumbra-like conditions in vitro. Our data demonstrate that resveratrol requires neuronal SIRT1 to elicit ischemic tolerance and identify a novel role for SIRT1 in the regulation of glycolytic function in brain. Identification of robust neuroprotective mechanisms that underlie ischemia tolerance and the metabolic adaptations mediated by SIRT1 in brain are crucial for the translation of therapies in cerebral ischemia and other neurological disorders. © 2017 American Heart Association, Inc.

[Ischemic origin of diabetic foot disease. Epidemiology, difficulties of diagnosis, options for prevention and revascularization].

Science.gov (United States)

Kolossváry, Endre; Bánsághi, Zoltán; Szabó, Gábor Viktor; Járai, Zoltán; Farkas, Katalin

2017-02-01

"Diabetic foot" as definition covers a multifactorial clinical condition. According to the recent epidemiological data, the role of lower limb ischemia is getting more influential over other pathological causes, like neuropathy, infections and bone or soft tissue deformity. In diabetes, vascular disease leads to increased risk for leg ulcers and minor or major amputations. The traditional diagnostic tools for recognition of peripheral arterial disease have limited value because of diabetes specific clinical manifestations. Available vascular centers with special expertise and diagnostic tools are the prerequisite for efficient diagnosis supporting timely recognition of peripheral arterial disease. In course of treatment of diabetic foot with ischemic origin, beyond effective medical treatment revascularization (open vascular surgery or endovascular procedures) has paramount importance for prevention of limb loss. Vascular teams of vascular specialists, vascular surgeons and interventional radiologist in dedicated centers in multidisciplinary cooperation with other professions represent public health issue in effective prevention. Orv. Hetil., 2017, 158(6), 203-211.

Functional reconstruction of ischemic contracture in the

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TANG Hao

2011-04-01

Full Text Available 【Abstract】Objective: To discuss the method of functional reconstruction of ischemic contracture in the lower limb and propose a classification protocol for ischemic contracture in the lower limb based on its severity and prognosis. Methods: A total of 42 patients with ischemic contracture in the lower limb were included in this study. According to different types of disturbance and degrees of severity, surgical reconstructions consisting of nerve decompression, tendon lengthening or transfer, intrinsic foot muscle release and sural-tibial nerve anastomosis were performed in every patient. Results: Postoperatively, all patients were able to walk on flat ground. Drop foot was corrected in 10 patients, and 5 patients still felt some difficulty during stair activity. Split Achilles tendon transfer to flexor hallucis longus tendon was performed in 12 patients, and their walking stability was improved. Seven patients accepted ipsilateral suraltibial nerve anastomosis, and sensitivity recovery reached to S2 in 2 patients and S3 in 5 patients. Conclusions: Ischemic contracture in the lower limb is a devastating complication after lower limb trauma. The prevention of contracture is much more important than the treatment of an established contracture. Split Achilles tendon transfer to flexor hallucis longus tendon and sural-tibial nerve anastomosis, which was initially implemented by us, could improve the functional recovery of ischemic contracture in lower limbs, and thus provides a new alternative for functional reconstruction of ischemic contracture in the lower limb. Key words: Ischemic contracture; Classification; Recovery of function

Hemostatic system changes predictive value in patients with ischemic brain disorders

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Raičević Ranko

2002-01-01

Full Text Available The aim of this research was to determine the importance of tracking the dynamics of changes of the hemostatic system factors (aggregation of thrombocytes, D-dimer, PAI-1, antithrombin III, protein C and protein S, factor VII and factor VIII, fibrin degradation products, euglobulin test and the activated partial thromboplastin time – aPTPV in relation to the level of the severity of ischemic brain disorders (IBD and the level of neurological and functional deficiency in the beginning of IBD manifestation from 7 to 10 days, 19 to 21 day, and after 3 to 6 months. The research results confirmed significant predictive value of changes of hemostatic system with the predomination of procoagulant factors, together with the insufficiency of fibrinolysis. Concerning the IBD severity and it's outcome, the significant predictive value was shown in the higher levels of PAI-1 and the lower level of antithrombin III, and borderline significant value was shown in the accelerated aggregation of thrombocytes and the increased concentration of D-dimer. It could be concluded that the tracking of the dynamics of changes in parameters of hemostatic system proved to be an easily accessible method with the significant predictive value regarding the development of more severe. IBD cases and the outcome of the disease itself.

Transient Ischemic Attack Caused by Iron Deficiency Anemia

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Ufuk Emre

2006-02-01

Full Text Available Transient Ischemic Attack Caused by Iron Deficiency Anemia Transient ischemic attacks are episodes of transient focal ischemia involving the brain or brainstem. They are commonly two to thirty minutes in duration and lasting less than 24 hours. Anemia of iron deficiency isn’t frequently cause for transient ischemic attack. It has been reported as a risk factor for childhood ischemic strokes. In the iron deficiency anemia, T‹A may develop as result of hypercoagulable state and increased viscosity that is caused by anemic hypoxia that is result of reduce hemoglobine level, seconder thrombosis and microcytose As iron deficiency anemia has been reported so rarely in adult patients with transient ischemic attacks as a cause, we aimed to discuss the clinical and outcome features of two cases with iron deficiency anemia and transient ischemic attacks in this study. Materials and methods: Routine neurologic examination, biochemical screen, serological tests, vasculitic markers, thyroid function tests, vitamin B 12 level, cranial imaging, vertebral carotid doppler USG examination was conducted in the two patients. Anemia of iron deficiency was found as the only risk factor for TIA and the two patients were treated with replacement of iron and antiagregan therapy. Neurological examination revealed no abnormality through the two years of follow-up. The iron deficiency anemia may be cause of many neurologic problems such a irritability, lethargy, headache, development retardation except from T‹A. In the iron deficiency anemia, early diagnosis and treatment is important

Lycium barbarum Extracts Protect the Brain from Blood-Brain Barrier Disruption and Cerebral Edema in Experimental Stroke

Science.gov (United States)

Yang, Di; Li, Suk-Yee; Yeung, Chung-Man; Chang, Raymond Chuen-Chung; So, Kwok-Fai; Wong, David; Lo, Amy C. Y.

2012-01-01

Background and Purpose Ischemic stroke is a destructive cerebrovascular disease and a leading cause of death. Yet, no ideal neuroprotective agents are available, leaving prevention an attractive alternative. The extracts from the fruits of Lycium barbarum (LBP), a Chinese anti-aging medicine and food supplement, showed neuroprotective function in the retina when given prophylactically. We aim to evaluate the protective effects of LBP pre-treatment in an experimental stroke model. Methods C57BL/6N male mice were first fed with either vehicle (PBS) or LBP (1 or 10 mg/kg) daily for 7 days. Mice were then subjected to 2-hour transient middle cerebral artery occlusion (MCAO) by the intraluminal method followed by 22-hour reperfusion upon filament removal. Mice were evaluated for neurological deficits just before sacrifice. Brains were harvested for infarct size estimation, water content measurement, immunohistochemical analysis, and Western blot experiments. Evans blue (EB) extravasation was determined to assess blood-brain barrier (BBB) disruption after MCAO. Results LBP pre-treatment significantly improved neurological deficits as well as decreased infarct size, hemispheric swelling, and water content. Fewer apoptotic cells were identified in LBP-treated brains by TUNEL assay. Reduced EB extravasation, fewer IgG-leaky vessels, and up-regulation of occludin expression were also observed in LBP-treated brains. Moreover, immunoreactivity for aquaporin-4 and glial fibrillary acidic protein were significantly decreased in LBP-treated brains. Conclusions Seven-day oral LBP pre-treatment effectively improved neurological deficits, decreased infarct size and cerebral edema as well as protected the brain from BBB disruption, aquaporin-4 up-regulation, and glial activation. The present study suggests that LBP may be used as a prophylactic neuroprotectant in patients at high risk for ischemic stroke. PMID:22438957

Health behavior of patients with ischemic heart disease

OpenAIRE

Paweł Węgorowski; Joanna Michalik; Rafał Zarzeczny; Renata Domżał-Drzewiecka; Grzegorz Nowicki

2017-01-01

Admission By analyzing the available scientific literature, it is possible to define ischemic heart disease as a set of disease symptoms that are a consequence of a chronic state of imbalance between the ability to supply nutrients and oxygen and the real need of myocardial cells for these substances. Adapting life-style behaviors to healthy living is a priority to prevent the onset and development of cardiovascular disease, especially ischemic heart disease, Purpose of research T...

The Effect of Hydroxylated Fullerene Nanoparticles on Antioxidant Defense System in Brain Ischemia Rat

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2017-05-01

Full Text Available Background and Objectives: According to the previous findings, brain ischemia attenuates the brain antioxidant defense system. This study aimed to investigate the effect of hydroxylated fullerene nanoparticle on antioxidant defense system in ischemic brain rat. Methods: In this Experimental study, rats were divided into three groups (n=6 in each group: sham, ischemic control, and ischemic treatment group. Brain ischemia was induced by middle cerebral artery (MCA occlusion for 90 minutes followed by a 24-hour reperfusion. Ischemic treatment animals received fullerene nanoparticles intraperitoneally at a dose of 10mg/kg immediately after the end of MCA occlusion. After 24-h reperfusion period, brain catalase and superoxide dismutase (SOD, and glutathione activities were assessed by biochemical methods. The data were analyzed using one-way ANOVA and Tukey post-hoc test. Results: The mean glutathione level and catalase and SOD activities in sham animals were 1±0.18%, 1±0.20%, and 1±0.04%, respectively. Induction of brain ischemia decreased the value of glutathione level and catalase and SOD activities in control ischemic rats and their values were obtained to be 0.55±0.09%, 0.44±0.05%, and 0.86±0.02%, respectively. Fullerene significantly increased the activities of catalase (0.93±0.29% and SOD (1.33±0.22% in ischemic treatment group compared to ischemic control rats, but did not change the glutathione level (0.52±0.25%. Conclusion: The results of this study showed that treatment with fullerene nanoparticles improves the brain antioxidant defense system, which is weakened during brain ischemia, through increasing catalase and SOD activities.

Long-Term Prognosis of Ischemic Stroke in Young Adults

OpenAIRE

Varona, Jose F.

2010-01-01

There is limited information about long-term prognosis of ischemic stroke in young adults. Giving the potentially negative impact in physical, social, and emotional aspects of an ischemic stroke in young people, providing early accurate long-term prognostic information is very important in this clinical setting. Moreover, detection of factors associated with bad outcomes (death, recurrence, moderate-to-severe disability) help physicians in optimizing secondary prevention strategies. The prese...

Pioglitazone after Ischemic Stroke or Transient Ischemic Attack.

Science.gov (United States)

Kernan, Walter N; Viscoli, Catherine M; Furie, Karen L; Young, Lawrence H; Inzucchi, Silvio E; Gorman, Mark; Guarino, Peter D; Lovejoy, Anne M; Peduzzi, Peter N; Conwit, Robin; Brass, Lawrence M; Schwartz, Gregory G; Adams, Harold P; Berger, Leo; Carolei, Antonio; Clark, Wayne; Coull, Bruce; Ford, Gary A; Kleindorfer, Dawn; O'Leary, John R; Parsons, Mark W; Ringleb, Peter; Sen, Souvik; Spence, J David; Tanne, David; Wang, David; Winder, Toni R

2016-04-07

Patients with ischemic stroke or transient ischemic attack (TIA) are at increased risk for future cardiovascular events despite current preventive therapies. The identification of insulin resistance as a risk factor for stroke and myocardial infarction raised the possibility that pioglitazone, which improves insulin sensitivity, might benefit patients with cerebrovascular disease. In this multicenter, double-blind trial, we randomly assigned 3876 patients who had had a recent ischemic stroke or TIA to receive either pioglitazone (target dose, 45 mg daily) or placebo. Eligible patients did not have diabetes but were found to have insulin resistance on the basis of a score of more than 3.0 on the homeostasis model assessment of insulin resistance (HOMA-IR) index. The primary outcome was fatal or nonfatal stroke or myocardial infarction. By 4.8 years, a primary outcome had occurred in 175 of 1939 patients (9.0%) in the pioglitazone group and in 228 of 1937 (11.8%) in the placebo group (hazard ratio in the pioglitazone group, 0.76; 95% confidence interval [CI], 0.62 to 0.93; P=0.007). Diabetes developed in 73 patients (3.8%) and 149 patients (7.7%), respectively (hazard ratio, 0.48; 95% CI, 0.33 to 0.69; Pischemic stroke or TIA, the risk of stroke or myocardial infarction was lower among patients who received pioglitazone than among those who received placebo. Pioglitazone was also associated with a lower risk of diabetes but with higher risks of weight gain, edema, and fracture. (Funded by the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT00091949.).

Human Umbilical Cord Blood Stem Cells: Rational for Use as a Neuroprotectant in Ischemic Brain Disease

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Hadar Arien-Zakay

2010-09-01

Full Text Available The use of stem cells for reparative medicine was first proposed more than three decades ago. Hematopoietic stem cells from bone marrow, peripheral blood and human umbilical cord blood (CB have gained major use for treatment of hematological indications. CB, however, is also a source of cells capable of differentiating into various non-hematopoietic cell types, including neural cells. Several animal model reports have shown that CB cells may be used for treatment of neurological injuries. This review summarizes the information available on the origin of CB-derived neuronal cells and the mechanisms proposed to explain their action. The potential use of stem/progenitor cells for treatment of ischemic brain injuries is discussed. Issues that remain to be resolved at the present stage of preclinical trials are addressed.

Pathogenesis of transient ischemic attacks within the vertebrobasilar arterial system

International Nuclear Information System (INIS)

Naritomi, H.; Sakai, F.; Meyer, J.S.

1979-01-01

Regional cerebral blood flow (rCBF) was measured by xenon 133 inhalation in 36 patients with vertebrobasilar arterial insufficiency (VBI), three patients with brain stem infarction, and 15 age-matched normal controls before and after inducing postural hypotension. Probes mounted over the suboccipital area by means of a helmet were used to measure rCBF over the brain stem and cerebellar regions. When lying flat, rCBF values measured over both cerebral hemispheres and the brain stem-cerebellar regions in patients with VBI were not significantly different from normal controls. Unlike carotid transient ischemic attacks, regional flow reduction rarely persisted for three weeks after transient ischemic symptoms in patients with VBI. When postural hypotension was induced, rCBF became significantly reduced in patients with VBI whether or not they were treated with papaverine. Dysautoregulation was restricted to vertebral, basilar, and posterior cerebral arterial distribution in patients with VBI of 1 to 12 months' duration, but was more widespread and involved both cerebral hemispheres in long-standing VBI. Hemodynamic factors and dysautoregulation appear to play a part in the pathogenesis of symptoms of VBI

Basic fibroblast growth factor enhances cell proliferation in the dentate gyrus of neonatal rats following hypoxic-ischemic brain damage.

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Zhu, Huan; Qiao, Lixing; Sun, Yao; Yin, Liping; Huang, Li; Jiang, Li; Li, Jiaqing

2018-04-23

Perinatal hypoxic-ischemic insult is considered a major contributor to child mortality and morbidity and leads to neurological deficits in newborn infants. There has been a lack of promising neurotherapeutic interventions for hypoxic-ischemic brain damage (HIBD) for clinical application in infants. The present study aimed to investigate the correlation between neurogenesis and basic fibroblast growth factor (bFGF) in the hippocampal dentate gyrus (DG) region in neonatal rats following HIBD. Cell proliferation was examined by detecting BrdU signals, and the role of bFGF in cell proliferation in the DG region following neonatal HIBD was investigated. Cell proliferation was induced by HIBD in the hippocampal DG of neonatal rats. Furthermore, bFGF gene expression was upregulated in the hippocampus in neonatal rats, particularly between 7 and 14 days after HIBD. Moreover, intraperitoneal injection of exogenous bFGF enhanced cell proliferation in the hippocampal DG following neonatal HIBD. Taken together, these data indicate that cell proliferation in the DG could be induced by neonatal HIBD, and bFGF promotes proliferation following neonatal HIBD. Copyright © 2018 Elsevier B.V. All rights reserved.

Brain magnetic resonance imaging of infants exposed prenatally to buprenorphine

International Nuclear Information System (INIS)

Kahila, H.; Kivitie-Kallio, S.; Halmesmaki, E.; Valanne, L.; Autti, T.

2007-01-01

Purpose: To evaluate the brains of newborns exposed to buprenorphine prenatally. Material and Methods: Seven neonates followed up antenatally in connection with their mothers' buprenorphine replacement therapy underwent 1.5T magnetic resonance imaging (MRI) of the brain before the age of 2 months. The infants were born to heavy drug abusers. Four mothers were hepatitis C positive, and all were HIV negative. All mothers smoked tobacco and used benzodiazepines. All pregnancies were full term, and no perinatal asphyxia occurred. All but one neonate had abstinence syndrome and needed morphine replacement therapy. Results: Neither structural abnormalities nor abnormalities in signal intensity were recorded. Conclusion: Buprenorphine replacement therapy does not seem to cause any major structural abnormalities of the brain, and it may prevent known hypoxic-ischemic brain changes resulting from uncontrolled drug abuse. Longitudinal studies are needed to assess possible abnormalities in the brain maturation process

Brain magnetic resonance imaging of infants exposed prenatally to buprenorphine

Energy Technology Data Exchange (ETDEWEB)

Kahila, H.; Kivitie-Kallio, S.; Halmesmaki, E.; Valanne, L.; Autti, T. [Dept. of Obstetrics and Gynecology, Dept. of Pediatrics, and Helsinki Medical Imaging Center, Helsinki Univ. Central Hospital (Finland)

2007-02-15

Purpose: To evaluate the brains of newborns exposed to buprenorphine prenatally. Material and Methods: Seven neonates followed up antenatally in connection with their mothers' buprenorphine replacement therapy underwent 1.5T magnetic resonance imaging (MRI) of the brain before the age of 2 months. The infants were born to heavy drug abusers. Four mothers were hepatitis C positive, and all were HIV negative. All mothers smoked tobacco and used benzodiazepines. All pregnancies were full term, and no perinatal asphyxia occurred. All but one neonate had abstinence syndrome and needed morphine replacement therapy. Results: Neither structural abnormalities nor abnormalities in signal intensity were recorded. Conclusion: Buprenorphine replacement therapy does not seem to cause any major structural abnormalities of the brain, and it may prevent known hypoxic-ischemic brain changes resulting from uncontrolled drug abuse. Longitudinal studies are needed to assess possible abnormalities in the brain maturation process.

Neuroprotection by selective neuronal deletion of Atg7 in neonatal brain injury

Science.gov (United States)

Xie, Cuicui; Ginet, Vanessa; Sun, Yanyan; Koike, Masato; Zhou, Kai; Li, Tao; Li, Hongfu; Li, Qian; Wang, Xiaoyang; Uchiyama, Yasuo; Truttmann, Anita C.; Kroemer, Guido; Puyal, Julien; Blomgren, Klas; Zhu, Changlian

2016-01-01

ABSTRACT Perinatal asphyxia induces neuronal cell death and brain injury, and is often associated with irreversible neurological deficits in children. There is an urgent need to elucidate the neuronal death mechanisms occurring after neonatal hypoxia-ischemia (HI). We here investigated the selective neuronal deletion of the Atg7 (autophagy related 7) gene on neuronal cell death and brain injury in a mouse model of severe neonatal hypoxia-ischemia. Neuronal deletion of Atg7 prevented HI-induced autophagy, resulted in 42% decrease of tissue loss compared to wild-type mice after the insult, and reduced cell death in multiple brain regions, including apoptosis, as shown by decreased caspase-dependent and -independent cell death. Moreover, we investigated the lentiform nucleus of human newborns who died after severe perinatal asphyxia and found increased neuronal autophagy after severe hypoxic-ischemic encephalopathy compared to control uninjured brains, as indicated by the numbers of MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3)-, LAMP1 (lysosomal-associated membrane protein 1)-, and CTSD (cathepsin D)-positive cells. These findings reveal that selective neuronal deletion of Atg7 is strongly protective against neuronal death and overall brain injury occurring after HI and suggest that inhibition of HI-enhanced autophagy should be considered as a potential therapeutic target for the treatment of human newborns developing severe hypoxic-ischemic encephalopathy. PMID:26727396

The in vitro blood-brain barrier model under OGD condition

DEFF Research Database (Denmark)

Tornabene, Erica; Helms, Hans Christian Cederberg; Berndt, Philipp

Introduction - The blood-brain barrier (BBB) is a physical, transport and metabolic barrier which plays a key role in preventing uncontrolled exchanges between blood and brain, ensuring an optimal environment for neurons activity. This extent interface is created by the endothelial cells forming...... the wall of brain capillaries. The restrictive nature of the BBB is due to the presence of tight junctions, which seal the paracellular space, a low number of endocytotic vesicles and the presence of efflux transporters, resulting in a very tight layer. Ischemic insult and the subsequent reperfusion...... of therapies to treat this devastating disease. Materials and Methods - Primary cultures of endothelial cells from bovine brain microvessels were cocultured with rat astrocytes in transwell inserts. At day 11, cells were treated with 4h of OGD by changing the culture medium with glucose-free medium...

Rapid and long-term induction of effector immediate early genes (BDNF, Neuritin and Arc) in peri-infarct cortex and dentate gyrus after ischemic injury in rat brain

DEFF Research Database (Denmark)

Rickhag, Karl Mattias; Teilum, Maria; Wieloch, Tadeusz

2007-01-01

including cerebral cortex and hippocampus. Brain-derived neurotrophic factor (BDNF), Neuritin and Activity-regulated cytoskeleton-associated protein (Arc) belong to a subgroup of immediate early genes implicated in synaptic plasticity known as effector immediate early genes. Here, we investigated...... at 0-6 h of reperfusion for Neuritin and 0-12 h of reperfusion for Arc while BDNF was induced 0-9 h of reperfusion. Our study demonstrates a rapid and long-term activation of effector immediate early genes in distinct brain areas following ischemic injury in rat. Effector gene activation may be part...

Ischemic tolerance modulates TRAIL expression and its receptors and generates a neuroprotected phenotype

OpenAIRE

Cantarella, G; Pignataro, G; Di Benedetto, G; Anzilotti, S; Vinciguerra, A; Cuomo, O; Di Renzo, G F; Parenti, C; Annunziato, L; Bernardini, R

2014-01-01

TNF-related apoptosis inducing ligand (TRAIL), a member of the TNF superfamily released by microglia, appears to be involved in the induction of apoptosis following focal brain ischemia. Indeed, brain ischemia is associated with progressive enlargement of damaged areas and prominent inflammation. As ischemic preconditioning reduces inflammatory response to brain ischemia and ameliorates brain damage, the purpose of the present study was to evaluate the role of TRAIL and its receptors in strok...

Computed Tomography-Based Imaging of Voxel-Wise Lesion Water Uptake in Ischemic Brain: Relationship Between Density and Direct Volumetry.

Science.gov (United States)

Broocks, Gabriel; Flottmann, Fabian; Ernst, Marielle; Faizy, Tobias Djamsched; Minnerup, Jens; Siemonsen, Susanne; Fiehler, Jens; Kemmling, Andre

2018-04-01

Net water uptake per volume of brain tissue may be calculated by computed tomography (CT) density, and this imaging biomarker has recently been investigated as a predictor of lesion age in acute stroke. However, the hypothesis that measurements of CT density may be used to quantify net water uptake per volume of infarct lesion has not been validated by direct volumetric measurements so far. The purpose of this study was to (1) develop a theoretical relationship between CT density reduction and net water uptake per volume of ischemic lesions and (2) confirm this relationship by quantitative in vitro and in vivo CT image analysis using direct volumetric measurements. We developed a theoretical rationale for a linear relationship between net water uptake per volume of ischemic lesions and CT attenuation. The derived relationship between water uptake and CT density was tested in vitro in a set of increasingly diluted iodine solutions with successive CT measurements. Furthermore, the consistency of this relationship was evaluated using human in vivo CT images in a retrospective multicentric cohort. In 50 edematous infarct lesions, net water uptake was determined by direct measurement of the volumetric difference between the ischemic and normal hemisphere and was correlated with net water uptake calculated by ischemic density measurements. With regard to in vitro data, water uptake by density measurement was equivalent to direct volumetric measurement (r = 0.99, P volumetry was 44.7 ± 26.8 mL and the mean percent water uptake per lesion volume was 22.7% ± 7.4%. This was equivalent to percent water uptake obtained from density measurements: 21.4% ± 6.4%. The mean difference between percent water uptake by direct volumetry and percent water uptake by CT density was -1.79% ± 3.40%, which was not significantly different from 0 (P < 0.0001). Volume of water uptake in infarct lesions can be calculated quantitatively by relative CT density measurements. Voxel-wise imaging

[Importance of hypertensive left ventricular hypertrophy in patients with ischemic events of the heart or brain].

Science.gov (United States)

Castilla-Guerra, L; Fernández-Moreno, M C; Aguilera-Saborido, A; Solanella-Soler, J

2016-01-01

Hypertensive left ventricular hypertrophy (H-LVH) is a potentially modifiable vascular risk factor (VRF) often overlooked in clinical practice. We aimed to evaluate the frequency of H-LVH in patients with coronary heart disease (CHD) or ischemic stroke (IS). We retrospectively assessed all the echocardiography studies of patients admitted with the diagnosis CHD or IS over a 4-year period. We studied 533 patients, 330 with CHD and 203 with IS. Mean age was 69 (±11) years, 61.5% males. Hypertension was the most common RF: 362 patients (67.9%) (CHD vs. IS: 70 vs. 64.5%; P=NS). H-LVH was seen in 234 patients (43.9%) (CHD vs. IS: 44.8 vs. 42.3%; P=NS). Patients with H-LVH were older and received a greater number of antihypertensive drugs at discharge. Half of patients with hypertension presented H-LVH (184 patients; 50.8%), with similar frequency in both groups (CHD vs. IS: 50.6 vs. 51.1%; P=NS). Neither patients' characteristics nor VRF with the exception of hypertension (P=.0001) were associated with H-LVH. H-LVH is a major VRF in patients with ischemic events in the heart and brain. Nearly half the patients present H-LVH, with a similar frequency in both groups. It is important to identify H-LVH in these patients to optimize treatment and improve long-term prognosis. Copyright © 2015 SEHLELHA. Published by Elsevier España, S.L.U. All rights reserved.

Distribution territories and causative mechanisms of ischemic stroke

Energy Technology Data Exchange (ETDEWEB)

Rovira, A.; Grive, E.; Alvarez-Sabin, J. [Unidad de Resonancia Magnetica, Hospital Vall d' Hebron, Barcelona (Spain)

2005-03-01

Ischemic stroke prognosis, risk of recurrence, clinical assessment, and treatment decisions are influenced by stroke subtype (anatomic distribution and causative mechanism of infarction). Stroke subtype diagnosis is better achieved in the early phase of acute ischemia with the use of multimodal MR imaging. The pattern of brain lesions as shown by brain MR imaging can be classified according to a modified Oxfordshire method, based on the anatomic distribution of the infarcts into six groups: (1) total anterior circulation infarcts, (2) partial anterior circulation infarcts, (3) posterior circulation infarcts, (4) watershed infarcts, (5) centrum ovale infarcts, and (6) lacunar infarcts. The subtype of stroke according to its causative mechanism is based on the TOAST method, which classifies stroke into five major etiologic groups: (1) large-vessel atherosclerotic disease, (2) small-vessel atherosclerotic disease, (3) cardioembolic source, (4) other determined etiologies, and (5) undetermined or multiple possible etiologies. The different MR imaging patterns of acute ischemic brain lesions visualized using diffusion-weighted imaging and the pattern of vessel involvement demonstrated with MR angiography are essential factors that can suggest the most likely causative mechanism of infarction. This information may have an impact on decisions regarding therapy and the performance of additional diagnostic tests. (orig.)

Pathophysiology and Biomarkers in Acute Ischemic Stroke – A Review

African Journals Online (AJOL)

The pathophysiology of ischemic stroke is complex, and majorly involves excitotoxicity, oxidative stress, inflammation, blood-brain barrier dysfunction, apoptosis, etc. Several of the biomarkers are related to these pathophysiologic mechanisms and they may have applications in stroke prediction, diagnosis, assessment, ...

Hypothermia for the treatment of ischemic and hemorrhagic stroke.

Science.gov (United States)

Linares, Guillermo; Mayer, Stephan A

2009-07-01

Hypothermia is considered nature's "gold standard" for neuroprotection, and its efficacy for improving outcome in patients with hypoxic-ischemic brain injury as a result of cardiac arrest is well-established. Hypothermia reduces brain edema and intracranial pressure in patients with traumatic brain injury. By contrast, only a few small pilot studies have evaluated hypothermia as a treatment for acute ischemic stroke, and no controlled trials of hypothermia for hemorrhagic stroke have been performed. Logistic challenges present an important barrier to the widespread application of hypothermia for stroke, most importantly the need for high-quality critical care to start immediately in the emergency department. Rapid induction of hypothermia within 3 to 6 hrs of onset has been hampered by slow cooling rates, but is feasible. Delayed cooling for the treatment of cytotoxic brain edema does not provide definitive or lasting treatment for intracranial mass effect, and should not be used as an alternative to hemicraniectomy. Sustained fever control is feasible in patients with intracerebral and subarachnoid hemorrhage, but has yet to be tested in a phase III study. Important observations from studies investigating the use of hypothermia for stroke to date include the necessity for proactive antishivering therapy for successful cooling, the importance of slow controlled rewarming to avoid rebound brain edema, and the high risk for infectious and cardiovascular complications in this patient population. More research is clearly needed to bring us closer to the successful application of hypothermia in the treatment for stroke.

Cranial anatomy and detection of ischemic stroke in the cat by nuclear magnetic resonance imaging

International Nuclear Information System (INIS)

Buonanno, F.S.; Pykett, I.L.; Kistler, J.P.; Vielma, J.; Brady, T.J.; Hinshaw, W.S.; Goldman, M.R.; Newhouse, J.H.; Pohost, G.M.

1982-01-01

Proton nuclear magnetic resonance (NMR) images of cat heads were obtained using a small, experimental imaging system. As a prelude to the study of experimental ischemic brain infarction, the normal cat head was imaged for identification of anatomical features. Images of one cat which had undergone ligation of the middle cerebral artery three weeks previously showed brain changes associated with chronic ischemic stroke and compared favorably with findings on computed tomography (CT). The NMR images have millimetric spatial resolution. NMR parameters inherent in the tissues provide intensity variations and are sufficiently sensitive to yield contrast resolution surpassing that of CT

[Ischemic stroke in the young adult].

Science.gov (United States)

Calvet, D

2016-01-01

Ischemic stroke is not rare in young adults since one in ten stroke patients are less than 50 years old. This incidence increased over the past last years, mainly due to the rise in the prevalence of traditional vascular risk factors in this sub-group of age but also of illegal drug use. Even though both survival and functional outcome of young stroke patients are better than those observed in older patients, socio-economic and quality of life consequences make this disease a main objective in terms of primary and secondary prevention. Identifying the cause of ischemic stroke in young adults is of major importance to prevent stroke recurrence. However, given the wide variety of potential underlying causes, the etiologic work-up of stroke in young adults requires a different approach from that in the elderly. In this context, a sequential diagnostic work-up is needed in order to optimize the yield of diagnostic tests, to reduce their cost and risks for the patient. Arterial dissection is the most frequent cause of stroke in young adults but other less frequent causes are numerous. Despite a comprehensive work-up, about one third of cases remains unexplained leading to the diagnosis of cryptogenic ischemic stroke. Copyright © 2015 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Automatic detection of ischemic stroke based on scaling exponent electroencephalogram using extreme learning machine

Science.gov (United States)

Adhi, H. A.; Wijaya, S. K.; Prawito; Badri, C.; Rezal, M.

2017-03-01

Stroke is one of cerebrovascular diseases caused by the obstruction of blood flow to the brain. Stroke becomes the leading cause of death in Indonesia and the second in the world. Stroke also causes of the disability. Ischemic stroke accounts for most of all stroke cases. Obstruction of blood flow can cause tissue damage which results the electrical changes in the brain that can be observed through the electroencephalogram (EEG). In this study, we presented the results of automatic detection of ischemic stroke and normal subjects based on the scaling exponent EEG obtained through detrended fluctuation analysis (DFA) using extreme learning machine (ELM) as the classifier. The signal processing was performed with 18 channels of EEG in the range of 0-30 Hz. Scaling exponents of the subjects were used as the input for ELM to classify the ischemic stroke. The performance of detection was observed by the value of accuracy, sensitivity and specificity. The result showed, performance of the proposed method to classify the ischemic stroke was 84 % for accuracy, 82 % for sensitivity and 87 % for specificity with 120 hidden neurons and sine as the activation function of ELM.

Zinc-dependent multi-conductance channel activity in mitochondria isolated from ischemic brain.

Science.gov (United States)

Bonanni, Laura; Chachar, Mushtaque; Jover-Mengual, Teresa; Li, Hongmei; Jones, Adrienne; Yokota, Hidenori; Ofengeim, Dimitry; Flannery, Richard J; Miyawaki, Takahiro; Cho, Chang-Hoon; Polster, Brian M; Pypaert, Marc; Hardwick, J Marie; Sensi, Stefano L; Zukin, R Suzanne; Jonas, Elizabeth A

2006-06-21

Transient global ischemia is a neuronal insult that induces delayed cell death. A hallmark event in the early post-ischemic period is enhanced permeability of mitochondrial membranes. The precise mechanisms by which mitochondrial function is disrupted are, as yet, unclear. Here we show that global ischemia promotes alterations in mitochondrial membrane contact points, a rise in intramitochondrial Zn2+, and activation of large, multi-conductance channels in mitochondrial outer membranes by 1 h after insult. Mitochondrial channel activity was associated with enhanced protease activity and proteolytic cleavage of BCL-xL to generate its pro-death counterpart, deltaN-BCL-xL. The findings implicate deltaN-BCL-xL in large, multi-conductance channel activity. Consistent with this, large channel activity was mimicked by introduction of recombinant deltaN-BCL-xL to control mitochondria and blocked by introduction of a functional BCL-xL antibody to post-ischemic mitochondria via the patch pipette. Channel activity was also inhibited by nicotinamide adenine dinucleotide, indicative of a role for the voltage-dependent anion channel (VDAC) of the outer mitochondrial membrane. In vivo administration of the membrane-impermeant Zn2+ chelator CaEDTA before ischemia or in vitro application of the membrane-permeant Zn2+ chelator tetrakis-(2-pyridylmethyl) ethylenediamine attenuated channel activity, suggesting a requirement for Zn2+. These findings reveal a novel mechanism by which ischemic insults disrupt the functional integrity of the outer mitochondrial membrane and implicate deltaN-BCL-xL and VDAC in the large, Zn2+-dependent mitochondrial channels observed in post-ischemic hippocampal mitochondria.

Acupuncture at Waiguan (SJ5) and sham points influences activation of functional brain areas of ischemic stroke patients: a functional magnetic resonance imaging study

OpenAIRE

Qi, Ji; Chen, Junqi; Huang, Yong; Lai, Xinsheng; Tang, Chunzhi; Yang, Junjun; Chen, Hua; Qu, Shanshan

2014-01-01

Most studies addressing the specificity of meridians and acupuncture points have focused mainly on the different neural effects of acupuncture at different points in healthy individuals. This study examined the effects of acupuncture on brain function in a pathological context. Sixteen patients with ischemic stroke were randomly assigned to true point group (true acupuncture at right Waiguan (SJ5)) and sham point group (sham acupuncture). Results of functional magnetic resonance imaging revea...

A prototypical Sigma-1 receptor antagonist protects against brain ischemia

OpenAIRE

Schetz, John A.; Perez, Evelyn; Liu, Ran; Chen, Shiuhwei; Lee, Ivan; Simpkins, James W.

2007-01-01

Previous studies indicate that the Sigma-1 ligand 4-phenyl-1-(4-phenylbutyl) piperidine (PPBP) protects the brain from ischemia. Less clear is whether protection is mediated by agonism or antagonism of the Sigma-1 receptor, and whether drugs already in use for other indications and that interact with the Sigma-1 receptor might also prevent oxidative damage due to conditions such as cerebral ischemic stroke. The antipsychotic drug haloperidol is an antagonist of Sigma-1 receptors and in this s...

Overexpression of HIF-1α in mesenchymal stem cells contributes to repairing hypoxic-ischemic brain damage in rats.

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Lin, Deju; Zhou, Liping; Wang, Biao; Liu, Lizhen; Cong, Li; Hu, Chuanqin; Ge, Tingting; Yu, Qin

2017-01-01

Preclinical researches on mesenchymal stem cells (MSCs) transplantation, which is used to treat hypoxic-ischemic (HI) brain damage, have received inspiring achievements. However, the insufficient migration of active cells to damaged tissues has limited their potential therapeutic effects. There are some evidences that hypoxia inducible factor-1 alpha (HIF-1α) promotes the viability and migration of the cells. Here, we aim to investigate whether overexpression of HIF-1α in MSCs could improve the viability and migration capacity of cells, and its therapeutic efficiency on HI brain damage. In the study, MSCs with HIF-1α overexpression was achieved by recombinant lentiviral vector and transplanted to the rats subsequent to HI. Our data indicated that overexpression of HIF-1α promoted the viability and migration of MSCs, HIF-1α overexpressed MSCs also had a stronger therapeutic efficiency on HI brain damaged treatment by mitigating the injury on behavioral and histological changes evoked by HI insults, accompanied with more MSCs migrating to cerebral damaged area. This study demonstrated that HIF-1α overexpression could increase the MSCs' therapeutic efficiency in HI and the promotion of the cells' directional migration to cerebral HI area by overexpression may be responsible for it, which showed that transplantation of MSCs with HIF-1α overexpression is an attractive therapeutic option to treat HI-induced brain injury in the future. Copyright © 2016 Académie des sciences. Published by Elsevier SAS. All rights reserved.

Ischemic stroke and transient ischemic attack in young adults: risk factors, diagnostic yield, neuroimaging, and thrombolysis.

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Ji, Ruijun; Schwamm, Lee H; Pervez, Muhammad A; Singhal, Aneesh B

2013-01-01

Approximately 10% to 14% of ischemic strokes occur in young adults. To investigate the yield of diagnostic tests, neuroimaging findings, and treatment of ischemic strokes in young adults. We retrospectively reviewed data from our Get with the Guidelines-Stroke database from 2005 through 2010. University hospital tertiary stroke center. A total of 215 consecutive inpatients aged 18 to 45 years with ischemic stroke/transient ischemic attack. The mean (SD) age was 37.5 (7) years; 51% were male. There were high incidence rates of hypertension (20%), diabetes mellitus (11%), dyslipidemia (38%), and smoking (34%). Relevant abnormalities were shown on cerebral angiography in 136 of 203 patients, on cardiac ultrasonography in 100 of 195, on Holter monitoring in 2 of 192; and on hypercoagulable panel in 30 of 189 patients. Multiple infarcts were observed in 31% and were more prevalent in individuals younger than age 35 years. Relevant arterial lesions were frequently detected in the middle cerebral artery (23%), internal carotid artery (13%), and vertebrobasilar arteries (13%). Cardioembolic stroke occurred in 47% (including 17% with isolated patent foramen ovale), and 11% had undetermined stroke etiology. The median National Institutes of Health Stroke Scale score was 3 (interquartile range, 0-9) and 81% had good outcome at hospital discharge. Of the 29 patients receiving thrombolysis (median National Institutes of Health Stroke Scale score, 14; interquartile range, 9-17), 55% had good outcome at hospital discharge and none developed symptomatic brain hemorrhage. This study shows the contemporary profile of ischemic stroke in young adults admitted to a tertiary stroke center. Stroke etiology can be determined in nearly 90% of patients with modern diagnostic tests. The causes are heterogeneous; however, young adults have a high rate of traditional vascular risk factors. Thrombolysis appears safe and short-term outcomes are favorable.

Is opium addiction a risk factor for ischemic heart disease and ischemic stroke?

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Mohammad Reza Rezvani

2012-01-01

Full Text Available Background: The main source of studies about effects of opium consumption on heart and brain attacks originates from Iran Therefore the aim of the present study was to assess opium addiction as a probable influencing factor for ischemic heart disease and ischemic stroke. Materials and Methods: A cross-sectional study was carried out in two Cardiology and Neurology clinics in Eastern Iran in 2011. Diagnosis of Ischemic Heart Disease (IHD and Ischemic Stroke (IS was made by Cardiologist and Stroke Neurologist respectively. The influence of gender, hypertension, diabetes, hyperlipidemia, cigarette smoking, oral and inhaled opium consumption on distribution of IHD and IS were evaluated. Results: Five hundred fifty eight patients (307 females, 251 males with mean age 56.2 years enrolled the study. On adjusted odds ratios of our whole 558 patients, only hypertension and diabetes had a significant influence on occurrence of IHD; (P = 0.000 and P = 0.000 respectively. Oral and inhaled routes of opium addiction did not have a significant effect on occurrence of IHD; [OR = 1.172, 95% CI = 0.624-2.203, P = 0.621] and [OR = 1.820, 95% CI = 0.811-4.085, P = 0.147] respectively. Hypertension and diabetes were significant risk factors of IS in our 558 patients at multivariate analysis; (P = 0.000, P = 0.020. Oral opium addiction was as significant protective factor of IS in our study group; OR = 0.211, 95% CI = 0.079-0.564, P = 0.002, while inhaled opium addiction did not have a significant effect on occurrence of IS in our patients at; OR = 1.760, 95% CI = 0.760-4.076, P = 0.187. Conclusion: Oral opium consumption is a protective factor of IS but not IHD. Inhaled opium addiction does not have a significant influence on occur r ence of IS and IHD.

Is opium addiction a risk factor for ischemic heart disease and ischemic stroke?

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Rezvani, Mohammad Reza; Ghandehari, Kavian

2012-10-01

The main source of studies about effects of opium consumption on heart and brain attacks originates from Iran Therefore the aim of the present study was to assess opium addiction as a probable influencing factor for ischemic heart disease and ischemic stroke. A cross-sectional study was carried out in two Cardiology and Neurology clinics in Eastern Iran in 2011. Diagnosis of Ischemic Heart Disease (IHD) and Ischemic Stroke (IS) was made by Cardiologist and Stroke Neurologist respectively. The influence of gender, hypertension, diabetes, hyperlipidemia, cigarette smoking, oral and inhaled opium consumption on distribution of IHD and IS were evaluated. Five hundred fifty eight patients (307 females, 251 males) with mean age 56.2 years enrolled the study. On adjusted odds ratios of our whole 558 patients, only hypertension and diabetes had a significant influence on occurrence of IHD; (P = 0.000 and P = 0.000) respectively. Oral and inhaled routes of opium addiction did not have a significant effect on occurrence of IHD; [OR = 1.172, 95% CI = 0.624-2.203, P = 0.621] and [OR = 1.820, 95% CI = 0.811-4.085, P = 0.147] respectively. Hypertension and diabetes were significant risk factors of IS in our 558 patients at multivariate analysis; (P = 0.000, P = 0.020). Oral opium addiction was as significant protective factor of IS in our study group; OR = 0.211, 95% CI = 0.079-0.564, P = 0.002, while inhaled opium addiction did not have a significant effect on occurrence of IS in our patients at; OR = 1.760, 95% CI = 0.760-4.076, P = 0.187. Oral opium consumption is a protective factor of IS but not IHD. Inhaled opium addiction does not have a significant influence on occurrence of IS and IHD.

Hypothermia Modulates Cytokine Responses After Neonatal Rat Hypoxic-Ischemic Injury and Reduces Brain Damage

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Xiangpeng Yuan

2014-11-01

Full Text Available While hypothermia (HT is the standard-of-care for neonates with hypoxic ischemic injury (HII, the mechanisms underlying its neuroprotective effect are poorly understood. We examined ischemic core/penumbra and cytokine/chemokine evolution in a 10-day-old rat pup model of HII. Pups were treated for 24 hr after HII with HT (32℃; n = 18 or normothermia (NT, 35℃; n = 15. Outcomes included magnetic resonance imaging (MRI, neurobehavioral testing, and brain cytokine/chemokine profiling (0, 24, 48, and 72 hr post-HII. Lesion volumes (24 hr were reduced in HT pups (total 74%, p < .05; penumbra 68%, p < .05; core 85%, p = .19. Lesion volumes rebounded at 72 hr (48 hr post-HT with no significant differences between NT and HT pups. HT reduced interleukin-1β (IL-1β at all time points (p < .05; monocyte chemoattractant protein-1 (MCP-1 trended toward being decreased in HT pups (p = .09. The stem cell signaling molecule, stromal cell-derived factor-1 (SDF-1 was not altered by HT. Our data demonstrate that HT reduces total and penumbral lesion volumes (at 24 and 48 hr, potentially by decreasing IL-1β without affecting SDF-1. Disassociation between the increasing trend in HII volumes from 48 to 72 hr post-HII when IL-1β levels remained low suggests that after rewarming, mechanisms unrelated to IL-1β expression are likely to contribute to this delayed increase in injury. Additional studies should be considered to determine what these mechanisms might be and also to explore whether extending the duration or degree of HT might ameliorate this delayed increase in injury.

[Brain protection against cerebral ischemia].

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Kitagawa, Kazuo

2013-01-01

Previous clinical trials failed to show the benefit of several potentially protective drugs in acute ischemic stroke. However, there would be three main approaches for brain protection against stroke. The first is to develop a novel thrombolytic agent which is more efficient and safer than alteplase. Tenecteplase and desmoteplase are in progress as a new thrombolytic drug. The second strategy is to augment collateral circulation through leptomeningeal anastomosis. Administration of G-CSF could enhance arteriogenesis, but it takes several days to develop functional collateral. For this purpose, partial aortic balloon clumping or stimulation of pterygopalatine ganglion may be promising. The third one is to protect neurovascular unit against reperfusion injury. Brain hypothermia is the most effective strategy in experimental ischemia, and the clinical trial for hypothermia combined with thrombolysis therapy is in progress. Activation of endogenous protective response, as presented by ischemic tolerance, has focused on remote ischemic conditioning. Although the precise mechanisms of remote preconditioning remain unclear, intermittent limb ischemia is a safe approach. Remote ischemic conditioning is now investigated in acute patients with thrombolysis therapy.

Electrical stunning and exsanguination decrease the extracellular volume in the broiler brain as studied with brain impedance recordings

NARCIS (Netherlands)

Savenije, B; Lambooij, E; Pieterse, C; Korf, J

Electrical stunning in the process of slaughtering poultry is used to induce unconsciousness and immobilize the animal for easier processing. Unconsciousness is a function of brain damage. Brain damage has been studied with brain impedance recordings under ischemic conditions. This experiment

Diagnosis, management and prevention of ischemic stroke for non-neurologists

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Kavian Ghandehari

2011-07-01

Full Text Available Background: Stroke is the third common cause of disability and death. Diagnosis of stroke is based on its clinical manifestations and/or observation of infarct in the neuroimaging. Standard battery of diagnostic investigations and classification criteria is required for detection of stroke etiology. Materials and Method: This review article deals with the diagnosis and management of brain infarction particularly in our country and is provided for non-neurologists. Using online scientific search engines and in some parts referring to laboratory archives constituted base of this review article.Results: Acute stroke management is almost similar in its various etiologies. Neuroprotective drugs have little value in acute stroke management. At present time, a few Iranian medical centers have infrastructure of thrombolysis therapy. Prevention of stroke is based on the detection and control of its risk factors. Aspirin, 80 mg per day is the most common drug for stroke prevention. Co-administration of aspirin 80 mg/d and Dipyridamole 200-400 mg/d increases the preventive effects of aspirin. Clopidogrel 75 mg/d is the stroke preventive drug of choice in patients with peptic ulcer and coronary artery disease. Co-administration of aspirin and clopidogrel is more effective in stroke prevention but has more hemorrhagic complications. Using warfarin for stroke prevention is suggested only in patients who have facilities for repetitive coagulation tests. Carotid endarterectomy is indicated in symptomatic patients with more than 70% stenosis of extracranial internal carotid artery, if performed only by vascular surgeons experienced in carotid surgery.Conclusion: Many stroke patients are managed by general practitioners and non-neurologists, e.g. internists, cardiologists and neurosurgeons. This review article provides continuous medical education according to Iranian medical curriculum

Monotherapy of aspirin or warfarin for prevention of ischemic stroke in low-risk atrial fibrillation: A Easter Asian population-based study.

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Liu, Chieh-Yu; Chen, Hui-Chun

2018-05-02

This study aimed to investigate the effectiveness of monotherapy aspirin and warfarin for stroke prevention in low-risk atrial fibrillation (AF) by using a population-based cohort study in Taiwan. A newly diagnosed low-risk AF patient cohort were identified by using National Health Insurance Research Database (NHIRD) in Taiwan in 2008. The study cohort was observed with a follow-up of 2 years to examine the onset of ischemic stroke (IS) (to 2010). The longitudinal data were analyzed by using generalized estimation equations (GEE). A total of 8,065 newly-diagnosed low-risk AF patients were identified in 2008. 7.4% were prescribed with aspirin and 4.6% were prescribed with warfarin. The GEE results showed that low-risk AF patients with hypertension who received warfarin were associated with a statistically significant 58.4% reduction of IS risk (OR = 0.416, p = 0.024, 95% CI 0.194-0.891). Additionally, low-risk AF patients with hyperlipidemia who received warfarin were associated with a 69.3% reduction of IS risk (OR = 0.307, p = 0.044, 95% CI 0.097-0.969). Warfarin is suggested to be prescribed in preventing ischemic stroke for low-stroke-risk atrial fibrillation patients with hypertension and hyperlipidemia.

Rehabilitation outcome in hemorrhagic transformation of ischemic stroke: a case presentation

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Ioana Stanescu

2018-06-01

Full Text Available Hemorrhagic transformation (HT may occur as a part of the natural history of acute ischemic stroke, with incidence between 13-43% in computer-tomography (CT studies. Detection of HT in a patient with ischemic stroke is important in establishing treatment in the acute phase in assessing prognosis and in taking therapeutical decisions for secondary stroke prevention. There were controversies regarding optimal treatment in acute ischemic stroke with HT, especially if the patient needs further anticoagulant or antiplatelet treatment. Rehabilitation treatment needs to be continued for post-stroke patients who developed HT, because HT does not decrease rehabilitation outcome. We present rehabilitation treatment and prognosis in a case of hemorrhagic transformation after an embolic ischemic stroke treated with anticoagulants, which required reinitiation of anticoagulant treatment.

A rare cause of ischemic stroke: Intravasculer B cell lymphoma

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Şeyma Çiftçi

2014-08-01

Full Text Available Intravascular B cell lymphoma is rare and an agressive form of large B cell lymphoma which can affect central nervous system. Because of its varied clinical symptoms and the absence of lymphadenopathy, it is generally diagnosed postmortem. Cerebral infarction due to occlusion of arteries can be seen as a rare clinical form of central nervous system involvement. Large artery atherosclerosis, cardiyoembolism and small artery occlusion are the important causes of ischemic stroke but no any cause is detected in %15-40 of all cases. In this report, with the discussion of a case with ischemia like encephalopathy and multiple cerebral ischemic lesions at different stages in cranial MRI which was diagnosed by the help of brain biopsy as a intravascular B cell lymphoma, it is aimed to take attention intravascular lymphoma as a rare cause of ischemic stroke.

Exacerbation of oxygen-glucose deprivation-induced blood-brain barrier disruption: potential pathogenic role of interleukin-9 in ischemic stroke.

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Tan, Sha; Shan, Yilong; Wang, Yuge; Lin, Yinyao; Liao, Siyuan; Deng, Zhezhi; Zhou, Li; Cai, Wei; Zeng, Qin; Zhang, Lei; Zhang, Bingjun; Men, Xuejiao; Li, Haiyan; Hu, Xueqiang; Wu, Changyou; Peng, Lisheng; Lu, Zhengqi

2017-07-01

Interleukin (IL)-9 exerts a variety of functions in autoimmune diseases. However, its role in ischemic brain injury remains unknown. The present study explored the biological effects of IL-9 in ischemic stroke (IS). We recruited 42 patients newly diagnosed with IS and 22 age- and sex-matched healthy controls. The expression levels of IL-9 and percentages of IL-9-producing T cells, including CD3 + CD4 + IL-9 + and CD3 + CD8 + IL-9 + cells, were determined in peripheral blood mononuclear cells (PBMCs) obtained from patients and control individuals. We also investigated the effects of IL-9 on the blood-brain barrier (BBB) following oxygen-glucose deprivation (OGD) and the potential downstream signaling pathways. We found that patients with IS had higher IL-9 expression levels and increased percentages of IL-9-producing T cells in their PBMCs. The percentages of CD3 + CD4 + IL-9 + and CD3 + CD8 + IL-9 + T cells were positively correlated with the severity of illness. In in vitro experiments using bEnd.3 cells, exogenously administered IL-9 exacerbated the loss of tight junction proteins (TJPs) in cells subjected to OGD plus reoxygenation (RO). This effect was mediated via activation of IL-9 receptors, which increased the level of endothelial nitric oxide synthase (eNOS), as well as through up-regulated phosphorylation of signal transducer and activator of transcription 1 and 3 and down-regulated phosphorylated protein kinase B/phosphorylated phosphatidylinositol 3-kinase signaling. These results indicate that IL-9 has a destructive effect on the BBB following OGD, at least in part by inducing eNOS production, and raise the possibility of targetting IL-9 for therapeutic intervention in IS. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Chronic Treatment with a Water-Soluble Extract from the Culture Medium of Ganoderma lucidum Mycelia Prevents Apoptosis and Necroptosis in Hypoxia/Ischemia-Induced Injury of Type 2 Diabetic Mouse Brain

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Meiyan Xuan

2015-01-01

Full Text Available Type 2 diabetes mellitus has been known to increase systemic oxidative stress by chronic hyperglycemia and visceral obesity and aggravate cerebral ischemic injury. On the basis of our previous study regarding a water-soluble extract from the culture medium of Ganoderma lucidum mycelia (designed as MAK, which exerts antioxidative and neuroprotective effects, the present study was conducted to evaluate the preventive effects of MAK on apoptosis and necroptosis (a programmed necrosis induced by hypoxia/ischemia (H/I in type 2 diabetic KKAy mice. H/I was induced by a combination of unilateral common carotid artery ligation with hypoxia (8% O2 for 20 min and subsequent reoxygenation. Pretreatment with MAK (1 g/kg, p.o. for a week significantly reduced H/I-induced neurological deficits and brain infarction volume assessed at 24 h of reoxygenation. Histochemical analysis showed that MAK significantly suppressed superoxide production, neuronal cell death, and vacuolation in the ischemic penumbra, which was accompanied by a decrease in the numbers of TUNEL- or cleaved caspase-3-positive cells. Furthermore, MAK decreased the expression of receptor-interacting protein kinase 3 mRNA and protein, a key molecule for necroptosis. These results suggest that MAK confers resistance to apoptotic and necroptotic cell death and relieves H/I-induced cerebral ischemic injury in type 2 diabetic mice.

Endovascular Intervention for Acute Ischemic Stroke in Light of Recent Trials

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Kenan Alkhalili

2014-01-01

Full Text Available Three recently published trials, MR RESCUE, IMS III, and SYNTHESIS Expansion, evaluating the efficacy and safety of endovascular treatment of acute ischemic stroke have generated concerns about the future of endovascular approach. However, the tremendous evolution that imaging and endovascular treatment modalities have undergone over the past several years has raised doubts about the validity of these trials. In this paper, we review the role of endovascular treatment strategies in acute ischemic stroke and discuss the limitations and shortcomings that prevent generalization of the findings of recent trials. We also provide our experience in endovascular treatment of acute ischemic stroke.

Perception of Recurrent Stroke Risk among Black, White and Hispanic Ischemic Stroke and Transient Ischemic Attack Survivors: The SWIFT Study

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Boden-Albala, Bernadette; Carman, Heather; Moran, Megan; Doyle, Margaret; Paik, Myunghee C.

2011-01-01

Objectives Risk modification through behavior change is critical for primary and secondary stroke prevention. Theories of health behavior identify perceived risk as an important component to facilitate behavior change; however, little is known about perceived risk of vascular events among stroke survivors. Methods The SWIFT (Stroke Warning Information and Faster Treatment) study includes a prospective population-based ethnically diverse cohort of ischemic stroke and transient ischemic attack survivors. We investigate the baseline relationship between demographics, health beliefs, and knowledge on risk perception. Regression models examined predictors of inaccurate perception. Results Only 20% accurately estimated risk, 10% of the participants underestimated risk, and 70% of the 817 study participants significantly overestimated their risk for a recurrent stroke. The mean perceived likelihood of recurrent ischemic stroke in the next 10 years was 51 ± 7%. We found no significant differences by race-ethnicity with regard to accurate estimation of risk. Inaccurate estimation of risk was associated with attitudes and beliefs [worry (p risk factors. Conclusion This paper provides a unique perspective on how factors such as belief systems influence risk perception in a diverse population at high stroke risk. There is a need for future research on how risk perception can inform primary and secondary stroke prevention. Copyright © 2011 S. Karger AG, Basel PMID:21894045

Evidence That Ly6C(hi) Monocytes are Protective in Acute Ischemic Stroke by Promoting M2 Macrophage Polarization.

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Chu, Hannah X; Broughton, Brad R S; Kim, Hyun Ah; Lee, Seyoung; Drummond, Grant R; Sobey, Christopher G

2015-07-01

Ly6C(hi) monocytes are generally thought to exert a proinflammatory role in acute tissue injury, although their impact after injuries to the central nervous system is poorly defined. CC chemokine receptor 2 is expressed on Ly6C(hi) monocytes and plays an essential role in their extravasation and transmigration into the brain after cerebral ischemia. We used a selective CC chemokine receptor 2 antagonist, INCB3344, to assess the effect of Ly6C(hi) monocytes recruited into the brain early after ischemic stroke. Male C57Bl/6J mice underwent occlusion of the middle cerebral artery for 1 hour followed by 23 hours of reperfusion. Mice were administered either vehicle (dimethyl sulfoxide/carboxymethylcellulose) or INCB3344 (10, 30 or 100 mg/kg IP) 1 hour before ischemia and at 2 and 6 hours after ischemia. At 24 hours, we assessed functional outcomes, infarct volume, and quantified the immune cells in blood and brain by flow cytometry or immunofluorescence. Gene expression of selected inflammatory markers was assessed by quantitative polymerase chain reaction. Ly6C(hi) monocytes were increased 3-fold in the blood and 10-fold in the brain after stroke, and these increases were selectively prevented by INCB3344 in a dose-dependent manner. Mice treated with INCB3344 exhibited markedly worse functional outcomes and larger infarct volumes, in association with reduced M2 polarization and increased peroxynitrite production in macrophages, compared with vehicle-treated mice. Our data suggest that Ly6C(hi) monocytes exert an acute protective effect after ischemic stroke to limit brain injury and functional deficit that involves promotion of M2 macrophage polarization. © 2015 American Heart Association, Inc.

EVALUATION OF EARLY ISCHEMIC CHANGES IN STROKE PATIENTS TREATED WITH THROMBOLYTIC THERAPY

OpenAIRE

Kolevski Goran; Korneti-Pekevska Kostandina

2016-01-01

Introduction:The aim of this study is to evaluate early brain ischemic changes on CT scan in stroke patients in correlation with the clinical outcome, as well as to evaluate if there is prognostic and predictive features that can be used. Patients and methods: We examined 20 patients with acute ischemic stroke, from which 12 were male and 8 were female, at the age from 47 to 76 years. Results: The hyperdense medial artery (HMA) sign was present in 10 (50%) patients. Concerning the ASPECTS s...

Polymorphonuclear neutrophil in brain parenchyma after experimental intracerebral hemorrhage.

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Zhao, Xiurong; Sun, Guanghua; Zhang, Han; Ting, Shun-Ming; Song, Shen; Gonzales, Nicole; Aronowski, Jaroslaw

2014-10-01

Polymorphonuclear neutrophils (PMNs) infiltration into brain parenchyma after cerebrovascular accidents is viewed as a key component of secondary brain injury. Interestingly, a recent study of ischemic stroke suggests that after ischemic stroke, PMNs do not enter brain parenchyma and as such may cause no harm to the brain. Thus, the present study was designed to determine PMNs' behavior after intracerebral hemorrhage (ICH). Using the autologous blood injection model of ICH in rats and immunohistochemistry for PMNs and vascular components, we evaluated the temporal and spatial PMNs distribution in the ICH-affected brain. We found that, similar to ischemia, there is a robust increase in presence of PMNs in the ICH-injured tissue that lasts for at least 1 to 2 weeks. However, in contrast to what was suggested for ischemia, besides PMNs that stay in association with the vasculature, after ICH, we found abundance of intraparenchymal PMNs (with no obvious association with vessels) in the ICH core and hematoma border, especially between 1 and 7 days after the ictus. Interestingly, the increased presence of intraparenchymal PMNs after ICH coincided with the massive loss of microvascular integrity, suggesting vascular disruption as a potential cause of PMNs presence in the brain parenchyma. Our study indicates that in contrast to ischemic stroke, after ICH, PMNs target not only vascular compartment but also brain parenchyma in the affected brain. As such, it is possible that the pathogenic role and therapeutic implications of targeting PMNs after ICH could be different from these after ischemic stroke. Our work suggests the needs for more studies addressing the role of PMNs in ICH.

A pathophysiological role of TRPV1 in ischemic injury after transient focal cerebral ischemia in mice

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Miyanohara, Jun [Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University (Japan); Shirakawa, Hisashi, E-mail: shirakaw@pharm.kyoto-u.ac.jp [Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University (Japan); Sanpei, Kazuaki [Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University (Japan); Nakagawa, Takayuki [Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University (Japan); Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital (Japan); Kaneko, Shuji [Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University (Japan)

2015-11-20

Transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel with high Ca{sup 2+} permeability, which functions as a polymodal nociceptor activated by heat, protons and several vanilloids, including capsaicin and anandamide. Although TRPV1 channels are widely distributed in the mammalian brain, their pathophysiological roles in the brain remain to be elucidated. In this study, we investigated whether TRPV1 is involved in cerebral ischemic injury using a middle cerebral artery (MCA) occlusion model in wild-type (WT) and TRPV1-knockout (KO) mice. For transient ischemia, the left MCA of C57BL/6 mice was occluded for 60 min and reperfused at 1 and 2 days after ischemia. We found that neurological and motor deficits, and infarct volumes in TRPV1-KO mice were lower than those of WT mice. Consistent with these results, intracerebroventricular injection of a TRPV1 antagonist, capsazepine (20 nmol), 30 min before the onset of ischemia attenuated neurological and motor deficits and improved infarct size without influencing cerebral blood flow in the occluded MCA territory. The protective effect of capsazepine on ischemic brain damage was not observed in TRPV1-KO mice. WT and TRPV1-KO mice did not show any differences with respect to the increased number of Iba1-positive microglia/macrophages, GFAP-positive astrocytes, and Gr1-positive neutrophils at 1 and 2 days after cerebral ischemia. Taken together, we conclude that brain TRPV1 channels are activated by ischemic stroke and cause neurological and motor deficits and infarction after brain ischemia. - Highlights: • We investigated whether TRPV1 is involved in transient ischemic brain damage in mice. • Neurological deficits and infarct volumes were lower in TRPV1-KO mice than in WT mice. • Injection of a TRPV1 antagonist, capsazepine, attenuated neurological deficits and improved infarct size. • No differences in astrocytic or microglial activation were observed between WT and TRPV1-KO mice.

A pathophysiological role of TRPV1 in ischemic injury after transient focal cerebral ischemia in mice

International Nuclear Information System (INIS)

Miyanohara, Jun; Shirakawa, Hisashi; Sanpei, Kazuaki; Nakagawa, Takayuki; Kaneko, Shuji

2015-01-01

Transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel with high Ca"2"+ permeability, which functions as a polymodal nociceptor activated by heat, protons and several vanilloids, including capsaicin and anandamide. Although TRPV1 channels are widely distributed in the mammalian brain, their pathophysiological roles in the brain remain to be elucidated. In this study, we investigated whether TRPV1 is involved in cerebral ischemic injury using a middle cerebral artery (MCA) occlusion model in wild-type (WT) and TRPV1-knockout (KO) mice. For transient ischemia, the left MCA of C57BL/6 mice was occluded for 60 min and reperfused at 1 and 2 days after ischemia. We found that neurological and motor deficits, and infarct volumes in TRPV1-KO mice were lower than those of WT mice. Consistent with these results, intracerebroventricular injection of a TRPV1 antagonist, capsazepine (20 nmol), 30 min before the onset of ischemia attenuated neurological and motor deficits and improved infarct size without influencing cerebral blood flow in the occluded MCA territory. The protective effect of capsazepine on ischemic brain damage was not observed in TRPV1-KO mice. WT and TRPV1-KO mice did not show any differences with respect to the increased number of Iba1-positive microglia/macrophages, GFAP-positive astrocytes, and Gr1-positive neutrophils at 1 and 2 days after cerebral ischemia. Taken together, we conclude that brain TRPV1 channels are activated by ischemic stroke and cause neurological and motor deficits and infarction after brain ischemia. - Highlights: • We investigated whether TRPV1 is involved in transient ischemic brain damage in mice. • Neurological deficits and infarct volumes were lower in TRPV1-KO mice than in WT mice. • Injection of a TRPV1 antagonist, capsazepine, attenuated neurological deficits and improved infarct size. • No differences in astrocytic or microglial activation were observed between WT and TRPV1-KO mice.

Role of homocysteine in the ischemic stroke nad development of ischemic tolerance

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Jan Lehotsky

2016-11-01

Full Text Available Homocysteine (Hcy is a toxic, sulfur-containing intermediate of methionine metabolism. Hyperhomocysteinemia (hHcy, as a consequence of impaired Hcy metabolism or defects in crucial co-factors that participate in its recycling, is assumed as an independent human stroke risk factor. Neural cells are sensitive to prolonged hHcy treatment, because Hcy cannot be metabolized either by the transsulfuration pathway or by the folate/vitamin B12 independent remethylation pathway. Its detrimental effect after ischemia-induced damage includes accumulation of reactive oxygen species (ROS and posttranslational modifications of proteins via homocysteinylation and thiolation. Ischemic preconditioning (IPC is an adaptive response of the CNS to sub-lethal ischemia, which elevates tissues tolerance to subsequent ischemia. The main focus of this review is on the recent data on homocysteine metabolism and mechanisms of its neurotoxicity. In this context, the review documents an increased oxidative stress and functional modification of enzymes involved in redox balance in experimentally induced hyperhomocysteinemia. It also gives an interpretation whether hyperhomocysteinemia alone or in combination with IPC affects the ischemia-induced neurodegenerative changes as well as intracellular signalling. Studies document that hHcy alone significantly increased Fluoro-Jade C- and TUNEL-positive cell neurodegeneration in the rat hippocampus as well as in the cortex. IPC, even if combined with hHcy, could still preserve the neuronal tissue from the lethal ischemic effects. This review also describes the changes in the mitogen-activated protein kinase (MAPK protein pathways following ischemic injury and IPC. These studies provide evidence for the interplay and tight integration between ERK and p38 MAPK signalling mechanisms in response to the hHcy and also in association of hHcy with ischemia/IPC challenge in the rat brain. Further investigations of the protective factors

Global Proteomic Analysis of Brain Tissues in Transient Ischemia Brain Damage in Rats

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Jiann-Hwa Chen

2015-05-01

Full Text Available Ischemia-reperfusion injury resulting from arterial occlusion or hypotension in patients leads to tissue hypoxia with glucose deprivation, which causes endoplasmic reticulum (ER stress and neuronal death. A proteomic approach was used to identify the differentially expressed proteins in the brain of rats following a global ischemic stroke. The mechanisms involved the action in apoptotic and ER stress pathways. Rats were treated with ischemia-reperfusion brain injuries by the bilateral occlusion of the common carotid artery. The cortical neuron proteins from the stroke animal model (SAM and the control rats were separated using two-dimensional gel electrophoresis (2-DE to purify and identify the protein profiles. Our results demonstrated that the SAM rats experienced brain cell death in the ischemic core. Fifteen proteins were expressed differentially between the SAM rats and control rats, which were assayed and validated in vivo and in vitro. Interestingly, the set of differentially expressed, down-regulated proteins included catechol O-methyltransferase (COMT and cathepsin D (CATD, which are implicated in oxidative stress, inflammatory response and apoptosis. After an ischemic stroke, one protein spot, namely the calretinin (CALB2 protein, showed increased expression. It mediated the effects of SAM administration on the apoptotic and ER stress pathways. Our results demonstrate that the ischemic injury of neuronal cells increased cell cytoxicity and apoptosis, which were accompanied by sustained activation of the IRE1-alpha/TRAF2, JNK1/2, and p38 MAPK pathways. Proteomic analysis suggested that the differential expression of CALB2 during a global ischemic stroke could be involved in the mechanisms of ER stress-induced neuronal cell apoptosis, which occurred via IRE1-alpha/TRAF2 complex formation, with activation of JNK1/2 and p38 MAPK. Based on these results, we also provide the molecular evidence supporting the ischemia

Transient ischemic attacks and presence of an acute brain lesion in diffusion-weighted MRI: study of 50 patients

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Sabeti M

2012-10-01

Full Text Available Background: Finding an acute brain lesion by diffusion-weighted (DW MRI upon an episode of transient ischemic attack (TIA is a predictor of imminent stroke in the near future. Therefore, exploring risk factors associated with lesions in DW-MRI of the brain is important in adopting an approach to TIA management. In the current study, we tried to determine the risk factors associated with lesions in DW-MRI of the brain in patients experiencing TIA episodes.Methods: Fifty patients with TIA were recruited consecutively in Sina Hospital, Tehran, Iran, over a 6-month period between July 2008 and January 2009. All of the patients underwent a complete neurological examination and laboratory tests. Brain DW-MRIs were performed for all the patients within 72 hours of a TIA episode.Results: DW-MRI revealed an acute lesion in 16% of the participants. There was a significant correlation between presence of an acute lesion in DW-MRI and TIA duration, history of diabetes mellitus and presence of unilateral facial palsy (P=0.0003, P=0.02 and P=0.008, respectively. Other variables such as age, hypertension, hyperlipidemia, past history of TIA, headache, vertigo, and sensory or visual disturbances had no significant relation with the presence of an acute lesion in DW-MRI.Conclusion: Duration of TIA, presence of diabetes mellitus and unilateral facial palsy are risk factors for an acute lesion in DW-MRI, meaning that patients with such risk factors are at risk for stroke in the near future.

Atomoxetine, a selective norepinephrine reuptake inhibitor, improves short-term histological outcomes after hypoxic-ischemic brain injury in the neonatal male rat.

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Toshimitsu, Masatake; Kamei, Yoshimasa; Ichinose, Mari; Seyama, Takahiro; Imada, Shinya; Iriyama, Takayuki; Fujii, Tomoyuki

2018-03-30

Despite the recent progress of perinatal medicine, perinatal hypoxic-ischemic (HI) insult remains an important cause of brain injury in neonates, and is pathologically characterized by neuronal loss and the presence of microglia. Neurotransmitters, such as norepinephrine (NE) and glutamate, are involved in the pathogenesis of hypoxic-ischemic encephalopathy via the interaction between neurons and microglia. Although it is well known that the monoamine neurotransmitter NE acts as an anti-inflammatory agent in the brain under pathological conditions, its effects on perinatal HI insult remains elusive. Atomoxetine, a selective NE reuptake inhibitor, has been used clinically for the treatment of attention-deficit hyperactivity disorder in children. Here, we investigated whether the enhancement of endogenous NE by administration of atomoxetine could protect neonates against HI insult by using the neonatal male rat model. We also examined the involvement of microglia in this process. Unilateral HI brain injury was induced by the combination of left carotid artery dissection followed by ligation and hypoxia (8% O 2 , 2 h) in postnatal day 7 (P7) male rat pups. The pups were randomized into three groups: the atomoxetine treatment immediately after HI insult, the atomoxetine treatment at 3 h after HI insult, or the vehicle treatment group. The pups were euthanized on P8 and P14, and the brain regions including the cortex, striatum, hippocampus, and thalamus were evaluated by immunohistochemistry. HI insult resulted in severe brain damage in the ipsilateral hemisphere at P14. Atomoxetine treatment immediately after HI insult significantly increased NE levels in the ipsilateral hemisphere at 1 h after HI insult and reduced the neuronal damage via the increased phosphorylation of cAMP response element-binding protein (pCREB) in all brain regions examined. In addition, the number of microglia was maintained under atomoxetine treatment compared with that of the vehicle

Economic impact of enoxaparin after acute ischemic stroke based on PREVAIL.

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Pineo, Graham; Lin, Jay; Stern, Lee; Subrahmanian, Tarun; Annemans, Lieven

2011-04-01

The efficacy and safety of low-molecular-weight heparins (LMWHs) versus unfractionated heparin (UFH) has been demonstrated for the prevention of venous thromboembolism (VTE) after acute ischemic stroke. Few data exist regarding the economic impact of LMWHs versus UFH in this population. A decision-analytic model was constructed using clinical information from the Prevention of VTE after Acute Ischemic stroke with LMWH Enoxaparin (PREVAIL) study, and drug costs and mean Centers for Medicare & Medicaid Services event costs. When considering the total cost of events and drugs, enoxaparin was associated with cost-savings of $895 per patient compared with UFH ($2018 vs $2913). Findings were retained within the univariate and multivariate analyses. From a payer perspective, enoxaparin was cost-effective compared with UFH in patients with acute ischemic stroke. The difference was driven by the lower clinical event rates with enoxaparin. Use of enoxaparin may help to reduce the clinical and economic burden of VTE.

Young ischemic stroke in Tunisia: a multicentric study.

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Kefi, Asma; Larbi, Thara; Abdallah, Meya; Ouni, Amira El; Bougacha, Neil; Bouslama, Kamel; Hamzaoui, Saloua; M'rad, Skander

2017-04-01

There is wanting data regarding young ischemic stroke in developing countries, especially in Tunisia. The purpose of this study was to investigate risk factors and etiologies of young ischemic stroke in Tunisian and make a comparison with previous reports. A total of 102 young ischemic stroke patients (15-45 years old) were admitted, between January 1996 and August 2007, to 11 departments of internal medicine in different Tunisian hospitals. The risk factors for stroke were documented and assessed. Diagnosis workup consisted of anamnesis, complete physical examination and extensive laboratory, radiologic, immunologic, neurologic and cardiologic examination. Stroke etiologies were classified according the Trial of ORG 10172 in acute stroke treatment. There were 42 men (41.2%) and 60 women (58.89%) with a mean age at onset of 35.7 years. As regards stroke subtype, large-artery atherosclerosis was diagnosed in 6.9% of cases, cardioembolism in 11.8%, small-vessel occlusion in 8.8%, other determined etiology in 37.3% and undetermined etiology in 35.3%. Concerning the traditional risk factors, smoking (31.4%), hypertension and diabetes mellitus (12.7% for each one) and a family history of stroke (10.8%) were the most common. The mean follow-up period was 30.5 months. In our study, traditional risk factors were not-so-uncommon in young adults with ischemic stroke suggesting that prevention can go through controlling these factors. Stroke of other determined etiology was the most common among our patients, so that a broad and detailed diagnostic workup is crucial to puzzle out the etiology for more and better stroke prevention.

Glibenclamide reduces secondary brain damage after experimental traumatic brain injury.

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Zweckberger, K; Hackenberg, K; Jung, C S; Hertle, D N; Kiening, K L; Unterberg, A W; Sakowitz, O W

2014-07-11

Following traumatic brain injury (TBI) SUR1-regulated NCCa-ATP (SUR1/TRPM4) channels are transcriptionally up-regulated in ischemic astrocytes, neurons, and capillaries. ATP depletion results in depolarization and opening of the channel leading to cytotoxic edema. Glibenclamide is an inhibitor of SUR-1 and, thus, might prevent cytotoxic edema and secondary brain damage following TBI. Anesthetized adult Sprague-Dawley rats underwent parietal craniotomy and were subjected to controlled cortical impact injury (CCI). Glibenclamide was administered as a bolus injection 15min after CCI injury and continuously via osmotic pumps throughout 7days. In an acute trial (180min) mean arterial blood pressure, heart rate, intracranial pressure, encephalographic activity, and cerebral metabolism were monitored. Brain water content was assessed gravimetrically 24h after CCI injury and contusion volumes were measured by MRI scanning technique at 8h, 24h, 72h, and 7d post injury. Throughout the entire time of observation neurological function was quantified using the "beam-walking" test. Glibenclamide-treated animals showed a significant reduction in the development of brain tissue water content(80.47%±0.37% (glibenclamide) vs. 80.83%±0.44% (control); pbeam-walking test throughout 7days. In accordance to these results and the available literature, glibenclamide seems to have promising potency in the treatment of TBI. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Elevated lactate as an early marker of brain injury in inflicted traumatic brain injury

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Makoroff, Kathi L.; Cecil, Kim M.; Ball, William S.; Care, Marguerite

2005-01-01

Patients with inflicted traumatic brain injury and evidence of hypoxic-ischemic injury as indicated by elevated lactate on MRS tend to have worse early neurological status and early outcome scores. Lactate levels as sampled by MRS might predict early clinical outcome in inflicted traumatic brain injury. (orig.)

Astrocytes, therapeutic targets for neuroprotection and neurorestoration in ischemic stroke

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Liu, Zhongwu; Chopp, Michael

2015-01-01

Astrocytes are the most abundant cell type within the central nervous system. They play essential roles in maintaining normal brain function, as they are a critical structural and functional part of the tripartite synapses and the neurovascular unit, and communicate with neurons, oligodendrocytes and endothelial cells. After an ischemic stroke, astrocytes perform multiple functions both detrimental and beneficial, for neuronal survival during the acute phase. Aspects of the astrocytic inflammatory response to stroke may aggravate the ischemic lesion, but astrocytes also provide benefit for neuroprotection, by limiting lesion extension via anti-excitotoxicity effects and releasing neurotrophins. Similarly, during the late recovery phase after stroke, the glial scar may obstruct axonal regeneration and subsequently reduce the functional outcome; however, astrocytes also contribute to angiogenesis, neurogenesis, synaptogenesis, and axonal remodeling, and thereby promote neurological recovery. Thus, the pivotal involvement of astrocytes in normal brain function and responses to an ischemic lesion designates them as excellent therapeutic targets to improve functional outcome following stroke. In this review, we will focus on functions of astrocytes and astrocyte-mediated events during stroke and recovery. We will provide an overview of approaches on how to reduce the detrimental effects and amplify the beneficial effects of astrocytes on neuroprotection and on neurorestoration post stroke, which may lead to novel and clinically relevant therapies for stroke. PMID:26455456

Distribution of ischemic infarction and stenosis of intra- and extracranial arteries in young Chinese patients with ischemic stroke.

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Ojha, Rajeev; Huang, Dongya; An, Hedi; Liu, Rong; Du, Cui; Shen, Nan; Tu, Zhilan; Li, Ying

2015-11-23

The distribution of cerebral ischemic infarction and stenosis in ischemic stroke may vary with age-group, race and gender. This study was conducted to understand the risk factors and characteristics of cerebral infarction and stenosis of vessels in young Chinese patients with ischemic stroke. This was a retrospective study, from January 2007 to July 2012, of 123 patients ≤50 years diagnosed with acute ischemic stroke. Patient characteristics were compared according to sex (98 males and 25 females) and age group (51 patients were ≤45 years and 72 patients were 46-50 years). Characteristics of acute ischemic infarction were studied by diffusion weighted imaging. Stenosis of intra- and extracranial arteries was diagnosed by duplex sonography, head magnetic resonance angiography (MRA) or cervical MRA. Common risk factors were hypertension (72.4 %), dyslipidemia (55.3 %), smoking (54.4 %) and diabetes (33.3 %). Lacunar Infarction was most common in our patients (41.5 %). Partial anterior circulation infarction was predominant in females (52.0 vs 32.7 %; P = 0.073) and posterior circulation infarction in males (19.8 vs 4 %; P = 0.073). Multiple brain infarctions were found in 38 patients (30.9 %). Small artery atherosclerosis was found in 54 patients (43.9 %), with higher prevalence in patients of the 46-50 years age-group. Intracranial stenosis was more common than extracranial stenosis, and middle cerebral artery stenosis was most prevalent (27.3 %). Stenosis in the anterior circulation was more frequent than in the posterior circulation (P young patients, hypertension, smoking, dyslipidemia and diabetes were common risk factors. Intracranial stenosis was most common. The middle cerebral artery was highly vulnerable.

Toll-like receptor 2 deficiency leads to delayed exacerbation of ischemic injury

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Bohacek Ivan

2012-08-01

Full Text Available Abstract Background Using a live imaging approach, we have previously shown that microglia activation after stroke is characterized by marked and long-term induction of the Toll-like receptor (TLR 2 biophotonic signals. However, the role of TLR2 (and potentially other TLRs beyond the acute innate immune response and as early neuroprotection against ischemic injury is not well understood. Methods TLR2−/− mice were subjected to transient middle cerebral artery occlusion followed by different reperfusion times. Analyses assessing microglial activation profile/innate immune response were performed using in situ hybridization, immunohistochemistry analysis, flow cytometry and inflammatory cytokine array. The effects of the TLR2 deficiency on the evolution of ischemic brain injury were analyzed using a cresyl violet staining of brain sections with appropriate lesion size estimation. Results Here we report that TLR2 deficiency markedly affects post-stroke immune response resulting in delayed exacerbation of the ischemic injury. The temporal analysis of the microglia/macrophage activation profiles in TLR2−/− mice and age-matched controls revealed reduced microglia/macrophage activation after stroke, reduced capacity of resident microglia to proliferate as well as decreased levels of monocyte chemotactic protein-1 (MCP-1 and consequently lower levels of CD45high/CD11b+ expressing cells as shown by flow cytometry analysis. Importantly, although acute ischemic lesions (24 to 72 h were smaller in TLR2−/− mice, the observed alterations in innate immune response were more pronounced at later time points (at day 7 after initial stroke, which finally resulted in delayed exacerbation of ischemic lesion leading to larger chronic infarctions as compared with wild-type mice. Moreover, our results revealed that TLR2 deficiency is associated with significant decrease in the levels of neurotrophic/anti-apoptotic factor Insulin-like growth factor-1 (IGF-1

Diffusion-weighted magnetic resonance imaging (MRI) in acute brain stem infarction

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Narisawa, Aya; Shamoto, Hiroshi; Shimizu, Hiroaki; Tominaga, Teiji; Yoshimoto, Takashi

2001-01-01

Diffusion-weighted magnetic resonance imaging (DWI) provides one of the earliest demonstrations of ischemic lesions. However some lesions may be missed in the acute stage due to technical limitation of DWI. We therefore conducted the study to clarify the sensitivity of DWI to acute brain stem infarctions. Twenty-eight patients with the final diagnosis of brain stem infarction (midbrain 2, pons 9, medulla oblongata 17) who had been examined by DWI within 24 hours of onset were retrospectively analyzed for how sensitively the initial DWI demonstrated the final ischemic lesion. Only obvious (distinguishable with DWI alone without referring clinical symptoms and other informations) hyperintensity on DWI was regarded to show an ischemic lesion. Sixteen (57.1%) out of 28 patients had brain stem infarctions demonstrated by initial DWI. In the remaining 12 cases, no obvious ischemic lesion was evident on initial DWI. Subsequent MRI studies obtained 127 hours, on average after the onset showed infarction in the medulla oblongate in 11 cases and in the pons in one case. Negative findings of DWI in the acute stage does not exclude possibility of the brain stem infarction, in particularly medulla oblongata infarction. (author)

Platelet aggregation inhibitors in primary and secondary prevention of ischemic stroke

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von der Schulenburg, Johann-Matthias

2006-04-01

Full Text Available Background: The ischaemic stroke (IS is one of the most frequent cause of death in Germany. Besides of non-drug many drug-based interventions are used in primary or secondary prevention of IS, among them the thrombocyte aggregation inhibitors (TAI. Objectives: The evaluation addresses the questions on medical efficacy and cost-effectiveness of the TAI administration in the prevention of IS as compared to the management of risk factors alone as well as to the use of anticoagulant drugs. Methods: The literature search for articles published after 1997 was conducted in December 2003 in the most important medical and economic databases. The medical analysis was performed on the basis of the most up-to date meta-analyses of randomised controlled trials (RCT as well as of new published RCT. The data from the studies for stroke, bleeding complications as well as for the combined endpoint "severe vascular events" (SVE: death or stroke or myocardial infarction were summarised in meta-analyses.In order to include grey literature contact has been taken up with the pharmaceutical manufacturers of TAI. Results are presented in a descriptive way. Results: The medical analysis included data from 184 RCT (vs. placebo and from 22 RCT (vs. anticoagulant drugs. The absolute reduction of IS (4.8% vs. 6.6%; p<0,00001 and SVE (10.0% vs. 12.4%; p<0,00001 were definitely higher than the absolute increase of bleeding complications (1.6% vs. 0.9%; p<0,00001, but relatively similar to this absolute increase in a subpopulation with a low risk for SVE. With regard to the stroke prevention, evidence of efficacy could be yielded for acetylsalicil acid (ASA, dipyridamole, cilostazol, ridogrel and the combination ASA with dipyridamole. ASA is less effective than anticoagulants in the prevention of ischaemic stroke in atrial fibrillation, however, it causes fewer bleeding complications.Low dosed ASA can be considered cost-effective in secondary prevention of ischemic stroke

The fate of medications evaluated for ischemic stroke pharmacotherapy over the period 1995–2015

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Xiaoling Chen

2016-10-01

Full Text Available Stroke is a brain damage caused by a loss of blood supply to a portion of the brain, which requires prompt and effective treatment. The current pharmacotherapy for ischemic stroke primarily relies on thrombolysis using recombinant tissue plasminogen activators (rt-PAs to breakdown blood clots. Neuroprotective agents that inhibit excitatory neurotransmitters are also used to treat ischemic stroke but have failed to translate into clinical benefits. This poses a major challenge in biomedical research to understand what causes the progressive brain cell death after stroke and how to develop an effective pharmacotherapy for stroke. This brief review analyzes the fate of about 430 potentially useful stroke medications over the period 1995–2015 and describes in detail those that successfully reached the market. Hopefully, the information from this analysis will shed light on how future stroke research can improve stroke drug discovery.

Design and Rationale of the Intima-Medial Thickness Sub-Study of the PreventIon of CArdiovascular Events in iSchemic Stroke Patients with High Risk of Cerebral hemOrrhage (PICASSO-IMT) Study.

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Seo, Woo-Keun; Kim, Yong Jae; Lee, Juneyoung; Kwon, Sun U

2017-09-01

Atherosclerosis is one of the main mechanisms of stroke and cardiovascular diseases and is associated with increased risk of recurrent stroke and cardiovascular events. Intima-medial thickness (IMT) is a well-known surrogate marker of atherosclerosis and has been used to predict stroke and cardiovascular events. However, the clinical significance of IMT and IMT change in stroke has not been investigated in well-designed studies. The PreventIon of CArdiovascular events in iSchemic Stroke patients with high risk of cerebral hemOrrhage-Intima-Media Thickness (PICASSO-IMT) sub-study is designed to investigate the effects of cilostazol, probucol, or both on IMT in patients with stroke. PICASSO-IMT is a prospective sub-study of the PICASSO study designed to measure IMT and plaque score at 1, 13, 25, 37, and 49 months after randomization. The primary outcome is the change in mean carotid IMT, which is defined as the mean of the far-wall IMTs of the right and left common carotid arteries, between baseline and 13 months after randomization. PICASSO-IMT will provide the largest IMT data set in a stroke population and will provide valuable information about the clinical significance of IMT in patients with ischemic stroke. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

In vivo imaging of brain ischemia using an oxygen-dependent degradative fusion protein probe.

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Youshi Fujita

Full Text Available Within the ischemic penumbra, blood flow is sufficiently reduced that it results in hypoxia severe enough to arrest physiological function. Nevertheless, it has been shown that cells present within this region can be rescued and resuscitated by restoring perfusion and through other protective therapies. Thus, the early detection of the ischemic penumbra can be exploited to improve outcomes after focal ischemia. Hypoxia-inducible factor (HIF-1 is a transcription factor induced by a reduction in molecular oxygen levels. Although the role of HIF-1 in the ischemic penumbra remains unknown, there is a strong correlation between areas with HIF-1 activity and the ischemic penumbra. We recently developed a near-infrared fluorescently labeled-fusion protein, POH-N, with an oxygen-dependent degradation property identical to the alpha subunit of HIF-1. Here, we conduct in vivo imaging of HIF-active regions using POH-N in ischemic brains after transient focal cerebral ischemia induced using the intraluminal middle cerebral artery occlusion technique in mice. The results demonstrate that POH-N enables the in vivo monitoring and ex vivo detection of HIF-1-active regions after ischemic brain injury and suggest its potential in imaging and drug delivery to HIF-1-active areas in ischemic brains.

[New approaches in neurosurgery and hyperbaric medicine--the importance of preventive and industrial medicine].

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Kohshi, K; Munaka, M; Abe, H; Tosaki, T

1999-12-01

Neurosurgical patients have been mainly treated by surgical procedures over the past decades. In addition, hyperbaric oxygen (HBO) therapy in neurosurgery has been used in patients with ischemic cerebrovascular diseases, head trauma, spinal damage, postoperative brain edema and others. However, the main therapeutic methods for neurosurgical diseases have changed dramatically due to developments in radiological techniques, such as radiosurgery and intravascular surgery. With changes in therapeutic methods, HBO therapy may become a very important treatment option for neurosurgical patients. For example, HBO therapy combined with radiotherapy (UOEH regimen) and anticoagulant therapy appear to be very effective in the treatments of malignant brain tumors and ischemic cerebrovascular diseases, respectively. On the other hand, medical examinations under hyper- and hypobaric environments have not yet been fully studied in the central nervous system compared to those in the cardiopulmonary systems. Moreover, the mechanisms of cerebral lesions in decompression sickness and acute mountain sickness remain unclear. Clinical neurologic approaches are very important in these fields. Hence, clinicians and researchers skilled in both neurosurgery and hyperbaric medicine will be required for advanced treatment and preventive and industrial medicine.

Effects of Cannabidiol and Hypothermia on Short-Term Brain Damage in New-Born Piglets after Acute Hypoxia-Ischemia

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Lafuente, Hector; Pazos, Maria R.; Alvarez, Antonia; Mohammed, Nagat; Santos, Martín; Arizti, Maialen; Alvarez, Francisco J.; Martinez-Orgado, Jose A.

2016-01-01

Hypothermia is a standard treatment for neonatal encephalopathy, but nearly 50% of treated infants have adverse outcomes. Pharmacological therapies can act through complementary mechanisms with hypothermia improving neuroprotection. Cannabidiol could be a good candidate. Our aim was to test whether immediate treatment with cannabidiol and hypothermia act through complementary brain pathways in hypoxic-ischemic newborn piglets. Hypoxic-ischemic animals were randomly divided into four groups receiving 30 min after the insult: (1) normothermia and vehicle administration; (2) normothermia and cannabidiol administration; (3) hypothermia and vehicle administration; and (4) hypothermia and cannabidiol administration. Six hours after treatment, brains were processed to quantify the number of damaged neurons by Nissl staining. Proton nuclear magnetic resonance spectra were obtained and analyzed for lactate, N-acetyl-aspartate and glutamate. Metabolite ratios were calculated to assess neuronal damage (lactate/N-acetyl-aspartate) and excitotoxicity (glutamate/Nacetyl-aspartate). Western blot studies were performed to quantify protein nitrosylation (oxidative stress), content of caspase-3 (apoptosis) and TNFα (inflammation). Individually, the hypothermia and the cannabidiol treatments reduced the glutamate/Nacetyl-aspartate ratio, as well as TNFα and oxidized protein levels in newborn piglets subjected to hypoxic-ischemic insult. Also, both therapies reduced the number of necrotic neurons and prevented an increase in lactate/N-acetyl-aspartate ratio. The combined effect of hypothermia and cannabidiol on excitotoxicity, inflammation and oxidative stress, and on cell damage, was greater than either hypothermia or cannabidiol alone. The present study demonstrated that cannabidiol and hypothermia act complementarily and show additive effects on the main factors leading to hypoxic-ischemic brain damage if applied shortly after the insult. PMID:27462203

Effects of radiation dose reduction in Volume Perfusion CT imaging of acute ischemic stroke

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Othman, Ahmed E.; Brockmann, Carolin; Afat, Saif; Pjontek, Rastislav; Nikobashman, Omid; Brockmann, Marc A.; Wiesmann, Martin; Yang, Zepa; Kim, Changwon; Kim, Jong Hyo

2015-01-01

To examine the influence of radiation dose reduction on image quality and sensitivity of Volume Perfusion CT (VPCT) maps regarding the detection of ischemic brain lesions. VPCT data of 20 patients with suspected ischemic stroke acquired at 80 kV and 180 mAs were included. Using realistic reduced-dose simulation, low-dose VPCT datasets with 144 mAs, 108 mAs, 72 mAs and 36 mAs (80 %, 60 %, 40 % and 20 % of the original levels) were generated, resulting in a total of 100 datasets. Perfusion maps were created and signal-to-noise-ratio (SNR) measurements were performed. Qualitative analyses were conducted by two blinded readers, who also assessed the presence/absence of ischemic lesions and scored CBV and CBF maps using a modified ASPECTS-score. SNR of all low-dose datasets were significantly lower than those of the original datasets (p <.05). All datasets down to 72 mAs (40 %) yielded sufficient image quality and high sensitivity with excellent inter-observer-agreements, whereas 36 mAs datasets (20 %) yielded poor image quality in 15 % of the cases with lower sensitivity and inter-observer-agreements. Low-dose VPCT using decreased tube currents down to 72 mAs (40 % of original radiation dose) produces sufficient perfusion maps for the detection of ischemic brain lesions. (orig.)

Early behavioral intervention, brain plasticity, and the prevention of autism spectrum disorder.

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Dawson, Geraldine

2008-01-01

Advances in the fields of cognitive and affective developmental neuroscience, developmental psychopathology, neurobiology, genetics, and applied behavior analysis have contributed to a more optimistic outcome for individuals with autism spectrum disorder (ASD). These advances have led to new methods for early detection and more effective treatments. For the first time, prevention of ASD is plausible. Prevention will entail detecting infants at risk before the full syndrome is present and implementing treatments designed to alter the course of early behavioral and brain development. This article describes a developmental model of risk, risk processes, symptom emergence, and adaptation in ASD that offers a framework for understanding early brain plasticity in ASD and its role in prevention of the disorder.

Reconsideration of Secondary Risk Management Strategies in Patients with Ischemic Heart Disease.

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Kashiyama, Kuninobu; Sonoda, Shinjo; Otsuji, Yutaka

2017-01-01

The main risk factors in ischemic heart diseases, including myocardial infarction, are hypertension, dyslipidemia, diabetes, obesity and smoking. The incidence of ischemic heart disease in Japan has been lower than that in Western countries because of differences in lifestyle and the anatomy of the coronary arteries, but the situation has been changing recently because of the westernization of lifestyle. Cardiovascular diseases have become the second most common cause of death in Japan, and 40% of those deaths are attributed to ischemic heart disease. Patients with a history of myocardial infarction, especially, have an increased risk of re-infarction, so strict management of coronary risk factors is important for the prevention of secondary ischemic heart disease. Although there are many guidelines about how to manage the risk factors, there are still many problems. Although lipid management has been demonstrated to have a protective effect against coronary artery disease and arteriosclerotic guidelines have been developed, it is reported that only about one third of patients achieved the low-density lipoprotein (LDL) target value under secondary prevention. Moreover, it is unclear whether the lower target value is required for high-risk patients. Recent research on diabetes has reported increased mortality in patients with intensive glycemic control. We should discuss when to start treatment, which medicine to use, and to what extent we should manage glycemic control. Strict management based on current therapeutic guidelines is effective for secondary prevention of ischemic heart disease, with target values of less than 135/85 mmHg for home blood pressure, less than 100 mg/dl for LDL-C, more than 40 mg/dl for HDL-C, less than 150 mg/dl for TG, and, for diabetic patients, less than 7.0% for HbA1c (NGSP).

Specific uptake of DHA by the brain from a structured phospholipid, AceDoPC®

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Bernoud-Hubac Nathalie

2017-03-01

Full Text Available Docosahexaenoic acid (DHA; 22:6 ω-3 is highly enriched in the brain and is required for proper brain development and function. Its deficiency has been shown to be linked with the emergence of neurological diseases. Dietary ω-3 fatty acid supplements including DHA have been suggested to improve neuronal development and enhance cognitive functions. Findings suggested that DHA is better incorporated into the brain when esterified at the sn-2 position of a lysophosphatidylcholine (LysoPC-DHA. AceDoPC® is a structured phospholipid or acetyl-LysoPC-DHA. As previously shown for LysoPC-DHA, AceDoPC® is a specific and preferred carrier of DHA to the brain. When AceDoPC® was injected to rats that were subjected to an ischemic stroke, it prevents the extension of brain lesions. Regarding the essential role of DHA for cerebral functions, targeting the brain with specific carriers of DHA might provide novel therapeutic approaches to neurodegenerative diseases.

Regional cerebral blood flow in patients with transient ischemic attacks studied by Xenon-133 inhalation and emission tomography

International Nuclear Information System (INIS)

Vorstrup, S.; Hemmingsen, R.; Henriksen, L.; Lindewald, H.; Engell, H.C.; Lassen, N.A.

1983-01-01

Cerebral blood flow CBF was studied in 14 patients with transient ischemic attacks TIA and arteriosclerotic neck vessel disease. CBF was measured by a rapidly rotating single photon emission computerized tomograph using Xenon-133 inhalation. This method yields images of 3 brain slices depicting CBF with a spatial resolution of 1.7 cm. Based primarily on the clinical evidence and on the angiographical findings embolism was considered the pathogenetic factor in 10 cases, whereas chronic hemodynamic insufficiency rendered symptomatic by postural factors probably accounted for the symptoms in 4 patients. Of the 14 patients, all studied days to weeks after the most recent TIA, four showed hypoperfused areas on the CBF-tomograms and with roughly the same location hypodense areas on CT-scanning, i.e. areas of complete infarction. However, an additional five patients showed reduction of CBF in areas with no abnormality on the CT-scan. The abnormal blood flow pattern was found to be unchanged after clinically successful reconstructive vascular surgery. This suggests the presence of irreversible ischemic tissue damage without gross emollition (incomplete infarction). It is concluded, that TIAs are often harmful events, as no less than 9 of the 14 patients studied had evidence of complete and/or incomplete infarction. Thorough examination and rational therapy should be instituted as soon as possible to prevent further ischemic lesions

[Brain repair after ischemic stroke: role of neurotransmitters in post-ischemic neurogenesis].

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Sánchez-Mendoza, Eduardo; Bellver-Landete, Víctor; González, María Pilar; Merino, José Joaquín; Martínez-Murillo, Ricardo; Oset-Gasque, María Jesús

2012-11-01

Brain ischemia and reperfusion produce alterations in the microenvironment of the parenchyma, including ATP depletion, ionic homeostasis alterations, inflammation, release of multiple cytokines and abnormal release of neurotransmitters. As a consequence, the induction of proliferation and migration of neural stem cells towards the peri-infarct region occurs. The success of new neurorestorative treatments for damaged brain implies the need to know, with greater accuracy, the mechanisms in charge of regulating adult neurogenesis, both under physiological and pathological conditions. Recent evidence demonstrates that many neurotransmitters, glutamate in particular, control the subventricular zone, thus being part of the complex signalling network that influences the production of new neurons. Neurotransmitters provide a link between brain activity and subventricular zone neurogenesis. Therefore, a deeper knowledge of the role of neurotransmitters systems, such as glutamate and its transporters, in adult neurogenesis, may provide a valuable tool to be used as a neurorestorative therapy in this pathology.

Hypercholesterolemia in patients of ischemic stroke

International Nuclear Information System (INIS)

Saeed, E.; Ali, R.; Din, M.J.U.; Saeed, A.; Jadoon, R.J.

2015-01-01

Background: Stroke is a common neurological disease that results in significant mortality and morbidity globally. Several risk factors have been identified for stroke among which hyperlipidaemia is one of the modifiable risk factors. Recent clinical trials have shown a reduction in ischemic stroke for patients taking lipid lowering medications. Therefore, the aim of this study was to find out the frequency of hypercholesterolemia in patients of ischemic stroke in Hazara region. Method: This cross sectional study was carried out in the Medical Department of Ayub Teaching Hospital, Abbottabad. Ninety patients of stroke confirmed as ischemic by CT scan brain were enrolled in the study after informed consent. The frequency of hypercholesterolemia in patients was recorded. Results: There were 55 (61.1 percentage) males. The mean age of patients was 64.4±11.5 years. The mean serum cholesterol in all patients was 4.16±1.1 mmol/l. The mean serum cholesterol of male patients was 4.3±1.2 mmol/l and 4.0±10.9 mmol/l in the case of females. Conclusions: Hypercholesterolemia could not be established as a major risk factor for stroke in our setup through this study that allude to the fact that other risk factors might be contributing more to the incidence of cerebrovascular accident in our population. (author)

EEG and MR Spectroscopy in Hypoxic-Ischemic Encephalopathy in Term Newborns

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J Gordon Millichap

2010-01-01

Researchers from the University of Bologna, Italy, studied the relation of amplitude integrated EEG findings in the first 24 hrs of life to brain metabolic changes, detected by proton MR spectroscopy (H-MRS) at 7-10 days of life, in 32 term newborns with hypoxic-ischemic encephalopathy (HIE).

Fluoro-Jade and TUNEL staining as useful tools to identify ischemic brain damage following moderate extradural compression of sensorimotor cortex.

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Kundrotiene, Jurgita; Wägner, Anna; Liljequist, Sture

2004-01-01

Cerebral ischemia was produced by moderate compression for 30 min of a specific brain area in the sensorimotor cortex of Sprague-Dawley rats. On day 1, that is 24 h after the transient sensorimotor compression, ischemia-exposed animals displayed a marked focal neurological deficit documented as impaired beam walking performance. This functional disturbance was mainly due to contralateral fore- and hind-limb paresis. As assessed by daily beam walking tests it was shown that there was a spontaneous recovery of motor functions over a period of five to seven days after the ischemic event. Using histopathological analysis (Nissl staining) we have previously reported that the present experimental paradigm does not produce pannecrosis (tissue cavitation) despite the highly reproducible focal neurological deficit. We now show how staining with fluorescent markers for neuronal death, that is Fluoro-Jade and TUNEL, respectively, identifies regional patterns of selective neuronal death. These observations add further support to the working hypothesis that the brain damage caused by cortical compression-induced ischemia consists of scattered, degenerating neurons in specific brain regions. Postsurgical administration of the AMPA receptor specific antagonist, LY326325 (30 mg/kg; i.p., 70 min after compression), not only improved beam walking performance on day 1 to 3, respectively but also significantly reduced the number of Fluoro-Jade stained neurons on day 5. These results suggest that enhanced AMPA/glutamate receptor activity is at least partially responsible for the ischemia-produced brain damage detected by the fluorescent marker Fluoro-Jade.

Effectiveness of mesenchymal stems cells cultured by hanging drop vs. conventional culturing on the repair of hypoxic-ischemic-damaged mouse brains, measured by stemness gene expression

OpenAIRE

Lou Yongli; Guo Dewei; Zhang Hui; Song Laijun

2016-01-01

In this study, we investigated the therapeutic effects of Human Mesenchymal Stem Cells (hMSCs) cultured by hanging drop and conventional culturing methods on cerebellar repair in hypoxic-ischemic (HI) brain injured mice. Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to analyze the expression levels of three stemness genes, Oct4, Sox2 and Nanog, and the migration related gene CXCR4. MSC prepared by hanging drop or conventional techniques were adminis...

Protective effects of the angiotensin II ATreceptor agonist compound 21 in ischemic stroke

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Bennion, Douglas M; Jones, Chad H; Dang, Alex N

2018-01-01

) and systemic administration, are unsuitable for translation into humans; in the latter case because AT2receptor agonists are blood-brain barrier (BBB) impermeable. To circumvent this problem, in the current study we utilized the nose-to-brain (N2B) route of administration to bypass the BBB and deliver...... in certain human central nervous system diseases, the N2B application of AT2receptor agonists may become a viable mode of delivering these neuroprotective agents for human ischemic stroke patients.......-administered C21 did not affect blood pressure or heart rate. Thus, these data provide proof-of-principle for the idea that N2B application of an AT2receptor agonist can exert neuroprotective actions when administered following ischemic stroke. Since N2B delivery of other agents has been shown to be effective...

Limb Remote Ischemic Conditioning: Mechanisms, Anesthetics, and the Potential for Expanding Therapeutic Options

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Chen, Gangling; Thakkar, Mrugesh; Robinson, Christopher; Doré, Sylvain

2018-01-01

Novel and innovative approaches are essential in developing new treatments and improving clinical outcomes in patients with ischemic stroke. Remote ischemic conditioning (RIC) is a series of mechanical interruptions in blood flow of a distal organ, following end organ reperfusion, shown to significantly reduce infarct size through inhibition of oxidation and inflammation. Ischemia/reperfusion (I/R) is what ultimately leads to the irreversible brain damage and clinical picture seen in stroke patients. There have been several reports and reviews about the potential of RIC in acute ischemic stroke; however, the focus here is a comprehensive look at the differences in the three types of RIC (remote pre-, per-, and postconditioning). There are some limited uses of preconditioning in acute ischemic stroke due to the unpredictability of the ischemic event; however, it does provide the identification of biomarkers for clinical studies. Remote limb per- and postconditioning offer a more promising treatment during patient care as they can be harnessed during or after the initial ischemic insult. Though further research is needed, it is imperative to discuss the importance of preclinical data in understanding the methods and mechanisms involved in RIC. This understanding will facilitate translation to a clinically feasible paradigm for use in the hospital setting. PMID:29467715

A Novel Rodent Model of Posterior Ischemic Optic Neuropathy

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Wang, Yan; Brown, Dale P.; Duan, Yuanli; Kong, Wei; Watson, Brant D.; Goldberg, Jeffrey L.

2014-01-01

Objectives To develop a reliable, reproducible rat model of posterior ischemic optic neuropathy (PION) and study the cellular responses in the optic nerve and retina. Methods Posterior ischemic optic neuropathy was induced in adult rats by photochemically induced ischemia. Retinal and optic nerve vasculature was examined by fluorescein isothiocyanate–dextran extravasation. Tissue sectioning and immunohistochemistry were used to investigate the pathologic changes. Retinal ganglion cell survival at different times after PION induction, with or without neurotrophic application, was quantified by fluorogold retrograde labeling. Results Optic nerve injury was confirmed after PION induction, including local vascular leakage, optic nerve edema, and cavernous degeneration. Immunostaining data revealed microglial activation and focal loss of astrocytes, with adjacent astrocytic hypertrophy. Up to 23%, 50%, and 70% retinal ganglion cell loss was observed at 1 week, 2 weeks, and 3 weeks, respectively, after injury compared with a sham control group. Experimental treatment by brain-derived neurotrophic factor and ciliary neurotrophic factor remarkably prevented retinal ganglion cell loss in PION rats. At 3 weeks after injury, more than 40% of retinal ganglion cells were saved by the application of neurotrophic factors. Conclusions Rat PION created by photochemically induced ischemia is a reproducible and reliable animal model for mimicking the key features of human PION. Clinical Relevance The correspondence between the features of this rat PION model to those of human PION makes it an ideal model to study the pathophysiologic course of the disease, most of which remains to be elucidated. Furthermore, it provides an optimal model for testing therapeutic approaches for optic neuropathies. PMID:23544206

Pathways to ischemic neuronal cell death: are sex differences relevant?

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McCullough Louise D

2008-06-01

Full Text Available Abstract We have known for some time that the epidemiology of human stroke is sexually dimorphic until late in life, well beyond the years of reproductive senescence and menopause. Now, a new concept is emerging: the mechanisms and outcome of cerebral ischemic injury are influenced strongly by biological sex as well as the availability of sex steroids to the brain. The principal mammalian estrogen (17 β estradiol or E2 is neuroprotective in many types of brain injury and has been the major focus of investigation over the past several decades. However, it is becoming increasingly clear that although hormones are a major contributor to sex-specific outcomes, they do not fully account for sex-specific responses to cerebral ischemia. The purpose of this review is to highlight recent studies in cell culture and animal models that suggest that genetic sex determines experimental stroke outcome and that divergent cell death pathways are activated after an ischemic insult. These sex differences need to be identified if we are to develop efficacious neuroprotective agents for use in stroke patients.

Intranasally administered mesenchymal stem cells promote a regenerative niche for repair of neonatal ischemic brain injury.

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Donega, Vanessa; Nijboer, Cora H; van Tilborg, Geralda; Dijkhuizen, Rick M; Kavelaars, Annemieke; Heijnen, Cobi J

2014-11-01

Previous work from our group has shown that intranasal MSC-treatment decreases lesion volume and improves motor and cognitive behavior after hypoxic-ischemic (HI) brain damage in neonatal mice. Our aim was to determine the kinetics of MSC migration after intranasal administration, and the early effects of MSCs on neurogenic processes and gliosis at the lesion site. HI brain injury was induced in 9-day-old mice and MSCs were administered intranasally at 10days post-HI. The kinetics of MSC migration were investigated by immunofluorescence and MRI analysis. BDNF and NGF gene expression was determined by qPCR analysis following MSC co-culture with HI brain extract. Nestin, Doublecortin, NeuN, GFAP, Iba-1 and M1/M2 phenotypic expression was assessed over time. MRI and immunohistochemistry analyses showed that MSCs reach the lesion site already within 2h after intranasal administration. At 12h after administration the number of MSCs at the lesion site peaks and decreases significantly at 72h. The number of DCX(+) cells increased 1 to 3days after MSC administration in the SVZ. At the lesion, GFAP(+)/nestin(+) and DCX(+) expression increased 3 to 5days after MSC-treatment. The number of NeuN(+) cells increased within 5days, leading to a dramatic regeneration of the somatosensory cortex and hippocampus at 18days after intranasal MSC administration. Interestingly, MSCs expressed significantly more BDNF gene when exposed to HI brain extract in vitro. Furthermore, MSC-treatment resulted in the resolution of the glial scar surrounding the lesion, represented by a decrease in reactive astrocytes and microglia and polarization of microglia towards the M2 phenotype. In view of the current lack of therapeutic strategies, we propose that intranasal MSC administration is a powerful therapeutic option through its functional repair of the lesion represented by regeneration of the cortical and hippocampal structure and decrease of gliosis. Copyright © 2014. Published by Elsevier Inc.

Texture analysis of computed tomography images of acute ischemic stroke patients

International Nuclear Information System (INIS)

Oliveira, M.S.; Castellano, G.; Fernandes, P.T.; Avelar, W.M.; Santos, S.L.M.; Li, L.M.

2009-01-01

Computed tomography (CT) images are routinely used to assess ischemic brain stroke in the acute phase. They can provide important clues about whether to treat the patient by thrombolysis with tissue plasminogen activator. However, in the acute phase, the lesions may be difficult to detect in the images using standard visual analysis. The objective of the present study was to determine if texture analysis techniques applied to CT images of stroke patients could differentiate between normal tissue and affected areas that usually go unperceived under visual analysis. We performed a pilot study in which texture analysis, based on the gray level co-occurrence matrix, was applied to the CT brain images of 5 patients and of 5 control subjects and the results were compared by discriminant analysis. Thirteen regions of interest, regarding areas that may be potentially affected by ischemic stroke, were selected for calculation of texture parameters. All regions of interest for all subjects were classified as lesional or non-lesional tissue by an expert neuroradiologist. Visual assessment of the discriminant analysis graphs showed differences in the values of texture parameters between patients and controls, and also between texture parameters for lesional and non-lesional tissue of the patients. This suggests that texture analysis can indeed be a useful tool to help neurologists in the early assessment of ischemic stroke and quantification of the extent of the affected areas. (author)

Dolichoectasia and Small Vessel Disease in Young Patients With Transient Ischemic Attack and Stroke.

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Thijs, Vincent; Grittner, Ulrike; Fazekas, Franz; McCabe, Dominick J H; Giese, Anne-Katrin; Kessler, Christof; Martus, Peter; Norrving, Bo; Ringelstein, Erich Bernd; Schmidt, Reinhold; Tanislav, Christian; Putaala, Jukka; Tatlisumak, Turgut; von Sarnowski, Bettina; Rolfs, Arndt; Enzinger, Christian

2017-09-01

We evaluated whether basilar dolichoectasia is associated with markers of cerebral small vessel disease in younger transient ischemic attack and ischemic stroke patients. We used data from the SIFAP1 study (Stroke in Young Fabry Patients), a large prospective, hospital-based, screening study for Fabry disease in young (ischemic attack/stroke patients in whom detailed clinical data and brain MRI were obtained, and stroke subtyping with TOAST classification (Trial of ORG 10172 in Acute Stroke Treatment) was performed. Dolichoectasia was found in 508 of 3850 (13.2%) of patients. Dolichoectasia was associated with older age (odds ratio per decade, 1.26; 95% confidence interval, 1.09-1.44), male sex (odds ratio, 1.96; 95% confidence interval, 1.59-2.42), and hypertension (odds ratio, 1.39; 95% confidence interval, 1.13-1.70). Dolichoectasia was more common in patients with small infarctions (33.9% versus 29.8% for acute lesions, P =0.065; 29.1% versus 16.5% for old lesions, P ischemic attack and ischemic stroke. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00414583. © 2017 American Heart Association, Inc.

Hypoxic ischemic encephalopathy in children : CT findings related to prognosis

International Nuclear Information System (INIS)

Cho, Jae Min; Il, Yim Byung; Kim, Ok Hwa; Kang, Doo Kyoung; Suh, Jung Ho

1997-01-01

To evaluate prognosis-related CT findings in hypoxic ischemic encephalopathy. For the purpose of prognosis, 28 children with a clinical history and CT findings suggestive of hypoxic ischemic encephalopathy (HIE) were restrospectively reviewed. The diagnostic criteria for HIE, as seen on CT scanning, were as follows : 1, ventricular collapse;2, effacement of cortical sulci;3, prominent enhancement of cortical vessels;4, poor differentiation of gray and white matter;5, reversal sign;6, obliteration of perimesencephalic cistern;7, high density on tentorial edge, as seen on precontrast scans;and 8, low density in thalamus, brain stem and basal ganglia. On the basis of clinical outcome, we divided the patients into three groups, as follows:group I(good prognosis);group II(neurologic sequelae), and group III(vegetative state or expire), and among these, compared CT findings. There were thirteen patients in group I, six in group II, and nine in group III. Ventricular collapse, effacement of cortical sulci, and prominent enhancement of cortical vessels were noted in all groups, whereas poor differentiation of gray and white matter, reversal sign, obliteration of perimesencephalic cistern, high density on tentorial edge, on precontrast scan, and low density in brain stem and basal ganglia were observed only in groups II and III. CT findings showed distinct differences between groups in whom prognosis was good, and in whom it was poor. An awareness of poor prognostic CT findings may be clinically helpful in the evaluation of patients with hypoxic ischemic encephalopathy

Smoking and Risk of Ischemic Stroke in Young Men.

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Markidan, Janina; Cole, John W; Cronin, Carolyn A; Merino, Jose G; Phipps, Michael S; Wozniak, Marcella A; Kittner, Steven J

2018-05-01

There is a strong dose-response relationship between smoking and risk of ischemic stroke in young women, but there are few data examining this association in young men. We examined the dose-response relationship between the quantity of cigarettes smoked and the odds of developing an ischemic stroke in men under age 50 years. The Stroke Prevention in Young Men Study is a population-based case-control study of risk factors for ischemic stroke in men ages 15 to 49 years. The χ 2 test was used to test categorical comparisons. Logistic regression models were used to calculate the odds ratio for ischemic stroke occurrence comparing current and former smokers to never smokers. In the first model, we adjusted solely for age. In the second model, we adjusted for potential confounding factors, including age, race, education, hypertension, myocardial infarction, angina, diabetes mellitus, and body mass index. The study population consisted of 615 cases and 530 controls. The odds ratio for the current smoking group compared with never smokers was 1.88. Furthermore, when the current smoking group was stratified by number of cigarettes smoked, there was a dose-response relationship for the odds ratio, ranging from 1.46 for those smoking strong dose-response relationship between the number of cigarettes smoked daily and ischemic stroke among young men. Although complete smoking cessation is the goal, even smoking fewer cigarettes may reduce the risk of ischemic stroke in young men. © 2018 American Heart Association, Inc.

Painless Legs and Moving Toes as an Initial Presentation of Ischemic Stroke

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Se Mi Oh

2009-05-01

Full Text Available Painless legs and moving toes is an unusual syndrome, which has not previously been reported as an initial presentation of ischemic stroke. We encountered a 78-year-old woman who developed dysarthria and involuntary movement of her left toes that was clinically regarded as painless legs and moving toes. These symptoms appeared abruptly and simultaneously as the initial symptoms of stroke, and improved gradually with conservative management by intravenous hydration for a month. We suggest that, in our case, a cortical brain lesion caused by ischemic stroke might be associated with the development of painless legs and moving toes.

Diagnostic evaluation of brain SPECT imaging in diseases of nervous system

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Yongsheng, Jiang; Chengmo, Zhu; Jixian, Zhang; Weijia, Tian [Shanghai Second Medical Univ. (China). Ruijing Hospital

1992-11-01

The dynamic distributions of home made ECD and the Amersham brain SPECT imaging agent 'Ceretec' in normal person as well as their diagnostic use in diseases of nervous system were investigated. Semi-quantitative analysis combined with direct observation was more accurate for the diagnosis. Aside from cerebrovascular diseases, SPECT brain imaging has its unique value for the diagnosis of transient ischemic attack, Alzheimer disease, multiple ischemic dementia and epilepsy etc.

Early cerebral hemodynamic, metabolic and histological changes in hypoxic-ischemic fetal lambs during postnatal life

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Carmen eRey-Santano

2011-09-01

Full Text Available The hemodynamic, metabolic and biochemical changes produce during transition from fetal to neonatal life could be aggravated if asphyctic event occur during fetal life. The aim of the study was to examine the regional cerebral blood flow (RCBF, histological changes, and cerebral brain metabolism in preterm lambs, and to analyze the role of oxidative stress for the first hours of postnatal life following severe fetal asphyxia. 18 chronically instrumented fetal lambs were assigned to: hypoxic-ischemic group, following fetal asphyxia animals were delivered and maintained on intermittent-positive-pressure-ventilation for 3 hours, and non-injured animals that were managed similarly to the previous group and used as control group. During hypoxic-ischemic insult, injured group developed acidosis, hypoxia, hypercapnia, latacidaemia and tachycardia in comparison to control group, without hypotension. Intermittent-positive-pressure-ventilation transiently improved gas exchange and cardiovascular parameters. After HI injury and during ventilation-support, the increased RCBF in inner zones was maintained for hypoxic-ischemic group, but cortical flow did not exhibit differences compared to the control group. Also, the increase of TUNEL positive cells (apoptosis and antioxidant enzymes, and decrease of ATP reserves was significantly higher in the brain regions where the RCBF were not increased.In conclusion, early metabolic, histological and hemodynamic changes involved in brain damage have been intensively investigated and reported in premature asphyctic lambs for the first 3 hours of postnatal life. Those changes have been described in human neonates, so our model could be useful to test the security and the effectiveness of different neuroprotective or ventilatory strategies when are applied in the first hours after fetal hypoxic-ischemic injury.

Selected acute phase CSF factors in ischemic stroke: findings and prognostic value

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Intskirveli Nino

2011-03-01

Full Text Available Abstract Background Study aimed at investigation of pathogenic role and prognostic value of several selected cerebrospinal fluid acute phase factors that can reflect the severity of ischemic brain damage. Methods Ninety five acute ischemic stroke patients were investigated. Ischemic region visualized at the twenty fourth hour by conventional Magnetic Resonance Imaging. Stroke severity evaluated by National Institute Health Stroke Scale. One month outcome of disease was assessed by Barthel Index. Cerebrospinal fluid was taken at the sixth hour of stroke onset. CSF pro- and anti-inflammatory cytokines were studied by Enzyme Linked Immunosorbent Assay. Nitric Oxide and Lipoperoxide radical were measured by Electron Paramagnetic Resonance. CSF Nitrate levels were detected using the Griess reagent. Statistics performed by SPSS-11.0. Results At the sixth hour of stroke onset, cerebrospinal fluid cytokine levels were elevated in patients against controls. Severe stroke patients had increased interleukin-6 content compared to less severe strokes (P Conclusion According to present study the cerebrospinal fluid contents of interleukin-6 and nitrates seem to be the most reliable prognostic factors in acute phase of ischemic stroke.

Coronary heart disease risk in patients with stroke or transient ischemic attack and no known coronary heart disease: findings from the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial

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Amarenco, Pierre; Goldstein, Larry B; Sillesen, Henrik

2010-01-01

Noncoronary forms of atherosclerosis (including transient ischemic attacks or stroke of carotid origin or >50% stenosis of the carotid artery) are associated with a 10-year vascular risk of >20% and are considered as a coronary heart disease (CHD) -risk equivalent from the standpoint of lipid...... management. The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial included patients with stroke or transient ischemic attack and no known CHD regardless of the presence of carotid atherosclerosis. We evaluated the risk of developing clinically recognized CHD in SPARCL patients....

Effects of hypoxic–ischemic brain injury on striatal dopamine transporter in newborn piglets: evaluation of 11C-CFT PET/CT for DAT quantification

International Nuclear Information System (INIS)

Zhang Yanfen; Wang Xiaoyu; Cao Li; Guo Qiyong; Wang Xiaoming

2011-01-01

Introduction: Alterations of dopamine in striatal presynaptic terminals play an important role in the hypoxic–ischemic (HI) brain injury. Quantification of DAT levels in the presynaptic site using 11 C-N-2-carbomethoxy-3-(4-fluorophenyl)-tropane ( 11 C-CFT) with positron emission tomography (PET) was applied in studies for Parkinson's disease. The current study investigated the changes in striatal DAT following HI brain injury in newborn piglets using 11 C-CFT PET. Methods: Newborn piglets were subjected to occlusion of bilateral common carotid arteries for 30 min and simultaneous peripheral hypoxia. Brain DAT imaging was performed using PET/CT with 11 C-CFT as the probe in each group (including the control group and HI insult groups). Brain tissues were collected for DAT immunohistochemical (IHC) analysis at each time point post the PET/CT procedure. Sham controls had some operation without HI procedure. Results: A few minutes after intravenous injection of 11 C-CFT, radioactive signals for DAT clearly appeared in the cortical area, striatum and cerebellum of newborn piglets of sham control group and HI insult groups. HI brain insult markedly increased striatal DAT at an early period (P 11 C-CFT PET imaging data and IHC DAT staining data were highly correlated (r=0.844, P 11 C-CFT PET/CT imaging data reflected the dynamic changes of DAT in the striatum in vivo.

Transcatheter closure of patent foramen ovale for secondary prevention of ischemic stroke: Quantitative synthesis of pooled randomized trial data.

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Hakeem, Abdul; Cilingiroglu, Mehmet; Katramados, Angelos; Boudoulas, Konstantinos Dean; Iliescu, Cezar; Gundogdu, Betul; Marmagkiolis, Konstantinos

2018-01-14

To evaluate the safety and efficacy of percutaneous device closure of patent foramen ovale (PFO) for secondary prevention of ischemic stroke BACKGROUND: Stroke remains the leading cause of serious long-term disability in the United States. The effectiveness of a percutaneous PFO closure in the prevention of recurrent cryptogenic strokes has not been established. We performed a literature search using PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Google Scholar, and Internet-based sources from January 2003 to September 2017. Randomized controlled trails (RCTs) comparing percutaneous PFO closure to medical therapy alone. Five RCTs (CLOSURE I, PC Trial, REDUCE, RESPECT, and CLOSE) with 1,829 patients in the device group and 1,611 patients in the medical group met inclusion criteria. The cumulative incidence of recurrent stroke was 2.02% in the PFO closure arm and 4.4% in the medical therapy group (RR 0.42, 95%CI 0.20, 0.91; P = 0.03). There was no difference in the incidence of death [0.7% vs. 0.9%; RR 0.76 (95% CI 0.35, 1.64), P = 0.49] or adverse events during the follow-up period [24.6% vs. 23.7% (RR 1.03; 95% CI 0.91, 1.16), P = 0.65] between the closure and medical therapy groups. Incidence of atrial fibrillation was significantly higher in closure group compared to medical therapy [4% vs. 0.6% (RR 4.73; 95% CI 2.09, 10.70), P = 0.0002]. The comparative effectiveness of PFO closure (compared to medical therapy) was significantly more pronounced in those younger than 45 years, males, larger shunts and disc design platforms (P < 0.05). Based on the results of this analysis of randomized trial data, percutaneous PFO closure appears to be a safe and effective therapeutic option for the secondary prevention of ischemic stroke in patients with PFO and cryptogenic stroke. © 2018 Wiley Periodicals, Inc.

Gait improvement after treadmill training in ischemic stroke survivors: A critical review of functional MRI studies ☆

OpenAIRE

Xiao, Xiang; Huang, Dongfeng; O’Young, Bryan

2012-01-01

Stroke survivors often present with abnormal gait, movement training can improve the walking performance post-stroke, and functional MRI can objectively evaluate the brain functions before and after movement training. This paper analyzes the functional MRI changes in patients with ischemic stroke after treadmill training with voluntary and passive ankle dorsiflexion. Functional MRI showed that there are some changes in some regions of patients with ischemic stroke including primary sensorimot...

Protective effect of Kombucha tea on brain damage induced by transient cerebral ischemia and reperfusion in rat

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Najmeh Kabiri; Mahbubeh Setorki

2016-01-01

The aim of study was to investigate the potential neuroprotective effects of Kombucha on cerebral damage induced by ischemia in rats (n=99). Cerebral infarct volume in the ischemic rats received Kombucha solution showed no significance alteration. However, the permeability of blood-brain barrier significantly decreased in both ischemic rats received 15 mg/kg Kombucha tea and Sham group. In addition, brain water content in the ischemic groups treated with Kombucha solution was significantly hi...

Risk factors in various subtypes of ischemic stroke according to TOAST criteria.

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Aquil, Nadia; Begum, Imtiaz; Ahmed, Arshia; Vohra, Ejaz Ahmed; Soomro, Bashir Ahmed

2011-05-01

To identify the frequency of risk factors in various subtypes of acute ischemic stroke according to TOAST criteria. Cross-sectional, observational study. Ziauddin Hospital, Karachi, from January to December 2007. Patients with acute ischemic stroke were enrolled. Studied variables included demographic profile, history of risk factors, physical and neurological examination, and investigations relevant with the objectives of the study. Findings were described as frequency percentages. Proportions of risk factors against subtypes was compared using chi-square test with significance at p dyslipedemia in 22%, smoking in 9%, atrial fibrillation in 5%, and previous history of stroke in 29%. The various subtypes of acute ischemic stroke were lacunar infarct in 43%, large artery atherosclerosis in 31%, cardioembolic type in 8%, stroke of other determined etiology in 1% and stroke of undetermined etiology in 18%. Hypertension and Diabetes were the most important risk factors in both large and small artery atherosclerosis. In patients with cardio-embolic stroke significant association was found with ischemic heart disease (p=0.01). Importance and relevance of risk factors evaluated for subtypes rather than ischemic stroke as a whole should be reflected in preventive efforts against the burden of ischemic stroke.

The complexity of atrial fibrillation newly diagnosed after ischemic stroke and transient ischemic attack: advances and uncertainties

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Cerasuolo, Joshua O.; Cipriano, Lauren E.; Sposato, Luciano A.

2017-01-01

Purpose of review Atrial fibrillation is being increasingly diagnosed after ischemic stroke and transient ischemic attack (TIA). Patient characteristics, frequency and duration of paroxysms, and the risk of recurrent ischemic stroke associated with atrial fibrillation detected after stroke and TIA (AFDAS) may differ from atrial fibrillation already known before stroke occurrence. We aim to summarize major recent advances in the field, in the context of prior evidence, and to identify areas of uncertainty to be addressed in future research. Recent findings Half of all atrial fibrillations in ischemic stroke and TIA patients are AFDAS, and most of them are asymptomatic. Over 50% of AFDAS paroxysms last less than 30 s. The rapid initiation of cardiac monitoring and its duration are crucial for its timely and effective detection. AFDAS comprises a heterogeneous mix of atrial fibrillation, possibly including cardiogenic and neurogenic types, and a mix of both. Over 25 single markers and at least 10 scores have been proposed as predictors of AFDAS. However, there are considerable inconsistencies across studies. The role of AFDAS burden and its associated risk of stroke recurrence have not yet been investigated. Summary AFDAS may differ from atrial fibrillation known before stroke in several clinical dimensions, which are important for optimal patient care strategies. Many questions remain unanswered. Neurogenic and cardiogenic AFDAS need to be characterized, as it may be possible to avoid some neurogenic cases by initiating timely preventive treatments. AFDAS burden may differ in ischemic stroke and TIA patients, with distinctive diagnostic and treatment implications. The prognosis of AFDAS and its risk of recurrent stroke are still unknown; therefore, it is uncertain whether AFDAS patients should be treated with oral anticoagulants. PMID:27984303

[Broad ischemic stroke revealing infective endocarditis in a young patient: about a case].

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Ravelosaona, Fanomezantsoa Noella; Razafimahefa, Julien; Randrianasolo, Rahamefy Odilon; Rakotoarimanana, Solofonirina; Tehindrazanarivelo, Djacoba Alain

2016-01-01

Broad ischemic stroke is mainly due to a cardiac embolus or to an atheromatous plaque. In young subjects, one of the main causes of ischemic stroke (broad ischemic stroke in particolar) is embolic heart disease including infective endocarditis. Infective endocarditis is a contraindication against the anticoagulant therapy (which is indicated for the treatment of embolic heart disease complicated by ischemic stroke). One neurologic complications of infective endocarditis is ischemic stroke which often occurs in multiple sites. We here report the case of a 44-year old man with afebrile acute onset of severe left hemiplegia associated with a sistolic mitral murmur, who had fever in hospital on day 5 with no other obvious source of infection present. Brain CT scan showed full broad ischaemic stroke of the right middle cerebral artery territory and doppler ultrasound, performed after stroke onset, showed infective endocarditis affecting the small mitral valve. He was treated with 4 weeks of antibiotic therapy without anticoagulant therapy ; evolution was marked by the disappearance of mitral valve vegetations and by movement sequelae involving the left side of the body. In practical terms, our problem was the onset of the fever which didn't accompany or pre-exist patient's deficit, leading us to the misdiagnosis of ischemic stroke of cardioembolic origin. This case study underlines the importance of doppler ultrasound, in the diagnosis of all broad ischemic strokes, especially superficial, before starting anticoagulant therapy.

EFFECTS OF CANNABIDIOL PLUS HYPOTHERMIA ON SHORT-TERM NEWBORN PIG BRAIN DAMAGE AFTER ACUTE HYPOXIA-ISCHEMIA

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Hector Lafuente

2016-07-01

Full Text Available Background: Hypothermia is standard treatment for neonatal encephalopathy, but near 50% of treated infants have adverse outcomes. Pharmacological therapies can act through complementary mechanisms to hypothermia and would improve neuroprotection. Cannabidiol could be a good candidate.Objective: To test whether immediate treatment with cannabidiol and hypothermia act through complementary brain pathways in hypoxic-ischemic newborn piglets.Methods: Hypoxic-ischemic animals were randomized to receive 30 min after the insult: 1 normothermia- and vehicle-treated group; 2 normothermia- and cannabidiol-treated group; 3 hypothermia- and vehicle-treated group; and 4 hypothermia- and cannabidiol-treated group. Six hours after treatment, brains were processed to qualify the number of neurons by Nissl staining. Proton nuclear magnetic resonance spectra were obtained and analyzed for lactate, N-acetyl-aspartate and glutamate. Metabolite ratios were calculated to assess neuronal damage (lactate/N-acetyl-aspartate and excitotoxicity (glutamate/Nacetyl-aspartate. Western blot studies were performed to quantify protein nitrosylation (oxidative stress and expression of caspase-3 (apoptosis and TNFα (inflammation.Results: Individually, the hypothermia and the cannabidiol treatments reduced the glutamate/Nacetyl-aspartate ratio, as well as TNFα and oxidized protein levels. Also, both therapies reduced the number of necrotic neurons and prevented an increase in lactate/N-acetyl-aspartate ratio. The combined effect of hypothermia and cannabidiol on excitotoxicity, inflammation and oxidative stress, and on histological damage, was greater than either hypothermia or cannabidiol alone.Conclusion: Cannabidiol and hypothermia act complementarily and show additive effects on the main factors leading to hypoxic-ischemic brain damage.

Analysis of risk factors and risk assessment for ischemic stroke recurrence

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Xiu-ying LONG

2016-08-01

Full Text Available Objective To screen the risk factors for recurrence of ischemic stroke and to assess the risk of recurrence. Methods Essen Stroke Risk Score (ESRS was used to evaluate the risk of recurrence in 176 patients with ischemic stroke (96 cases of first onset and 80 cases of recurrence. Univariate and multivariate stepwise Logistic regression analysis was used to screen risk factors for recurrence of ischemic stroke.  Results There were significant differences between first onset group and recurrence group on age, the proportion of > 75 years old, hypertension, diabetes, coronary heart disease, peripheral angiopathy, transient ischemic attack (TIA or ischemic stroke, drinking and ESRS score (P < 0.05, for all. First onset group included one case of ESRS 0 (1.04%, 8 cases of 1 (8.33%, 39 cases of 2 (40.63%, 44 cases of 3 (45.83%, 4 cases of 4 (4.17%. Recurrence group included 2 cases of ESRS 3 (2.50%, 20 cases of 4 (25% , 37 cases of 5 (46.25% , 18 cases of 6 (22.50% , 3 cases of 7 (3.75% . There was significant difference between 2 groups (Z = -11.376, P = 0.000. Logistic regression analysis showed ESRS > 3 score was independent risk factor for recurrence of ischemic stroke (OR = 31.324, 95%CI: 3.934-249.430; P = 0.001.  Conclusions ESRS > 3 score is the independent risk factor for recurrence of ischemic stroke. It is important to strengthen risk assessment of recurrence of ischemic stroke. To screen and control risk factors is the key to secondary prevention of ischemic stroke. DOI: 10.3969/j.issn.1672-6731.2016.07.011

The protective effect of ischemic preconditioning on rat testis

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Ciralik Harun

2007-12-01

Full Text Available Abstract Background It has been demonstrated that brief episodes of sublethal ischemia-reperfusion, so-called ischemic preconditioning, provide powerful tissue protection in different tissues such as heart, brain, skeletal muscle, lung, liver, intestine, kidney, retina, and endothelial cells. Although a recent study has claimed that there are no protective effects of ischemic preconditioning in rat testis, the protective effects of ischemic preconditioning on testicular tissue have not been investigated adequately. The present study was thus planned to investigate whether ischemic preconditioning has a protective effect on testicular tissue. Methods Rats were divided into seven groups that each contained seven rats. In group 1 (control group, only unilateral testicular ischemia was performed by creating a testicular torsion by a 720 degree clockwise rotation for 180 min. In group 2, group 3, group 4, group 5, group 6, and group 7, unilateral testicular ischemia was performed for 180 min following different periods of ischemic preconditioning. The ischemic preconditioning periods were as follows: 10 minutes of ischemia with 10 minutes of reperfusion in group 2; 20 minutes of ischemia with 10 minutes of reperfusion in group 3; 30 minutes of ischemia with 10 minutes of reperfusion in group 4; multiple preconditioning periods were used (3 × 10 min early phase transient ischemia with 10 min reperfusion in all episodes in group 5; multiple preconditioning periods were used (5, 10, and 15 min early phase transient ischemia with 10 min reperfusion in all episodes in group 6; and, multiple preconditioning periods were used (10, 20, and 30 min early phase transient ischemia with 10 min reperfusion in all episodes in group 7. After the ischemic protocols were carried out, animals were sacrificed by cervical dislocation and testicular tissue samples were taken for biochemical measurements (protein, malondialdehyde, nitric oxide and histological examination

Cocktail treatment, a promising strategy to treat acute cerebral ischemic stroke?

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Li-jun Liang

2016-01-01

Full Text Available Up to now, over 1,000 experimental treatments found in cells and rodents have been difficult to translate to human ischemic stroke. Since ischemia and reperfusion, two separate stages of ischemic stroke, have different pathophysiological mechanisms leading to brain injury, a combination of protective agents targeting ischemia and reperfusion respectively may obtain substantially better results than a single agent. Normobaric hyperoxia (NBO has been shown to exhibit neuro- and vaso-protective effects by improving tissue oxygenation when it is given during ischemia, however the effect of NBO would diminish when the duration of ischemia and reperfusion was extended. Therefore, during reperfusion drug treatment targeting inflammation, oxidative stress and free radical scavenger would be a useful adjuvant to extend the therapeutic window of tissue plasminogen activator, the only United States Food and Drug Administration (FDA approved treatment for acute ischemic stroke. In this review, we discussed the neuro- and vaso-protective effects of NBO and recent finding of combining NBO with other drugs.

Nonfasting triglycerides, cholesterol, and ischemic stroke in the general population

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Varbo, Anette; Nordestgaard, Børge G; Tybjaerg-Hansen, Anne

2011-01-01

Current guidelines on stroke prevention have recommendations on desirable cholesterol levels, but not on nonfasting triglycerides. We compared stepwise increasing levels of nonfasting triglycerides and cholesterol for their association with risk of ischemic stroke in the general population....

Implementation of Telephone-Based Secondary Preventive Intervention after Stroke and Transient Ischemic Attack - Participation Rate, Reasons for Nonparticipation and One-Year Mortality

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Anna-Lotta Irewall

2014-02-01

Full Text Available Background and Purpose: Patients who experience a stroke or transient ischemic attack (TIA are known to be at high risk of subsequent vascular events, underscoring the need for secondary preventive intervention. However, previous studies have indicated insufficiency in the implementation of secondary prevention, emphasizing the need to develop effective methods of follow-up. In the present study, we examined the potential of implementing a telephone-based, nurse-led, secondary preventive follow-up in stroke and TIA patients on a population level by analyzing the participation rate, reasons for nonparticipation, and one-year mortality. Methods: Between January 1, 2010 and December 31, 2011, all patients admitted to Östersund hospital, Sweden, and diagnosed with either stroke or TIA were considered for inclusion into the secondary preventive follow-up. Baseline data were collected at the hospital, and reasons for nonparticipation were documented. Multivariate logistic regression was performed to identify predictors of the patient decision not to participate and to explore independent associations between baseline characteristics and exclusion. A one-year follow-up of mortality was also performed; the survival functions of the three groups (included, excluded, declining participation was calculated using the Kaplan-Meier estimator. Results: From a total of 810 identified patients, 430 (53.1% were included in the secondary preventive follow-up, 289 (35.7% were excluded mainly due to physical or cognitive disability, and 91 (11.2% declined participation. Age ≥85 years, ischemic and hemorrhagic stroke, modified Rankin scale score >3, body mass index ≥25, congestive heart failure, and lower education level were independently associated with exclusion, whereas lower education level was the only factor independently associated with the patient decision not to participate. Exclusion was associated with a more than 12 times higher risk of mortality

Targeting reactive nitrogen species: a promising therapeutic strategy for cerebral ischemia-reperfusion injury.

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Chen, Xing-miao; Chen, Han-sen; Xu, Ming-jing; Shen, Jian-gang

2013-01-01

Ischemic stroke accounts for nearly 80% of stroke cases. Recanalization with thrombolysis is a currently crucial therapeutic strategy for re-building blood supply, but the thrombolytic therapy often companies with cerebral ischemia-reperfusion injury, which are mediated by free radicals. As an important component of free radicals, reactive nitrogen species (RNS), including nitric oxide (NO) and peroxynitrite (ONOO(-)), play important roles in the process of cerebral ischemia-reperfusion injury. Ischemia-reperfusion results in the production of nitric oxide (NO) and peroxynitrite (ONOO(-)) in ischemic brain, which trigger numerous molecular cascades and lead to disruption of the blood brain barrier and exacerbate brain damage. There are few therapeutic strategies available for saving ischemic brains and preventing the subsequent brain damage. Recent evidence suggests that RNS could be a therapeutic target for the treatment of cerebral ischemia-reperfusion injury. Herein, we reviewed the recent progress regarding the roles of RNS in the process of cerebral ischemic-reperfusion injury and discussed the potentials of drug development that target NO and ONOO(-) to treat ischemic stroke. We conclude that modulation for RNS level could be an important therapeutic strategy for preventing cerebral ischemia-reperfusion injury.

An experimental study on cerebral ischemic penumbra imaging with 99Tcm-HL91

International Nuclear Information System (INIS)

Zhu Cansheng; Jiang Ningyi

2002-01-01

Objective: To investigate the biodistribution of 99 Tc m -4,9-diaza-3,3,10,10-tetramethyl dodecan-2,11-dione dioxime (HL91) in rat model of middle cerebral artery occlusion (MCAO). Methods: Thirty-one MCAO rats were established. Fourteen rats were used to study the biodistribution of 99 Tc m -HL91 and 15 rats were used to study the distribution of 99 Tc m -HL91 in the brain of MCAO model rats. Autoradiographic study of brain was also done in 16 MCAO model rats. Results: The liver and kidney retention were higher than that in other tissues. At 1 h after injection, small intestine retention was also high. But radioactivity in normal brain was low. Retention in target site was higher than that in non-target site. Difference between subgroups of operation and that of pseudo operation was significant (P 99 Tc m -HL91 at the target-ischemic area was shown in the autoradiograph. By using computer-enhanced image analysis, difference between target site and non-target site in the same autoradiograph and the differences between operation subgroups and that of pseudo-subgroups were all significant via Dunnett t-test and One-Way ANOVA. Conclusions: 99 Tc m -HL91 can be avidly taken up by ischemic penumbra and target/non-target ratio is high. 99 Tc m -HL91 is a potential agent for hypoxic tissue imaging, and 99 Tc m -HL91 SPECT is a promising modality in detecting the ischemic penumbra

Delayed treatment with ADAMTS13 ameliorates cerebral ischemic injury without hemorrhagic complication.

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Nakano, Takafumi; Irie, Keiichi; Hayakawa, Kazuhide; Sano, Kazunori; Nakamura, Yoshihiko; Tanaka, Masayoshi; Yamashita, Yuta; Satho, Tomomitsu; Fujioka, Masayuki; Muroi, Carl; Matsuo, Koichi; Ishikura, Hiroyasu; Futagami, Kojiro; Mishima, Kenichi

2015-10-22

Tissue plasminogen activator (tPA) is the only approved therapy for acute ischemic stroke. However, delayed tPA treatment increases the risk of cerebral hemorrhage and can result in exacerbation of nerve injury. ADAMTS13, a von Willebrand factor (VWF) cleaving protease, has a protective effect against ischemic brain injury and may reduce bleeding risk by cleaving VWF. We examined whether ADAMTS13 has a longer therapeutic time window in ischemic stroke than tPA in mice subjected to middle cerebral artery occlusion (MCAO). ADAMTS13 (0.1mg/kg) or tPA (10mg/kg) was administered i.v., immediately after reperfusion of after 2-h or 4-h MCAO for comparison of the therapeutic time windows in ischemic stroke. Infarct volume, hemorrhagic volume, plasma high-mobility group box1 (HMGB1) levels and cerebral blood flow were measured 24h after MCAO. Both ADAMTS13 and tPA improved the infarct volume without hemorrhagic complications in 2-h MCAO mice. On the other hand, ADAMTS13 reduced the infarct volume and plasma HMGB1 levels, and improved cerebral blood flow without hemorrhagic complications in 4-h MCAO mice, but tPA was not effective and these animals showed massive intracerebral hemorrhage. These results indicated that ADAMTS13 has a longer therapeutic time window in ischemic stroke than tPA, and ADAMTS13 may be useful as a new therapeutic agent for ischemic stroke. Copyright © 2015 Elsevier B.V. All rights reserved.

Aberrant functional connectivity of resting state networks in transient ischemic attack.

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Rong Li

Full Text Available BACKGROUND: Transient ischemic attack (TIA is usually defined as a neurologic ischemic disorder without permanent cerebral infarction. Studies have showed that patients with TIA can have lasting cognitive functional impairment. Inherent brain activity in the resting state is spatially organized in a set of specific coherent patterns named resting state networks (RSNs, which epitomize the functional architecture of memory, language, attention, visual, auditory and somato-motor networks. Here, we aimed to detect differences in RSNs between TIA patients and healthy controls (HCs. METHODS: Twenty one TIA patients suffered an ischemic event and 21 matched HCs were enrolled in the study. All subjects were investigated using cognitive tests, psychiatric tests and functional magnetic resonance imaging (fMRI. Independent component analysis (ICA was adopted to acquire the eight brain RSNs. Then one-sample t-tests were calculated in each group to gather the spatial maps of each RSNs, followed by second level analysis to investigate statistical differences on RSNs between twenty one TIA patients and 21 controls. Furthermore, a correlation analysis was performed to explore the relationship between functional connectivity (FC and cognitive and psychiatric scales in TIA group. RESULTS: Compared with the controls, TIA patients exhibited both decreased and increased functional connectivity in default mode network (DMN and self-referential network (SRN, and decreased functional connectivity in dorsal attention network (DAN, central-executive network (CEN, core network (CN, somato-motor network (SMN, visual network (VN and auditory network (AN. There was no correlation between neuropsychological scores and functional connectivity in regions of RSNs. CONCLUSIONS: We observed selective impairments of RSN intrinsic FC in TIA patients, whose all eight RSNs had aberrant functional connectivity. These changes indicate that TIA is a disease with widely abnormal brain

Risk of ischemic stroke after atrial fibrillation diagnosis: A national sample cohort.

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Mi Kyoung Son

Full Text Available Atrial fibrillation (AF is a major risk factor for ischemic stroke and associated with a 5-fold higher risk of stroke. In this retrospective cohort study, the incidence of and risk factors for ischemic stroke in patients with AF were identified. All patients (≥30 years old without previous stroke who were diagnosed with AF in 2007-2013 were selected from the National Health Insurance Service-National Sample Cohort. To identify factors that influenced ischemic stroke risk, Cox proportional hazard regression analysis was conducted. During a mean follow-up duration of 3.2 years, 1022 (9.6% patients were diagnosed with ischemic stroke. The overall incidence rate of ischemic stroke was 30.8/1000 person-years. Of all the ischemic stroke that occurred during the follow-up period, 61.0% occurred within 1-year after AF diagnosis. Of the patients with CHA2DS2-VASc score of ≥2, only 13.6% were receiving warfarin therapy within 30 days after AF diagnosis. Relative to no antithrombotic therapy, warfarin treatment for >90 days before the index event (ischemic stroke in stroke patients and death/study end in non-stroke patients associated with decreased ischemic stroke risk (Hazard Ratio = 0.41, 95%confidence intervals = 0.32-0.53. Heart failure, hypertension, and diabetes mellitus associated with greater ischemic stroke risk. AF patients in Korea had a higher ischemic stroke incidence rate than patients in other countries and ischemic stroke commonly occurred at early phase after AF diagnosis. Long-term (>90 days continuous warfarin treatment may be beneficial for AF patients. However, warfarin treatment rates were very low. To prevent stroke, programs that actively detect AF and provide anticoagulation therapy are needed.

Risk factors in various subtypes of ischemic stroke according to toast criteria

International Nuclear Information System (INIS)

Aquil, N.; Begum, I.; Ahmed, A.; Vohra, E.A.

2011-01-01

To identify the frequency of risk factors in various subtypes of acute ischemic stroke according to TOAST criteria. Study Design: Cross-sectional, observational study. Place and Duration of Study: Ziauddin Hospital, Karachi, from January to December 2007. Methodology: Patients with acute ischemic stroke were enrolled. Studied variables included demographic profile, history of risk factors, physical and neurological examination, and investigations relevant with the objectives of the study. Findings were described as frequency percentages. Proportions of risk factors against subtypes was compared using chi-square test with significance at p < 0.05. Results: Out of the 100 patients with acute ischemic stroke, mean age at presentation was 63.5 years. Risk factor distribution was hypertension in 85%, Diabetes mellitus in 49%, ischemic heart disease in 30%, dyslipedemia in 22%, smoking in 9%, atrial fibrillation in 5%, and previous history of stroke in 29%. The various subtypes of acute ischemic stroke were lacunar infarct in 43%, large artery atherosclerosis in 31%, cardioembolic type in 8%, stroke of other determined etiology in 1% and stroke of undetermined etiology in 18%. Hypertension and Diabetes were the most important risk factors in both large and small artery atherosclerosis. In patients with cardio-embolic stroke significant association was found with ischemic heart disease (p=0.01). Conclusion: Importance and relevance of risk factors evaluated for subtypes rather than ischemic stroke as a whole should be reflected in preventive efforts against the burden of ischemic stroke. (author)

Term Neonate with Atypical Hypoxic-Ischemic Encephalopathy Presentation: A Case Report.

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Townley, Nick; McNellis, Emily; Sampath, Venkatesh

2017-07-01

We describe a case of atypical hypoxic-ischemic encephalopathy (HIE) in a neonate following a normal pregnancy and delivery who was found to have an umbilical vein thrombosis. The infant arrived to our center with continuous bicycling movement of her lower extremities. She had a continuous electroencephalogram that showed burst suppression and magnetic resonance imaging of the brain showed diffusely abnormal cerebral cortical/subcortical diffusion restriction which may be secondary hypoxic-ischemic injury. Interestingly, a pathology report noted a focal umbilical vein thrombosis appearing to have compressed an umbilical artery with associated arterial dissection and hematoma. Our case illustrates how umbilical venous or arterial thrombosis may be associated with HIE and refractory seizures.

Effects of JPEG data compression on magnetic resonance imaging evaluation of small vessels ischemic lesions of the brain

International Nuclear Information System (INIS)

Kuriki, Paulo Eduardo de Aguiar; Abdala, Nitamar; Nogueira, Roberto Gomes; Carrete Junior, Henrique; Szejnfeld, Jacob

2006-01-01

Objective: to establish the maximum achievable JPEG compression ratio without affecting quantitative and qualitative magnetic resonance imaging analysis of ischemic lesion in small vessels of the brain. Material and method: fifteen DICOM images were converted to JPEG with a compression ratio of 1:10 to 1:60 and were assessed together with the original images by three neuro radiologists. The number, morphology and signal intensity of the lesions were analyzed. Results: lesions were properly identified up to a 1:30 ratio. More lesions were identified with a 1:10 ratio then in the original images. Morphology and edges were properly evaluated up toa 1:40 ratio. Compression did not affect signal. Conclusion: small lesions were identified ( < 2 mm ) and in all compression ratios the JPEG algorithm generated image noise that misled observers to identify more lesions in JPEG images then in DICOM images, thus generating false-positive results.(author)

MRI of fetal acquired brain lesions

International Nuclear Information System (INIS)

Prayer, Daniela; Brugger, Peter C.; Kasprian, Gregor; Witzani, Linde; Helmer, Hanns; Dietrich, Wolfgang; Eppel, Wolfgang; Langer, Martin

2006-01-01

Acquired fetal brain damage is suspected in cases of destruction of previously normally formed tissue, the primary cause of which is hypoxia. Fetal brain damage may occur as a consequence of acute or chronic maternal diseases, with acute diseases causing impairment of oxygen delivery to the fetal brain, and chronic diseases interfering with normal, placental development. Infections, metabolic diseases, feto-fetal transfusion syndrome, toxic agents, mechanical traumatic events, iatrogenic accidents, and space-occupying lesions may also qualify as pathologic conditions that initiate intrauterine brain damage. MR manifestations of acute fetal brain injury (such as hemorrhage or acute ischemic lesions) can easily be recognized, as they are hardly different from postnatal lesions. The availability of diffusion-weighted sequences enhances the sensitivity in recognizing acute ischemic lesions. Recent hemorrhages are usually readily depicted on T2 (*) sequences, where they display hypointense signals. Chronic fetal brain injury may be characterized by nonspecific changes that must be attributable to the presence of an acquired cerebral pathology. The workup in suspected acquired fetal brain injury also includes the assessment of extra-CNS organs that may be affected by an underlying pathology. Finally, the placenta, as the organ that mediates oxygen delivery from the maternal circulation to the fetus, must be examined on MR images

MRI of fetal acquired brain lesions

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Prayer, Daniela [Department of Radiodiagnostics, Medical University of Vienna (Austria)]. E-mail: daniela.prayer@meduniwien.ac.at; Brugger, Peter C. [Center of Anatomy and Cell Biology, Medical University of Vienna (Austria); Kasprian, Gregor [Department of Radiodiagnostics, Medical University of Vienna (Austria); Witzani, Linde [Department of Radiodiagnostics, Medical University of Vienna (Austria); Helmer, Hanns [Department of Obstetrics and Gynecology, Medical University of Vienna (Austria); Dietrich, Wolfgang [Department of Neurosurgery, Medical University of Vienna (Austria); Eppel, Wolfgang [Department of Obstetrics and Gynecology, Medical University of Vienna (Austria); Langer, Martin [Department of Obstetrics and Gynecology, Medical University of Vienna (Austria)

2006-02-15

Acquired fetal brain damage is suspected in cases of destruction of previously normally formed tissue, the primary cause of which is hypoxia. Fetal brain damage may occur as a consequence of acute or chronic maternal diseases, with acute diseases causing impairment of oxygen delivery to the fetal brain, and chronic diseases interfering with normal, placental development. Infections, metabolic diseases, feto-fetal transfusion syndrome, toxic agents, mechanical traumatic events, iatrogenic accidents, and space-occupying lesions may also qualify as pathologic conditions that initiate intrauterine brain damage. MR manifestations of acute fetal brain injury (such as hemorrhage or acute ischemic lesions) can easily be recognized, as they are hardly different from postnatal lesions. The availability of diffusion-weighted sequences enhances the sensitivity in recognizing acute ischemic lesions. Recent hemorrhages are usually readily depicted on T2 (*) sequences, where they display hypointense signals. Chronic fetal brain injury may be characterized by nonspecific changes that must be attributable to the presence of an acquired cerebral pathology. The workup in suspected acquired fetal brain injury also includes the assessment of extra-CNS organs that may be affected by an underlying pathology. Finally, the placenta, as the organ that mediates oxygen delivery from the maternal circulation to the fetus, must be examined on MR images.

Studies on cerebral protection of digoxin against hypoxic-ischemic brain damage in neonatal rats.

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Peng, Kaiwei; Tan, Danfeng; He, Miao; Guo, Dandan; Huang, Juan; Wang, Xia; Liu, Chentao; Zheng, Xiangrong

2016-08-17

Hypoxic-ischemic brain damage (HIBD) is a major cause of neonatal acute deaths and chronic nervous system damage. Our present study was designed to investigate the possible neuroprotective effect of digoxin-induced pharmacological preconditioning after hypoxia-ischemia and underlying mechanisms. Neonatal rats were assigned randomly to control, HIBD, or HIBD+digoxin groups. Pharmacological preconditioning was induced by administration of digoxin 72 h before inducing HIBD by carotid occlusion+hypoxia. Behavioral assays, and neuropathological and apoptotic assessments were performed to examine the effects; the expression of Na/K ATPase was also assessed. Rats in the HIBD group showed deficiencies on the T-maze, radial water maze, and postural reflex tests, whereas the HIBD+digoxin group showed significant improvements on all behavioral tests. The rats treated with digoxin showed recovery of pathological conditions, increased number of neural cells and proliferative cells, and decreased number of apoptotic cells. Meanwhile, an increased expression level of Na/K ATPase was observed after digoxin preconditioning treatment. The preconditioning treatment of digoxin contributed toward an improved functional recovery and exerted a marked neuroprotective effect including promotion of cell proliferation and reduction of apoptosis after HIBD, and the neuroprotective action was likely associated with increased expression of Na/K ATPase.

ACE Gene in Egyptian Ischemic Stroke Patients.

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Mostafa, Magdy A; El-Nabiel, Lobna M; Fahmy, Nagia Aly; Aref, Hany; Shreef, Edrees; Abd El-Tawab, Fathy; Abdulghany, Osama M

2016-09-01

Angiotensin-1-converting enzyme (ACE) is a crucial player in vascular homeostasis and in the pathogenesis of atherosclerosis and hypertension. The present study was conducted to determine whether there is an association between the ACE insertion/deletion (I/D) polymorphism and ischemic stroke in Egyptian population. Also, we analyzed the ACE gene I/D polymorphism as a risk factor for small-vessel (SV) versus large-vessel (LV) disease. Sixty patients with ischemic stroke were included: 30 with SV disease and 30 with LV disease. In addition, a control group of 30 apparent healthy subjects were studied. Clinical assessment, computed tomography, magnetic resonance imaging brain, and genetic study using the polymerase chain reaction of ACE gene were done for all subjects. We found that the distribution of ACE gene polymorphism frequency was significantly different between the 3 groups. The DD genotype was far more common in stroke patients compared to controls. It was also significantly more common in each of the patient groups compared to controls but rather similar in the 2 patient groups with SV and LV diseases. We found that the ACE gene deletion/deletion genotype is common in Egyptian patients with non-cardioembolic ischemic stroke but does not appear to be specific neither to SV nor to LV disease. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Reporting time of ischemic stroke patients within the time window for thrombolysis in a tertiary care hospital at rawalpindi

International Nuclear Information System (INIS)

Tariq, M.; Ishtiaq, S.; Anwar, S.O.

2014-01-01

To determine the reporting time of ischemic stroke patients within the time window for thrombolysis at Military Hospital (MH) Rawalpindi. Design: A descriptive study. Place and duration of Study: Military Hospital Rawalpindi over a period of four months from Dec 2013 to Mar 2014. Patients and Methods: Patients admitted to MH Rawalpindi with symptoms suggestive of stroke and having objective focal neurologic deficits consistent with stroke were included in the study. A CT scan of brain was carried out immediately to rule out intracranial bleed. The CT scan of brain was either normal or revealed radiological findings suggestive of an infarct. Results: A total of 86 patients met the inclusion criteria of the study. Only 19 (22%) patients with ischemic stroke presented to the hospital within 4.5 hours after onset of their symptoms. Conclusion: Only a small number of ischemic stroke patients report to the hospital within the therapeutic window for thrombolytic therapy. (author)

CT perfusion assessment of treatment response and complications in acute ischemic stroke

NARCIS (Netherlands)

Horsch, AD

2016-01-01

An acute ischemic stroke is caused by the sudden occlusion of a large blood vessel to a part of the brain. Current treatment options are to dissolve the clot with the injection of a solvent into a vein or to physically remove the clot with an interventional radiology procedure. A major complication

Modelling Ischemic Stroke and Temperature Intervention Using Vascular Porous Method

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Blowers, Stephen; Valluri, Prashant; Marshall, Ian; Andrews, Peter; Harris, Bridget; Thrippleton, Michael

2017-11-01

In the event of cerebral infarction, a region of tissue is supplied with insufficient blood flow to support normal metabolism. This can lead to an ischemic reaction which incurs cell death. Through a reduction of temperature, the metabolic demand can be reduced, which then offsets the onset of necrosis. This allows extra time for the patient to receive medical attention and could help prevent permanent brain damage from occurring. Here, we present a vascular-porous (VaPor) blood flow model that can simulate such an event. Cerebral blood flow is simulated using a combination of 1-Dimensional vessels embedded in 3-Dimensional porous media. This allows for simple manipulation of the structure and determining the effect of an obstructed vessel. Results show regional temperature increase of 1-1.5°C comparable with results from literature (in contrast to previous simpler models). Additionally, the application of scalp cooling in such an event dramatically reduces the temperature in the affected region to near hypothermic temperatures, which points to a potential rapid form of first intervention.

Rescuing the ischemic penumbra: Our experience

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Milosavljević Tamara

2013-12-01

Full Text Available Objectives: Over one million strokes per year are occurring in Europe. Brain stroke is one of the most important death and disability causes in Europe and USA. The main role of perfusion is to determine the border of insult core and ischemic penumbra. Penumbra can be saved with thrombolytic therapy but core have irreversible injuries and represent death of brain cells. Aim: to determine the role of CT brain perfusion in cases of acute brain stroke and following thrombolytic therapy. Methods: We examined 64 patients with acute brain stroke who received thrombolytic therapy after that. All patients were examining on 16 MDCT with 50 ml of iodine contrast agent following the standard procedure for CT perfusion. Patients were 34 male and 30 female with middle age of 64 years. MRI was made after thrombolytic therapy and compare with perfusion results before therapy. Results: Using an artery and a vein as reference three parameters were measured - blood flow (CBF, blood volume (CBV and mean transit time (MTT, for each patient. Hemorrhagic was find in 9 (14.01% patients after thrombolytic therapy. 4 (6.25% other patients develop new stroke of same but mostly other side of brain. 8 (12.50% more patients finished lethally. From other 42 patients with thrombolytic therapy we can positively say that in 31 (48.44% patients penumbra was rescued. For other 11 (17.19% stroke was same size like firstly involved core and penumbra but not bigger. Conclusion: CT perfusion plays major role by showing a curable parts of tissue in brain strokes.

DIDS prevents ischemic membrane degradation in cultured hippocampal neurons by inhibiting matrix metalloproteinase release.

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Matthew E Pamenter

Full Text Available During stroke, cells in the infarct core exhibit rapid failure of their permeability barriers, which releases ions and inflammatory molecules that are deleterious to nearby tissue (the penumbra. Plasma membrane degradation is key to penumbral spread and is mediated by matrix metalloproteinases (MMPs, which are released via vesicular exocytosis into the extracellular fluid in response to stress. DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid preserves membrane integrity in neurons challenged with an in vitro ischemic penumbral mimic (ischemic solution: IS and we asked whether this action was mediated via inhibition of MMP activity. In cultured murine hippocampal neurons challenged with IS, intracellular proMMP-2 and -9 expression increased 4-10 fold and extracellular latent and active MMP isoform expression increased 2-22 fold. MMP-mediated extracellular gelatinolytic activity increased ∼20-50 fold, causing detachment of 32.1±4.5% of cells from the matrix and extensive plasma membrane degradation (>60% of cells took up vital dyes and >60% of plasma membranes were fragmented or blebbed. DIDS abolished cellular detachment and membrane degradation in neurons and the pathology-induced extracellular expression of latent and active MMPs. DIDS similarly inhibited extracellular MMP expression and cellular detachment induced by the pro-apoptotic agent staurosporine or the general proteinase agonist 4-aminophenylmercuric acetate (APMA. Conversely, DIDS-treatment did not impair stress-induced intracellular proMMP production, nor the intracellular cleavage of proMMP-2 to the active form, suggesting DIDS interferes with the vesicular extrusion of MMPs rather than directly inhibiting proteinase expression or activation. In support of this hypothesis, an antagonist of the V-type vesicular ATPase also inhibited extracellular MMP expression to a similar degree as DIDS. In addition, in a proteinase-independent model of vesicular exocytosis, DIDS

Ischemic stroke due to embolic heart diseases and associated factors in Benin hospital setting.

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Gnonlonfoun, Dieudonné; Adjien, Constant; Gnimavo, Ronald; Goudjinou, Gérard; Hotcho, Corine; Nyangui Mapaga, Jennifer; Sowanou, Arlos; Gnigone, Pupchen; Domingo, Rodrigue; Houinato, Dismand

2018-04-15

Poor access to cardiovascular checkups is a major cause of ignorance of embolic heart diseases as the etiology for ischemic stroke. Study ischemic strokes due to embolic heart diseases and their associated factors. It was a cross-sectional, prospective, descriptive and analytical study conducted from November 1, 2014 to August 31, 2015 on 104 patients with ischemic stroke confirmed through brain imaging. Embolic heart diseases included arrhythmia due to atrial fibrillation (AF), atrial flutter, myocardial infarction (MI), heart valve diseases and atrial septal aneurysm (ASA). The dependent variable was embolic heart disease while independent variables encompassed socio-demographic factors, patients' history, and lifestyle. Data analysis was carried out through SAS 9.3. The rate of embolic heart diseases (EHD) as etiology for ischemic stroke was 26% (28/104). AF accounted for 69% of embolic heart diseases and 22.8% of etiologies for ischemic stroke. Ischemic strokes prevalence was 3.5%, 2.5% and 1.2% respectively for heart valve diseases, MI and ASA. The associated factor was age (p=0.000). The diagnosis of a potential cardiac source of embolism is essential because of therapeutic and prognostic implications. Wherefore, there is need for cardiovascular examination particularly Holter ECG and cardiac ultrasound examination which are not always accessible to our populations. Copyright © 2018 Elsevier B.V. All rights reserved.

Association of brain injury and neonatal cytokine response during therapeutic hypothermia in newborns with hypoxic-ischemic encephalopathy.

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Orrock, Janet E; Panchapakesan, Karuna; Vezina, Gilbert; Chang, Taeun; Harris, Kari; Wang, Yunfei; Knoblach, Susan; Massaro, An N

2016-05-01

Cytokines have been proposed as mediators of neonatal brain injury via neuroinflammatory pathways triggered by hypoxia-ischemia. Limited data are available on cytokine profiles in larger cohorts of newborns with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH). Serum cytokines interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-13, tumor necrosis factor-α, and interferon-γ were measured in newborns with HIE at 24 and 72 h of TH. Differences between infants with favorable (survivors with mild/no magnetic resonance imaging (MRI) injury) vs. adverse outcome (death or moderate/severe MRI injury) were compared using mixed models to adjust for covariates. Data from 36 term newborns with HIE (favorable outcome: n = 20, adverse outcome: n = 16) were evaluated. Cytokines IL-1β, IL-2, IL-6, IL-8, IL-10, and IL-13 were elevated in the adverse relative to favorable outcome group at 24 h. IL-6 remained significantly elevated in the adverse outcome group at 72 h. IL-6 and IL-10 remained significantly associated with outcome group after controlling for covariates. Inflammatory cytokines are elevated in HIE newborns with brain injury by MRI. In particular, IL-6 and IL-10 were associated with adverse outcomes after controlling for baseline characteristics and severity of presentation. These data suggest that cytokine response may identify infants in need of additional neuroprotective interventions.

β2-Adrenergic Receptor-Mediated HIF-1α Upregulation Mediates Blood Brain Barrier Damage in Acute Cerebral Ischemia

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Yanyun Sun

2017-08-01

Full Text Available Disruption of the blood brain barrier (BBB within the thrombolytic time window is an antecedent event to intracerebral hemorrhage in ischemic stroke. Our recent studies showed that 2-h cerebral ischemia induced BBB damage in non-infarcted area and secreted matrix metalloproteinase-2 (MMP-2 accounted for this disruption. However, the factors that affect MMP-2 secretion and regulate BBB damage remains unknown. Since hypoxia-inducible factor-1 alpha (HIF-1α was discovered as a mater regulator in hypoxia, we sought to investigate the roles of HIF-1α in BBB damage as well as the factors regulating HIF-1α expression in the ischemic brain. in vivo rat middle cerebral artery occlusion (MCAO and in vitro oxygen glucose deprivation (OGD models were used to mimic ischemia. Pretreatment with HIF-1α inhibitor YC-1 significantly inhibited 2-h MCAO-induced BBB damage, which was accompanied by suppressed occludin degradation and vascular endothelial growth factor (VEGF mRNA upregulation. Interestingly, β2-adrenergic receptor (β2-AR antagonist ICI 118551 attenuated ischemia-induced BBB damage by regulating HIF-1α expression. Double immunostaining showed that HIF-1α was upregulated in ischemic neurons but not in astrocytes andendothelial cells. Of note, HIF-1α inhibition with inhibitor YC-1 or siRNA significantly prevented OGD-induced VEGF upregulation as well as the secretion of VEGF and MMP-2 in neurons. More importantly, blocking β2-AR with ICI 118551 suppressedHIF-1α upregulation in ischemic neurons and attenuated occludin degradation induced by the conditioned media of OGD-treatedneurons. Taken together, blockade of β2-AR-mediated HIF-1α upregulation mediates BBB damage during acute cerebral ischemia. These findings provide new mechanistic understanding of early BBB damage in ischemic stroke and may help reduce thrombolysis-related hemorrhagic complications.

Biological Signatures of Brain Damage Associated with High Serum Ferritin Levels in Patients with Acute Ischemic Stroke and Thrombolytic Treatment

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Millán, Mónica; Sobrino, Tomás; Arenillas, Juan Francisco; Rodríguez-Yáñez, Manuel; García, María; Nombela, Florentino; Castellanos, Mar; de la Ossa, Natalia Pérez; Cuadras, Patricia; Serena, Joaquín; Castillo, José; Dávalos, Antoni

2008-01-01

Background and purpose: Increased body iron stores have been related to greater oxidative stress and brain injury in clinical and experimental cerebral ischemia and reperfusion. We aimed to investigate the biological signatures of excitotoxicity, inflammation and blood brain barrier disruption potentially associated with high serum ferritin levels-related damage in acute stroke patients treated with i.v. t-PA. Methods: Serum levels of ferritin (as index of increased cellular iron stores), glutamate, interleukin-6, matrix metalloproteinase-9 and cellular fibronectin were determined in 134 patients treated with i.v. t-PA within 3 hours from stroke onset in blood samples obtained before t-PA treatment, at 24 and 72 hours. Results: Serum ferritin levels before t-PA infusion correlated to glutamate (r = 0.59, p < 0.001) and interleukin-6 (r = 0.55, p <0.001) levels at baseline, and with glutamate (r = 0.57,p <0.001), interleukin-6 (r = 0.49,p <0.001), metalloproteinase-9 (r = 0.23, p = 0.007) and cellular fibronectin (r = 0.27, p = 0.002) levels measured at 24 hours and glutamate (r = 0.415, p < 0.001), interleukin-6 (r = 0.359, p < 0.001) and metalloproteinase-9 (r = 0.261, p = 0.004) at 72 hours. The association between ferritin and glutamate levels remained after adjustment for confounding factors in generalized linear models. Conclusions: Brain damage associated with increased iron stores in acute ischemic stroke patients treated with iv. tPA may be mediated by mechanisms linked to excitotoxic damage. The role of inflammation, blood brain barrier disruption and oxidative stress in this condition needs further research. PMID:19096131

DETERMINANTS OF PREVENTIVE BEHAVIOR REGARDING CARDIOVASCULAR DISEASES AND RISK FACTORS IN PATIENTS WITH ESSENTIAL HYPERTENSION AND CHRONIC ISCHEMIC HEART DISEASE

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D. Yu. Platonov

2011-01-01

Full Text Available Aim. To analyze potential determinants of preventive behavior (PB in patients with essential hypertension (HT and chronic ischemic heart disease (CIHD, and to establish their significance and hierarchy. Material and methods. Patients with HT (n=285 and CIHD (n=223 were studied. Questioning of all patients was performed to assess the characteristics of their PB. Differentiated multivariate analysis of activity and efficacy of PB determinants was performed in HT and CIHD patients by the method of step-by-step backward logistic regression. Results. Awareness of the cardiovascular diseases (CVD and its prevention (odds ratio [OR] 6.08 as well as high level of general education (OR=2.29 were the most significant determinants of active PB in HT patients. Sufficient social support (OR=3.77, awareness of CVD and its prevention (OR=3.16 were the most significant determinants of active PB in patients with CIHD. Efficacy of PB in patients with HT and CIHD mostly depends on satisfaction of medical service (OR=10.2 and 6.63, respectively, social support (OR=6.25 and 10.5, respectively, adequate awareness of CVD and its prevention (OR, 6.92 and 6.64, respectively. Conclusion. PB activity and efficacy in patients with HT and CIHD depends on many contributing and impeding factors. Disregarding these factors can result in failure in preventive efforts at both individual and population levels.

Semi-quantitative Assessment of Brain Maturation by Conventional Magnetic Resonance Imaging in Neonates with Clinically Mild Hypoxic-ischemic Encephalopathy

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Gao, Jie; Sun, Qin-Li; Zhang, Yu-Miao; Li, Yan-Yan; Li, Huan; Hou, Xin; Yu, Bo-Lang; Zhou, Xi-Hui; Yang, Jian

2015-01-01

Background: Mild hypoxic-ischemic encephalopathy (HIE) injury is becoming the major type in neonatal brain diseases. The aim of this study was to assess brain maturation in mild HIE neonatal brains using total maturation score (TMS) based on conventional magnetic resonance imaging (MRI). Methods: Totally, 45 neonates with clinically mild HIE and 45 matched control neonates were enrolled. Gestated age, birth weight, age after birth and postmenstrual age at magnetic resonance (MR) scan were homogenous in the two groups. According to MR findings, mild HIE neonates were divided into three subgroups: Pattern I, neonates with normal MR appearance; Pattern II, preterm neonates with abnormal MR appearance; Pattern III, full-term neonates with abnormal MR appearance. TMS and its parameters, progressive myelination (M), cortical infolding (C), involution of germinal matrix tissue (G), and glial cell migration bands (B), were employed to assess brain maturation and compare difference between HIE and control groups. Results: The mean of TMS was significantly lower in mild HIE group than it in the control group (mean ± standard deviation [SD] 11.62 ± 1.53 vs. 12.36 ± 1.26, P < 0.001). In four parameters of TMS scores, the M and C scores were significantly lower in mild HIE group. Of the three patterns of mild HIE, Pattern I (10 cases) showed no significant difference of TMS compared with control neonates, while Pattern II (22 cases), III (13 cases) all had significantly decreased TMS than control neonates (mean ± SD 10.56 ± 0.93 vs. 11.48 ± 0.55, P < 0.05; 12.59 ± 1.28 vs. 13.25 ± 1.29, P < 0.05). It was M, C, and GM scores that significantly decreased in Pattern II, while for Pattern III, only C score significantly decreased. Conclusions: The TMS system, based on conventional MRI, is an effective method to detect delayed brain maturation in clinically mild HIE. The conventional MRI can reveal the different retardations in subtle structures and development processes

Transient ischemic attack and minor stroke are the most common manifestations of acute cerebrovascular disease: a prospective, population-based study--the Aarhus TIA study.

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von Weitzel-Mudersbach, Paul; Andersen, Grethe; Hundborg, Heidi H; Johnsen, Søren P

2013-01-01

Severity of acute vascular illness may have changed in the last decades due to improvements in primary and secondary prevention. Population-based data on the severity of acute ischemic cerebrovascular disease are sparse. We aimed to examine incidence, characteristics and severity of acute ischemic cerebrovascular disease in a well-defined population. All patients admitted with transient ischemic attack (TIA) or acute ischemic stroke from March 1, 2007, to February 29, 2008, with residence in the Aarhus area, were included. Incidence rates and characteristics of TIA and ischemic stroke were compared. TIA accounted for 30%, TIA and minor stroke combined for 65% of all acute ischemic cerebrovascular events. Age-adjusted incidence rates of TIA and ischemic stroke were 72.2/100,000 and 129.5/100,000 person-years, respectively. TIA patients were younger than stroke patients (66.3 vs. 72.7 years; p TIA and stroke patients share many characteristics; however, TIA patients are younger and have fewer manifestations of atherosclerotic diseases, indicating a high potential for secondary prevention. Copyright © 2012 S. Karger AG, Basel.

Hemispheric distribution of middle cerebral artery ischemic strokes in patients admitted to military hospital rawalpindi

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Tariq, M.; Ishtiaq, S.; Zulfiqar, S.O.

2016-01-01

Objective: To determine the difference in the frequency of middle cerebral artery (MCA) ischemic strokes between left and right cerebral hemispheres in the adult patients admitted to the Military Hospital (MH) Rawalpindi. Study Design: A descriptive study. Place and Duration of Study: MH Rawalpindi from 01 Dec 2013 to 30 Mar 2014. Patients and Methods: Seventy eight adult patients admitted to MH Rawalpindi with neurologic deficits consistent with MCA strokes and having no evidence of intracerebral haemorrhage on Computed Tomographic (CT) scan of brain. Descriptive Statistics were calculated using SPSS version 17. Results: A total of 78 patients met the inclusion criteria of the study; 35 (45 percent) patients had right MCA stroke while 43 (55 percent) had left MCA stroke. Conclusion: Left MCA ischemic strokes are more common than right MCA ischemic strokes. (author)

Noninvasive evaluation of ischemic stroke with SPECT

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Gomez, C.R.; Malik, M.M.; Gomez, S.M.; Wingkun, E.C.

1988-01-01

Technetium Tc 99m DTPA single photon emission computerized tomography (SPECT) brain scans of 20 patients with acute ischemic stroke were reviewed retrospectively and compared with clinical and radiologic (CT) data. Fourteen of the patients had abnormal SPECT studies. The abnormal findings were demonstrated by static views in eight patients, by the flow study in one patient, and by both sets of images in the other five patients. All abnormalities correlated with the clinical syndrome of presentation, and only two of the patients had no corresponding lesions on CT. Of the six patients with normal SPECT scans, two had abnormal CT studies, and in the other four, no lesions were shown at all. The ability of /sup 99m/Tc DTPA SPECT to display cerebral infarctions appears to be, at best, comparable to that of CT. SPECT also provides qualitative information regarding flow dynamics in the affected hemisphere of some patients (6/20 in our review). This, we believe, represents the objective demonstration of the preexisting insufficient collateral flow in the hemisphere at risk for ischemic stroke

Patent foramen ovale closure with GORE HELEX or CARDIOFORM Septal Occluder vs. antiplatelet therapy for reduction of recurrent stroke or new brain infarct in patients with prior cryptogenic stroke: Design of the randomized Gore REDUCE Clinical Study.

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Kasner, Scott E; Thomassen, Lars; Søndergaard, Lars; Rhodes, John F; Larsen, Coby C; Jacobson, Joth

2017-12-01

Rationale The utility of patent foramen ovale (PFO) closure for secondary prevention in patients with prior cryptogenic stroke is uncertain despite multiple randomized trials completed to date. Aims The Gore REDUCE Clinical Study (REDUCE) aims to establish superiority of patent foramen ovale closure in conjunction with antiplatelet therapy over antiplatelet therapy alone in reducing the risk of recurrent clinical ischemic stroke or new silent brain infarct in patients who have had a cryptogenic stroke. Methods and design This controlled, open-label trial randomized 664 subjects with cryptogenic stroke at 63 multinational sites in a 2:1 ratio to either antiplatelet therapy plus patent foramen ovale closure (with GORE® HELEX® Septal Occluder or GORE® CARDIOFORM Septal Occluder) or antiplatelet therapy alone. Subjects will be prospectively followed for up to five years. Neuroimaging is required for all subjects at baseline and at two years or study exit. Study outcomes The two co-primary endpoints for the study are freedom from recurrent clinical ischemic stroke through at least 24 months post-randomization and incidence of new brain infarct (defined as clinical ischemic stroke or silent brain infarct) through 24 months. The primary analyses are an unadjusted log-rank test and a binomial test of subject-based proportions, respectively, both on the intent-to-treat population, with adjustment for testing multiplicity. Discussion The REDUCE trial aims to target a patient population with truly cryptogenic strokes. Medical therapy is limited to antiplatelet agents in both arms thereby reducing confounding. The trial should determine whether patent foramen ovale closure with the Gore septal occluders is safe and more effective than medical therapy alone for the prevention of recurrent clinical ischemic stroke or new silent brain infarct; the neuroimaging data will provide an opportunity to further support the proof of concept. The main results are anticipated in 2017

Study on the Mechanism of mTOR-Mediated Autophagy during Electroacupuncture Pretreatment against Cerebral Ischemic Injury

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Zhou-Quan Wu

2016-01-01

Full Text Available This study is aimed at investigating the association between the electroacupuncture (EA pretreatment-induced protective effect against early cerebral ischemic injury and autophagy. EA pretreatment can protect cerebral ischemic and reperfusion injuries, but whether the attenuation of early cerebral ischemic injury by EA pretreatment was associated with autophagy is not yet clear. This study used the middle cerebral artery occlusion model to monitor the process of ischemic injury. For rats in the EA pretreatment group, EA pretreatment was conducted at Baihui acupoint before ischemia for 30 min for 5 consecutive days. The results suggested that EA pretreatment significantly increased the expression of autophagy in the cerebral cortical area on the ischemic side of rats. But the EA pretreatment-induced protective effects on the brain could be reversed by the specific inhibitor 3-methyladenine of autophagy. Additionally, the Pearson correlation analysis indicated that the impact of EA pretreatment on p-mTOR (2481 was negatively correlated with its impact on autophagy. In conclusion, the mechanism of EA pretreatment at Baihui acupoint against cerebral ischemic injury is mainly associated with the upregulation of autophagy expression, and its regulation of autophagy may depend on mTOR-mediated signaling pathways.

Stroke Prevention: Managing Modifiable Risk Factors

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Silvia Di Legge

2012-01-01

Full Text Available Prevention plays a crucial role in counteracting morbidity and mortality related to ischemic stroke. It has been estimated that 50% of stroke are preventable through control of modifiable risk factors and lifestyle changes. Antihypertensive treatment is recommended for both prevention of recurrent stroke and other vascular events. The use of antiplatelets and statins has been shown to reduce the risk of recurrent stroke and other vascular events. Angiotensin-converting enzyme inhibitors (ACEIs and angiotensin II receptor blockers (ARBs are indicated in stroke prevention because they also promote vascular health. Effective secondary-prevention strategies for selected patients include carotid revascularization for high-grade carotid stenosis and vitamin K antagonist treatment for atrial fibrillation. The results of recent clinical trials investigating new anticoagulants (factor Xa inhibitors and direct thrombin inhibitors clearly indicate alternative strategies in stroke prevention for patients with atrial fibrillation. This paper describes the current landscape and developments in stroke prevention with special reference to medical treatment in secondary prevention of ischemic stroke.

Smartphone electrographic monitoring for atrial fibrillation in acute ischemic stroke and transient ischemic attack.

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Tu, Hans T; Chen, Ziyuan; Swift, Corey; Churilov, Leonid; Guo, Ruibing; Liu, Xinfeng; Jannes, Jim; Mok, Vincent; Freedman, Ben; Davis, Stephen M; Yan, Bernard

2017-10-01

Rationale Paroxysmal atrial fibrillation is a common and preventable cause of devastating strokes. However, currently available monitoring methods, including Holter monitoring, cardiac telemetry and event loop recorders, have drawbacks that restrict their application in the general stroke population. AliveCor™ heart monitor, a novel device that embeds miniaturized electrocardiography (ECG) in a smartphone case coupled with an application to record and diagnose the ECG, has recently been shown to provide an accurate and sensitive single lead ECG diagnosis of atrial fibrillation. This device could be used by nurses to record a 30-s ECG instead of manual pulse taking and automatically provide a diagnosis of atrial fibrillation. Aims To compare the proportion of patients with paroxysmal atrial fibrillation detected by AliveCor™ ECG monitoring with current standard practice. Sample size 296 Patients. Design Consecutive ischemic stroke and transient ischemic attack patients presenting to participating stroke units without known atrial fibrillation will undergo intermittent AliveCor™ ECG monitoring administered by nursing staff at the same frequency as the vital observations of pulse and blood pressure until discharge, in addition to the standard testing paradigm of each participating stroke unit to detect paroxysmal atrial fibrillation. Study outcome Proportion of patients with paroxysmal atrial fibrillation detected by AliveCor™ ECG monitoring compared to 12-lead ECG, 24-h Holter monitoring and cardiac telemetry. Discussion Use of AliveCor™ heart monitor as part of routine stroke unit nursing observation has the potential to be an inexpensive non-invasive method to increase paroxysmal atrial fibrillation detection, leading to improvement in stroke secondary prevention.

Molecular Basis of Impaired Glycogen Metabolism during Ischemic Stroke and Hypoxia

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Hossain, Mohammed Iqbal; Roulston, Carli Lorraine; Stapleton, David Ian

2014-01-01

Background Ischemic stroke is the combinatorial effect of many pathological processes including the loss of energy supplies, excessive intracellular calcium accumulation, oxidative stress, and inflammatory responses. The brain's ability to maintain energy demand through this process involves metabolism of glycogen, which is critical for release of stored glucose. However, regulation of glycogen metabolism in ischemic stroke remains unknown. In the present study, we investigate the role and regulation of glycogen metabolizing enzymes and their effects on the fate of glycogen during ischemic stroke. Results Ischemic stroke was induced in rats by peri-vascular application of the vasoconstrictor endothelin-1 and forebrains were collected at 1, 3, 6 and 24 hours post-stroke. Glycogen levels and the expression and activity of enzymes involved in glycogen metabolism were analyzed. We found elevated glycogen levels in the ipsilateral hemispheres compared with contralateral hemispheres at 6 and 24 hours (25% and 39% increase respectively; PGlycogen synthase activity and glycogen branching enzyme expression were found to be similar between the ipsilateral, contralateral, and sham control hemispheres. In contrast, the rate-limiting enzyme for glycogen breakdown, glycogen phosphorylase, had 58% lower activity (Pglycogen debranching enzyme expression 24 hours post-stroke was 77% (Pglycogen phosphorylase activity and increased glycogen accumulation but did not alter glycogen synthase activity. Furthermore, elevated glycogen levels provided metabolic support to astrocytes during hypoxia. Conclusion Our study has identified that glycogen breakdown is impaired during ischemic stroke, the molecular basis of which includes reduced glycogen debranching enzyme expression level together with reduced glycogen phosphorylase and PKA activity. PMID:24858129

The mitochondria-targeted antioxidants and remote kidney preconditioning ameliorate brain damage through kidney-to-brain cross-talk.

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Denis N Silachev

Full Text Available BACKGROUND: Many ischemia-induced neurological pathologies including stroke are associated with high oxidative stress. Mitochondria-targeted antioxidants could rescue the ischemic organ by providing specific delivery of antioxidant molecules to the mitochondrion, which potentially suffers from oxidative stress more than non-mitochondrial cellular compartments. Besides direct antioxidative activity, these compounds are believed to activate numerous protective pathways. Endogenous anti-ischemic defense may involve the very powerful neuroprotective agent erythropoietin, which is mainly produced by the kidney in a redox-dependent manner, indicating an important role of the kidney in regulation of brain ischemic damage. The goal of this study is to track the relations between the kidney and the brain in terms of the amplification of defense mechanisms during SkQR1 treatment and remote renal preconditioning and provide evidence that the kidney can generate signals inducing a tolerance to oxidative stress-associated brain pathologies. METHODOLOGY/PRINCIPAL FINDINGS: We used the cationic plastoquinone derivative, SkQR1, as a mitochondria-targeted antioxidant to alleviate the deleterious consequences of stroke. A single injection of SkQR1 before cerebral ischemia in a dose-dependent manner reduces infarction and improves functional recovery. Concomitantly, an increase in the levels of erythropoietin in urine and phosphorylated glycogen synthase kinase-3β (GSK-3β in the brain was detected 24 h after SkQR1 injection. However, protective effects of SkQR1 were not observed in rats with bilateral nephrectomy and in those treated with the nephrotoxic antibiotic gentamicin, indicating the protective role of humoral factor(s which are released from functional kidneys. Renal preconditioning also induced brain protection in rats accompanied by an increased erythropoietin level in urine and kidney tissue and P-GSK-3β in brain. Co-cultivation of SkQR1-treated

The mitochondria-targeted antioxidants and remote kidney preconditioning ameliorate brain damage through kidney-to-brain cross-talk.

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Silachev, Denis N; Isaev, Nikolay K; Pevzner, Irina B; Zorova, Ljubava D; Stelmashook, Elena V; Novikova, Svetlana V; Plotnikov, Egor Y; Skulachev, Vladimir P; Zorov, Dmitry B

2012-01-01

Many ischemia-induced neurological pathologies including stroke are associated with high oxidative stress. Mitochondria-targeted antioxidants could rescue the ischemic organ by providing specific delivery of antioxidant molecules to the mitochondrion, which potentially suffers from oxidative stress more than non-mitochondrial cellular compartments. Besides direct antioxidative activity, these compounds are believed to activate numerous protective pathways. Endogenous anti-ischemic defense may involve the very powerful neuroprotective agent erythropoietin, which is mainly produced by the kidney in a redox-dependent manner, indicating an important role of the kidney in regulation of brain ischemic damage. The goal of this study is to track the relations between the kidney and the brain in terms of the amplification of defense mechanisms during SkQR1 treatment and remote renal preconditioning and provide evidence that the kidney can generate signals inducing a tolerance to oxidative stress-associated brain pathologies. We used the cationic plastoquinone derivative, SkQR1, as a mitochondria-targeted antioxidant to alleviate the deleterious consequences of stroke. A single injection of SkQR1 before cerebral ischemia in a dose-dependent manner reduces infarction and improves functional recovery. Concomitantly, an increase in the levels of erythropoietin in urine and phosphorylated glycogen synthase kinase-3β (GSK-3β) in the brain was detected 24 h after SkQR1 injection. However, protective effects of SkQR1 were not observed in rats with bilateral nephrectomy and in those treated with the nephrotoxic antibiotic gentamicin, indicating the protective role of humoral factor(s) which are released from functional kidneys. Renal preconditioning also induced brain protection in rats accompanied by an increased erythropoietin level in urine and kidney tissue and P-GSK-3β in brain. Co-cultivation of SkQR1-treated kidney cells with cortical neurons resulted in enchanced

Voxelwise distribution of acute ischemic stroke lesions in patients with newly diagnosed atrial fibrillation: Trigger of arrhythmia or only target of embolism?

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Timolaos Rizos

Full Text Available Atrial fibrillation (AF is frequently detected after ischemic stroke for the first time, and brain regions involved in autonomic control have been suspected to trigger AF. We examined whether specific brain regions are associated with newly detected AF after ischemic stroke.Patients with acute cerebral infarctions on diffusion-weighted magnetic resonance imaging were included in this lesion mapping study. Lesions were mapped and modeled voxelwise using Bayesian Spatial Generalised Linear Mixed Modeling to determine differences in infarct locations between stroke patients with new AF, without AF and with AF already known before the stroke.582 patients were included (median age 68 years; 63.2% male. AF was present in 109/582 patients [(18.7%; new AF: 39/109 (35.8%, known AF: 70/109 (64.2%]. AF patients had larger infarct volumes than patients without AF (mean: 29.7 ± 45.8 ml vs. 15.2 ± 35.1 ml; p<0.001. Lesions in AF patients accumulated in the right central middle cerebral artery territory. Increasing stroke size predicted progressive cortical but not pontine and thalamic involvement. Patients with new AF had more frequently lesions in the right insula compared to patients without AF when stroke size was not accounted for, but no specific brain region was more frequently involved after adjustment for infarct volume. Controlled for stroke size, left parietal involvement was less likely for patients with new AF than for those without AF or with known AF.In the search for brain areas potentially triggering cardiac arrhythmias infarct size should be accounted for. After controlling for infarct size, there is currently no evidence that ischemic stroke lesions of specific brain areas are associated with new AF compared to patients without AF. This challenges the neurogenic hypothesis of AF according to which a relevant proportion of new AF is triggered by ischemic brain lesions of particular locations.

A TIGAR-regulated metabolic pathway is critical for protection of brain ischemia.

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Li, Mei; Sun, Meiling; Cao, Lijuan; Gu, Jin-hua; Ge, Jianbin; Chen, Jieyu; Han, Rong; Qin, Yuan-Yuan; Zhou, Zhi-Peng; Ding, Yuqiang; Qin, Zheng-Hong

2014-05-28

TP53-induced glycolysis and apoptosis regulator (TIGAR) inhibits glycolysis and increases the flow of pentose phosphate pathway (PPP), which generates NADPH and pentose. We hypothesized that TIGAR plays a neuroprotective role in brain ischemia as neurons do not rely on glycolysis but are vulnerable to oxidative stress. We found that TIGAR was highly expressed in brain neurons and was rapidly upregulated in response to ischemia/reperfusion insult in a TP53-independent manner. Overexpression of TIGAR in normal mice with lentivirus reduced ischemic neuronal injury, whereas lentivirus-mediated TIGAR knockdown aggravated it. In cultured primary neurons, increasing TIGAR expression reduced oxygen and glucose deprivation (OGD)/reoxygenation-induced injury, whereas decreasing its expression worsened the injury. The glucose 6-phosphate dehydrogenase was upregulated in mouse and cellular models of stroke, and its upregulation was further enhanced by overexpression of TIGAR. Supplementation of NADPH also reduced ischemia/reperfusion brain injury and alleviated TIGAR knockdown-induced aggravation of ischemic injury. In animal and cellular stroke models, ischemia/reperfusion increased mitochondrial localization of TIGAR. OGD/reoxygenation-induced elevation of ROS, reduction of GSH, dysfunction of mitochondria, and activation of caspase-3 were rescued by overexpression of TIGAR or supplementation of NADPH, while knockdown of TIGAR aggravated these changes. Together, our results show that TIGAR protects ischemic brain injury via enhancing PPP flux and preserving mitochondria function, and thus may be a valuable therapeutic target for ischemic brain injury. Copyright © 2014 the authors 0270-6474/14/347458-14$15.00/0.

Risk factors of short-term stroke recurrence in patients with minor ischemic cerebrovascular events

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Kavian Ghandehari

2013-03-01

Full Text Available BACKGROUND: Assessing the risk of recurrent ischemic events in patients with transient ischemic attack (TIA and minor ischemic stroke (MIS is of a great importance in clinical practice. METHODS: Consecutive patients with TIA or MIS who were visited in Ghaem Hospital, (Mashhad, Iran were enrolled in a prospective cohort study during 2010 to 2011. Diagnosis of TIA or MIS was accomplished by a stroke neurologist. Only those who presented within 24 hours from the onset of symptoms were recruited. MIS was considered as an ischemic stroke with National Institutes of Health Stroke Scale (NIHSS < 4. The endpoint of the study was a new ischemic cerebrovascular event or vascular death in 90 days and additionally in 3 days. The decision to admit and type of treatment in each case was left to the discretion of the stroke neurologist. The association between 20 potential factors with recurrent ischemic events in 3 and 90 days was investigated using univariate and multivariate analysis (MVA. RESULTS: 393 TIA patients (238 males and 155 females and 118 MIS patients (77 males and 41 females were enrolled in the study. Stroke occurred in 117 (23.2% patients, TIA in 99 (19.6%, and there was 11 (2.2% vascular deaths within 3 months in the total 511 patients with minor ischemic events. Crescendo TIAs and multiple TIAs were associated with greater risk of stroke in 3 days in a univariate analysis (OR = 5.12, P < 0.001 and (OR = 3.98, P = 0.003, respectively. Patients with index stroke had 11.5% lower risk of recurrent stroke in 3 days than patients with index TIA in multivariate analysis (OR = 0.115, P = 0.039. Diabetes was independently associated with 3 months stroke recurrence in the patients with minor ischemic events (OR = 2.65, P = 0.039. CONCLUSION: Multiple and crescendo TIAs are the main predictors of stroke recurrence, derived from the univariate analysis of the patients with minor ischemic events.   Keywords: Transient Ischemic Attacks, Infarction, Brain

[Effect of a new derivative of glutamic and apovincaminic acids on brain metabolism in post-ischemic period].

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Makarova, L M; Prikhod'ko, M A; Pogorelyĭ, V E; Skachilova, S Ia; Mirzoian, R S

2014-01-01

Neuroprotective properties of the new derivative of glutamic and apovincaminic acids, ethyl -(3-alpha,16-alpha)-eburnamenin-14-carbopxylate of 2-aminopentadionic acid (LHT 1-02) were studied on a model of acute brain ischemia in cats. LHT 1-02 has proved to be more effective than the reference drugs vinpocetin and glycine in preventing the reperfusive damage, which was manifested by decreased postischemic hyperglycemia, activated utilization of oxygen in the brain, and suppressed postischemic metabolic lactate acidosis. Thus, the results of this comparative study show expediency of further investigations of LHT 1 - 02 as a potential neuroprotective drug.

Late Thrombolytic Treatment In A Patient With Ischemic Stroke Caused By Biatrial Thrombus

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Halit CINARKA

2015-07-01

Full Text Available Venous thromboembolism is a preventable disease when necessary precautions are taken and it occurs along with deep vein thrombosis and pulmonary embolism. Mortality related to venous thromboembolism may be high in the acute phase of the disease and it may become chronic. Intracardiac thrombus may be detected in some venous thromboemboli cases. Cardiac embolism is responsible for most of the ischemic strokes which can be very mortal or may cause serious morbidity when they are not treated in time. In this report, we aimed to present the results of late antithrombolytic treatment in a 77-year old patient who developed deep vein thrombosis, biatrial thrombosis and ischemic stroke following hydrocephalus shunt operation.   Key words: Venous thromboembolism; ischemic stroke; thrombolytic therapy

Transcranial diffuse optical monitoring of microvascular cerebral hemodynamics after thrombolysis in ischemic stroke

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Zirak, Peyman; Delgado-Mederos, Raquel; Dinia, Lavinia; Carrera, David; Martí-Fàbregas, Joan; Durduran, Turgut

2014-01-01

The ultimate goal of therapeutic strategies for ischemic stroke is to reestablish the blood flow to the ischemic region of the brain. However, currently, the local cerebral hemodynamics (microvascular) is almost entirely inaccessible for stroke clinicians at the patient bed-side, and the recanalization of the major cerebral arteries (macrovascular) is the only available measure to evaluate the therapy, which does not always reflect the local conditions. Here we report the case of an ischemic stroke patient whose microvascular cerebral blood flow and oxygenation were monitored by a compact hybrid diffuse optical monitor during thrombolytic therapy. This monitor combined diffuse correlation spectroscopy and near-infrared spectroscopy. The reperfusion assessed by hybrid diffuse optics temporally correlated with the recanalization of the middle cerebral artery (assessed by transcranial-Doppler) and was in agreement with the patient outcome. This study suggests that upon further investigation, diffuse optics might have a potential for bed-side acute stroke monitoring and therapy guidance by providing hemodynamics information at the microvascular level.

Histopathology of motor cortex in an experimental focal ischemic stroke in mouse model.

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de Oliveira, Juçara Loli; Crispin, Pedro di Tárique Barreto; Duarte, Elisa Cristiana Winkelmann; Marloch, Gilberto Domingos; Gargioni, Rogério; Trentin, Andréa Gonçalves; Alvarez-Silva, Marcio

2014-05-01

Experimental ischemia results in cortical brain lesion followed by ischemic stroke. In this study, focal cerebral ischemia was induced in mice by occlusion of the middle cerebral artery. We studied cortical layers I, II/III, V and VI in the caudal forelimb area (CFA) and medial agranular cortex (AGm) from control and C57BL/6 mice induced with ischemic stroke. Based on our analysis of CFA and AGm motor cortex, significant differences were observed in the numbers of neurons, astrocytes and microglia in the superficial II/III and deep V cortical layers. Cellular changes were more prominent in layer V of the CFA with nuclear pyknosis, chromatin fragmentation, necrosis and degeneration, as well as, morphological evidence of apoptosis, mainly in neurons. As result, the CFA was more severely impaired than the AGm in this focal cerebral ischemic model, as evidenced by the proliferation of astrocytes, potentially resulting in neuroinflammation by microglia-like cells. Copyright © 2014 Elsevier B.V. All rights reserved.

Clinic-like animal model for causal-pathogenetical investigations of hypoxic-ischemic brain injuries. Combined application of the radioactive labelled microsphere method and Positron Emission Tomography. Kliniknahes Tiermodell fuer kausal-pathogenetische Untersuchungen hypoxisch-ischaemischer Hirnschaedigung. Kombinierter Einsatz von Mikrosphaeren-Methode und Positronen-Emissions-Tomographie

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Bauer, R.; Zwiener, U.; Bergmann, R. (Univ. Jena, Inst. fuer Pathologische Physiologie (Germany)); Manfrass, P.; Enghardt, W.; Fromm, W.D. (Zentralinstitut fuer Kernforschung, Bereich Festkoeper- und Kernphysik, Rossendorf (Germany)); Hoyer, D.; Guenther, K. (Leipzig Univ., Radiologische Klinik (Germany)); Schubert, H. (Univ. Jena, Tierexperimentelles Zentrum (Germany)); Beyer, R.; Beyer, G.J.; Steinbach, J.; Kretzschmer, M. (Zentralinstitut fuer Kernforschung, Bereich Radioaktive Isotope, Rossendorf (Germany))

1990-01-01

The complex nature of the pathogenesis in hypoxic-ischemic brain injuries equires the combined determination of the dynamics of main factors in these disturbing processes. The application of suitable methods for registration of such pathogenetic processes is shown in an adequate animal model for simulating the early hypoxic-ischemic brain injuries. That the radioactive labelled microsphere technique is suitable to comprehend quantitively the dynamics of the intracerebral redistribution of the circulating blood due to hypoxia/hypercapnia by simultaneous-multiple measuring of the regional cerebral blood flow. Therefore, at the first time an inadequate hypoxic-induced blood flow increase was shown in large parts of the forebrain in intrauterine growth retarded newborn piglets. For estimation of the regional cerebral glucose utilization in newborn piglets, the {sup 18}F-FDG Positron Emission Tomography is introduced. The measurements were carried out on a stationary high-density avalanche chamber (HIDAC) camera and yielded the fundamental application of this camera model for PET investigations also in the newborn brain due to the very good spatial resolution. (orig.).

Insulin-like growth factor -1 (IGF-1) derived neuropeptides, a novel strategy for the development of pharmaceuticals for managing ischemic brain injury.

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Guan, Jian

2011-08-01

Insulin-Like Growth Factor-1 (IGF-1) is neuroprotective and improves long-term function after brain injury. However, its clinical application to neurological disorders is limited by its large molecular size, poor central uptake, and mitogenic potential. Glycine-proline-glutamate (GPE) is naturally cleaved from the IGF-1 N-terminal and is also neuroprotective after ischemic injury, thus providing a potential novel strategy of drug discovery for management of neurological disorders. GPE is not enzymatically stable, thus intravenous infusion of GPE becomes necessary for stable and potent neuroprotection. The broad effective dose range and treatment window of 3-7 h after the lesion suggest its potential for treating acute brain injuries. The neuroprotective action of GPE is not age selective, is not dependent on cerebral reperfusion, plasma glucose concentrations, and core body temperature. G-2mPE, a GPE analogue designed to be more resistant to enzymatic activity, has a prolonged plasma half-life and is more potent in neuroprotection. Neuroprotection by GPE and its analogue may be involved in modulation of inflammation, promotion of astrocytosis, inhibition of apoptosis, and in vascular remodeling. Small neuropeptides have advantages over growth factors in the treatment of brain injury, and modified neuropeptides, designed to overcome the limitations of their endogenous counterparts, represent a novel strategy of pharmaceutical discovery for neurological disorders. © 2010 Blackwell Publishing Ltd.

Modulation of Synaptic Plasticity by Exercise Training as a Basis for Ischemic Stroke Rehabilitation.

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Nie, Jingjing; Yang, Xiaosu

2017-01-01

In recent years, rehabilitation of ischemic stroke draws more and more attention in the world, and has been linked to changes of synaptic plasticity. Exercise training improves motor function of ischemia as well as cognition which is associated with formation of learning and memory. The molecular basis of learning and memory might be synaptic plasticity. Research has therefore been conducted in an attempt to relate effects of exercise training to neuroprotection and neurogenesis adjacent to the ischemic injury brain. The present paper reviews the current literature addressing this question and discusses the possible mechanisms involved in modulation of synaptic plasticity by exercise training. This review shows the pathological process of synaptic dysfunction in ischemic roughly and then discusses the effects of exercise training on scaffold proteins and regulatory protein expression. The expression of scaffold proteins generally increased after training, but the effects on regulatory proteins were mixed. Moreover, the compositions of postsynaptic receptors were changed and the strength of synaptic transmission was enhanced after training. Finally, the recovery of cognition is critically associated with synaptic remodeling in an injured brain, and the remodeling occurs through a number of local regulations including mRNA translation, remodeling of cytoskeleton, and receptor trafficking into and out of the synapse. We do provide a comprehensive knowledge of synaptic plasticity enhancement obtained by exercise training in this review.

Mobilization of endogenous bone marrow derived endothelial progenitor cells and therapeutic potential of parathyroid hormone after ischemic stroke in mice.

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Li-Li Wang

Full Text Available Stroke is a major neurovascular disorder threatening human life and health. Very limited clinical treatments are currently available for stroke patients. Stem cell transplantation has shown promising potential as a regenerative treatment after ischemic stroke. The present investigation explores a new concept of mobilizing endogenous stem cells/progenitor cells from the bone marrow using a parathyroid hormone (PTH therapy after ischemic stroke in adult mice. PTH 1-34 (80 µg/kg, i.p. was administered 1 hour after focal ischemia and then daily for 6 consecutive days. After 6 days of PTH treatment, there was a significant increase in bone marrow derived CD-34/Fetal liver kinase-1 (Flk-1 positive endothelial progenitor cells (EPCs in the peripheral blood. PTH treatment significantly increased the expression of trophic/regenerative factors including VEGF, SDF-1, BDNF and Tie-1 in the brain peri-infarct region. Angiogenesis, assessed by co-labeled Glut-1 and BrdU vessels, was significantly increased in PTH-treated ischemic brain compared to vehicle controls. PTH treatment also promoted neuroblast migration from the subventricular zone (SVZ and increased the number of newly formed neurons in the peri-infarct cortex. PTH-treated mice showed significantly better sensorimotor functional recovery compared to stroke controls. Our data suggests that PTH therapy improves endogenous repair mechanisms after ischemic stroke with functional benefits. Mobilizing endogenous bone marrow-derived stem cells/progenitor cells using PTH and other mobilizers appears an effective and feasible regenerative treatment after ischemic stroke.

Reducing cannabinoid abuse and preventing relapse by enhancing endogenous brain levels of kynurenic acid

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Justinova, Zuzana; Mascia, Paola; Wu, Hui-Qiu; Secci, Maria E.; Redhi, Godfrey H.; Panlilio, Leigh V.; Scherma, Maria; Barnes, Chanel; Parashos, Alexandra; Zara, Tamara; Fratta, Walter; Solinas, Marcello; Pistis, Marco; Bergman, Jack; Kangas, Brian D.; Ferré, Sergi; Tanda, Gianluigi; Schwarcz, Robert; Goldberg, Steven R.

2013-01-01

In the reward circuitry of the brain, alpha-7-nicotinic acetylcholine receptors (α7nAChRs) modulate effects of delta-9-tetrahydrocannabinol (THC), marijuana’s main psychoactive ingredient. Kynurenic acid (KYNA) is an endogenous negative allosteric modulator of α7nAChRs. Here we report that the kynurenine 3-monooxygenase (KMO) inhibitor Ro 61-8048 increases brain KYNA levels and attenuates cannabinoid-induced increases in extracellular dopamine in reward-related brain areas. In the self-administration model of drug abuse, Ro 61-8048 reduced the rewarding effects of THC and the synthetic cannabinoid WIN 55,212-2 in squirrel monkeys and rats, respectively, and it also prevented relapse to drug-seeking induced by re-exposure to cannabinoids or cannabinoid-associated cues. The effects of enhancing endogenous KYNA levels with Ro 61-8048 were prevented by positive allosteric modulators of α7nAChRs. Despite a clear need, there are currently no medications approved for treatment of marijuana dependence. Modulation of KYNA provides a novel pharmacological strategy for achieving abstinence from marijuana and preventing relapse. PMID:24121737

Near-infrared spectroscopy versus magnetic resonance imaging to study brain perfusion in newborns with hypoxic-ischemic encephalopathy treated with hypothermia.

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Wintermark, P; Hansen, A; Warfield, S K; Dukhovny, D; Soul, J S

2014-01-15

The measurement of brain perfusion may provide valuable information for assessment and treatment of newborns with hypoxic-ischemic encephalopathy (HIE). While arterial spin labeled perfusion (ASL) magnetic resonance imaging (MRI) provides noninvasive and direct measurements of regional cerebral blood flow (CBF) values, it is logistically challenging to obtain. Near-infrared spectroscopy (NIRS) might be an alternative, as it permits noninvasive and continuous monitoring of cerebral hemodynamics and oxygenation at the bedside. The purpose of this study is to determine the correlation between measurements of brain perfusion by NIRS and by MRI in term newborns with HIE treated with hypothermia. In this prospective cohort study, ASL-MRI and NIRS performed during hypothermia were used to assess brain perfusion in these newborns. Regional cerebral blood flow (CBF) values, measured from 1-2 MRI scans for each patient, were compared to mixed venous saturation values (SctO2) recorded by NIRS just before and after each MRI. Analysis included groupings into moderate versus severe HIE based on their initial background pattern of amplitude-integrated electroencephalogram. Twelve concomitant recordings were obtained of seven neonates. Strong correlation was found between SctO2 and CBF in asphyxiated newborns with severe HIE (r=0.88; p value=0.0085). Moreover, newborns with severe HIE had lower CBF (likely lower oxygen supply) and extracted less oxygen (likely lower oxygen demand or utilization) when comparing SctO2 and CBF to those with moderate HIE. NIRS is an effective bedside tool to monitor and understand brain perfusion changes in term asphyxiated newborns, which in conjunction with precise measurements of CBF obtained by MRI at particular times, may help tailor neuroprotective strategies in term newborns with HIE. Copyright © 2013 Elsevier Inc. All rights reserved.

The neuroblast and angioblast chemotaxic factor SDF-1 (CXCL12 expression is briefly up regulated by reactive astrocytes in brain following neonatal hypoxic-ischemic injury

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Walker Aisha L

2005-10-01

Full Text Available Abstract Background Stromal cell-derived factor 1 (SDF-1 or CXCL12 is chemotaxic for CXCR4 expressing bone marrow-derived cells. It functions in brain embryonic development and in response to ischemic injury in helping guide neuroblast migration and vasculogenesis. In experimental adult stroke models SDF-1 is expressed perivascularly in the injured region up to 30 days after the injury, suggesting it could be a therapeutic target for tissue repair strategies. We hypothesized that SDF-1 would be expressed in similar temporal and spatial patterns following hypoxic-ischemic (HI injury in neonatal brain. Results Twenty-five 7-day-old C57BL/J mice underwent HI injury. SDF-1 expression was up regulated up to 7 days after the injury but not at the later time points. The chief sites of SDF-1 up regulation were astrocytes, their foot processes along blood vessels and endothelial cells. Conclusion The localization of SDF-1 along blood vessels in the HI injury zone suggests that these perivascular areas are where chemotaxic signaling for cellular recruitment originates and that reactive astrocytes are major mediators of this process. The associated endothelium is likely to be the site for vascular attachment and diapedesis of CXCR4 receptor expressing cells to enter the injured tissue. Here we show that, relative to adults, neonates have a significantly smaller window of opportunity for SDF-1 based vascular chemotaxic recruitment of bone marrow-derived cells. Therefore, without modification, following neonatal HI injury there is only a narrow period of time for endogenous SDF-1 mediated chemotaxis and recruitment of reparative cells, including exogenously administered stem/progenitor cells.

Astroglial Activation by an Enriched Environment after Transplantation of Mesenchymal Stem Cells Enhances Angiogenesis after Hypoxic-Ischemic Brain Injury

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Sung-Rae Cho

2016-09-01

Full Text Available Transplantation of mesenchymal stem cells (MSCs has paracrine effects; however, the effects are known to be largely limited. Here we investigated the combination effects of cell transplantation and enriched environment (EE in a model of hypoxic-ischemic brain injury. Brain damage was induced in seven-day-old mice by unilateral carotid artery ligation and exposure to hypoxia (8% O2 for 90 min. At six weeks of age, the mice were randomly assigned to four groups: phosphate-buffered saline (PBS-control (CON, PBS-EE, MSC-CON, and MSC-EE. Rotarod and grip strength tests were performed to evaluate neurobehavioral functions. Histologic evaluations were also performed to confirm the extent of astrocyte activation and endogenous angiogenesis. An array-based multiplex ELISA and Western blot were used to identify growth factors in vivo and in vitro. Two weeks after treatment, levels of astrocyte density and angiogenic factors were increased in MSC-EE mice, but glial scarring was not increased. Eight weeks after treatment, angiogenesis was increased, and behavioral outcomes were synergistically improved in the MSC-EE group. Astrocytes co-cultured with MSCs expressed higher levels of angiogenic factors than astrocytes cultured alone. The mechanisms of this synergistic effect included enhanced repair processes, such as increased endogenous angiogenesis and upregulation of angiogenic factors released from activated astrocytes.

Using Ferumoxytol-Enhanced MRI to Measure Inflammation in Patients With Brain Tumors or Other Conditions of the CNS

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2017-08-30

Brain Injury; Central Nervous System Degenerative Disorder; Central Nervous System Infectious Disorder; Central Nervous System Vascular Malformation; Hemorrhagic Cerebrovascular Accident; Ischemic Cerebrovascular Accident; Primary Brain Neoplasm; Brain Cancer; Brain Tumors

Ischemic stroke in patient with existing congenital hypoplasia of the middle cerebral artery

International Nuclear Information System (INIS)

Manchev, I.; Manolova, T.; Manchev, L.

2015-01-01

Presented is a clinical case of a woman 29 years old with ischemic stroke (IS), which has developed abruptly in existing congenital hypoplasia and occlusion of the middle cerebral artery. There are no other well or less well documented risk factors for cerebrovascular disease. In family history noted that the father of the patient died suddenly at the age of 45 years from stroke, also without evidence of vascular disease. On magnetic resonance imaging (MRI) of the brain is found high signal zone in the left nucleus lentiformis. We discussed the possibilities for implementing conventional angiography and eventually surgical procedures unfortunately rejected due to the high risk to the patient. Key words: Ischemic Stroke. Magnetic Resonance Imaging. Hypoplasia

Computed tomographic, electrocardiographic and clinical investigations in patients with ischemic strokes

International Nuclear Information System (INIS)

Manchev, L.; Mitev, M.; Milanova, V.; Zafirova, E.; Manolova, T.; Manchev, I.; Toneva, J.

2013-01-01

The Computed Tomography (CT) is a widely available and reliable method for the diagnosis of cerebrovascular disease. It allows in the first hours of the occurrence of vascular events to be established the type of brain stroke and creates conditions for timely fibrinolytic or surgical treatment. In many cases where it cannot be performed echocardiographic examination modern electrocardiography (ECG) makes it possible to demonstrate the presence of cardiac disease. These two methods in combination with neurological status create conditions for determining the treatment strategy for ischemic brain stroke (IBS). We studied 222 patients (92 men and 110 women with a middle age 59.7 years) selected randomized. At a computed tomography study in the early hours of IBS were found pathological findings in 115 patients (51.8%) slightly more often in women. IBS in the carotid system were greatly predominant in comparison with those in the vertebrobasilar system (VBS), which can be explained with the blood flow to the brain stem. When ECG is most commonly met diagnosis: hypertension HSSN 111 stage II - III functional class NYUHA, ischemic cardiomyopathy in 64 patients overall, with almost equal frequency in men 30 (17.5%) and women - 34 (19.8%). In neurological examination significantly predominant clinical symptoms karoditnata vasculature, in 154 patients (69.3%) compared to that of the VBS- 68 (30.7%). Fulfilled study shows the need for better coordination of the activities of specialists in diagnostic imaging and neurologists for their work in specialized hospitals (Stroke Units). (authors)

Clinical characteristics of patients with ischemic stroke following the 2016 Kumamoto earthquake.

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Inatomi, Yuichiro; Nakajima, Makoto; Yonehara, Toshiro; Ando, Yukio

2017-12-01

To investigate the clinical characteristics of patients with ischemic stroke following the 2016 Kumamoto earthquake. We retrospectively studied patients with ischemic stroke admitted to our hospital for 12weeks following the earthquake. We compared the clinical backgrounds and characteristics of the patients: before (the same period from the previous 3years) and after the earthquake; and the early (first 2weeks) and late (subsequent 10weeks) phases. A total of 194 patients with ischemic stroke were admitted to our hospital after the earthquake; 496 (165.3/year) patients were admitted before the earthquake. No differences between the two groups were noted for the clinical backgrounds, characteristics, or biomarkers. Past history of sleeping in a shelter or small vehicle was found in 13% and 28% of patients, respectively. Sleeping in a shelter (27% vs. 10%, p=0.013) was found more frequently in patients during the early phase than during the late phase after the earthquake. Admission of patients with ischemic stroke increased after the earthquake; however no differences between before and after the earthquake were noted for their clinical characteristics. To prevent ischemic stroke following earthquakes, mental stress and physical status of evacuees must be assessed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Inflammation, caffeine and adenosine in neonatal hypoxic ischemic brain injury

OpenAIRE

Winerdal, Max

2014-01-01

Background: Brain injury during the neonatal period has potentially lifelong consequences for a child. Perinatal infections and inflammation can induce preterm birth and unfavorable cognitive development, Thus inflammation has received enthusiastic interest for potential therapeutic approaches seeking to protect the newborn brain. Experimental evidence demonstrates that inflammation induces brain injury succeeding the initial insult. A key cytokine in brain injury is the tumor necrosis factor...

Modulation of Acid-sensing Ion Channel 1a by Intracellular pH and Its Role in Ischemic Stroke.

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Li, Ming-Hua; Leng, Tian-Dong; Feng, Xue-Chao; Yang, Tao; Simon, Roger P; Xiong, Zhi-Gang

2016-08-26

An important contributor to brain ischemia is known to be extracellular acidosis, which activates acid-sensing ion channels (ASICs), a family of proton-gated sodium channels. Lines of evidence suggest that targeting ASICs may lead to novel therapeutic strategies for stroke. Investigations of the role of ASICs in ischemic brain injury have naturally focused on the role of extracellular pH in ASIC activation. By contrast, intracellular pH (pHi) has received little attention. This is a significant gap in our understanding because the ASIC response to extracellular pH is modulated by pHi, and activation of ASICs by extracellular protons is paradoxically enhanced by intracellular alkalosis. Our previous studies show that acidosis-induced cell injury in in vitro models is attenuated by intracellular acidification. However, whether pHi affects ischemic brain injury in vivo is completely unknown. Furthermore, whereas ASICs in native neurons are composed of different subunits characterized by distinct electrophysiological/pharmacological properties, the subunit-dependent modulation of ASIC activity by pHi has not been investigated. Using a combination of in vitro and in vivo ischemic brain injury models, electrophysiological, biochemical, and molecular biological approaches, we show that the intracellular alkalizing agent quinine potentiates, whereas the intracellular acidifying agent propionate inhibits, oxygen-glucose deprivation-induced cell injury in vitro and brain ischemia-induced infarct volume in vivo Moreover, we find that the potentiation of ASICs by quinine depends on the presence of the ASIC1a, ASIC2a subunits, but not ASIC1b, ASIC3 subunits. Furthermore, we have determined the amino acids in ASIC1a that are involved in the modulation of ASICs by pHi. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

A Microarray Study of Middle Cerebral Occlusion Rat Brain with Acupuncture Intervention

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Chao Zhang

2015-01-01

Full Text Available Microarray analysis was used to investigate the changes of gene expression of ischemic stroke and acupuncture intervention in middle cerebral artery occlusion (MCAo rat brain. Results showed that acupuncture intervention had a remarkable improvement in neural deficit score, cerebral blood flow, and cerebral infarction volume of MCAo rats. Microarray analysis showed that a total of 627 different expression genes were regulated in ischemic stroke. 417 genes were upregulated and 210 genes were downregulated. A total of 361 different expression genes were regulated after acupuncture intervention. Three genes were upregulated and 358 genes were downregulated. The expression of novel genes after acupuncture intervention, including Tph1 and Olr883, was further analyzed by Real-Time Quantitative Polymerase Chain Reaction (RT-PCR. Upregulation of Tph1 and downregulation of Olr883 indicated that the therapeutic effect of acupuncture for ischemic stroke may be closely related to the suppression of poststroke depression and regulation of olfactory transduction. In conclusion, the present study may enrich our understanding of the multiple pathological process of ischemic brain injury and indicate possible mechanisms of acupuncture on ischemic stroke.

CSF transthyretin neuroprotection in a mouse model of brain ischemia

DEFF Research Database (Denmark)

Santos, Sofia Duque; Lambertsen, Kate Lykke; Clausen, Bettina Hjelm

2010-01-01

Brain injury caused by ischemia is a major cause of human mortality and physical/cognitive disability worldwide. Experimentally, brain ischemia can be induced surgically by permanent middle cerebral artery occlusion. Using this model, we studied the influence of transthyretin in ischemic stroke. ...

Time Is Brain: The Stroke Theory of Relativity.

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Gomez, Camilo R

2018-04-25

Since the introduction of the philosophical tenet "Time is Brain!," multiple lines of research have demonstrated that other factors contribute to the degree of ischemic injury at any one point in time, and it is now clear that the therapeutic window of acute ischemic stroke is more protracted than it was first suspected. To define a more realistic relationship between time and the ischemic process, we used computational modeling to assess how these 2 variables are affected by collateral circulatory competence. Starting from the premise that the expression "Time=Brain" is mathematically false, we reviewed the existing literature on the attributes of cerebral ischemia over time, with particular attention to relevant clinical parameters, and the effect of different variables, particularly collateral circulation, on the time-ischemia relationship. We used this information to construct a theoretical computational model and applied it to categorically different yet abnormal cerebral perfusion scenarios, allowing comparison of their behavior both overall (i.e., final infarct volume) and in real-time (i.e., instantaneous infarct growth rate). Optimal collateral circulatory competence was predictably associated with slower infarct growth rates and prolongation of therapeutic window. Modeling of identifiable specific types of perfusion maps allows forecasting of the fate of the ischemic process over time. Distinct cerebral perfusion map patterns can be readily identified in patients with acute ischemic stroke. These patterns have inherently different behaviors relative to the time-ischemia construct, allowing the possibility of improving parsing and treatment allocation. It is clearly evident that the effect of time on the ischemic process is relative. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

New asymptomatic ischemic lesions on diffusion-weighted imaging after cerebral angiography

International Nuclear Information System (INIS)

Shibazaki, Kensaku

2006-01-01

Conventional cerebral angiography (CAG) is relatively low risk for neurological complications. However, diffusion-weighted imaging (DWI) after CAG occasionally reveal an asymptomatic ischemic lesion on the brain. The aim of this study was to investigate the frequency of new asymptomatic or symptomatic DWI lesions after CAG and to clarify the factors associated with them. Fifty-six patients with acute ischemic stroke and transient ischemic attack were prospectively enrolled. Magnetic resonance imaging (MRI) studies including DWI were studied twice, within 48 hours before and after CAG. The following factors were assessed; age, gender, history of stroke, history of ischemic heart disease, vascular risk factors, National Institutes of Health Stroke Scale (NIHSS) score on admission, stroke subtype, treatment before stroke or transient ischemic attack (TIA) (antiplatelets or warfarin), approach for catheters (transbrachial or femoral artery), amount of contrast medium used, length of the angiographic procedure, and fluoroscophy time. We divided the patients into two groups according to the presence of new DWI lesions after CAG; Positive group had new DWI lesions, whereas the Negative group had none. After CAG, no patients had new neurological deficits. New asymptomatic DWI lesions were observed in 24 patients (42.9%). The significant differences observed between two groups were as follows; age (69.8±11.3 for the Positive group versus 61.9±11.3 for the Negative group, p=0.043), female (54% versus 28%, p=0.048), non-small vessel occlusion (100% versus 66%, p=0.009), catheter approach for transfemoral artery (63% versus 13%, p<0.001), mean length of the angiographic procedure (63.1±21.6 min versus 43.7±14.2 min, p<0.001), mean fluoroscopy time (26.5±13.0 min versus 14.9±5.9 mm, p<0.001). Sensitivity and specificity analysis to discriminate the positive and negative groups revealed 17 minutes to be the critical threshold point (sensitivity 66.6% and specificity 68

Targeting brain-health from "cradle to grave": Can we prevent or delay dementia?

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Bhaskara P. Shelley

2014-01-01

Full Text Available Dementia or the "silver tsunami" is a public health challenge of epidemic proportions of the 21 st century. It imposes enormous burden in terms of economic and social impact on the health care systems and the quality of life of people with dementia, their families and caregivers. For a number of decades, clinicians, researchers, and pharmaceutical companies have laid emphasis on the development of a drug armamentarium for fighting dementia. However, the neurotherapy of dementia targeting the "pathogenesis model" still remains disappointing with no breakthrough in-sight. The cure for dementia is worthy, but an elusive and frustrating goal. On the contrary, epidemiological research does spell optimism and provides a substantial amount of evidence of modifiable risk and protective factors to delay, prevent or shorten dementia. Thus time has come for a "strategic vision for the future" to move away from the current paradigm of curative therapies to a strategy of "preemptive medicine" that identifies disease processes at the earliest stages and prevents rather than attempting to reverse disability. Such a strategy is not only a safer, more dignified option, but also a step forward for a sustainable society in an aging world in order to preserve the mental capital and brain well-being of nations. This would reiterate the concept of "anthroposophical medicine," neurocentric health and preventive neurology strategies to promote healthy brain aging and brain protection. The need to rethink and redefine dementia from a "salutogenesis" perspective as a "lifestyle disorder" and implement multiple preventative life-course approaches through well-designed randomized controlled trials is quintessential to delay, prevent or keep dementia at bay.

Retinoic acid-pretreated Wharton's jelly mesenchymal stem cells in combination with triiodothyronine improve expression of neurotrophic factors in the subventricular zone of the rat ischemic brain injury.

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Sabbaghziarani, Fatemeh; Mortezaee, Keywan; Akbari, Mohammad; Kashani, Iraj Ragerdi; Soleimani, Mansooreh; Moini, Ashraf; Ataeinejad, Nahid; Zendedel, Adib; Hassanzadeh, Gholamreza

2017-02-01

Stroke is the consequence of limited blood flow to the brain with no established treatment to reduce the neurological deficits. Focusing on therapeutic protocols in targeting subventricular zone (SVZ) neurogenesis has been investigated recently. This study was designed to evaluate the effects of retinoic acid (RA)-pretreated Wharton's jelly mesenchymal stem cells (WJ-MSCs) in combination with triiodothyronine (T3) in the ischemia stroke model. Male Wistar rats were used to induce focal cerebral ischemia by middle cerebral artery occlusion (MCAO). There were seven groups of six animals: Sham, Ischemic, WJ-MSCs, RA-pretreated WJ-MSCs, T3, WJ-MSCs +T3, and RA-pretreated WJ-MSCs + T3. The treatment was performed at 24 h after ischemia, and animals were sacrificed one week later for assessments of retinoid X receptor β (RXRβ), brain-derived neurotrophic factor (BDNF), Sox2 and nestin in the SVZ. Pro-inflammatory cytokines in sera were measured at days four and seven after ischemia. RXRβ, BDNF, Sox2 and nestin had the significant expressions in gene and protein levels in the treatment groups, compared with the ischemic group, which were more vivid in the RA-pretreated WJ-MSCs + T3 (p ≤ 0.05). The same trend was also resulted for the levels of TNF-α and IL-6 at four days after ischemia (p ≤ 0.05). In conclusion, application of RA-pretreated WJ-MSCs + T3 could be beneficial in exerting better neurotrophic function probably via modulation of pro-inflammatory cytokines.

Dosimetric analysis of the alopecia preventing effect of hippocampus sparing whole brain radiation therapy

International Nuclear Information System (INIS)

Mahadevan, Anand; Sampson, Carrie; LaRosa, Salvatore; Floyd, Scott R.; Wong, Eric T.; Uhlmann, Erik J.; Sengupta, Soma; Kasper, Ekkehard M.

2015-01-01

Whole brain radiation therapy (WBRT) is widely used for the treatment of brain metastases. Cognitive decline and alopecia are recognized adverse effects of WBRT. Recently hippocampus sparing whole brain radiation therapy (HS-WBRT) has been shown to reduce the incidence of memory loss. In this study, we found that multi-field intensity modulated radiation therapy (IMRT), with strict constraints to the brain parenchyma and to the hippocampus, reduces follicular scalp dose and prevents alopecia. Suitable patients befitting the inclusion criteria of the RTOG 0933 trial received Hippocampus sparing whole brain radiation. On follow up, they were noticed to have full scalp hair preservation. 5 mm thickness of follicle bearing scalp in the radiation field was outlined in the planning CT scans. Conventional opposed lateral WBRT radiation fields were applied to these patient-specific image sets and planned with the same nominal dose of 30 Gy in 10 fractions. The mean and maximum dose to follicle bearing skin and Dose Volume Histogram (DVH) data were analyzed for conventional and HS-WBRT. Paired t-test was used to compare the means. All six patients had fully preserved scalp hair and remained clinically cognitively intact 1–3 months after HS-WBRT. Compared to conventional WBRT, in addition to the intended sparing of the Hippocampus, HS-WBRT delivered significantly lower mean dose (22.42 cGy vs. 16.33 cGy, p < 0.0001), V 24 (9 cc vs. 44 cc, p < 0.0000) and V 30 (9 cc vs. 0.096 cc, p = 0.0106) to follicle hair bearing scalp and prevented alopecia. There were no recurrences in the Hippocampus area. HS-WBRT, with an 11-field set up as described, while attempting to conserve hippocampus radiation and maintain radiation dose to brain inadvertently spares follicle-bearing scalp and prevents alopecia

Neuroprotective Effects of Cannabidiol in Hypoxic Ischemic Insult. The Therapeutic Window in Newborn Mice.

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Mohammed, Nagat; Ceprian, Maria; Jimenez, Laura; Pazos, M Ruth; Martínez-Orgado, Jose

2017-01-01

A relevant therapeutic time window (TTW) is an important criterion for considering the clinical relevance of a substance preventing newborn hypoxic-ischemic (HI) brain damage. To test the TTW of the neuroprotective effects of cannabidol (CBD), a non-psychoactive cannabinoid in a model of newborn HI brain damage. 9-10 day-old C57BL6 mice underwent a HI insult (10% oxygen for 90 min after left carotid artery electrocoagulation). Then, CBD 1 mg/kg or vehicle were administered s.c. 15 min, or 1, 3, 6, 12, 18 or 24 h after the end of the HI insult. Seven days later brain damage was assessed using T2W Magnetic Resonance Imaging scan (ipsilateral hemisphere volume loss, IVHL) and histological studies: Nissl staining (neuropathological score), TUNEL staining (apoptotic damage) and immunohistochemistry with glial fibrillary acidic protein (astrocyte viability) or ionized calcium binding adaptor molecule (microglial activation). CBD administered up to 18 h after HI reduced IHVL and neuropathological score by 60%, TUNEL+ count by 90% and astrocyte damage by 50%. In addition, CBD blunted the HI-induced increase in microglial population. When CBD administration was delayed 24 h, however, the neuroprotective effect was lost in terms of IHVL, apoptosis or astrogliosis reduction. CBD shows a TTW of 18 h when administered to HI newborn mice, which represents a broader TTW than reported for other neuroprotective treatments including hypothermia. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Alpha-Tocopherol Reduces Brain Edema and Protects Blood-Brain Barrier Integrity following Focal Cerebral Ischemia in Rats.

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Haghnejad Azar, Adel; Oryan, Shahrbanoo; Bohlooli, Shahab; Panahpour, Hamdollah

2017-01-01

This study was conducted to examine the neuroprotective effects of α-tocopherol against edema formation and disruption of the blood-brain barrier (BBB) following transient focal cerebral ischemia in rats. Ninety-six male Sprague-Dawley rats were divided into 3 major groups (n = 32 in each), namely the sham, and control and α-tocopherol-treated (30 mg/kg) ischemic groups. Transient focal cerebral ischemia (90 min) was induced by occlusion of the left middle cerebral artery. At the end of the 24-hour reperfusion period, the animals were randomly selected and used for 4 investigations (n = 8) in each of the 3 main groups: (a) assessment of neurological score and measurement of infarct size, (b) detection of brain edema formation by the wet/dry method, (c) evaluation of BBB permeability using the Evans blue (EB) extravasation technique, and (d) assessment of the malondialdehyde (MDA) and reduced glutathione (GSH) concentrations using high-performance liquid chromatography methods. Induction of cerebral ischemia in the control group produced extensive brain edema (brain water content 83.8 ± 0.11%) and EB leakage into brain parenchyma (14.58 ± 1.29 µg/g) in conjunction with reduced GSH and elevated MDA levels (5.86 ± 0.31 mmol/mg and 63.57 ± 5.42 nmol/mg, respectively). Treatment with α-tocopherol significantly lowered brain edema formation and reduced EB leakage compared with the control group (p < 0.001, 80.1 ± 0.32% and 6.66 ± 0.87 µg/g, respectively). Meanwhile, treatment with α-tocopherol retained tissue GSH levels and led to a lower MDA level (p < 0.01, 10.17 ± 0.83 mmol/mg, and p < 0.001, 26.84 ± 4.79 nmol/mg, respectively). Treatment with α-tocopherol reduced ischemic edema formation and produced protective effects on BBB function following ischemic stroke occurrence. This effect could be through increasing antioxidant activity. © 2016 S. Karger AG, Basel.

LONG-TERM CLINICAL OUTCOME IN NORMAL VOLUNTEERS AND PATIENTS WITH CEREBRAL TRANSIENT ISCHEMIC ATTACKS

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J.Lotfi

1999-06-01

Full Text Available Detection and modification of the risk factors of stroke may be the most effective strategy for preventing its often irreversible consequences. A longitudinal prospective study was implemented to evaluate the effect of several risk factors on the course of cerebrovascular disease. The study groups were composed of 3S8 normal volunteers, and 308 patients with transient ischemic attacks. The two groups were followed for 4.2 (. 3.3 and 2.S years, respectively. Endpoints were defined as the occurrence of the following: transient ischemic attacks, stroke, multii-infarct dementia, dementia of the Alzheimer's type, or death. .Stroke and death were 2.5 times more frequent in the second group. Hypertension was the single predictor of reaching the endpoints (P<0.014. By excluding the cases with dementia of Ahheimers type, no single predictor could be identified. This study suggests that ischemic events arc significantly more frequent inpatients with transient ischemic attacks. A dichowmous split was observed between neurogenic and cardiogenic endpoints.

Critical care management of acute ischemic stroke.

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Coplin, William M

2012-06-01

Acute ischemic stroke (AIS) can have profound and devastating effects on the CNS and several other organs. Approximately 15% to 20% of patients with AIS are admitted to an intensive care unit and cared for by a multidisciplinary team. This article discusses the critical care management of patients with AIS. Patients with AIS require attention to airway, pulmonary status, blood pressure, glucose, temperature, cardiac function, and, sometimes, life-threatening cerebral edema. The lack of disease-specific data has led to numerous management approaches and limited guidance on choosing among them. Existing guidelines emphasize risk factors, prevention, natural history, and prevention of bleeding but provide little discussion of the complex critical care issues involved in caring for patients with AIS.

Prokineticin 2 is an endangering mediator of cerebral ischemic injury

OpenAIRE

Cheng, Michelle Y.; Lee, Alex G.; Culbertson, Collin; Sun, Guohua; Talati, Rushi K.; Manley, Nathan C.; Li, Xiaohan; Zhao, Heng; Lyons, David M.; Zhou, Qun-Yong; Steinberg, Gary K.; Sapolsky, Robert M.

2012-01-01

Stroke causes brain dysfunction and neuron death, and the lack of effective therapies heightens the need for new therapeutic targets. Here we identify prokineticin 2 (PK2) as a mediator for cerebral ischemic injury. PK2 is a bioactive peptide initially discovered as a regulator of gastrointestinal motility. Multiple biological roles for PK2 have been discovered, including circadian rhythms, angiogenesis, and neurogenesis. However, the role of PK2 in neuropathology is unknown. Using primary co...

Human neural progenitor cell engraftment increases neurogenesis and microglial recruitment in the brain of rats with stroke.

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Zahra Hassani

Full Text Available Stem cell transplantation is to date one of the most promising therapies for chronic ischemic stroke. The human conditionally immortalised neural stem cell line, CTX0E03, has demonstrable efficacy in a rodent model of stroke and is currently in clinical trials. Nonetheless, the mechanisms by which it promotes brain repair are not fully characterised. This study investigated the cellular events occurring after CTX0E03 transplantation in the brains of rats that underwent ischemic stroke.We focused on the endogenous proliferative activity of the host brain in response to cell transplantation and determined the identity of the proliferating cells using markers for young neurons (doublecortin, Dcx and microglia (CD11b. So as to determine the chronology of events occurring post-transplantation, we analysed the engrafted brains one week and four weeks post-transplantation.We observed a significantly greater endogenous proliferation in the striatum of ischemic brains receiving a CTX0E03 graft compared to vehicle-treated ischemic brains. A significant proportion of these proliferative cells were found to be Dcx+ striatal neuroblasts. Further, we describe an enhanced immune response after CTX0E03 engraftment, as shown by a significant increase of proliferating CD11b+ microglial cells.Our study demonstrates that few Dcx+ neuroblasts are proliferative in normal conditions, and that this population of proliferative neuroblasts is increased in response to stroke. We further show that CTX0E03 transplantation after stroke leads to the maintenance of this proliferative activity. Interestingly, the preservation of neuronal proliferative activity upon CTX0E03 transplantation is preceded and accompanied by a high rate of proliferating microglia. Our study suggests that microglia might mediate in part the effect of CTX0E03 transplantation on neuronal proliferation in ischemic stroke conditions.

TOWARD THE QUESTION OF ISCHEMIC MYOCARDIAL DYSFUNCTION

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V. V. Kalyuzhin

2014-01-01

Full Text Available The authors of the review have analyzed papers published on the problem of ischemic myocardial dysfunction. They begin with a definition of the term “ischemia” (derived from two Greek words: ischō, meaning to hold back, and haima, meaning blood - a condition at which the arterial blood flow is insufficient to provide enough oxygen to prevent intracellular respiration from shifting from the aerobic to the anaerobic form. The poor rate of ATP generation from this process causes a decrease in cellular ATP, a concomitant rise in ADP, and ultimately, to depression inotropic (systolic and lusitropic (diastolic function of the affected segments of the myocardium. But with such simplicity of basic concepts, the consequences of ischemia so diverse. Influence of an ischemia on myocardial function so unequally at different patients, which is almost impossible to find two identical cases (as in the case of fingerprints. It depends on the infinite variety of lesions of coronary arteries, reperfusion (time and completeness of restoration of blood flow and reactions of a myocardium which, apparently, has considerable flexibility in its response. Ischemic myocardial dysfunction includes a number of discrete states, such as acute left ventricular failure in angina, acute myocardial infarction, ischemic cardiomyopathy, stunning, hibernation, pre- and postconditioning. There are widely differing underlying pathophysiologic states. The possibility exists that several of these states can coexist.

It's All about Timing: The Involvement of Kir4.1 Channel Regulation in Acute Ischemic Stroke Pathology

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Meagan Milton

2018-02-01

Full Text Available An acute ischemic stroke is characterized by the presence of a blood clot that limits blood flow to the brain resulting in subsequent neuronal loss. Acute stroke threatens neuronal survival, which relies heavily upon proper function of astrocytes. Neurons are more susceptible to cell death when an astrocyte is unable to carry out its normal functions in supporting the neuron in the area affected by the stroke (Rossi et al., 2007; Takano et al., 2009. For example, under normal conditions, astrocytes initially swell in response to changes in extracellular osmotic pressure and then reduce their regulatory volume in response to volume-activated potassium (K+ and chloride channels (Vella et al., 2015. This astroglial swelling may be overwhelmed, under ischemic conditions, due to the increased levels of glutamate and extracellular K+ (Lai et al., 2014; Vella et al., 2015. The increase in extracellular K+ contributes to neuronal damage and loss through the initiation of harmful secondary cascades (Nwaobi et al., 2016. Reducing the amount of extracellular K+ could, in theory, limit or prevent neuronal damage and loss resulting in an improved prognosis for individuals following ischemic stroke. Kir4.1, an inwardly rectifying K+ channel, has demonstrated an ability to regulate the rapid reuptake of this ion to return the cell to basal levels allowing it to fire again in rapid transmission (Sibille et al., 2015. Despite growing interest in this area, the underlying mechanism suggesting that neuroprotection could occur through modification of the Kir4.1 channel's activity has yet to be described. The purpose of this review is to examine the current literature and propose potential underlying mechanisms involving Kir4.1, specially the mammalian target of rapamycin (mTOR and/or autophagic pathways, in the pathogenesis of ischemic stroke. The hope is that this review will instigate further investigation of Kir4.1 as a modulator of stroke pathology.

Reduction of superoxide dismutase activity correlates with visualization of edema by T2-weighted MR imaging in focal ischemic rat brain

International Nuclear Information System (INIS)

Imaizumi, Shigeki; Chang, LeeHong; Cohen, Yoram; Chan, P.H.; Weinstein, P.R.; James, T.L.; Yoshimoto, Takashi.

1994-01-01

This study investigated the correlation between in vivo serial T 2 -weighted magnetic resonance (MR) imaging and changes in superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, and water, sodium ion (Na + ), and potassium ion (K + ) contents measured in vitro using rat brain following right middle cerebral artery occlusion in conjunction with bilateral common carotid artery (CCA) occlusion. One hour later the left CCA was released. Serial MR images showed edema developed from the outer cortex towards the center. The T 2 signal intensity of the injured right cortex increased with time compared to that of the contralateral cortex. Increased Na + and water and decreased K + contents occurred in the injured cortex, indicating that serial T 2 -weighted MR imaging reflects the changes in water content and Na + and K + concentrations determined by biochemical techniques. GSH-Px activity was little changed. Total SOD in the injured cortex decreased 1 hour after ischemia and remained low throughout the experiment. In contrast, SOD activity in the noninfarcted left cortex also decreased after 1 hour but returned to normal after 2 hours of ischemia. Our results suggest that oxygen free radicals are important in developing ischemic brain edema and cerebral infarction. (author)

Preferential cephalic redistribution of left ventricular cardiac output during therapeutic hypothermia for perinatal hypoxic-ischemic encephalopathy.

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Hochwald, Ori; Jabr, Mohammad; Osiovich, Horacio; Miller, Steven P; McNamara, Patrick J; Lavoie, Pascal M

2014-05-01

To determine the relationship between left ventricular cardiac output (LVCO), superior vena cava (SVC) flow, and brain injury during whole-body therapeutic hypothermia. Sixteen newborns with moderate or severe hypoxic-ischemic encephalopathy were studied using echocardiography during and immediately after therapeutic hypothermia. Measures were also compared with 12 healthy newborns of similar postnatal age. Newborns undergoing therapeutic hypothermia also had cerebral magnetic resonance imaging as part of routine clinical care on postnatal day 3-4. LVCO was markedly reduced (mean ± SD 126 ± 38 mL/kg/min) during therapeutic hypothermia, whereas SVC flow was maintained within expected normal values (88 ± 27 mL/kg/min) such that SVC flow represented 70% of the LVCO. The reduction in LVCO during therapeutic hypothermia was mainly accounted by a reduction in heart rate (99 ± 13 vs 123 ± 17 beats/min; P newborns without brain injury (P = .013). Newborns with perinatal hypoxic-ischemic encephalopathy showed a preferential systemic-to-cerebral redistribution of cardiac blood flow during whole-body therapeutic hypothermia, which may reflect a lack of cerebral vascular adaptation in newborns with more severe brain injury. Copyright © 2014 Elsevier Inc. All rights reserved.