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Sample records for cerebral ischemic rats

  1. Pharmacokinetic Study of Piracetam in Focal Cerebral Ischemic Rats.

    Science.gov (United States)

    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

  2. Sequential changes in ischemic edema following transient focal cerebral ischemia in rats; Magnetic resonance imaging study

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    Nagahiro, Shinji; Goto, Satoshi; Kogo, Kasei; Sumi, Minako; Takahashi, Mutsumasa; Ushio, Yukitaka [Kumamoto Univ. (Japan). School of Medicine

    1994-07-01

    Sequential and regional changes in ischemic edema following various durations of focal cerebral ischemia were studied by magnetic resonance (MR) imaging in a rat unilateral intraluminal middle cerebral artery occlusion model. Occlusion was performed from 5 minutes to 5 hours. T[sub 2]-weighted images were obtained chronologically 6 hours after onset of ischemia, on day 1 and day 7. An immunohistochemical study using antibodies to calcineurin and glial fibrillary acidic protein was performed to observe histological changes in the ischemic brain. The T[sub 2] high-signal-intensity areas representing ischemic edema were observed in the lateral striatum and/or the cerebral cortex by day 1 in all rats with 1- to 5-hour ischemia, and the areas were larger and detected earlier with longer durations of ischemia. In three of six rats with 15-minute ischemia and five of six rats with 30-minute ischemia, the T[sub 2] high-signal-intensity areas appeared transiently on day 1 in the dorsolateral striatum where loss of neurons expressing calcineurin immunoreactivity and associated gliosis were found. MR imaging in animal models of reversible focal ischemia can achieve sequential and noninvasive evaluation of dynamic regional changes in ischemic edema. (author).

  3. Characterization of neuronal damage by iomazenil binding and cerebral blood flow in an ischemic rat model

    International Nuclear Information System (INIS)

    Toyama, Hiroshi; Takeuchi, Akira; Koga, Sukehiko; Matsumura, Kaname; Nakashima, Hiromichi; Takeda, Kan; Yoshida, Toshimichi; Ichise, Masanori

    1998-01-01

    I-123-iomazenil is a SPECT probe for central benzodiazepine receptors (BZR) which may reflect intact cortical neuron density after ischemic insults. We evaluated whether neuronal damage in rats could be characterized by iomazenil as compared with cerebral blood flow (CBF). Serial changes in I-125-iomazenil for BZR and I-123-IMP for CBF were analyzed after the unilateral middle cerebral artery occlusion in rats by using an in vivo dualtracer technique. Uptake ratios of affected to contralateral regions were calculated. The iomazenil as well as IMP were decreased in all regions except for the cerebellum (remote area). Both iomazenil and IMP increased over time except in the temporal region (ischemic core). The iomazenil uptake was higher than IMP except in the ischemic core between 1 and 3-4 wk when iomazenil was lower than IMP. Iomazenil showed a moderate decrease in the proximal and middle parietal regions (peri-infarct areas) at 3-4 wk. The triphenyl-tetrazolium-chloride (TTC) stain at 1 wk demonstrated unstained tissue in the temporal region indicating tissue necrosis. With hematoxylin-eosin (HE) stain at 1 wk, widespread neuronal necrosis with occasional intact neurons were found in the proximal parietal region, and isolated necrotic neurons were represented in the distal parietal region. Iomazenil correlated well with the neuron distribution and the finding of a discrepancy between iomazenil and IMP might be useful in evaluating the neuronal damage. (author)

  4. Reduction of mitochondrial electron transport complex activity is restricted to the ischemic focus after transient focal cerebral ischemia in rats

    DEFF Research Database (Denmark)

    Christensen, Thomas; Diemer, Nils Henrik

    2003-01-01

    Using histochemical methods offering high topographical resolution for evaluation of changes in the ischemic focus and the penumbra, the mitochondrial electron transport chain (ETC) complexes I, II, and IV were examined in rats subjected to 2 h of proximal occlusion of the middle cerebral artery...

  5. Lysine and arginine reduce the effects of cerebral ischemic insults and inhibit glutamate-induced neuronal activity in rats

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    Takashi Kondoh

    2010-06-01

    Full Text Available Intravenous administration of arginine was shown to be protective against cerebral ischemic insults via nitric oxide production and possibly via additional mechanisms. The present study aimed at evaluating the neuroprotective effects of oral administration of lysine (a basic amino acid, arginine, and their combination on ischemic insults (cerebral edema and infarction and hemispheric brain swelling induced by transient middle cerebral artery occlusion/reperfusion in rats. Magnetic resonance imaging and 2,3,5-triphenyltetrazolium chloride staining were performed two days after ischemia induction. In control animals, the major edematous areas were observed in the cerebral cortex and striatum. The volumes associated with cortical edema were significantly reduced by lysine (2.0 g/kg, arginine (0.6 g/kg, or their combined administration (0.6 g/kg each. Protective effects of these amino acids on infarction were comparable to the inhibitory effects on edema formation. Interestingly, these amino acids, even at low dose (0.6 g/kg, were effective to reduce hemispheric brain swelling. Additionally, the effects of in vivo microiontophoretic (juxtaneuronal applications of these amino acids on glutamate-evoked neuronal activity in the ventromedial hypothalamus were investigated in awake rats. Glutamate-induced neuronal activity was robustly inhibited by microiontophoretic applications of lysine or arginine onto neuronal membranes. Taken together, our results demonstrate the neuroprotective effects of oral ingestion of lysine and arginine against ischemic insults (cerebral edema and infarction, especially in the cerebral cortex, and suggest that suppression of glutamate-induced neuronal activity might be the primary mechanism associated with these neuroprotective effects.

  6. Protective effects of alkaloid extract from Leonurus heterophyllus on cerebral ischemia reperfusion injury by middle cerebral ischemic injury (MCAO) in rats.

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    Liang, Hao; Liu, Ping; Wang, Yunshan; Song, Shuliang; Ji, Aiguo

    2011-07-15

    The neuronal damage following cerebral ischemia is a serious risk to stroke patients. The aim of this study was to investigate the neuroprotective effects of alkaloid extract from Leonurus heterophyllus (LHAE) on cerebral ischemic injury. After 24 h of reperfusion following ischemia for 2 h induced by middle cerebral artery occlusion (MCAO), some rats were intraperitoneally administered different doses of LHAE (3.6, 7.2, 14.4 mg/kg, respectively). Neurological examination was measured in all animals. Infarct volume, myeloperoxidase (MPO) activity, levels of nitrate/nitrite metabolite (NO) and apoptosis ratio of nerve fiber in brain were determined. The results showed that LHAE at 7.2 mg/kg or 14.4 mg/kg exerted significantly decreasing neurological deficit scores and reducing the infarct volume on rats with focal cerebral ischemic injury (pagent. Further studies are warranted to assess the efficacy and safety of LHAE in patients. Copyright © 2011 Elsevier GmbH. All rights reserved.

  7. Zingiber officinale Mitigates Brain Damage and Improves Memory Impairment in Focal Cerebral Ischemic Rat

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    Wattanathorn, Jintanaporn; Jittiwat, Jinatta; Tongun, Terdthai; Muchimapura, Supaporn; Ingkaninan, Kornkanok

    2011-01-01

    Cerebral ischemia is known to produce brain damage and related behavioral deficits including memory. Recently, accumulating lines of evidence showed that dietary enrichment with nutritional antioxidants could reduce brain damage and improve cognitive function. In this study, possible protective effect of Zingiber officinale, a medicinal plant reputed for neuroprotective effect against oxidative stress-related brain damage, on brain damage and memory deficit induced by focal cerebral ischemia was elucidated. Male adult Wistar rats were administrated an alcoholic extract of ginger rhizome orally 14 days before and 21 days after the permanent occlusion of right middle cerebral artery (MCAO). Cognitive function assessment was performed at 7, 14, and 21 days after MCAO using the Morris water maze test. The brain infarct volume and density of neurons in hippocampus were also determined. Furthermore, the level of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in cerebral cortex, striatum, and hippocampus was also quantified at the end of experiment. The results showed that cognitive function and neurons density in hippocampus of rats receiving ginger rhizome extract were improved while the brain infarct volume was decreased. The cognitive enhancing effect and neuroprotective effect occurred partly via the antioxidant activity of the extract. In conclusion, our study demonstrated the beneficial effect of ginger rhizome to protect against focal cerebral ischemia. PMID:21197427

  8. Zingiber officinale Mitigates Brain Damage and Improves Memory Impairment in Focal Cerebral Ischemic Rat

    Directory of Open Access Journals (Sweden)

    Jintanaporn Wattanathorn

    2011-01-01

    Full Text Available Cerebral ischemia is known to produce brain damage and related behavioral deficits including memory. Recently, accumulating lines of evidence showed that dietary enrichment with nutritional antioxidants could reduce brain damage and improve cognitive function. In this study, possible protective effect of Zingiber officinale, a medicinal plant reputed for neuroprotective effect against oxidative stress-related brain damage, on brain damage and memory deficit induced by focal cerebral ischemia was elucidated. Male adult Wistar rats were administrated an alcoholic extract of ginger rhizome orally 14 days before and 21 days after the permanent occlusion of right middle cerebral artery (MCAO. Cognitive function assessment was performed at 7, 14, and 21 days after MCAO using the Morris water maze test. The brain infarct volume and density of neurons in hippocampus were also determined. Furthermore, the level of malondialdehyde (MDA, superoxide dismutase (SOD, catalase (CAT, and glutathione peroxidase (GSH-Px in cerebral cortex, striatum, and hippocampus was also quantified at the end of experiment. The results showed that cognitive function and neurons density in hippocampus of rats receiving ginger rhizome extract were improved while the brain infarct volume was decreased. The cognitive enhancing effect and neuroprotective effect occurred partly via the antioxidant activity of the extract. In conclusion, our study demonstrated the beneficial effect of ginger rhizome to protect against focal cerebral ischemia.

  9. Changes of cerebral contents of neuropeptides in rat models of multiple ischemic dementia (MID)

    International Nuclear Information System (INIS)

    Zheng Xianghong; Guo Jingcai; Song Changyi; Wang Shejiao; Chen Wei

    2005-01-01

    Objective: To investigate the significance of changes of cerebral contents of the neuropeptides somatostatin (SS), arginine vasopressin (AVP) and substance P in rat models of MID. Methods: The rat models consisted of 15 rats undergoing intracarotid injection of autogenous thrombus powder. Another group of 15 rats undergoing sham operation served as controls. Learning and memory ability in these rats was assessed with daily passive avoidance task testing for 10 consecutive days. The animals were sacrificed on 30d and contents of the neuropeptides in tissue homogenate from different areas of brain (frontal cortex, temporal cortex, hippocampus, thalamus and corpus striatum) were measured with (RIA). Results: On the first day of passive avoidance task testing, the frequency of errors in the MID group and the control group was about the same. From the third day on, the frequency of errors in the MID group was significantly higher than that in the control group (P<0.05). The neuropeptides contents of all these cerebral areas in the MID group were significantly higher than those in the control group (P<0.05 or P<0.01) with the only exception of the contents of substance P in thalamus (no significant difference between the contents in the two groups). Conclusion: The impairment of learning and memory in rat models with MID was possibly related to the lowered contents of SS, AVP and substance P in the brain tissue. (authors)

  10. UCAO (UNILATERAL CEREBRAL ARTERY OCCLUSSION METHOD INCREASES THE LEVEL OF MMP- 9 BRAIN TISSUE IN RATS MODEL OF ISCHEMIC STROKE

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    M. Rasjad Indra

    2016-07-01

    Full Text Available Background. For the last 5 years, 15.4% of total population died because of stroke, which 42.9% of those are caused by ischemic stroke. UCAO (Unilateral Cerebral Artery Occlusion is a stroke induction method by ligating mice’s carotid artery for 45 minutes. Thus, giving a hypoxic condition similar to stroke attack in human. This method is less complicated and far more efficient. MMP-9 is a stroke marker which is assayed by ELISA from the blood of test animal. Objective. This research was conducted to prove UCAO (Unilateral Cerebral Artery Occlusion method is capable to raise MMP-9 concentration in mice’s blood. Methods. This research was an experimental laboratory research with post-test only controlled group design. 8 male rats (8-10 weeks were divided into 2 groups, control and treatment which would be inducted into stroke by UCAO method. A day after the treatment group had been induced to stroke, both group were tested to measure the MMP-9 blood concentration through ELISA. Results. In this research, UCAO method had increased MMP-9 blood concentration in treatment group, compared to the control group. It is proved by the statistic tests, Mann-Whitney and Kruskal-Wallis, which showed a significant increase in treatment group (p < 0.05. Conclusion. Based on this result, it can be concluded that UCAO method is accepted as a method to create an ischemic stroke mice model.

  11. Early Exercise Protects against Cerebral Ischemic Injury through Inhibiting Neuron Apoptosis in Cortex in Rats

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    Junfa Wu

    2013-03-01

    Full Text Available Early exercise is an effective strategy for stroke treatment, but the underlying mechanism remains poorly understood. Apoptosis plays a critical role after stroke. However, it is unclear whether early exercise inhibits apoptosis after stroke. The present study investigated the effect of early exercise on apoptosis induced by ischemia. Adult SD rats were subjected to transient focal cerebral ischemia by middle cerebral artery occlusion model (MCAO and were randomly divided into early exercise group, non-exercise group and sham group. Early exercise group received forced treadmill training initiated at 24 h after operation. Fourteen days later, the cell apoptosis were detected by TdT-mediated dUTP-biotin nick-end labeling (TUNEL and Fluoro-Jade-B staining (F-J-B. Caspase-3, cleaved caspase-3 and Bcl-2 were determined by western blotting. Cerebral infarct volume and motor function were evaluated by cresyl violet staining and foot fault test respectively. The results showed that early exercise decreased the number of apoptotic cells (118.74 ± 6.15 vs. 169.65 ± 8.47, p < 0.05, n = 5, inhibited the expression of caspase-3 and cleaved caspase-3 (p < 0.05, n = 5, and increased the expression of Bcl-2 (p < 0.05, n = 5. These data were consistent with reduced infarct volume and improved motor function. These results suggested that early exercise could provide neuroprotection through inhibiting neuron apoptosis.

  12. 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.

  13. Electroacupuncture improves cerebral blood flow and attenuates moderate ischemic injury via Angiotensin II its receptors-mediated mechanism in rats.

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    Li, Jing; He, Jiaojun; Du, Yuanhao; Cui, Jingjun; Ma, Ying; Zhang, Xuezhu

    2014-11-11

    To investigate the effects and potential mechanism of electroacupuncture intervention on expressions of Angiotensin II and its receptors-mediated signaling pathway in experimentally induced cerebral ischemia. Totally 126 male Wistar rats were randomly divided into control group, model group and EA group. The latter two were further divided into ten subgroups (n = 6) following Middle Cerebral Artery Occlusion (MCAO). Changes in regional cerebral blood flow (rCBF) and expressions of Angiotensin II and its receptors (AT1R, AT2R), as well as effector proteins in phosphatidyl inositol signal pathway were monitored before and at different times after MCAO. MCAO-induced decline of ipsilateral rCBF was partially suppressed by electroacupuncture, and contralateral blood flow was also superior to that of model group. Angiotensin II level was remarkably elevated immediately after MCAO, while electroacupuncture group exhibited significantly lower levels at 1 to 3 h and the value was significantly increased thereafter. The enhanced expression of AT1R was partially inhibited by electroacupuncture, while increased AT2R level was further induced. Electroacupuncture stimulation attenuated and postponed the upregulated-expressions of Gq and CaM these upregulations. ELISA results showed sharply increased expressions of DAG and IP3, which were remarkably neutralized by electroacupuncture. MCAO induced significant increases in expression of Angiotensin II and its receptor-mediated signal pathway. These enhanced expressions were significantly attenuated by electroacupuncture intervention, followed by reduced vasoconstriction and improved blood supply in ischemic region, and ultimately conferred beneficial effects on cerebral ischemia.

  14. EEG patterns from acute to chronic stroke phases in focal cerebral ischemic rats: correlations with functional recovery.

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    Zhang, Shao-jie; Ke, Zheng; Li, Le; Yip, Shea-ping; Tong, Kai-yu

    2013-04-01

    Monitoring the neural activities from the ischemic penumbra provides critical information on neurological recovery after stroke. The purpose of this study is to evaluate the temporal alterations of neural activities using electroencephalography (EEG) from the acute phase to the chronic phase, and to compare EEG with the degree of post-stroke motor function recovery in a rat model of focal ischemic stroke. Male Sprague-Dawley rats were subjected to 90 min transient middle cerebral artery occlusion surgery followed by reperfusion for seven days (n = 58). The EEG signals were recorded at the pre-stroke phase (0 h), acute phase (3, 6 h), subacute phase (12, 24, 48, 72 h) and chronic phase (96, 120, 144, 168 h) (n = 8). This study analyzed post-stroke seizures and polymorphic delta activities (PDAs) and calculated quantitative EEG parameters such as the alpha-to-delta ratio (ADR). The ADR represented the ratio between alpha power and delta power, which indicated how fast the EEG activities were. Forelimb and hindlimb motor functions were measured by De Ryck's test and the beam walking test, respectively. In the acute phase, delta power increased fourfold with the occurrence of PDAs, and the histological staining showed that the infarct was limited to the striatum and secondary sensory cortex. In the subacute phase, the alpha power reduced to 50% of the baseline, and the infarct progressed to the forelimb cortical region. ADRs reduced from 0.23 ± 0.09 to 0.04 ± 0.01 at 3 h in the acute phase and gradually recovered to 0.22 ± 0.08 at 168 h in the chronic phase. In the comparison of correlations between the EEG parameters and the limb motor function from the acute phase to the chronic phase, ADRs were found to have the highest correlation coefficients with the beam walking test (r = 0.9524, p test (r = 0.8077, p < 0.05). This study measured EEG activities after focal cerebral ischemia and showed that functional recovery was closely correlated with the neural

  15. EEG patterns from acute to chronic stroke phases in focal cerebral ischemic rats: correlations with functional recovery

    International Nuclear Information System (INIS)

    Zhang, Shao-jie; Ke, Zheng; Tong, Kai-yu; Li, Le; Yip, Shea-ping

    2013-01-01

    Monitoring the neural activities from the ischemic penumbra provides critical information on neurological recovery after stroke. The purpose of this study is to evaluate the temporal alterations of neural activities using electroencephalography (EEG) from the acute phase to the chronic phase, and to compare EEG with the degree of post-stroke motor function recovery in a rat model of focal ischemic stroke. Male Sprague–Dawley rats were subjected to 90 min transient middle cerebral artery occlusion surgery followed by reperfusion for seven days (n = 58). The EEG signals were recorded at the pre-stroke phase (0 h), acute phase (3, 6 h), subacute phase (12, 24, 48, 72 h) and chronic phase (96, 120, 144, 168 h) (n = 8). This study analyzed post-stroke seizures and polymorphic delta activities (PDAs) and calculated quantitative EEG parameters such as the alpha-to-delta ratio (ADR). The ADR represented the ratio between alpha power and delta power, which indicated how fast the EEG activities were. Forelimb and hindlimb motor functions were measured by De Ryck's test and the beam walking test, respectively. In the acute phase, delta power increased fourfold with the occurrence of PDAs, and the histological staining showed that the infarct was limited to the striatum and secondary sensory cortex. In the subacute phase, the alpha power reduced to 50% of the baseline, and the infarct progressed to the forelimb cortical region. ADRs reduced from 0.23 ± 0.09 to 0.04 ± 0.01 at 3 h in the acute phase and gradually recovered to 0.22 ± 0.08 at 168 h in the chronic phase. In the comparison of correlations between the EEG parameters and the limb motor function from the acute phase to the chronic phase, ADRs were found to have the highest correlation coefficients with the beam walking test (r = 0.9524, p < 0.05) and De Ryck's test (r = 0.8077, p < 0.05). This study measured EEG activities after focal cerebral ischemia and showed that functional recovery was closely

  16. Protection by the gross saponins of Tribulus terrestris against cerebral ischemic injury in rats involves the NF-κB pathway

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    En-ping Jiang

    2011-06-01

    Full Text Available The aim of this study was to investigate whether the gross saponins of Tribulus terrestris (GSTT, a traditional Chinese herbal medicine, have neuroprotective effects on rats subjected to middle cerebral artery occlusion (MCAO, through nuclear factor-κB (NF-κB pathway and inflammatory mediators. Cerebral ischemia was produced by MCAO in either untreated (control or GSTT-pretreated rats, and the animals were examined for infarct volume, cerebral edema, neuro-behavioral abnormality and pathological changes. Meanwhile, the expression of NF-κB protein in brain tissue was analyzed on Western blots and the serum levels of TNF-α and IL-1 were determined by ELISA. The experimental results demonstrated that, compared with the control MCAO group, GSTT-pretreated MCAO group had significantly reduced infarct volume, brain edema and neuro-behavioral abnormality, and lesser degree of pathologic changes in the brain, as well as had lower levels of serum TNF-α and IL-1β, and higher levels of brain NF-κB (P<0.05. Furthermore, treatment with an NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC abolished the protective effects of GSTT against MCAO-induced cerebral ischemic injury. These results indicated that GSTT's ability to protect against cerebral ischemic injury was mediated through the NF-κB signaling pathway, and that GSTT may act through inhibition of the production of inflammatory mediators.

  17. 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.

  18. Effect of Pre-nutrion of Flax Seed Oil (Linum Usitatissimum on the amount of Cerebral ischemic lesion and motor nerve disorders in animal model rat.

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    SV Hosseini

    2015-10-01

    Full Text Available Background & aim: Stroke is the third death agent (factor in industrial countries after cardiovascular disease and cancer. With regard to high content of antioxidant materials in flax seed oil like &alpha-linolenic acid, lignan as well as phenolic combinations like secoisolarisirsinol (SDG, this study performed for studding relationship between of cerebral ischemic lesion and motor-nerve disorders in model of stroke in rat. Methods: in the study, 35 male mice from strain Wistar divided to 5 groups. The groups included control, sham and 3 experimental groups. They received doses 0.25, 0.5 and 0.75 ml/kg from flax seed oil orally. By gavage for 30 days two control and sham groups received aqua distillate (distil water. Two hours after the last gavaged dose, overly group with 7 pieces operated for measurement of the amount of cerebral lesion and motor-nerve disorders. (Middle Cerebral Artery Occlusion Model. Middle cerebral Artery Occlusion by the model resulted in local ischemic stroke in animal. Data analyzed by software SPSS, test ANOVA and disorders by test mann-Whitney. Findings: Average of records of motor-nerve disorders decreased significantly in group with dose 0.5 and 0.75 using flax seed oil (P<0.05. The amount of cerebral ischemic lesion in doses 0.5 and 0.75 than to control group is indicated meaning full different, but percent of the total cerebral lesion in control group in compared group with dose 0.25 is not indicated meaningful different. Percent of the amount of ischemic lesion in region penumbra in group 0.75 and 0.5 than to control group is indicated meaningful different, but percent of the amount of lesion in region penumbra in control group in compared region penumbra in group with dose 0.25 is not indicated meaning full different. Results: Findings of the study indicated that flax seed oil, particular in doses 0.5 and 0.75 resulted to decrease of the amount of cerebral ischemic lesion and decrease of motor-nerve disorders in

  19. A Promising Approach to Integrally Evaluate the Disease Outcome of Cerebral Ischemic Rats Based on Multiple-Biomarker Crosstalk

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    Guimei Ran

    2017-01-01

    Full Text Available Purpose. The study was designed to evaluate the disease outcome based on multiple biomarkers related to cerebral ischemia. Methods. Rats were randomly divided into sham, permanent middle cerebral artery occlusion, and edaravone-treated groups. Cerebral ischemia was induced by permanent middle cerebral artery occlusion surgery in rats. To form a simplified crosstalk network, the related multiple biomarkers were chosen as S100β, HIF-1α, IL-1β, PGI2, TXA2, and GSH-Px. The levels or activities of these biomarkers in plasma were detected before and after ischemia. Concurrently, neurological deficit scores and cerebral infarct volumes were assessed. Based on a mathematic model, network balance maps and three integral disruption parameters (k, φ, and u of the simplified crosstalk network were achieved. Results. The levels or activities of the related biomarkers and neurological deficit scores were significantly impacted by cerebral ischemia. The balance maps intuitively displayed the network disruption, and the integral disruption parameters quantitatively depicted the disruption state of the simplified network after cerebral ischemia. The integral disruption parameter u values correlated significantly with neurological deficit scores and infarct volumes. Conclusion. Our results indicate that the approach based on crosstalk network may provide a new promising way to integrally evaluate the outcome of cerebral ischemia.

  20. Interstitial pO2 in ischemic penumbra and core are differentially affected following transient focal cerebral ischemia in rats.

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    Liu, Shimin; Shi, Honglian; Liu, Wenlan; Furuichi, Takamitsu; Timmins, Graham S; Liu, Ke Jian

    2004-03-01

    Stroke causes heterogeneous changes in tissue oxygenation, with a region of decreased blood flow, the penumbra, surrounding a severely damaged ischemic core. Treatment of acute ischemic stroke aims to save this penumbra before its irreversible damage by continued ischemia. However, effective treatment remains elusive due to incomplete understanding of processes leading to penumbral death. While oxygenation is central in ischemic neuronal death, it is unclear exactly what actual changes occur in interstitial oxygen tension (pO2) in ischemic regions during stroke, particularly the penumbra. Using the unique capability of in vivo electron paramagnetic resonance (EPR) oximetry to measure localized interstitial pO2, we measured both absolute values, and temporal changes of pO2 in ischemic penumbra and core during ischemia and reperfusion in a rat model. Ischemia rapidly decreased interstitial pO2 to 32% +/- 7.6% and 4% +/- 0.6% of pre-ischemic values in penumbra and core, respectively 1 hour after ischemia. Importantly, whilst reperfusion restored core pO2 close to its pre-ischemic value, penumbral pO2 only partially recovered. Hyperoxic treatment significantly increased penumbral pO2 during ischemia, but not in the core, and also increased penumbral pO2 during reperfusion. These divergent, important changes in pO2 in penumbra and core were explained by combined differences in cellular oxygen consumption rates and microcirculation conditions. We therefore demonstrate that interstitial pO2 in penumbra and core is differentially affected during ischemia and reperfusion, providing new insights to the pathophysiology of stroke. The results support normobaric hyperoxia as a potential early intervention to save penumbral tissue in acute ischemic stroke.

  1. 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.

  2. Ischemia preconditioning is neuroprotective in a rat cerebral ischemic injury model through autophagy activation and apoptosis inhibition

    International Nuclear Information System (INIS)

    Xia, D.Y.; Li, W.; Qian, H.R.; Yao, S.; Liu, J.G.; Qi, X.K.

    2013-01-01

    Sublethal ischemic preconditioning (IPC) is a powerful inducer of ischemic brain tolerance. However, its underlying mechanisms are still not well understood. In this study, we chose four different IPC paradigms, namely 5 min (5 min duration), 5×5 min (5 min duration, 2 episodes, 15-min interval), 5×5×5 min (5 min duration, 3 episodes, 15-min intervals), and 15 min (15 min duration), and demonstrated that three episodes of 5 min IPC activated autophagy to the greatest extent 24 h after IPC, as evidenced by Beclin expression and LC3-I/II conversion. Autophagic activation was mediated by the tuberous sclerosis type 1 (TSC1)-mTor signal pathway as IPC increased TSC1 but decreased mTor phosphorylation. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and hematoxylin and eosin staining confirmed that IPC protected against cerebral ischemic/reperfusion (I/R) injury. Critically, 3-methyladenine, an inhibitor of autophagy, abolished the neuroprotection of IPC and, by contrast, rapamycin, an autophagy inducer, potentiated it. Cleaved caspase-3 expression, neurological scores, and infarct volume in different groups further confirmed the protection of IPC against I/R injury. Taken together, our data indicate that autophagy activation might underlie the protection of IPC against ischemic injury by inhibiting apoptosis

  3. Ischemia preconditioning is neuroprotective in a rat cerebral ischemic injury model through autophagy activation and apoptosis inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Xia, D.Y. [Department of Neurology, Navy General Hospital of PLA, Beijing (China); Li, W. [General Hospital of Shenyang Military Command, Department of Neurology, Shenyang, China, Department of Neurology, General Hospital of Shenyang Military Command, Shenyang (China); Qian, H.R.; Yao, S.; Liu, J.G.; Qi, X.K. [Department of Neurology, Navy General Hospital of PLA, Beijing (China)

    2013-08-10

    Sublethal ischemic preconditioning (IPC) is a powerful inducer of ischemic brain tolerance. However, its underlying mechanisms are still not well understood. In this study, we chose four different IPC paradigms, namely 5 min (5 min duration), 5×5 min (5 min duration, 2 episodes, 15-min interval), 5×5×5 min (5 min duration, 3 episodes, 15-min intervals), and 15 min (15 min duration), and demonstrated that three episodes of 5 min IPC activated autophagy to the greatest extent 24 h after IPC, as evidenced by Beclin expression and LC3-I/II conversion. Autophagic activation was mediated by the tuberous sclerosis type 1 (TSC1)-mTor signal pathway as IPC increased TSC1 but decreased mTor phosphorylation. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and hematoxylin and eosin staining confirmed that IPC protected against cerebral ischemic/reperfusion (I/R) injury. Critically, 3-methyladenine, an inhibitor of autophagy, abolished the neuroprotection of IPC and, by contrast, rapamycin, an autophagy inducer, potentiated it. Cleaved caspase-3 expression, neurological scores, and infarct volume in different groups further confirmed the protection of IPC against I/R injury. Taken together, our data indicate that autophagy activation might underlie the protection of IPC against ischemic injury by inhibiting apoptosis.

  4. Goreisan Inhibits Upregulation of Aquaporin 4 and Formation of Cerebral Edema in the Rat Model of Juvenile Hypoxic-Ischemic Encephalopathy

    Science.gov (United States)

    Yano, Hajime; Takahashi, Hisaaki; Yoshimoto, Kouhei; Tsuda, Shinji; Fujiyama, Kenta; Izumo-Shimizu, Yusuke; Motoie, Ryota; Ito, Masanori; Tanaka, Junya; Ishii, Eiichi

    2017-01-01

    Secondary cerebral edema regulation is of prognostic significance in hypoxic-ischemic encephalopathy (HIE), and aquaporin 4 (AQP4) plays an important role in the pathogenesis of cerebral edema. The traditional Japanese herbal medicine Goreisan relieves brain edema in adults; however, its effect and pharmacological mechanism in children are unknown. We investigated the effects of Goreisan on HIE-associated brain edema and AQP4 expression in a juvenile rat model, established by combined occlusion of middle cerebral and common carotid arteries. Magnetic resonance imaging showed that the lesion areas were significantly smaller in the Goreisan- (2 g/kg) treated group than in the nontreated (saline) group at 24 and 48 h postoperatively. AQP4 mRNA levels in the lesion and nonlesion sides were significantly suppressed in the Goreisan group compared with the nontreated group 36 h postoperatively. Western blotting revealed that levels of AQP4 protein were significantly decreased in the Goreisan group compared with the nontreated group in the lesion side 72 h postoperatively, but not at 12 or 36 h. After 14 days, the Goreisan group had a significantly better survival rate. These findings suggest that Goreisan suppresses brain edema in HIE and improves survival in juvenile rats, possibly via regulation of AQP4 expression and function. PMID:29234383

  5. Goreisan Inhibits Upregulation of Aquaporin 4 and Formation of Cerebral Edema in the Rat Model of Juvenile Hypoxic-Ischemic Encephalopathy

    Directory of Open Access Journals (Sweden)

    Yoshiaki Yano

    2017-01-01

    Full Text Available Secondary cerebral edema regulation is of prognostic significance in hypoxic-ischemic encephalopathy (HIE, and aquaporin 4 (AQP4 plays an important role in the pathogenesis of cerebral edema. The traditional Japanese herbal medicine Goreisan relieves brain edema in adults; however, its effect and pharmacological mechanism in children are unknown. We investigated the effects of Goreisan on HIE-associated brain edema and AQP4 expression in a juvenile rat model, established by combined occlusion of middle cerebral and common carotid arteries. Magnetic resonance imaging showed that the lesion areas were significantly smaller in the Goreisan- (2 g/kg treated group than in the nontreated (saline group at 24 and 48 h postoperatively. AQP4 mRNA levels in the lesion and nonlesion sides were significantly suppressed in the Goreisan group compared with the nontreated group 36 h postoperatively. Western blotting revealed that levels of AQP4 protein were significantly decreased in the Goreisan group compared with the nontreated group in the lesion side 72 h postoperatively, but not at 12 or 36 h. After 14 days, the Goreisan group had a significantly better survival rate. These findings suggest that Goreisan suppresses brain edema in HIE and improves survival in juvenile rats, possibly via regulation of AQP4 expression and function.

  6. Amelioration of cognitive, motor and endogenous defense functions with silymarin, piracetam and protocatechuic acid in the cerebral global ischemic rat model.

    Science.gov (United States)

    Muley, Milind M; Thakare, Vishnu N; Patil, Rajesh R; Bafna, Pallavi A; Naik, Suresh R

    2013-07-19

    The neuroprotective activities of silymarin, piracetam and protocatechuic acid ethyl ester (PCA) on cerebral global ischemic/reperfusion were evaluated in a rat model. A midline ventral incision was made in the throat region. The right and left common carotid arteries were located and a bilateral common carotid artery occlusion (BCCAO) was performed for 30min using atraumatic clamps followed by a 24h period of reperfusion. Neurological/behavioral functions (cognitive and motor), endogenous defense systems (lipid peroxidation, glutathione, catalase, and superoxide dismutase), reduced water content and infarct size and histopathological alterations were then studied. Silymarin and PCA treatments significantly improved cognitive, motor and endogenous defense functions, histopathological alterations, and, reduced both water content and infarct size compared to the vehicle-treated ischemic control group. Piracetam treatment improved neurological and histopathological alterations, reduced water content and infarct size, but failed to restore/prevent the impaired endogenous defense functions significantly. Silymarin showed better neuroprotection than piracetam and PCA in experimentally induced global ischemic/reperfusion and was able to facilitate mnemonic performance. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Establishment of modified reversible regional cerebral ischemic models

    International Nuclear Information System (INIS)

    Ji Xunming; Ling Feng; Zhao Xiqing; Xuan Yun; Wang Yueqin; Ling Xiaolan; Chang Hongjun; Zhang Zhiping

    2005-01-01

    Objective: Modifying the method of establishing reversible middle cerebral ischemic models in rats for improvement of the stability and rate of success, so as to raise the reliability of cerebral ischemic study. Methods: Sixty male Wistar rats were randomly divided into two groups, modified and control groups, 30 rats in each group. The method of silicone- tipping on one end of the nylon suture was used to modify the establishment of embolus, and tip-heating method was used to establish the traditional embolus with all the other steps of the procedure just the same. The Zea Longa 5 scoring scale was used to estimate the neurological deficiency while TTC staining method was used to measure and calculate the volume of cerebral infarction. The percentage of successful models with 3-4 grade scorings and the coefficient of the variations of cerebral infarct volume were used to estimate the stability of the models. Results: The rate of success of establishment models in the modification group was significantly higher in comparing with the traditional group (93% vs 60%, χ 2 =9.32, P=0.002). The percentage of model establishment with 3-4 grade neurological scores in modification group was higher than that in the traditional group 96.4% vs 61.2%, χ 2 =9.51, P=0.002). The cerebral infarct volume in modification group and traditional group were (4.1450±0.5019) cm 3 and (3.8435 ± 0.8164) cm 3 , and the coefficients of variation were 12.01% and 21.24% respectively, which indicated that the stability of models was significantly higher in modification group than in the traditional one. Conclusions: The rates of success and stability of the models for reversible focal cerebral ischemia made by the modification method were significantly improved, with decreasing the cost of model creation and increasing the accuracy of study of ischemic cerebral vascular disease. (authors)

  8. Monitoring stem cell transplantation in rat cerebral ischemic infarction model with 131I-FIAU/TK reporter gene system

    International Nuclear Information System (INIS)

    Wu Tao; An Rui; Zhang Binqing; Sun Xun; Lang Juntao

    2011-01-01

    Objective: To study the biodistribution of 131 I-2'-deoxy-1-β-D-arabinofuranosyl-5-iodouracil (FIAU) in the rat middle cerebral artery occlusion model and the expression of thymidine kinase (TK) gene in brain tissue after gene-modified stem cell transplantation, and thus evaluate the possibility of further noninvasive monitoring of stem cell transplantation therapy in cerebral infarction. Methods: Adenovirus recombinant Ad5-TK-internal ribosome entry site-brain derived heterotrophic factor-enhanced green florescent protein(IRES-BDNF-EGFP) carrying TK-IRES-BDNF gene was prepared. Cerebral infarction model was established in rats by intraluminal middle cerebral artery occlusion with nylon monofilament. Gene modified bone marrow mesenchymal stem cells were transplanted via intraparenchymal route, lateral ventricle, carotid artery and tail vein, respectively. The normal rats were used as controls. 131 I-FAU was prepared to be the tracer for biodistribution study and the % ID/g was calculated based on measurement of the tissue radioactivity counts. The expression of TK gene was evaluated by quantitative real-time PCR (QR-PCR) and Western blot analysis. Data were analyzed with independent-samples t-test, one-way analysis of variance (ANOVA) test, and Pearson linear correlation test. Results: The % ID/g of infarcted brain tissue in the intraparenchymal group was 0.124 ± 0.013, which was significantly higher than that in lateral ventricle group (0.052 ±0.004), carotid artery group (0.061 ±0.002), tail vein group (0.059 ±0.005) and control group (0.005 ±0.001) (t=2.913-5.652, all P<0.05), while there were no statistically significant differences among the other route transplanted groups (t=0.694-1.448, all P>0.05). The differences of % ID/g between the infarcted and contralateral sides of brain tissue in all transplanted groups were statistically significant (t=9.004-15.734, all P<0.05), while there was no statistically significant difference of this parameter

  9. Cerebral ischemic stroke: is gender important?

    Science.gov (United States)

    Gibson, Claire L

    2013-09-01

    Cerebral stroke continues to be a major cause of death and the leading cause of long-term disability in developed countries. Evidence reviewed here suggests that gender influences various aspects of the clinical spectrum of ischemic stroke, in terms of influencing how a patients present with ischemic stroke through to how they respond to treatment. In addition, this review focuses on discussing the various pathologic mechanisms of ischemic stroke that may differ according to gender and compares how intrinsic and hormonal mechanisms may account for such gender differences. All clinical trials to date investigating putative neuroprotective treatments for ischemic stroke have failed, and it may be that our understanding of the injury cascade initiated after ischemic injury is incomplete. Revealing aspects of the pathophysiological consequences of ischemic stroke that are gender specific may enable gender relevant and effective neuroprotective strategies to be identified. Thus, it is possible to conclude that gender does, in fact, have an important role in ischemic stroke and must be factored into experimental and clinical investigations of ischemic stroke.

  10. Gene interference regulates aquaporin-4 expression in swollen tissue of rats with cerebral ischemic edema: Correlation with variation in apparent diffusion coefficient.

    Science.gov (United States)

    Hu, Hui; Lu, Hong; He, Zhanping; Han, Xiangjun; Chen, Jing; Tu, Rong

    2012-07-25

    To investigate the effects of mRNA interference on aquaporin-4 expression in swollen tissue of rats with ischemic cerebral edema, and diagnose the significance of diffusion-weighted MRI, we injected 5 μL shRNA- aquaporin-4 (control group) or siRNA- aquaporin-4 solution (1:800) (RNA interference group) into the rat right basal ganglia immediately before occlusion of the middle cerebral artery. At 0.25 hours after occlusion of the middle cerebral artery, diffusion-weighted MRI displayed a high signal; within 2 hours, the relative apparent diffusion coefficient decreased markedly, aquaporin-4 expression increased rapidly, and intracellular edema was obviously aggravated; at 4 and 6 hours, the relative apparent diffusion coefficient slowly returned to control levels, aquaporin-4 expression slightly increased, and angioedema was observed. In the RNA interference group, during 0.25-6 hours after injection of siRNA- aquaporin-4 solution, the relative apparent diffusion coefficient slightly fluctuated and aquaporin-4 expression was upregulated; during 0.5-4 hours, the relative apparent diffusion coefficient was significantly higher, while aquaporin-4 expression was significantly lower when compared with the control group, and intracellular edema was markedly reduced; at 0.25 and 6 hours, the relative apparent diffusion coefficient and aquaporin-4 expression were similar when compared with the control group; obvious angioedema remained at 6 hours. Pearson's correlation test results showed that aquaporin-4 expression was negatively correlated with the apparent diffusion coefficient (r = -0.806, P coefficient. Aquaporin-4 gene interference can effectively inhibit the upregulation of aquaporin-4 expression during the stage of intracellular edema with time-effectiveness. Moreover, diffusion-weighted MRI can accurately detect intracellular edema.

  11. CT fogging effect with ischemic cerebral infarcts

    International Nuclear Information System (INIS)

    Becker, H.; Desch, H.; Hacker, H.; Pencz, A.; Frankfurt Univ.

    1979-01-01

    Systematic CT studies on ten patients with persistent ischemic cerebral infarct revealed a constant phenomenon, the fogging effect. The hypodense infarct at the beginning will be isodense, or close to isodense, on the plain CT during the second or third week and at a later stage will be hypodense again. The fogging infarcted area shows homogeneous intensive contrast enhancement. Knowledge of the fogging effect is important for correct interpretation of the CT image and the indication for contrast medium CT. CT without contrast medium may lead to misinterpretation during the second and third week after the onset of cerebral infarction. (orig.) [de

  12. CT fogging effect with ischemic cerebral infarcts

    Energy Technology Data Exchange (ETDEWEB)

    Becker, H; Desch, H; Hacker, H; Pencz, A [Frankfurt Univ. (Germany, F.R.). Abt. fuer Neurologie; Frankfurt Univ. (Germany, F.R.). Abt. fuer Neuroradiologie)

    1979-01-01

    Systematic CT studies on ten patients with persistent ischemic cerebral infarct revealed a constant phenomenon, the fogging effect. The hypodense infarct at the beginning will be isodense, or close to isodense, on the plain CT during the second or third week and at a later stage will be hypodense again. The fogging infarcted area shows homogeneous intensive contrast enhancement. Knowledge of the fogging effect is important for correct interpretation of the CT image and the indication for contrast medium CT. CT without contrast medium may lead to misinterpretation during the second and third week after the onset of cerebral infarction.

  13. Cerebral collateral therapeutics in acute ischemic stroke: A randomized preclinical trial of four modulation strategies.

    Science.gov (United States)

    Beretta, Simone; Versace, Alessandro; Carone, Davide; Riva, Matteo; Dell'Era, Valentina; Cuccione, Elisa; Cai, Ruiyao; Monza, Laura; Pirovano, Silvia; Padovano, Giada; Stiro, Fabio; Presotto, Luca; Paternò, Giovanni; Rossi, Emanuela; Giussani, Carlo; Sganzerla, Erik P; Ferrarese, Carlo

    2017-10-01

    Cerebral collaterals are dynamically recruited after arterial occlusion and highly affect tissue outcome in acute ischemic stroke. We investigated the efficacy and safety of four pathophysiologically distinct strategies for acute modulation of collateral flow (collateral therapeutics) in the rat stroke model of transient middle cerebral artery (MCA) occlusion. A composed randomization design was used to assign rats (n = 118) to receive phenylephrine (induced hypertension), polygeline (intravascular volume load), acetazolamide (cerebral arteriolar vasodilation), head down tilt (HDT) 15° (cerebral blood flow diversion), or no treatment, starting 30 min after MCA occlusion. Compared to untreated animals, treatment with collateral therapeutics was associated with lower infarct volumes (62% relative mean difference; 51.57 mm 3 absolute mean difference; p Collateral therapeutics acutely increased cerebral perfusion in the medial (+40.8%; p collaterals is feasible and provides a tissue-saving effect in the hyperacute phase of ischemic stroke prior to recanalization therapy.

  14. The Effects of Different Repetitive Transcranial Magnetic Stimulation (rTMS Protocols on Cortical Gene Expression in a Rat Model of Cerebral Ischemic-Reperfusion Injury.

    Directory of Open Access Journals (Sweden)

    Milos R Ljubisavljevic

    Full Text Available Although repetitive Transcranial Magnetic Stimulation (rTMS in treatment of stroke in humans has been explored over the past decade the data remain controversial in terms of optimal stimulation parameters and the mechanisms of rTMS long-term effects. This study aimed to explore the potential of different rTMS protocols to induce changes in gene expression in rat cortices after acute ischemic-reperfusion brain injury. The stroke was induced by middle cerebral artery occlusion (MCAO with subsequent reperfusion. Changes in the expression of 96 genes were examined using low-density expression arrays after MCAO alone and after MCAO combined with 1Hz, 5Hz, continuous (cTBS and intermittent (iTBS theta-burst rTMS. rTMS over the lesioned hemisphere was given for two weeks (with a 2-day pause in a single daily session and a total of 2400 pulses. MCAO alone induced significant upregulation in the expression of 44 genes and downregulation in 10. Two weeks of iTBS induced significant increase in the expression of 52 genes. There were no downregulated genes. 1Hz and 5Hz had no significant effects on gene expression, while cTBS effects were negligible. Upregulated genes included those involved in angiogenesis, inflammation, injury response and cellular repair, structural remodeling, neuroprotection, neurotransmission and neuronal plasticity. The results show that long-term rTMS in acute ischemic-reperfusion brain injury induces complex changes in gene expression that span multiple pathways, which generally promote the recovery. They also demonstrate that induced changes primarily depend on the rTMS frequency (1Hz and 5Hz vs. iTBS and pattern (cTBS vs. iTBS. The results further underlines the premise that one of the benefits of rTMS application in stroke may be to prime the brain, enhancing its potential to cope with the injury and to rewire. This could further augment its potential to favorably respond to rehabilitation, and to restore some of the loss

  15. The Effects of Different Repetitive Transcranial Magnetic Stimulation (rTMS) Protocols on Cortical Gene Expression in a Rat Model of Cerebral Ischemic-Reperfusion Injury

    Science.gov (United States)

    Ljubisavljevic, Milos R.; Javid, Asma; Oommen, Joji; Parekh, Khatija; Nagelkerke, Nico; Shehab, Safa; Adrian, Thomas E.

    2015-01-01

    Although repetitive Transcranial Magnetic Stimulation (rTMS) in treatment of stroke in humans has been explored over the past decade the data remain controversial in terms of optimal stimulation parameters and the mechanisms of rTMS long-term effects. This study aimed to explore the potential of different rTMS protocols to induce changes in gene expression in rat cortices after acute ischemic-reperfusion brain injury. The stroke was induced by middle cerebral artery occlusion (MCAO) with subsequent reperfusion. Changes in the expression of 96 genes were examined using low-density expression arrays after MCAO alone and after MCAO combined with 1Hz, 5Hz, continuous (cTBS) and intermittent (iTBS) theta-burst rTMS. rTMS over the lesioned hemisphere was given for two weeks (with a 2-day pause) in a single daily session and a total of 2400 pulses. MCAO alone induced significant upregulation in the expression of 44 genes and downregulation in 10. Two weeks of iTBS induced significant increase in the expression of 52 genes. There were no downregulated genes. 1Hz and 5Hz had no significant effects on gene expression, while cTBS effects were negligible. Upregulated genes included those involved in angiogenesis, inflammation, injury response and cellular repair, structural remodeling, neuroprotection, neurotransmission and neuronal plasticity. The results show that long-term rTMS in acute ischemic-reperfusion brain injury induces complex changes in gene expression that span multiple pathways, which generally promote the recovery. They also demonstrate that induced changes primarily depend on the rTMS frequency (1Hz and 5Hz vs. iTBS) and pattern (cTBS vs. iTBS). The results further underlines the premise that one of the benefits of rTMS application in stroke may be to prime the brain, enhancing its potential to cope with the injury and to rewire. This could further augment its potential to favorably respond to rehabilitation, and to restore some of the loss functions. PMID

  16. Andrographolide stimulates p38 mitogen-activated protein kinase-nuclear factor erythroid-2-related factor 2-heme oxygenase 1 signaling in primary cerebral endothelial cells for definite protection against ischemic stroke in rats.

    Science.gov (United States)

    Yen, Ting-Lin; Chen, Ray-Jade; Jayakumar, Thanasekaran; Lu, Wan-Jung; Hsieh, Cheng-Ying; Hsu, Ming-Jen; Yang, Chih-Hao; Chang, Chao-Chien; Lin, Yen-Kuang; Lin, Kuan-Hung; Sheu, Joen-Rong

    2016-04-01

    Stroke pathogenesis involves complex oxidative stress-related pathways. The nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) pathways have been considered molecular targets in pharmacologic intervention for ischemic diseases. Andrographolide, a labdane diterpene, has received increasing attention in recent years because of its various pharmacologic activities. We determined that andrographolide modulates the mitogen-activated protein kinase (MAPK)-Nrf2-HO-1 signaling cascade in primary cerebral endothelial cells (CECs) to provide positive protection against middle cerebral artery occlusion (MCAO)-induced ischemic stroke in rats. In the present study, andrographolide (10 μM) increased HO-1 protein and messenger RNA expressions, Nrf2 phosphorylation, and nuclear translocation in CECs, and these activities were disrupted by a p38 MAPK inhibitor, SB203580, but not by the extracellular signal-regulated kinase inhibitor PD98059 or c-Jun amino-terminal kinase inhibitor SP600125. Similar results were observed in confocal microscopy analysis. Moreover, andrographolide-induced Nrf2 and HO-1 protein expressions were significantly inhibited by Nrf2 small interfering RNA. Moreover, HO-1 knockdown attenuated the protective effect of andrographolide against oxygen-glucose deprivation-induced CEC death. Andrographolide (0.1 mg/kg) significantly suppressed free radical formation, blood-brain barrier disruption, and brain infarction in MCAO-insulted rats, and these effects were reversed by the HO-1 inhibitor zinc protoporphyrin IX. The mechanism is attributable to HO-1 activation, as directly evidenced by andrographolide-induced pronounced HO-1 expression in brain tissues, which was highly localized in the cerebral capillary. In conclusion, andrographolide increased Nrf2-HO-1 expression through p38 MAPK regulation, confirming that it provides protection against MCAO-induced brain injury. These findings provide strong evidence that andrographolide could

  17. Current status and outlook of endovascular therapy for cerebral ischemic diseases

    International Nuclear Information System (INIS)

    Li Minghua; Zhao Jungong

    2005-01-01

    Improvement of diagnostic technology and increasing advent of new materials for intervention has created a new area for endovascular therapy of cerebral ischemic diseases. Current research findings have shown that endovascular thrombolysis in acute stage of cerebral infarction can accelerate the rate of re-canalization of occluded arteries and greatly decrease the morbidity and mortality of cerebral ischemic vascular diseases. Stenting of arterial stenosis can the improve of blood supply distal to the lesion, prevent recurrent cerebral ischemic stroke. As a result, endovascular thrombolysis for acute cerebral infarction and stenting for intracranial and carotid arterial stenosis are booming both at home and abroad. Proper selection of patients of acute cerebral infarction for endovascular thrombolysis with less complications could be achieved through CT perfusion, MR perfusion-weighted image (PWI) and diffusion-weighted image (DWI), non-invasive vascular imaging technology including CEMRA and CTA for confirming and demonstrating the sites and causes of cerebral ischemia, and furthermore for evaluating the survival ability and etc. The research team administered albumin and magnesium sulfate as neurological protection drug to treat rat infarction model within 6 hours of onset resulting with the same effect of decreasing the damage of ischemic cerebral tissue and without hemorrhagic complication. It is certain that hemorrhagic complication in thrombolysis is a result of multiple factors with no single drug being able to solve the problem. It is predictable that, based on semi-quantitative or quantitative parameters of CT or MRI in conjunction with PWI/DWI mismatch model rather than simply on the onset time of infarction for proper selection of patients of cerebral infarction, mechanic thrombus-disruption and/or intra-arterial thrombolysis together with intervention of neurological protection drug will be the trend for treating acute cerebral infarction in the future

  18. Changes of resting cerebral activities in subacute ischemic stroke patients

    Directory of Open Access Journals (Sweden)

    Ping Wu

    2015-01-01

    Full Text Available This study aimed to detect the difference in resting cerebral activities between ischemic stroke patients and healthy participants, define the abnormal site, and provide new evidence for pathological mechanisms, clinical diagnosis, prognosis prediction and efficacy evaluation of ischemic stroke. At present, the majority of functional magnetic resonance imaging studies focus on the motor dysfunction and the acute stage of ischemic stroke. This study recruited 15 right-handed ischemic stroke patients at subacute stage (15 days to 11.5 weeks and 15 age-matched healthy participants. A resting-state functional magnetic resonance imaging scan was performed on each subject to detect cerebral activity. Regional homogeneity analysis was used to investigate the difference in cerebral activities between ischemic stroke patients and healthy participants. The results showed that the ischemic stroke patients had lower regional homogeneity in anterior cingulate and left cerebrum and higher regional homogeneity in cerebellum, left precuneus and left frontal lobe, compared with healthy participants. The experimental findings demonstrate that the areas in which regional homogeneity was different between ischemic stroke patients and healthy participants are in the cerebellum, left precuneus, left triangle inferior frontal gyrus, left inferior temporal gyrus and anterior cingulate. These locations, related to the motor, sensory and emotion areas, are likely potential targets for the neural regeneration of subacute ischemic stroke patients.

  19. Study on the Mechanism of mTOR-Mediated Autophagy during Electroacupuncture Pretreatment against Cerebral Ischemic Injury

    Directory of Open Access Journals (Sweden)

    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.

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

    OpenAIRE

    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...

  1. Imaging of cerebral ischemic edema and neuronal death

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  2. Anti-ischemic effect of curcumin in rat brain.

    Science.gov (United States)

    Shukla, Pradeep K; Khanna, Vinay K; Ali, Mohd M; Khan, Mohd Y; Srimal, Rikhab C

    2008-06-01

    Turmeric has been in use since ancient times as a condiment and due to its medicinal properties. Curcumin, the yellow colouring principle in turmeric, is polyphenolic and major active constituent. Besides anti-inflammatory, thrombolytic and anticarcinogenic activities, curcumin also possesses strong antioxidant property. In view of the novel combination of properties, neuroprotective efficacy of curcumin was studied in rat middle cerebral artery occlusion (MCAO) model. Rats were subjected to 2 h of focal ischemia followed by 72 h of reperfusion. They were pre-treated with curcumin (100 mg/kg, po) for 5 days prior to MCAO and for another 3 days after MCAO. The parameters studied were behavioural, biochemical and histological. Treatment with curcumin could significantly improve neurobehavioral performance compared to untreated ischemic rats as judged by its effect on rota-rod performance and grid walking. A significant inhibition in lipid peroxidation and an increase in superoxide dismutase (SOD) activity in corpus striatum and cerebral cortex was observed following treatment with curcumin in MCAO rats as compared to MCAO group. Intracellular calcium levels were decreased following treatment with curcumin in MCAO rats. Histologically, a reduction in the infarct area from 33% to 24% was observed in MCAO rats treated with curcumin. The study demonstrates the protective efficacy of curcumin in rat MCAO model.

  3. Investigation of Epidermal Growth Factor, Tumor Necrosis Factor-alpha and Thioredoxin System in Rats Exposed to Cerebral Ischemia

    Directory of Open Access Journals (Sweden)

    Erol-Demirbilek Melike

    2016-09-01

    Full Text Available Background: Thioredoxin reductase (TrxR, epidermal growth factor (EGF and tumor necrosis factor-α (TNF-α have neuroprotective/neurotoxic effects in cerebral ischemia. We aimed to investigate the TrxR activity, EGF and TNF-α levels in cerebral ischemic, sham-operated and non-ischemic rat brains.

  4. 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...

  5. Relationship between hypertensive cerebral hemorrhage and ischemic lesions

    International Nuclear Information System (INIS)

    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)

  6. Intra-artery thrombolytic therapy for acute ischemic cerebral infarction

    International Nuclear Information System (INIS)

    Du Wei; Shao Chengmin; Wang Jianlin; Lei Jin; Jia Fan; Cao Lanfang; Chai Ruchang; Su Wei; Gu Jinchuan

    2004-01-01

    Objective: To evaluate the clinical effects of intra-arterial thrombolytic therapy for acute ischemic cerebral infarction and analyze the factors influencing the clinical prognosis. Methods: 32 patients were treated with intra-arterial thrombolysis using urokinase (median dose, 65 x 10 4 U) within 2-20 hours, after the onset. The patient's condition was assessed by neurologists using National Institutes of Health Stroke Scale (NIHSS) score right at the admission. Clinical outcome was assessed after 3 months and graded as good for Modified Rankin Scale (MRS) scores of 0 to 3 and poor for MRS scores of 4 or 5 and death. Results: Follow up cerebral angiography of 14 cases treated within 6 hours after onset showed complete/partial recanalization in 13 cases. Other 18 patients whose treatment started beyond 6 hours after onset out-came with complete/partial in 7. 20 (62.5%) of the 32 patients had good out-come, 12(37.5%) had poor outcome and two patients(9.4%) died. Cerebral hemorrhage occurred in 2 of the 32 patients. Good outcome was associated with an initial NIHSS score of <20 (P<0.01) and vascular recanalization (P<0.025). Recanalization was more likely to be obtained if thrombolysis began within 6 hours (P<0.05). Conclusion: Intra-arterial thrombolysis is a safe and effective therapy for acute ischemic cerebral infarction. (authors)

  7. Potential neuroprotective effects of acupuncture stimulation on diabetes mellitus in a global ischemic rat model

    International Nuclear Information System (INIS)

    Choi, Samjin; Lee, Gi-Ja; Chae, Su-Jin; Kang, Sung Wook; Park, Hun-Kuk; Yin, Chang-Shik; Lee, Seung-Hoon; Choi, Seok Keun

    2010-01-01

    Acupuncture (ACU) is known to be effective in ischemia treatment, and glutamate (GLU) excitotoxicity is an important factor in neuronal cell death. We observed the effect of ACU on cerebral blood flow (%CBF) and ΔGLU (the changes in GLU release) in the ischemic stroke rat model of diabetic mellitus (DM). A global ischemia was induced using the eleven-vessel occlusion (11-VO) method in 14 Sprague-Dawley rats (DM), which were randomly divided into two groups: the control group and the ACU-treatment group. Extracellular ΔGLU was assessed using an intra-cerebral biosensor system measuring 256 samples per second, simultaneously with %CBF and electroencephalogram. ACU stimulation was applied to ACU points GB34 and GB39 during the ischemic period. Twenty-three diagnostic parameters were proposed first for a detailed analysis of changes in %CBF and GLU release during ischemia/reperfusion. ACU rats showed a significant decrease in ischemic (p < 0.05) and reperfusion %CBF (p < 0.0001) than control rats, and a significantly larger decrease in ischemic ΔGLU (p < 0.05) and peak level of reperfusion ΔGLU (p < 0.005) than control rats. From these results, we suggest that ACU stimulation is responsible for the potential protection of neurons through suppression of %CBF response in the increased plasma osmolality and extracellular ΔGLU in diabetic rats under ischemic conditions

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Function and mechanism of toll-like receptors in cerebral ischemic tolerance: from preconditioning to treatment

    OpenAIRE

    Wang, Peng-Fei; Xiong, Xiao-Yi; Chen, Jing; Wang, Yan-Chun; Duan, Wei; Yang, Qing-Wu

    2015-01-01

    Increasing evidence suggests that toll-like receptors (TLRs) play an important role in cerebral ischemia-reperfusion injury. The endogenous ligands released from ischemic neurons activate the TLR signaling pathway, resulting in the production of a large number of inflammatory cytokines, thereby causing secondary inflammation damage following cerebral ischemia. However, the preconditioning for minor cerebral ischemia or the preconditioning with TLR ligands can reduce cerebral ischemic injury b...

  10. Metabolite changes in the ipsilateral and contralateral cerebral hemispheres in rats with middle cerebral artery occlusion

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    Lei Ruan

    2017-01-01

    Full Text Available Cerebral ischemia not only causes pathological changes in the ischemic areas but also induces a series of secondary changes in more distal brain regions (such as the contralateral cerebral hemisphere. The impact of supratentorial lesions, which are the most common type of lesion, on the contralateral cerebellum has been studied in patients by positron emission tomography, single photon emission computed tomography, magnetic resonance imaging and diffusion tensor imaging. In the present study, we investigated metabolite changes in the contralateral cerebral hemisphere after supratentorial unilateral ischemia using nuclear magnetic resonance spectroscopy-based metabonomics. The permanent middle cerebral artery occlusion model of ischemic stroke was established in rats. Rats were randomly divided into the middle cerebral artery occlusion 1-, 3-, 9- and 24-hour groups and the sham group. 1H nuclear magnetic resonance spectroscopy was used to detect metabolites in the left and right cerebral hemispheres. Compared with the sham group, the concentrations of lactate, alanine, γ-aminobutyric acid, choline and glycine in the ischemic cerebral hemisphere were increased in the acute stage, while the concentrations of N-acetyl aspartate, creatinine, glutamate and aspartate were decreased. This demonstrates that there is an upregulation of anaerobic glycolysis (shown by the increase in lactate, a perturbation of choline metabolism (suggested by the increase in choline, neuronal cell damage (shown by the decrease in N-acetyl aspartate and neurotransmitter imbalance (evidenced by the increase in γ-aminobutyric acid and glycine and by the decrease in glutamate and aspartate in the acute stage of cerebral ischemia. In the contralateral hemisphere, the concentrations of lactate, alanine, glycine, choline and aspartate were increased, while the concentrations of γ-aminobutyric acid, glutamate and creatinine were decreased. This suggests that there is a

  11. Protective effect of zinc against ischemic neuronal injury in a middle cerebral artery occlusion model.

    Science.gov (United States)

    Kitamura, Youji; Iida, Yasuhiko; Abe, Jun; Ueda, Masashi; Mifune, Masaki; Kasuya, Fumiyo; Ohta, Masayuki; Igarashi, Kazuo; Saito, Yutaka; Saji, Hideo

    2006-02-01

    In this study, we investigated the effect of vesicular zinc on ischemic neuronal injury. In cultured neurons, addition of a low concentration (under 100 microM) of zinc inhibited both glutamate-induced calcium influx and neuronal death. In contrast, a higher concentration (over 150 microM) of zinc decreased neuronal viability, although calcium influx was inhibited. These results indicate that zinc exhibits biphasic effects depending on its concentration. Furthermore, in cultured neurons, co-addition of glutamate and CaEDTA, which binds extra-cellular zinc, increased glutamate-induced calcium influx and aggravated the neurotoxicity of glutamate. In a rat transient middle cerebral artery occlusion (MCAO) model, the infarction volume, which is related to the neurotoxicity of glutamate, increased rapidly on the intracerebral ventricular injection of CaEDTA 30 min prior to occlusion. These results suggest that zinc released from synaptic vesicles may provide a protective effect against ischemic neuronal injury.

  12. Eriodictyol-7-O-glucoside activates Nrf2 and protects against cerebral ischemic injury

    International Nuclear Information System (INIS)

    Jing, Xu; Ren, Dongmei; Wei, Xinbing; Shi, Huanying; Zhang, Xiumei; Perez, Ruth G.; Lou, Haiyan; Lou, Hongxiang

    2013-01-01

    Stroke is a complex disease that may involve oxidative stress-related pathways in its pathogenesis. The nuclear factor erythroid-2-related factor 2/antioxidant response element (Nrf2/ARE) pathway plays an important role in inducing phase II detoxifying enzymes and antioxidant proteins and thus has been considered a potential target for neuroprotection in stroke. The aim of the present study was to determine whether eriodictyol-7-O-glucoside (E7G), a novel Nrf2 activator, can protect against cerebral ischemic injury and to understand the role of the Nrf2/ARE pathway in neuroprotection. In primary cultured astrocytes, E7G increased the nuclear localization of Nrf2 and induced the expression of the Nrf2/ARE-dependent genes. Exposure of astrocytes to E7G provided protection against oxygen and glucose deprivation (OGD)-induced oxidative insult. The protective effect of E7G was abolished by RNA interference-mediated knockdown of Nrf2 expression. In vivo administration of E7G in a rat model of focal cerebral ischemia significantly reduced the amount of brain damage and ameliorated neurological deficits. These data demonstrate that activation of Nrf2/ARE signaling by E7G is directly associated with its neuroprotection against oxidative stress-induced ischemic injury and suggest that targeting the Nrf2/ARE pathway may be a promising approach for therapeutic intervention in stroke. - Highlights: • E7G activates Nrf2 in astrocytes. • E7G stimulates expression of Nrf2-mediated cytoprotective proteins in astrocytes. • E7G protects astrocytes against OGD-induced cell death and apoptosis. • The neuroprotective effect of E7G involves the Nrf2/ARE pathway. • E7G protects rats against cerebral ischemic injury

  13. Eriodictyol-7-O-glucoside activates Nrf2 and protects against cerebral ischemic injury

    Energy Technology Data Exchange (ETDEWEB)

    Jing, Xu [Department of Pharmacology, School of Medicine, Shandong University, Jinan 250012 (China); Ren, Dongmei [Department of Natural Product Chemistry, Key Lab of Chemical Biology of Ministry of Education, Shandong University, Jinan 250012 (China); Wei, Xinbing; Shi, Huanying; Zhang, Xiumei [Department of Pharmacology, School of Medicine, Shandong University, Jinan 250012 (China); Perez, Ruth G. [Health Science Center, Paul L. Foster School of Medicine, Texas Tech University, El Paso, TX, 79905 (United States); Lou, Haiyan, E-mail: louhaiyan@sdu.edu.cn [Department of Pharmacology, School of Medicine, Shandong University, Jinan 250012 (China); Lou, Hongxiang [Department of Natural Product Chemistry, Key Lab of Chemical Biology of Ministry of Education, Shandong University, Jinan 250012 (China)

    2013-12-15

    Stroke is a complex disease that may involve oxidative stress-related pathways in its pathogenesis. The nuclear factor erythroid-2-related factor 2/antioxidant response element (Nrf2/ARE) pathway plays an important role in inducing phase II detoxifying enzymes and antioxidant proteins and thus has been considered a potential target for neuroprotection in stroke. The aim of the present study was to determine whether eriodictyol-7-O-glucoside (E7G), a novel Nrf2 activator, can protect against cerebral ischemic injury and to understand the role of the Nrf2/ARE pathway in neuroprotection. In primary cultured astrocytes, E7G increased the nuclear localization of Nrf2 and induced the expression of the Nrf2/ARE-dependent genes. Exposure of astrocytes to E7G provided protection against oxygen and glucose deprivation (OGD)-induced oxidative insult. The protective effect of E7G was abolished by RNA interference-mediated knockdown of Nrf2 expression. In vivo administration of E7G in a rat model of focal cerebral ischemia significantly reduced the amount of brain damage and ameliorated neurological deficits. These data demonstrate that activation of Nrf2/ARE signaling by E7G is directly associated with its neuroprotection against oxidative stress-induced ischemic injury and suggest that targeting the Nrf2/ARE pathway may be a promising approach for therapeutic intervention in stroke. - Highlights: • E7G activates Nrf2 in astrocytes. • E7G stimulates expression of Nrf2-mediated cytoprotective proteins in astrocytes. • E7G protects astrocytes against OGD-induced cell death and apoptosis. • The neuroprotective effect of E7G involves the Nrf2/ARE pathway. • E7G protects rats against cerebral ischemic injury.

  14. 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

  15. Paradigms and mechanisms of inhalational anesthetics mediated neuroprotection against cerebral ischemic stroke

    OpenAIRE

    Wang, Hailian; Li, Peiying; Xu, Na; Zhu, Ling; Cai, Mengfei; Yu, Weifeng; Gao, Yanqin

    2016-01-01

    Cerebral ischemic stroke is a leading cause of serious long-term disability and cognitive dysfunction. The high mortality and disability of cerebral ischemic stroke is urging the health providers, including anesthesiologists and other perioperative professioners, to seek effective protective strategies, which are extremely limited, especially for those perioperative patients. Intriguingly, several commonly used inhalational anesthetics are recently suggested to possess neuroprotective effects...

  16. Prdx6 Upregulation by Curcumin Attenuates Ischemic Oxidative Damage via SP1 in Rats after Stroke

    Directory of Open Access Journals (Sweden)

    Gongwei Jia

    2017-01-01

    Full Text Available Background. The role of Peroxiredoxin 6 (Prdx6 in brain ischemia remains unclear. Curcumin (Cur treatment elicits neuroprotective effects against cerebral ischemic injury, and the associated mechanisms may involve Prdx6. In this study, we investigated whether Prdx6 and the transcription factor specific protein 1 (SP1 were involved in the antioxidant effect of Cur after stoke. Methods. Focal cerebral ischemic injury was induced by transient middle cerebral artery occlusion for 2 hours in male Sprague-Dawley rats treated with or without Prdx6 siRNA. Expression of Prdx6 in the penumbra was assessed by Real-Time PCR (RT-PCR, Western blot analysis, and immunoflourescent staining. In addition, infarct volume, neurological deficit score, and oxidative stress were evaluated. Prdx6 levels were also determined in the presence and absence of SP1 antagonist mithramycin A (MTM-A. Results. Cur treatment upregulated Prdx6 protein expression and the number of Prdx6-positive neuronal cells 24 hours after reperfusion. Cur treatment also attenuated oxidative stress and induced neuroprotective effects against ischemic damage, whereas the beneficial effects of Cur treatment were lost in animals treated with Prdx6-siRNA. Prdx6 upregulation by Cur treatment was abolished by SP1 antagonists MTM. Conclusions. Prdx6 upregulation by Cur treatment attenuates ischemic oxidative damage through SP1 induction in rats after stroke. This represents a novel mechanism of Cur-induced neuroprotection against cerebral ischemia.

  17. Cerebral hemodynamics in adult ischemic-type patients with moyamoya disease compared with those of atherothrombotic middle cerebral artery occlusion

    International Nuclear Information System (INIS)

    Idei, Masaru; Yamane, Kanji; Nishida, Masahiro; Manabe, Kazufumi; Yokota, Akira

    2005-01-01

    We measured regional cerebral blood flow (rCBF) in adult ischemic-type patients with moyamoya disease and in patients with atherothrombotic middle cerebral artery occlusion (MCAO) to investigate cerebral hemodynamics in adult ischemic-type of moyamoya disease. In this study we measured rCBF and regional cerebro-vascular response (rCVR) using acetazolamide by Xe-non-enhanced CT. Our subjects consisted of 15 adult ischemic-type patients with moyamoya disease and 27 atherothrombotic stroke patients with proximal occlusion of the middle cerebral artery. The region of inter est was conducted in the anterior cerebral artery, middle cerebral artery and posterior cerebral artery territories as well as basal ganglia regions. rGBF was preserved in all regions of patients with moyamoya disease. However, rCVR severely decreased in the anterior circulation territory in patients with moyamoya disease compared with those of MCAO. These results suggest that rCBF in the anterior circulation territory of adult ischemic-type patients with moyamoya disease is preserved by vasodilation of the cerebral arteries, while cerebral hemodynamic reserve capacity is severely reduced. The results indicated that basal moyamoya vessels are dilated. These findings may be one of the reasons why stroke occurs more frequently in adult than child patients with moyamoya disease. (author)

  18. Electrical stimulation of the vagus nerve protects against cerebral ischemic injury through an anti-infammatory mechanism

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    Yao-xian Xiang

    2015-01-01

    Full Text Available Vagus nerve stimulation exerts protective effects against ischemic brain injury; however, the underlying mechanisms remain unclear. In this study, a rat model of focal cerebral ischemia was established using the occlusion method, and the right vagus nerve was given electrical stimulation (constant current of 0.5 mA; pulse width, 0.5 ms; frequency, 20 Hz; duration, 30 seconds; every 5 minutes for a total of 60 minutes 30 minutes, 12 hours, and 1, 2, 3, 7 and 14 days after surgery. Electrical stimulation of the vagus nerve substantially reduced infarct volume, improved neurological function, and decreased the expression levels of tumor necrosis factor-and interleukin- 6 in rats with focal cerebral ischemia. The experimental findings indicate that the neuroprotective effect of vagus nerve stimulation following cerebral ischemia may be associated with the inhibition of tumor necrosis factor- and interleukin-6 expression.

  19. Computer assisted radionuclide angiography to confirm reversible ischemic cerebral dysfunction

    International Nuclear Information System (INIS)

    Buell, U.; Lanksch, W.; Tosch, U.; Kleinhans, E.; Steinhoff, H.

    1982-01-01

    Computer assisted radionuclide angiography (CARNA) was employed in patients with transient ischemic attack (TIA) or prolonged reversible ischemic neurologic deficit (PRIND) to establish the sensitivity of CARNA in detecting and quantifying changes of cerebral perfusion in such selected patients. Moreover, results of CARNA were compared with findings of cranial radiographic angiography (RGA) to obtain data on combined sensitivities of these methods. CARNA may be the preferred noninvasive procedure employed because it detects and quantifies the vascular supply disorder in patients with TIA and PRIND. If no computer assistance is used to evaluate cranial radionuclide angiography, results are considerable less accurate. Specifity of CARNA is 84.6%. If CARNA is negative (25.2% in TIA; 12.7% in PRIND), a further method must be employed to confirm the cranial vascular origin of the attack. This may be RGA in TIA and transmission computed axial tomography (T-CAT) T-CAT in PRIND. This diagnos - tic sequence lead to 92.4% true positive in TIA and to 93.2% true positives in PRIND

  20. Cerebral Vascular Disease and Neurovascular Injury in Ischemic Stroke

    Science.gov (United States)

    Hu, Xiaoming; De Silva, T. Michael; Chen, Jun; Faraci, Frank M.

    2017-01-01

    The consequences of cerebrovascular disease are among the leading health issues worldwide. Large and small cerebral vessel disease can trigger stroke and contribute to the vascular component of other forms of neurological dysfunction and degeneration. Both forms of vascular disease are driven by diverse risk factors, with hypertension as the leading contributor. Despite the importance of neurovascular disease and subsequent injury following ischemic events, fundamental knowledge in these areas lag behind our current understanding of neuroprotection and vascular biology in general. The goal of this review is to address select key structural and functional changes in the vasculature that promote hypoperfusion and ischemia, while also affecting the extent of injury and effectiveness of therapy. In addition, as damage to the blood-brain barrier (BBB) is one of the major consequences of ischemia, we discuss cellular and molecular mechanisms underlying ischemia-induced changes in BBB integrity and function, including alterations in endothelial cells and the contribution of pericytes, immune cells, and matrix metalloproteinases. Identification of cell types, pathways, and molecules that control vascular changes before and after ischemia may result in novel approaches to slow the progression of cerebrovascular disease and lessen both the frequency and impact of ischemic events. PMID:28154097

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

    Science.gov (United States)

    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.

  2. Sodium 4-phenylbutyrate protects against cerebral ischemic injury.

    Science.gov (United States)

    Qi, Xin; Hosoi, Toru; Okuma, Yasunobu; Kaneko, Masayuki; Nomura, Yasuyuki

    2004-10-01

    Sodium 4-phenylbutyrate (4-PBA) is a low molecular weight fatty acid that has been used for treatment of urea cycle disorders in children, sickle cell disease, and thalassemia. It has been demonstrated recently that 4-PBA can act as a chemical chaperone by reducing the load of mutant or mislocated proteins retained in the endoplasmic reticulum (ER) under conditions associated with cystic fibrosis and liver injury. In the present study, we evaluated the neuroprotective effect of 4-PBA on cerebral ischemic injury. Pre- or post-treatment with 4-PBA at therapeutic doses attenuated infarction volume, hemispheric swelling, and apoptosis and improved neurological status in a mouse model of hypoxia-ischemia. Moreover, 4-PBA suppressed ER-mediated apoptosis by inhibiting eukaryotic initiation factor 2alpha phosphorylation, CCAAT/enhancer-binding protein homologous protein induction, and caspase-12 activation. In neuroblastoma neuro2a cells, 4-PBA reduced caspase-12 activation, DNA fragmentation, and cell death induced by hypoxia/reoxygenation. It protected against ER stress-induced but not mitochondria-mediated cell death. Additionally, 4-PBA inhibited the expression of inducible nitric-oxide synthase and tumor necrosis factor-alpha in primary cultured glial cells under hypoxia/reoxygenation. These results indicate that 4-PBA could protect against cerebral ischemia through inhibition of ER stress-mediated apoptosis and inflammation. Therefore, the multiple actions of 4-PBA may provide a strong effect in treatment of cerebral ischemia, and its use as a chemical chaperone would provide a novel approach for the treatment of stroke.

  3. Actualities on molecular pathogenesis and repairing processes of cerebral damage in perinatal hypoxic-ischemic encephalopathy

    Directory of Open Access Journals (Sweden)

    Praticò Andrea D

    2010-09-01

    Full Text Available Abstract Hypoxic-ischemic encephalopathy (HIE is the most important cause of cerebral damage and long-term neurological sequelae in the perinatal period both in term and preterm infant. Hypoxic-ischemic (H-I injuries develop in two phases: the ischemic phase, dominated by necrotic processes, and the reperfusion phase, dominated by apoptotic processes extending beyond ischemic areas. Due to selective ischemic vulnerability, cerebral damage affects gray matter in term newborns and white matter in preterm newborns with the typical neuropathological aspects of laminar cortical necrosis in the former and periventricular leukomalacia in the latter. This article summarises the principal physiopathological and biochemical processes leading to necrosis and/or apoptosis of neuronal and glial cells and reports recent insights into some endogenous and exogenous cellular and molecular mechanisms aimed at repairing H-I cerebral damage.

  4. Identification of ischemic regions in a rat model of stroke.

    Science.gov (United States)

    Popp, Anke; Jaenisch, Nadine; Witte, Otto W; Frahm, Christiane

    2009-01-01

    Investigations following stroke first of all require information about the spatio-temporal dimension of the ischemic core as well as of perilesional and remote affected tissue. Here we systematically evaluated regions differently impaired by focal ischemia. Wistar rats underwent a transient 30 or 120 min suture-occlusion of the middle cerebral artery (MCAO) followed by various reperfusion times (2 h, 1 d, 7 d, 30 d) or a permanent MCAO (1 d survival). Brains were characterized by TTC, thionine, and immunohistochemistry using MAP2, HSP72, and HSP27. TTC staining reliably identifies the infarct core at 1 d of reperfusion after 30 min MCAO and at all investigated times following 120 min and permanent MCAO. Nissl histology denotes the infarct core from 2 h up to 30 d after transient as well as permanent MCAO. Absent and attenuated MAP2 staining clearly identifies the infarct core and perilesional affected regions at all investigated times, respectively. HSP72 denotes perilesional areas in a limited post-ischemic time (1 d). HSP27 detects perilesional and remote impaired tissue from post-ischemic day 1 on. Furthermore a simultaneous expression of HSP72 and HSP27 in perilesional neurons was revealed. TTC and Nissl staining can be applied to designate the infarct core. MAP2, HSP72, and HSP27 are excellent markers not only to identify perilesional and remote areas but also to discriminate affected neuronal and glial populations. Moreover markers vary in their confinement to different reperfusion times. The extent and consistency of infarcts increase with prolonged occlusion of the MCA. Therefore interindividual infarct dimension should be precisely assessed by the combined use of different markers as described in this study.

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

    Science.gov (United States)

    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.

  6. The experimental study of CT-guided hepatocyte growth factor gene therapy for cerebral ischemic diseases

    International Nuclear Information System (INIS)

    Zhang Xiaobo; Jin Zhengyu; Li Mingli; Wang Renzhi; Li Guilin; Kong Yanguo; Wang Jianming; Gao Shan; Guan Hongzhi; Wang Detian; Luo Yufeng

    2006-01-01

    Objectives: To investigate the feasibility of CT guided hepatocyte growth factor (HGF) gene therapy for cerebral ischemic diseases. Methods: Human HGF cDNA was ligated to pIRES 2 -EGFP vector. The recombinant plasmid was transfected into the penumbra tissue with liposome, guided by CT perfusion images. After seven days of transfer with recombinant plasmid, the cut sections of rat brain tissues of the treated and control groups were analyzed including immunohistochemistry, vessel count, cerebral blood flow and infarct volume etc. in order to investigate HGF gene expression and biological effect. Results: Enzymatic digestion and electrophoresis confirmed that HGF fragments had been correctly cloned into the space between the BamH I and Sal I sites of pIRES 2 -EGFP. After 7 days of HGF gene transfection, expression of HGF in transfected neurocytes of treated group was observed with immunohistochemistry. The number of vessels in penumbra tissues transfected with HGF vectors and the CBF measured by perfusion CT all were significantly increased than those of the controls (P 2 -EGFP-HGF complexes can transfect the penumbra tissues and definitely express HGF protein. The HGF gene products can stimulate angiogenesis, promote collateral circulation formation and reduce infarct volume in vivo and therefore is beneficial to the treatment of cerebral ischemia. (authors)

  7. Predictors of early infection in cerebral ischemic stroke.

    Science.gov (United States)

    Ashour, Wmr; Al-Anwar, A D; Kamel, A E; Aidaros, M A

    2016-01-01

    Infection is the most common complication of stroke. To determine the risk factors and predictors of post-stroke infection (PSI), which developed within 7 days from the onset of acute ischemic stroke. The study included 60 ischemic stroke patients admitted in the Neurology Department of Zagazig University, Egypt, who were subdivided into: [Non Stroke Associated Infection group (nSAI); 30 patients having stroke without any criteria of infection within 7 days from the onset and Stroke Associated Infection group (SAI); 30 patients having stroke with respiratory tract infection (RTI) or urinary tract infection within 7 days], in addition to 30 healthy sex and age-matching subjects as control. All the patients had a detailed history taking, thorough clinical general and neurological examination, laboratory tests (Urine analysis & urine culture, blood sugar, lipid profile and serum tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-10), a chest radiography to assess RTI and brain computed tomography (CT) to exclude the hemorrhagic stroke and to confirm the ischemic stroke. SAI patients were found to be significantly older with higher baseline blood glucose level. Also the number of patients with tube feeding, lower conscious level, more stroke severity and more large size infarcts were significantly higher in SAI patients. There was a significant elevation in the IL-10, a significant decrease in the TNF-α and a significant decrease in the TNF-α/ IL-10 ratio, in the SAI group. The baseline serum level of IL-10 ≥ 14.5 pg/ ml and size of infarct area > 3.5 cm3 were found to be the independent predictors of PSI. Patients with older age, tube feeding, lower conscious level, worse baseline stroke severity, large cerebral infarcts in CT scan, and increased IL-10 serum level were more susceptible to infection. The baseline serum level of IL-10 ≥ 14.5 pg/ ml and the size of infarct area > 3.5 cm3 were the independent predictors of PSI.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  10. Imaging of rat cerebral ischemia-reperfusion injury using99mTc-labeled duramycin

    International Nuclear Information System (INIS)

    Zhang Yuqing; Stevenson, Gail D.; Barber, Christy; Furenlid, Lars R.; Barrett, Harrison H.; Woolfenden, James M.; Zhao Ming; Liu Zhonglin

    2013-01-01

    Objectives: Prompt identification of necrosis and apoptosis in the infarct core and penumbra region is critical in acute stroke for delineating the underlying ischemic/reperfusion molecular pathologic events and defining therapeutic alternatives. The objective of this study was to investigate the capability of 99m Tc-labeled duramycin in detecting ischemia-reperfusion injury in rat brain after middle cerebral artery (MCA) occlusion. Methods: Ischemic cerebral injury was induced in ten rats by vascular insertion of a nylon suture in the left MCA for 3 hr followed by 21–24 hr reperfusion. After i.v. injection of 99m Tc-duramycin (1.0-3.5 mCi), dynamic cerebral images were acquired for 1 hr in six rats using a small-animal SPECT imager. Four other rats were imaged at 2 hr post-injection. Ex vivo images were obtained by autoradiography after sacrifice. Histologic analyses were performed to assess cerebral infarction and apoptosis. Results: SPECT images showed that 99m Tc-duramycin uptake in the left cerebral hemisphere was significantly higher than that in the right at 1 and 2 hr post-injection. The level of radioactive uptake in the ischemic brain varied based on ischemic severity. The average ratio of left cerebral hot-spot uptake to right hemisphere radioactivity, as determined by computerized ROI analysis, was 4.92 ± 0.79. Fractional washout at 1 hr was 38.2 ± 4.5% of peak activity for left cerebral hot-spot areas and 80.9 ± 2.0% for remote control areas (P 99m Tc-duramycin SPECT imaging may be useful for detecting and quantifying ongoing apoptotic neuronal cell loss induced by ischemia-reperfusion injury.

  11. Sulforaphane exerts neuroprotective effects via suppression of the inflammatory response in a rat model of focal cerebral ischemia

    OpenAIRE

    Ma, Li-Li; Xing, Guo-Ping; Yu, Yin; Liang, Hui; Yu, Tian-Xia; Zheng, Wei-Hong; Lai, Tian-Bao

    2015-01-01

    Inflammatory damage plays an important role in cerebral ischemic pathogenesis and may represent a promising target for treatment. Sulforaphane exerts protective effects in a rat model of focal cerebral ischemia/reperfusion injury by alleviating brain edema. However, the possible mechanisms of sulforaphane after cerebral ischemia/reperfusion injury have not been fully elucidated. Therefore, in the present study, we investigated the effect of sulforaphane on inflammatory reaction and the potent...

  12. The role of exogenous neural stem cells transplantation in cerebral ischemic stroke.

    Science.gov (United States)

    Chen, Lukui; Qiu, Rong; Li, Lushen; He, Dan; Lv, Haiqin; Wu, Xiaojing; Gu, Ning

    2014-11-01

    transplantation group. The Nissl dyeing showed that there was a large area of neuronal necrosis and apoptosis in the ischemia and PBS transplantation groups, and damage was mainly focused in the striatum. Degeneration and damage of nerve cells were significantly reduced in the NSCs transplantation group. The Tunel assay showed that the number of apoptosis-positive cells in the NSCs transplantation group was less than that in the PBS transplantation group at each time point. Double immunofluorescent labeling showed that the proliferation of endogenous neural stem cells began at the third day, reaching the peak at the 7th day, and was significantly reduced at the 14th day in the SVZ. The number of BrdU/NeuN increased significantly in the NSCs transplantation group compared to that in the PBS transplantation group (P < 0.05). The number of BrdU/GFAP decreased significantly in the NSCs transplantation group compared to that of PBS transplantation group (P < 0.05). The number of BrdU/GFAP-positive cells in the striatum was observed to be much more in the PBS transplantation group than in the NSCs transplantation group. Both neurological deficits and coordination capacity of rats with cerebral ischemia were significantly improved via transplantation of the neural stem cells. In conclusion, transplantation of neural stem cells can therefore possibly promote the differentiation of endogenous NSCs into neurons and reduce their differentiation towards glial cells. Transplantation of the neural stem cells may also change the ischemic microenvironment of striatum, possibly inhibiting the proliferation of glial cells.

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

    Science.gov (United States)

    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.

  14. Ischemic lesions related to cerebral angiography: Evaluation by diffusion weighted MR imaging

    International Nuclear Information System (INIS)

    Kato, Koki; Tomura, Noriaki; Takahashi, Satoshi; Sakuma, Ikuo; Watarai, Jiro

    2003-01-01

    We examined the incidence of ischemic lesions occurring after cerebral angiography by means of diffusion weighted MR imaging (DWI). Fifty patients were included in this study. Balloon occlusion tests of the internal carotid artery were performed in 9 of the 50 patients. DWI was performed on the same day as the cerebral angiography or on the following day. No new neurological deficits were found after cerebral angiography. However, 13 of the 50 cases revealed new ischemic lesions after cerebral angiography. The incidence of ischemic lesions was significantly different between patients who underwent balloon occlusion tests and patients who did not. The incidence of ischemic lesions was not influenced by the duration of the procedure, use of additional catheters, total amount of contrast material or the type of contrast material. The incidence of clinically silent ischemic lesions related to cerebral angiography is greater than the incidence of neurological complications. In patients who underwent occlusion tests of the internal carotid artery, the incidence of silent lesions was significantly higher than in patients who did not. (orig.)

  15. LXW7 ameliorates focal cerebral ischemia injury and attenuates inflammatory responses in activated microglia in rats

    International Nuclear Information System (INIS)

    Fang, T.; Zhou, D.; Lu, L.; Tong, X.; Wu, J.; Yi, L.

    2016-01-01

    Inflammation plays a pivotal role in ischemic stroke, when activated microglia release excessive pro-inflammatory mediators. The inhibition of integrin αvβ3 improves outcomes in rat focal cerebral ischemia models. However, the mechanisms by which microglia are neuroprotective remain unclear. This study evaluated whether post-ischemic treatment with another integrin αvβ3 inhibitor, the cyclic arginine-glycine-aspartic acid (RGD) peptide-cGRGDdvc (LXW7), alleviates cerebral ischemic injury. The anti-inflammatory effect of LXW7 in activated microglia within rat focal cerebral ischemia models was examined. A total of 108 Sprague-Dawley rats (250–280 g) were subjected to middle cerebral artery occlusion (MCAO). After 2 h, the rats were given an intravenous injection of LXW7 (100 μg/kg) or phosphate-buffered saline (PBS). Neurological scores, infarct volumes, brain water content (BWC) and histology alterations were determined. The expressions of pro-inflammatory cytokines [tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β)], and Iba1-positive activated microglia, within peri-ischemic brain tissue, were assessed with ELISA, western blot and immunofluorescence staining. Infarct volumes and BWC were significantly lower in LXW7-treated rats compared to those in the MCAO + PBS (control) group. The LXW7 treatment lowered the expression of pro-inflammatory cytokines. There was a reduction of Iba1-positive activated microglia, and the TNF-α and IL-1β expressions were attenuated. However, there was no difference in the Zea Longa scores between the ischemia and LXW7 groups. The results suggest that LXW7 protected against focal cerebral ischemia and attenuated inflammation in activated microglia. LXW7 may be neuroprotective during acute MCAO-induced brain damage and microglia-related neurodegenerative diseases

  16. LXW7 ameliorates focal cerebral ischemia injury and attenuates inflammatory responses in activated microglia in rats

    Energy Technology Data Exchange (ETDEWEB)

    Fang, T.; Zhou, D.; Lu, L.; Tong, X.; Wu, J.; Yi, L. [Department of Neurology, Shenzhen Hospital, Peking University, Shenzhen (China)

    2016-08-01

    Inflammation plays a pivotal role in ischemic stroke, when activated microglia release excessive pro-inflammatory mediators. The inhibition of integrin αvβ3 improves outcomes in rat focal cerebral ischemia models. However, the mechanisms by which microglia are neuroprotective remain unclear. This study evaluated whether post-ischemic treatment with another integrin αvβ3 inhibitor, the cyclic arginine-glycine-aspartic acid (RGD) peptide-cGRGDdvc (LXW7), alleviates cerebral ischemic injury. The anti-inflammatory effect of LXW7 in activated microglia within rat focal cerebral ischemia models was examined. A total of 108 Sprague-Dawley rats (250–280 g) were subjected to middle cerebral artery occlusion (MCAO). After 2 h, the rats were given an intravenous injection of LXW7 (100 μg/kg) or phosphate-buffered saline (PBS). Neurological scores, infarct volumes, brain water content (BWC) and histology alterations were determined. The expressions of pro-inflammatory cytokines [tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β)], and Iba1-positive activated microglia, within peri-ischemic brain tissue, were assessed with ELISA, western blot and immunofluorescence staining. Infarct volumes and BWC were significantly lower in LXW7-treated rats compared to those in the MCAO + PBS (control) group. The LXW7 treatment lowered the expression of pro-inflammatory cytokines. There was a reduction of Iba1-positive activated microglia, and the TNF-α and IL-1β expressions were attenuated. However, there was no difference in the Zea Longa scores between the ischemia and LXW7 groups. The results suggest that LXW7 protected against focal cerebral ischemia and attenuated inflammation in activated microglia. LXW7 may be neuroprotective during acute MCAO-induced brain damage and microglia-related neurodegenerative diseases.

  17. A Microarray Study of Middle Cerebral Occlusion Rat Brain with Acupuncture Intervention

    Directory of Open Access Journals (Sweden)

    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.

  18. Paeoniflorin, a Monoterpene Glycoside, Protects the Brain from Cerebral Ischemic Injury via Inhibition of Apoptosis.

    Science.gov (United States)

    Zhang, Yuqin; Li, Huang; Huang, Mingqing; Huang, Mei; Chu, Kedan; Xu, Wei; Zhang, Shengnan; Que, Jinhua; Chen, Lidian

    2015-01-01

    Paeoniflorin (PF) is a principal bioactive component, which exhibits many pharmacological effects, including protection against ischemic injury. This paper aimed to investigate the protective effect of PF both in vivo and in vitro. Middle cerebral artery occlusion (MCAO) was performed on male Sprague-Dawley (SD) rat for 2 h, and different doses of PF or vehicle were administered 2 h after reperfusion. Rats were sacrificed after 7 days treatment of PF/vehicle. PF treatment for 7 days ameliorated MCAO-induced neurological deficit and decreased the infarct area. Further study demonstrated that PF inhibited the over-activation of astrocytes and apoptosis of neurons, and PF promoted up-regulation of neuronal specific marker neuron-specific nuclear (NeuN) and microtubule-associated protein 2 (MAP-2) in brain. Moreover, NMDA-induced neuron apoptosis was employed. The in vitro study revealed that PF treatment protected against NMDA-induced cell apoptosis and neuronal loss via up-regulation of neuronal specific marker NeuN, MAP-2 and Bcl-2 and the down-regulation Bax. Taken together, the present study demonstrates that PF produces its protective effect by inhibiting the over-activation of astrocytes, apoptosis of neurons and up-regulation of neuronal specific marker NeuN, MAP-2, and B-cell lymphoma-2 (Bcl-2), and down-regulation Bax. Our study reveals that PF may be a potential neuroprotective agent for stroke and can provide basic data for clinical use.

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

    International Nuclear Information System (INIS)

    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

  20. Cerebral Microbleeds and the Risk of Incident Ischemic Stroke in CADASIL (Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy).

    Science.gov (United States)

    Puy, Laurent; De Guio, François; Godin, Ophélia; Duering, Marco; Dichgans, Martin; Chabriat, Hugues; Jouvent, Eric

    2017-10-01

    Cerebral microbleeds are associated with an increased risk of intracerebral hemorrhage. Recent data suggest that microbleeds may also predict the risk of incident ischemic stroke. However, these results were observed in elderly individuals undertaking various medications and for whom causes of microbleeds and ischemic stroke may differ. We aimed to test the relationship between the presence of microbleeds and incident stroke in CADASIL (Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy)-a severe monogenic small vessel disease known to be responsible for both highly prevalent microbleeds and a high incidence of ischemic stroke in young patients. We assessed microbleeds on baseline MRI in all 378 patients from the Paris-Munich cohort study. Incident ischemic strokes were recorded during 54 months. Survival analyses were used to test the relationship between microbleeds and incident ischemic stroke. Three hundred sixty-nine patients (mean age, 51.4±11.4 years) were followed-up during a median time of 39 months (interquartile range, 19 months). The risk of incident ischemic stroke was higher in patients with microbleeds than in patients without (35.8% versus 19.6%, hazard ratio, 1.87; 95% confidence interval, 1.16-3.01; P =0.009). These results persisted after adjustment for history of ischemic stroke, age, sex, vascular risk factors, and antiplatelet agents use (hazard ratio, 1.89; 95% confidence interval, 1.10-3.26; P =0.02). The presence of microbleeds is an independent risk marker of incident ischemic stroke in CADASIL, emphasizing the need to carefully interpret MRI data. © 2017 American Heart Association, Inc.

  1. Dipyridamole cerebral flow stress test evaluating ischemic cerebrovascular diseases

    International Nuclear Information System (INIS)

    Xiu, Y.; Chen, S.; Sun, X.; Liu, S.; Li, W.; Fan, W.; Wang, X.

    2000-01-01

    To detect the clinical value of dipyridamole cerebral blood flow stress test in cerebrovascular diseases (CVD). Nineteen patients (9 male, 10 female, mean age=65) who were diagnosed as CVD were included. One suffered from infarct, two suffered from thrombosis, one feel dizziness. All 4 performed rest and stress test. The other 15 were VBI, 9 of them performed stress test. Rest and stress test were done two-day method using Elscint Apex SP-6 SPECT equipped with low energy all purpose collimator. Rest perfusion imaging was started 30 min after injecting 1.11 GBq 99m Tc-ECD. Dipyridamole stress test was done within one week. 0.56 mg/Kg dipyridamole was injected intravenously during 4 min the same dose of ECD was injected 2 min later. The acquisition started 30 min later with the same parameter. Heart rate, ECG and the patient's complaint were monitored 2 min before and after dipyridamole. After correction for attenuation, transverse, coronal and sagittal slices were reconstructed. Eighteen ROIs were drawn symmetrically on cingulate, frontal, temporal-parietal, temporal, occipital, vision cortex, basal ganglia, superior frontal and parietal on the 3 rd , 6 th , 9 th transverse slices, selecting the contralateral as the reference region. The counts per pixel in each ROI were divided by the counts of the mirror region to obtain the relative uptake ratio. We think it abnormality when the ratio is above 1,1 or below 0.9. The sensitivity for rest and stress rCBF test was compared. rCBF was decreased at 10 of 19 patients (sensitivity 52.6%). 14 had low rCBF after dipyridamole (sensitivity 72.3%), Among the patients who studied stress test, 6 had normal rCBF at rest and low rCBF after stress. The abnormal area was enlarged after dipyridamole for 1 patients, 2 improved and 2 unchanged. 8 of 15 VBI had normal rCBF at rest (sensitivity 53.3%). 9 of 15 VBI performed stress test. rCBF was normal at rest for 5 patients, rCBF was decreased after stress, it was improved for one

  2. [Identification of early irreversible damage area in a rat model of cerebral ischemia and reperfusion].

    Science.gov (United States)

    Liu, S; Guo, Y

    2000-02-01

    To observe the early neuron ischemic damage in focal cerebral ischemia/reperfusion with histostaining methods of argyrophil III (AG III), Toludine blue(TB), and H&E, and to make out the 'separating line' between the areas of reversible and irreversible early ischemic damage. Forty-two male Wistar rats were randomly divided into the following groups: pseudo-surgical, blank-control, O2R0(occluded for 2 hours and reperfused for 0 hour), O2R0.5, O2R2, O2R4, O2R24. There were 6 rats in each group. Rats in experimental groups were suffered focal cerebral ischemia/reperfusion through a nylon suture method. After a special processor for tissue manage, the brain were coronal sectioned and stained with H&E, TB, and AG III. The area where dark neurons dwell in (ischemic core) were calculated with image analysis system. The success rate of ischemic model for this experiment is 90%. After being stained with argyrophil III method, normal neurons appear yellow or pale brown, which is hardly distinguished from the pale brown background. The ischemic neuron stained black, and has collapsed body and "corkscrew-like" axon or dentries, which were broken to some extent. The neuropil in the dark neurons dwelt area appears gray or pale black, which is apparently different from the pale brown neighborhood area. The distribution of dark neurons in cortex varies according to different layers, and has a character of columnar form. The dark neurons present as early as 2 hours ischemia without reperfusion with AG III method. AG III stain could selectively display early ischemic neurons, the area dwelt by dark neurons represent early ischemic core. Dark neuron is possibly the irreversibly damaged neuron. Identification of dark neurons could be helpful in the discrimination between early ischemic center and penumbra.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Cerebral microbleeds in a neonatal rat model.

    Directory of Open Access Journals (Sweden)

    Brianna Carusillo Theriault

    Full Text Available In adult humans, cerebral microbleeds play important roles in neurodegenerative diseases but in neonates, the consequences of cerebral microbleeds are unknown. In rats, a single pro-angiogenic stimulus in utero predisposes to cerebral microbleeds after birth at term, a time when late oligodendrocyte progenitors (pre-oligodendrocytes dominate in the rat brain. We hypothesized that two independent pro-angiogenic stimuli in utero would be associated with a high likelihood of perinatal microbleeds that would be severely damaging to white matter.Pregnant Wistar rats were subjected to intrauterine ischemia (IUI and low-dose maternal lipopolysaccharide (mLPS at embryonic day (E 19. Pups were born vaginally or abdominally at E21-22. Brains were evaluated for angiogenic markers, microhemorrhages, myelination and axonal development. Neurological function was assessed out to 6 weeks.mRNA (Vegf, Cd31, Mmp2, Mmp9, Timp1, Timp2 and protein (CD31, MMP2, MMP9 for angiogenic markers, in situ proteolytic activity, and collagen IV immunoreactivity were altered, consistent with an angiogenic response. Vaginally delivered pups exposed to prenatal IUI+mLPS had spontaneous cerebral microbleeds, abnormal neurological function, and dysmorphic, hypomyelinated white matter and axonopathy. Pups exposed to the same pro-angiogenic stimuli in utero but delivered abdominally had minimal cerebral microbleeds, preserved myelination and axonal development, and neurological function similar to naïve controls.In rats, pro-angiogenic stimuli in utero can predispose to vascular fragility and lead to cerebral microbleeds. The study of microbleeds in the neonatal rat brain at full gestation may give insights into the consequences of microbleeds in human preterm infants during critical periods of white matter development.

  5. 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.

  6. Baicalin attenuates focal cerebral ischemic reperfusion injury through inhibition of nuclear factor κB p65 activation

    International Nuclear Information System (INIS)

    Xue, Xia; Qu, Xian-Jun; Yang, Ying; Sheng, Xie-Huang; Cheng, Fang; Jiang, E-Nang; Wang, Jian-hua; Bu, Wen; Liu, Zhao-Ping

    2010-01-01

    Research highlights: → Permanent NF-κB p65 activation contributes to the infarction after ischemia-reperfusion injury in rats. → Baicalin can markedly inhibit the nuclear NF-κB p65 expression and m RNA levels after ischemia-reperfusion injury in rats. → Baicalin decreased the cerebral infarction area via inhibiting the activation of nuclear NF-κB p65. -- Abstract: Baicalin is a flavonoid compound purified from plant Scutellaria baicalensis Georgi. We aimed to evaluate the neuroprotective effects of baicalin against cerebral ischemic reperfusion injury. Male Wistar rats were subjected to middle cerebral artery occlusion (MCAO) for 2 h followed by reperfusion for 24 h. Baicalin at doses of 50, 100 and 200 mg/kg was intravenously injected after ischemia onset. Twenty-four hours after reperfusion, the neurological deficit was scored and infarct volume was measured. Hematoxylin and eosin (HE) staining was performed to analyze the histopathological changes of cortex and hippocampus neurons. We examined the levels of NF-κB p65 in ischemic cortexes by Western blot analysis and RT-PCR assay. The results showed that the neurological deficit scores were significantly decreased from 2.0 ± 0.7 to 1.2 ± 0.4 and the volume of infarction was reduced by 25% after baicalin injection. Histopathological examination showed that the increase of neurons with pycnotic shape and condensed nuclear in cortex and hippocampus were not observed in baicalin treated animals. Further examination showed that NF-κB p65 in cortex was increased after ischemia reperfusion injury, indicating the molecular mechanism of ischemia reperfusion injury. The level of NF-κB p65 was decreased by 73% after baicalin treatment. These results suggest that baicalin might be useful as a potential neuroprotective agent in stroke therapy. The neuroprotective effects of baicalin may relate to inhibition of NF-κB p65.

  7. Extracranial cerebral arterial atherosclerosis in Iranian patients suffering ischemic strokes

    Directory of Open Access Journals (Sweden)

    Sayed Ali Mousavi

    2006-12-01

    Full Text Available BACKGROUND: To determine the distribution and severity of extracranial carotid arterial atherosclerosis in Iranian patients with ischemic stroke. METHODS: 328 patients with ischemic stroke were included in this study. Doppler ultrasound was used for evaluation of atherosclerosis in extracranial carotid arteries. The NASCET criteria were used to measure carotid stenosis. RESULTS: Ninety of 328 patients (27.4% were found to have atherosclerotic plaques; 40 of these patients were women and 50 were men. Sixty-eight patients (20.7% had artery stenosis <50%, 13 patients (3.95% had 50-70 % artery stenosis and 6 (1.8% had >70% artery stenosis. CONCLUSIONS: Extracranial atherosclerosis is not rare in Iranian patients with ischemic stroke, but most carotid artery lesions were plaques with <50% stenosis. KEY WORDS: Atherosclerosis, ischemic stroke, carotid stenosis.

  8. Toll-like receptors in cerebral ischemic inflammatory injury

    OpenAIRE

    Wang, Yan-Chun; Lin, Sen; Yang, Qing-Wu

    2011-01-01

    Abstract Cerebral ischemia triggers acute inflammation, which has been associated with an increase in brain damage. The mechanisms that regulate the inflammatory response after cerebral ischemia are multifaceted. An important component of this response is the activation of the innate immune system. However, details of the role of the innate immune system within the complex array of mechanisms in cerebral ischemia remain unclear. There have been recent great strides in our understanding of the...

  9. Cerebral blood flow in acute and chronic ischemic stroke using xenon-133 inhalation tomography

    DEFF Research Database (Denmark)

    Vorstrup, S; Paulson, O B; Lassen, N A

    1986-01-01

    Serial measurements of cerebral blood flow (CBF) were performed in 12 patients with acute symptoms of ischemic cerebrovascular disease. CBF was measured by xenon-133 inhalation and single photon emission computer tomography. Six patients had severe strokes and large infarcts on the CT scan...

  10. Hemispheric distribution of middle cerebral artery ischemic strokes in patients admitted to military hospital rawalpindi

    International Nuclear Information System (INIS)

    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)

  11. Opiates and cerebral functional activity in rats

    International Nuclear Information System (INIS)

    Trusk, T.C.

    1986-01-01

    Cerebral activity was measured using the free-fatty acid [1- 14 C] octanoate as a fast functional tracer in conscious, unrestrained rats 5 minutes after intravenous injection of heroin, cocaine or saline vehicle. Regional changes of octanoate labeling density in the autoradiograms relative to saline-injected animals were used to determine the functional activity effects of each drug. Heroin and cocaine each produced a distinctive pattern of activity increases and suppression throughout the rat brain. Similar regional changes induced by both drugs were found in limbic brain regions implicated in drug reinforcement. Labeled octanoate autoradiography was used to measure the cerebral functional response to a tone that had previously been paired to heroin injections. Rats were trained in groups of three consisting of one heroin self-administration animal, and two animals receiving yoked infusion of heroin or saline. A tone was paired with each infusion during training. Behavioral experiments in similarly trained rats demonstrated that these training conditions impart secondary reinforcing properties to the tone in animals previously self-administering heroin, while the tone remains behaviorally neutral in yoked-infusion rats. Cerebral functional activity was measured during presentation of the tone without drug infusion. Octanoate labeling density changed in fifteen brain areas in response to the tone previously paired to heroin without response contingency. Labeling density was significantly modified in sixteen regions as a result of previously pairing the tone to response-contingent heroin infusions

  12. Opiates and cerebral functional activity in rats

    Energy Technology Data Exchange (ETDEWEB)

    Trusk, T.C.

    1986-01-01

    Cerebral activity was measured using the free-fatty acid (1-/sup 14/C) octanoate as a fast functional tracer in conscious, unrestrained rats 5 minutes after intravenous injection of heroin, cocaine or saline vehicle. Regional changes of octanoate labeling density in the autoradiograms relative to saline-injected animals were used to determine the functional activity effects of each drug. Heroin and cocaine each produced a distinctive pattern of activity increases and suppression throughout the rat brain. Similar regional changes induced by both drugs were found in limbic brain regions implicated in drug reinforcement. Labeled octanoate autoradiography was used to measure the cerebral functional response to a tone that had previously been paired to heroin injections. Rats were trained in groups of three consisting of one heroin self-administration animal, and two animals receiving yoked infusion of heroin or saline. A tone was paired with each infusion during training. Behavioral experiments in similarly trained rats demonstrated that these training conditions impart secondary reinforcing properties to the tone in animals previously self-administering heroin, while the tone remains behaviorally neutral in yoked-infusion rats. Cerebral functional activity was measured during presentation of the tone without drug infusion. Octanoate labeling density changed in fifteen brain areas in response to the tone previously paired to heroin without response contingency. Labeling density was significantly modified in sixteen regions as a result of previously pairing the tone to response-contingent heroin infusions.

  13. Protective effects of incensole acetate on cerebral ischemic injury.

    Science.gov (United States)

    Moussaieff, Arieh; Yu, Jin; Zhu, Hong; Gattoni-Celli, Sebastiano; Shohami, Esther; Kindy, Mark S

    2012-03-14

    The resin of Boswellia species is a major anti-inflammatory agent that has been used for centuries to treat various conditions including injuries and inflammatory conditions. Incensole acetate (IA), a major constituent of this resin, has been shown to inhibit NF-κB activation and concomitant inflammation, as well as the neurological deficit following head trauma. Here, we show that IA protects against ischemic neuronal damage and reperfusion injury in mice, attenuating the inflammatory nature of ischemic damage. IA given post-ischemia, reduced infarct volumes and improved neurological activities in the mouse model of ischemic injury in a dose dependent fashion. The protection from damage was accompanied by inhibition of TNF-α, IL-1β and TGF-β expression, as well as NF-κB activation following injury. In addition, IA is shown to have a therapeutic window of treatment up to 6h after ischemic injury. Finally, the protective effects of IA were partially mediated by TRPV3 channels as determined by the TRPV3 deficient mice and channel blocker studies. This study suggests that the anti-inflammatory and neuroprotective activities of IA may serve as a novel therapeutic treatment for ischemic and reperfusion injury, and as a tool in the ongoing research of mechanisms for neurological damage. Published by Elsevier B.V.

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

    Science.gov (United States)

    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.

  15. Reperfusion promotes mitochondrial dysfunction following focal cerebral ischemia in rats.

    Directory of Open Access Journals (Sweden)

    Jun Li

    Full Text Available BACKGROUND AND PURPOSE: Mitochondrial dysfunction has been implicated in the cell death observed after cerebral ischemia, and several mechanisms for this dysfunction have been proposed. Reperfusion after transient cerebral ischemia may cause continued and even more severe damage to the brain. Many lines of evidence have shown that mitochondria suffer severe damage in response to ischemic injury. The purpose of this study was to observe the features of mitochondrial dysfunction in isolated mitochondria during the reperfusion period following focal cerebral ischemia. METHODS: Male Wistar rats were subjected to focal cerebral ischemia. Mitochondria were isolated using Percoll density gradient centrifugation. The isolated mitochondria were fixed for electron microscopic examination; calcium-induced mitochondrial swelling was quantified using spectrophotometry. Cyclophilin D was detected by Western blotting. Fluorescent probes were used to selectively stain mitochondria to measure their membrane potential and to measure reactive oxidative species production using flow cytometric analysis. RESULTS: Signs of damage were observed in the mitochondrial morphology after exposure to reperfusion. The mitochondrial swelling induced by Ca(2+ increased gradually with the increasing calcium concentration, and this tendency was exacerbated as the reperfusion time was extended. Cyclophilin D protein expression peaked after 24 hours of reperfusion. The mitochondrial membrane potential was decreased significantly during the reperfusion period, with the greatest decrease observed after 24 hours of reperfusion. The surge in mitochondrial reactive oxidative species occurred after 2 hours of reperfusion and was maintained at a high level during the reperfusion period. CONCLUSIONS: Reperfusion following focal cerebral ischemia induced significant mitochondrial morphological damage and Ca(2+-induced mitochondrial swelling. The mechanism of this swelling may be mediated by

  16. Cerebroprotective Effect of Moringa oleifera against Focal Ischemic Stroke Induced by Middle Cerebral Artery Occlusion

    Directory of Open Access Journals (Sweden)

    Woranan Kirisattayakul

    2013-01-01

    Full Text Available The protection against ischemic stroke is still required due to the limitation of therapeutic efficacy. Based on the role of oxidative stress in stroke pathophysiology, we determined whether Moringa oleifera, a plant possessing potent antioxidant activity, protected against brain damage and oxidative stress in animal model of focal stroke. M. oleifera leaves extract at doses of 100, 200 and 400 mg·kg−1 was orally given to male Wistar rats (300–350 g once daily at a period of 2 weeks before the occlusion of right middle cerebral artery (Rt.MCAO and 3 weeks after Rt.MCAO. The determinations of neurological score and temperature sensation were performed every 7 days throughout the study period, while the determinations of brain infarction volume, MDA level, and the activities of SOD, CAT, and GSH-Px were performed 24 hr after Rt.MCAO. The results showed that all doses of extract decreased infarction volume in both cortex and subcortex. The protective effect of medium and low doses of extract in all areas occurred mainly via the decreased oxidative stress. The protective effect of the high dose extract in striatum and hippocampus occurred via the same mechanism, whereas other mechanisms might play a crucial role in cortex. The detailed mechanism required further exploration.

  17. Neonatal rat hearts cannot be protected by ischemic postconditioning

    Czech Academy of Sciences Publication Activity Database

    Doul, J.; Charvátová, Z.; Ošťádalová, Ivana; Kohutiar, M.; Maxová, H.; Ošťádal, Bohuslav

    2015-01-01

    Roč. 64, č. 6 (2015), s. 789-794 ISSN 0862-8408 Institutional support: RVO:67985823 Keywords : neonatal rats * ischemic postconditioning * tolerance to ischemia * contractile function * lactate dehydrogenase Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 1.643, year: 2015

  18. The synergetic effect of edaravone and borneol in the rat model of ischemic stroke.

    Science.gov (United States)

    Wu, Hai-Yin; Tang, Ying; Gao, Li-Yan; Sun, Wei-Xiang; Hua, Yao; Yang, Shi-Bao; Zhang, Zheng-Ping; Liao, Gao-Yong; Zhou, Qi-Gang; Luo, Chun-Xia; Zhu, Dong-Ya

    2014-10-05

    Free radical production contributes to the early ischemic response and the neuroinflammatory response to injury initiates the second wave of cell death following ischemic stroke. Edaravone is a free radical scavenger, and borneol has shown anti-inflammatory effect. We investigated the synergistic effect of these two drugs in the rat model of transient cerebral ischemia. Edaravone scavenged OH, NO and ONOO─ concentration-dependently, and borneol inhibited ischemia/reperfusion-induced tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), interleukin-1β (IL-1β) and cyclooxygenase-2 (COX-2) expressions. In the rat model of transient cerebral ischemia and reperfusion, the combination of edaravone and borneol significantly ameliorated ischemic damage with an optimal proportion of 4:1. Emax (% inhibition) of edaravone, borneol and two drugs in combination was 55.7%, 65.8% and 74.3% respectively. ED50 of edaravone and borneol was 7.17 and 0.36 mg/kg respectively. When two drugs in combination, ED50 was 0.484 mg/kg, in which edaravone was 0.387 mg/kg (ineffective dose) and borneol was 0.097 mg/kg (ineffective dose). Combination index (CI)edaravone and borneol. The combination exhibited a therapeutic time window of 6h in ischemia/reperfusion model, and significantly ameliorated damages in permanent ischemia model. Moreover, two drugs in combination promoted long-term effect, including improved elemental vital signs, sensorimotor functions and spatial cognition. Our results suggest that the combination of edaravone and borneol have a synergistic effect for treating ischemic stroke. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Intake of antioxidants and B vitamins is inversely associated with ischemic stroke and cerebral atherosclerosis

    Science.gov (United States)

    Choe, Hansaem; Hwang, Ji-Yun; Yun, Jin A; Kim, Ji-Myung; Song, Tae-Jin; Chang, Namsoo; Kim, Yong-Jae

    2016-01-01

    BACKGROUND/OBJECTIVES This study was conducted to examine relationships between dietary habits and intakes of antioxidants and B vitamins and the risk of ischemic stroke, and to compare dietary factors according to the presence of cerebral artery atherosclerosis and stroke subtypes. SUBJECTS/METHODS A total of 147 patients and 144 control subjects were recruited consecutively in the metropolitan area of Seoul, Korea. Sixty participants each in the case and control groups were included in analyses after 1:1 frequency matching. In addition, 117 acute ischemic stroke patients were classified into subtypes according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) guidelines. Dietary intake was measured using a semi-quantitative food frequency questionnaire composed of 111 food items and plasma lipid and homocysteine levels were analyzed. RESULTS When compared with control subjects, stroke patients had unfavorable dietary behaviors and lower intakes of fruits (73.1 ± 83.2 g vs. 230.9 ± 202.1 g, P < 0.001), vegetables (221.1 ± 209.0 g vs. 561.7 ± 306.6 g, P < 0.001), and antioxidants, including vitamins C, E, B6, β-carotene, and folate. The intakes of fruits, vegetables, vitamin C, and folate were inversely associated with the risk of ischemic stroke after adjusting for confounding factors. Intakes of vegetables, vitamins C, B6, B12, and folate per 1,000 kcal were lower in ischemic stroke with cerebral atherosclerosis than in those without. Overall vitamin B12 intake per 1,000 kcal differed according to the TOAST classification (P = 0.004), but no differences among groups existed based on the post-hoc test. CONCLUSIONS When compared with control subjects, ischemic stroke patients, particularly those with cerebral atherosclerosis, had unfavorable dietary intake, which may have contributed to the development of ischemic stroke. These results indicate that proper dietary recommendations are important for the prevention of ischemic stroke. PMID:27698959

  20. Niosomes of Ascorbic Acid and α-Tocopherol in the Cerebral Ischemia-Reperfusion Model in Male Rats

    OpenAIRE

    Varshosaz, Jaleh; Taymouri, Somayeh; Pardakhty, Abbas; Asadi-Shekaari, Majid; Babaee, Abodolreza

    2014-01-01

    The objective of the present study was to prepare a stable iv injectable formulation of ascorbic acid and α-tocopherol in preventing the cerebral ischemia. Different niosomal formulations were prepared by Span and Tween mixed with cholesterol. The physicochemical characteristics of niosomal formulations were evaluated in vitro. For in vivo evaluation, the rats were made ischemic by middle cerebral artery occlusion model for 30 min and the selected formulation was used for determining its neur...

  1. Hemopexin induces neuroprotection in the rat subjected to focal cerebral ischemia.

    Science.gov (United States)

    Dong, Beibei; Cai, Min; Fang, Zongping; Wei, Haidong; Zhu, Fangyun; Li, Guochao; Dong, Hailong; Xiong, Lize

    2013-06-10

    The plasma protein hemopexin (HPX) exhibits the highest binding affinity to free heme. In vitro experiments and gene-knock out technique have suggested that HPX may have a neuroprotective effect. However, the expression of HPX in the brain was not well elucidated and its expression after cerebral ischemia-reperfusion injury was also poorly studied. Furthermore, no in vivo data were available on the effect of HPX given centrally on the prognosis of focal cerebral ischemia. In the present study, we systematically investigated expression of HPX in normal rat brain by immunofluorescent staining. The results showed that HPX was mainly expressed in vascular system and neurons, as well as in a small portion of astrocytes adjacent to the vessels in normal rat brain. Further, we determined the role of HPX in the process of focal cerebral ischemic injury and explored the effects of HPX treatment in a rat model of transient focal cerebral ischemia. After 2 h' middle cerebral artery occlusion (MCAO) followed by 24 h' reperfusion, the expression of HPX was increased in the neurons and astrocytes in the penumbra area, as demonstrated by immunohistochemistry and Western blot techniques. Intracerebroventricular injection of HPX at the onset of reperfusion dose-dependently reduced the infarct volumes and improved measurements of neurological function of the rat subjected to transient focal cerebral ischemia. The neuroprotective effects of HPX sustained for up to 7 days after experiments. Our study provides a new insight into the potential neuroprotective role of HPX as a contributing factor of endogenous protective mechanisms against focal cerebral ischemia injury, and HPX might be developed as a potential agent for treatment of ischemic stroke.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. 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)

  4. Transcranial diffuse optical monitoring of microvascular cerebral hemodynamics after thrombolysis in ischemic stroke

    Science.gov (United States)

    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.

  5. Arctigenin protects focal cerebral ischemia-reperfusion rats through inhibiting neuroinflammation.

    Science.gov (United States)

    Fan, Tao; Jiang, Wei Long; Zhu, Jian; Feng Zhang, Yu

    2012-01-01

    Stroke is the third leading cause of death in industrialized countries and the most important cause of acquired adult disability. Many evidences suggest that inflammation accounts for the progression of cerebral ischemic injury. Arctigenin, a phenylpropanoid dibenzylbutyrolactone lignin isolated from certain plants, has shown anti-inflammatory activity against diabetes and Alzheimer's disease. In this study, we tested whether arctigenin can protect middle cerebral artery occluded (MCAO) rats. Male Sprague-Dawley rats were pretreated with arctigenin or vehicle for 7 d before being subjected to transient occlusion of middle cerebral artery and reperfusion. Rats were evaluated at 24 h after MCAO for neurological deficit scoring. Furthermore, the mechanism of the anti-inflammatory effect of arctigenin was investigated with a focus on inflammatory cells, proinflammatory cytokines, and transcriptional factors. Arctigenin significantly reduced cerebral infarction and improved neurological outcome. Arctigenin suppressed the activation of microglia and decreased the expression of interleukin (IL)- 1β and tumor necrosis factor (TNF)-α. These results revealed that arctigenin has a promising therapeutic effect in ischemic stroke treatment through an anti-inflammatory mechanism.

  6. Therapeutic effects of different durations of acupuncture on rats with middle cerebral artery occlusion

    Directory of Open Access Journals (Sweden)

    Chao Zhang

    2015-01-01

    Full Text Available Acupuncture is regarded as an effective therapy for cerebral ischemia. Different acupuncture manipulations and durations may result in different therapeutic effects. In the present study, the Neiguan (PC6 acupoint of rats with occluded middle cerebral arteries was needled at a fixed frequency (3 Hz with different durations, i.e., 5, 60 and 180 seconds under a twisting-rotating acupuncture method. Results showed that different durations of acupuncture had different therapeutic effects, with 60 seconds yielding a better therapeutic effect than the other two groups. This duration of treatment demonstrated rapid cerebral blood flow, encouraging recovery of neurological function, and small cerebral infarct volume. Experimental findings indicated that under 3 Hz frequency, the treatment of needling Neiguan for 60 seconds is effective for ischemic stroke

  7. Topical fentanyl stimulates healing of ischemic wounds in diabetic rats

    Science.gov (United States)

    FAROOQUI, Mariya; ERICSON, Marna E; GUPTA, Kalpna

    2016-01-01

    Background Topically applied opioids promote angiogenesis and healing of ischemic wounds in rats. We examined if topical fentanyl stimulates wound healing in diabetic rats by stimulating growth-promoting signaling, angiogenesis, lymphangiogenesis and nerve regeneration. Methods We used Zucker diabetic fatty rats that develop obesity and diabetes on a high fat diet due to a mutation in the Leptin receptor. Fentanyl blended with hydrocream was applied topically on ischemic wounds twice daily, and wound closure was analyzed regularly. Wound histology was analyzed by hematoxylin and eosin staining. Angiogenesis, lymphangiogenesis, nerve fibers and phospho-PDGFR-β were visualized by CD31-, lymphatic vessel endothelium-1, protein gene product 9.5- and anti-phospho PDGFR-β-immunoreactivity, respectively. Nitric oxide synthase (NOS) and PDGFR-β signaling were analyzed using Western immunoblotting. Results Fentanyl significantly promoted wound closure as compared to PBS. Histology scores were significantly higher in fentanyl-treated wounds, indicative of increased granulation tissue formation, reduced edema and inflammation, and increased matrix deposition. Fentanyl treatment resulted in increased wound angiogenesis, lymphatic vasculature, nerve fibers, nitric oxide, NOS and PDGFR-β signaling as compared to PBS. Phospho PDGFR-β co-localized with CD31 co-staining for vasculature. Conclusions Topically applied fentanyl promotes closure of ischemic wounds in diabetic rats. Increased angiogenesis, lymphangiogenesis, peripheral nerve regeneration, NO and PDGFR-β signaling are associated with fentanyl-induced tissue remodeling and wound healing. PMID:25266258

  8. Compensatory cerebral motor control following presumed perinatal ischemic stroke

    NARCIS (Netherlands)

    van der Hoorn, Anouk; Potgieser, Adriaan R E; Brouwer, Oebele F; de Jong, Bauke M

    Case: A fifteen year-old left-handed girl presented with right-sided focal motor seizures. Neuroimaging showed a large left hemisphere lesion compatible with a middle cerebral artery stroke of presumed perinatal origin. She was not previously diagnosed with a motor deficit, although neurological

  9. The protective effect of ischemic preconditioning on rat testis

    Directory of Open Access Journals (Sweden)

    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

  10. Compromised Wound Healing in Ischemic Type 2 Diabetic Rats.

    Directory of Open Access Journals (Sweden)

    Peilang Yang

    Full Text Available Ischemia is one of the main epidemic factors and characteristics of diabetic chronic wounds, and exerts a profound effect on wound healing. To explore the mechanism of and the cure for diabetic impaired wound healing, we established a type 2 diabetic rat model. We used an 8 weeks high fat diet (HFD feeding regimen followed by multiple injections of streptozotocin (STZ at a dose of 10mg/kg to induce Wister rat to develop type 2 diabetes. Metabolic characteristics were assessed at the 5th week after the STZ injections to confirm the establishment of diabetes mellitus on the rodent model. A bipedicle flap, with length to width ratio 1.5, was performed on the back of the rat to make the flap area ischemic. Closure of excisional wounds on this bipedicle flap and related physiological and pathological changes were studied using histological, immunohistochemical, real time PCR and protein immunoblot approaches. Our results demonstrated that a combination of HFD feeding and a low dose of STZ is capable of inducing the rats to develop type 2 diabetes with noticeable insulin resistance, persistent hyperglycemia, moderate degree of insulinemia, as well as high serum cholesterol and high triglyceride levels. The excision wounds on the ischemic double pedicle flap showed deteriorative healing features comparing with non-ischemic diabetic wounds, including: delayed healing, exorbitant wound inflammatory response, excessive and prolonged ROS production and excessive production of MMPs. Our study suggested that HFD feeding combined with STZ injection could induce type 2 diabetes in rat. Our ischemic diabetic wound model is suitable for the investigation of human diabetic related wound repair; especically for diabetic chronic wounds.

  11. 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.

  12. Tanshinone IIA attenuates the cerebral ischemic injury-induced increase in levels of GFAP and of caspases-3 and -8.

    Science.gov (United States)

    Zhou, L; Bondy, S C; Jian, L; Wen, P; Yang, F; Luo, H; Li, W; Zhou, Jun

    2015-03-12

    Tanshinone IIA (TSA) is a lipid soluble agent derived from the root of Salvia miltiorrhiza (Danshen). This plant is a traditional Chinese herb, which has been used widely in China especially for enhancing circulation. However mechanisms underlying its efficacy remain poorly understood. The present study was designed to illuminate events that may underlie the apparently neuroprotective effects of TSA following ischemic insult. Adult Sprague-Dawley rats were subjected to transient focal cerebral ischemia by use of a middle cerebral artery occlusion model. They were then randomly divided into a sham-operated control group, and cerebral ischemia/reperfusion groups receiving a two-hour occlusion. Further subsets of groups received the same durations of occlusion or were sham-operated but then received daily i.p. injections of high or low doses of TSA, for seven or 15days. Hematoxylin and eosin staining revealed lesions in the entorhinal cortex of both rats subject to ischemia and to a lesser extent to those receiving TSA after surgery. Levels of glial fibrillary acidic protein (GFAP), caspase-3 and caspase-8, were quantified by both immunohistochemistry and Western blotting. TSA treatment after middle cerebral artery occlusion, markedly reduced infarct size, and reduced the expression of caspase-3 and caspase-8. These changes were considered protective and were generally proportional to the dose of TSA used. These results suggest that TSA may effect neuroprotection by way of reduction of the extent of cell inflammation and death within affected regions. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  13. Paradigms and mechanisms of inhalational anesthetics mediated neuroprotection against cerebral ischemic stroke.

    Science.gov (United States)

    Wang, Hailian; Li, Peiying; Xu, Na; Zhu, Ling; Cai, Mengfei; Yu, Weifeng; Gao, Yanqin

    2016-01-01

    Cerebral ischemic stroke is a leading cause of serious long-term disability and cognitive dysfunction. The high mortality and disability of cerebral ischemic stroke is urging the health providers, including anesthesiologists and other perioperative professioners, to seek effective protective strategies, which are extremely limited, especially for those perioperative patients. Intriguingly, several commonly used inhalational anesthetics are recently suggested to possess neuroprotective effects against cerebral ischemia. This review introduces multiple paradigms of inhalational anesthetic treatments that have been investigated in the setting of cerebral ischemia, such as preconditioning, proconditioning and postconditioning with a variety of inhalational anesthetics. The pleiotropic mechanisms underlying these inhalational anesthetics-afforded neuroprotection against stroke are also discussed in detail, including the common pathways shared by most of the inhalational anesthetic paradigms, such as anti-excitotoxicity, anti-apoptosis and anti-inflammation. There are also distinct mechanisms involved in specific paradigms, such as preserving blood brain barrier integrity, regulating cerebral blood flow and catecholamine release. The ready availability of these inhalational anesthetics bedside and renders them a potentially translatable stroke therapy attracting great efforts for understanding of the underlying mechanisms.

  14. Paradigms and mechanisms of inhalational anesthetics mediated neuroprotection against cerebral ischemic stroke

    Directory of Open Access Journals (Sweden)

    Hailian Wang

    2016-01-01

    Full Text Available Cerebral ischemic stroke is a leading cause of serious long-term disability and cognitive dysfunction. The high mortality and disability of cerebral ischemic stroke is urging the health providers, including anesthesiologists and other perioperative professioners, to seek effective protective strategies, which are extremely limited, especially for those perioperative patients. Intriguingly, several commonly used inhalational anesthetics are recently suggested to possess neuroprotective effects against cerebral ischemia. This review introduces multiple paradigms of inhalational anesthetic treatments that have been investigated in the setting of cerebral ischemia, such as preconditioning, proconditioning and postconditioning with a variety of inhalational anesthetics. The pleiotropic mechanisms underlying these inhalational anesthetics-afforded neuroprotection against stroke are also discussed in detail, including the common pathways shared by most of the inhalational anesthetic paradigms, such as anti-excitotoxicity, anti-apoptosis and anti-inflammation. There are also distinct mechanisms involved in specific paradigms, such as preserving blood brain barrier integrity, regulating cerebral blood flow and catecholamine release. The ready availability of these inhalational anesthetics bedside and renders them a potentially translatable stroke therapy attracting great efforts for understanding of the underlying mechanisms.

  15. Cerebral blood flow in acute and chronic ischemic stroke using xenon-133 inhalation tomography

    DEFF Research Database (Denmark)

    Vorstrup, S; Paulson, O B; Lassen, N A

    1986-01-01

    . They showed in the acute phase (Days 1-3) very large low-flow areas, larger than the hypodense areas seen on the CT scan. The cerebral vasoconstrictor and vasodilator capacity was tested in the acute phase following aminophylline and acetazolamide, respectively. A preserved but reduced reactivity was seen......Serial measurements of cerebral blood flow (CBF) were performed in 12 patients with acute symptoms of ischemic cerebrovascular disease. CBF was measured by xenon-133 inhalation and single photon emission computer tomography. Six patients had severe strokes and large infarcts on the CT scan...

  16. 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.

  17. Cerebral ammonia metabolism in hyperammonemic rats

    Energy Technology Data Exchange (ETDEWEB)

    Cooper, A J; Mora, S N; Cruz, N F; Gelbard, A S

    1985-06-01

    The short-term metabolic fate of blood-borne (/sup 13/N)ammonia was determined in the brains of chronically (8- or 14-week portacaval-shunted rats) or acutely (urease-treated) hyperammonemic rats. Using a freeze-blowing technique it was shown that the overwhelming route for metabolism of blood-borne (/sup 13/N)ammonia in normal, chronically hyperammonemic and acutely hyperammonemic rat brain was incorporation into glutamine (amide). However, the rate of turnover of (/sup 13/N)ammonia to L-(amide-/sup 13/N)glutamine was slower in the hyperammonemic rat brain than in the normal rat brain. The activities of several enzymes involved in cerebral ammonia and glutamate metabolism were also measured in the brains of 14-week portacaval-shunted rats. The rat brain appears to have little capacity to adapt to chronic hyperammonemia because there were no differences in activity compared with those of weight-matched controls for the following brain enzymes involved in glutamate/ammonia metabolism: glutamine synthetase, glutamate dehydrogenase, aspartate aminotransferase, glutamine transaminase, glutaminase, and glutamate decarboxylase. The present findings are discussed in the context of the known deleterious effects on the CNS of high ammonia levels in a variety of diseases.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  19. 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.

  20. Point application with Angong Niuhuang sticker protects hippocampal and cortical neurons in rats with cerebral ischemia

    Directory of Open Access Journals (Sweden)

    Dong-shu Zhang

    2015-01-01

    Full Text Available Angong Niuhuang pill, a Chinese materia medica preparation, can improve neurological functions after acute ischemic stroke. Because of its inconvenient application and toxic components (Cinnabaris and Realgar, we used transdermal enhancers to deliver Angong Niuhuang pill by modern technology, which expanded the safe dose range and clinical indications. In this study, Angong Niuhuang stickers administered at different point application doses (1.35, 2.7, and 5.4 g/kg were administered to the Dazhui (DU14, Qihai (RN6 and Mingmen (DU4 of rats with chronic cerebral ischemia, for 4 weeks. The Morris water maze was used to determine the learning and memory ability of rats. Hematoxylin-eosin staining and Nissl staining were used to observe neuronal damage of the cortex and hippocampal CA1 region in rats with chronic cerebral ischemia. The middle- and high-dose point application of Angong Niuhuang stickers attenuated neuronal damage in the cortex and hippocampal CA1 region, and improved the memory of rats with chronic cerebral ischemia with an efficacy similar to interventions by electroacupuncture at Dazhui (DU14, Qihai (RN6 and Mingmen (DU4. Our experimental findings indicate that point application with Angong Niuhuang stickers can improve cognitive function after chronic cerebral ischemia in rats and is neuroprotective with an equivalent efficacy to acupuncture.

  1. Feasibility of arterial blood bypass using microcatheter in intraarterial thrombolysis for acute cerebral ischemic stroke

    International Nuclear Information System (INIS)

    Wang Wei; Li Cheng; Liu Zhensheng; Zhang Xinjiang; Zhou Longjiang; Yin Haiyan

    2010-01-01

    Objective: To assess the feasibility of arterial blood bypass using microcatheter in intraarterial thrombolysis for acute cerebral ischemic stroke. Methods: Six patients with acute cerebral infarction within 6 hours underwent intraarterial thrombolysis, in which arterial blood bypass was used. A 2.3 F microcatheter was advanced through the clot and two milliliters of contrast was injected beyond the clot that remained stagnant in the major branches. At this point, 20 ml of oxygenated blood from femoral artery was injected for 2 minutes through the microcatheter past the occluding clot. Then, conventional intraarterial thrombolysis, including fibrinolytic agents infusion and mechanical disruption, was performed. Intraarterial thrombolysis and oxygenated blood infusion alternated every 30 minutes. Results: Every patient received arterial blood bypass with average three times (from 1 to 5 times) in the process of the intraarterial thrombolysis, which cost (8.0 ± 3.2) min. Recanalization was achieved in all 6 patients, but minor subarachnoid hemorrhage developed in one patient. All the patients got favorable clinical outcome. The life conditions is excellent in 4 cases and good in 2 cases. Conclusions: Arterial blood bypass using microcatheter in intraarterial thrombolysis for acute cerebral ischemic stroke might be feasible, which did not interfere with conventional intraarterial thrombolysis and prolong the operation time significantly but could protect ischemic penumbra. (authors)

  2. Electroacupuncture preconditioning reduces cerebral ischemic injury via BDNF and SDF-1α in mice

    Directory of Open Access Journals (Sweden)

    Kim Ji Hyun

    2013-01-01

    Full Text Available Abstract Background This study was designed to determine if electroacupuncture (EA preconditioning improves tissue outcome and functional outcome following experimentally induced cerebral ischemia in mice. In addition, we investigated whether the expression of brain-derived neurotrophic factor (BDNF and stromal cell derived factor-1α (SDF-1α and infarct volume were related with improvement in neurological and motor function by interventions in this study. Methods After treatment with EA at the acupoints ‘Baihui (GV20’ and ‘Dazhui (GV14’ for 20 min, BDNF was assessed in the cortical tissues based on Western blot and the SDF-1α and vascular endothelial growth factor (VEGF levels in the plasma determined by ELISA. To assess the protective effects of EA against ischemic injury, the mice received once a day 20 min EA preconditioning for three days prior to the ischemic event. Focal cerebral ischemia was then induced by photothrombotic cortical ischemia. Infarct volumes, neurobehavioral deficit and motor deficit were evaluated 24 h after focal cerebral ischemia. Results The expression of BDNF protein increased significantly from 6 h, reaching a plateau at 12 h after the end of EA treatment in the cerebral cortex. Furthermore, SDF-1α, not VEGF, increased singnificantly from 12 h to 48 h after EA stimulation in the plasma. Moreover, EA preconditioning reduced the infarct volume by 43.5% when compared to control mice at 24 h after photothrombotic cortical ischemia. Consistent with a smaller infarct size, EA preconditioning showed prominent improvement of neurological function and motor function such as vestibule-motor function, sensori-motor function and asymmetric forelimb use. The expression of BDNF colocalized within neurons and SDF-1α colocalized within the cerebral vascular endothelium was observed throughout the ischemic cortex by EA. Conclusions Pretreatment with EA increased the production of BDNF and SDF-1α, which elicited

  3. Gender and post-ischemic recovery of hypertrophied rat hearts

    Directory of Open Access Journals (Sweden)

    Popov Kirill M

    2006-03-01

    Full Text Available Abstract Background Gender influences the cardiac response to prolonged increases in workload, with differences at structural, functional, and molecular levels. However, it is unknown if post-ischemic function or metabolism of female hypertrophied hearts differ from male hypertrophied hearts. Thus, we tested the hypothesis that gender influences post-ischemic function of pressure-overload hypertrophied hearts and determined if the effect of gender on post-ischemic outcome could be explained by differences in metabolism, especially the catabolic fate of glucose. Methods Function and metabolism of isolated working hearts from sham-operated and aortic-constricted male and female Sprague-Dawley rats before and after 20 min of no-flow ischemia (N = 17 to 27 per group were compared. Parallel series of hearts were perfused with Krebs-Henseleit solution containing 5.5 mM [5-3H/U-14C]-glucose, 1.2 mM [1-14C]-palmitate, 0.5 mM [U-14C]-lactate, and 100 mU/L insulin to measure glycolysis and glucose oxidation in one series and oxidation of palmitate and lactate in the second. Statistical analysis was performed using two-way analysis of variance. The sequential rejective Bonferroni procedure was used to correct for multiple comparisons and tests. Results Female gender negatively influenced post-ischemic function of non-hypertrophied hearts, but did not significantly influence function of hypertrophied hearts after ischemia such that mass-corrected hypertrophied heart function did not differ between genders. Before ischemia, glycolysis was accelerated in hypertrophied hearts, but to a greater extent in males, and did not differ between male and female non-hypertrophied hearts. Glycolysis fell in all groups after ischemia, except in non-hypertrophied female hearts, with the reduction in glycolysis after ischemia being greatest in males. Post-ischemic glycolytic rates were, therefore, similarly accelerated in hypertrophied male and female hearts and higher in

  4. Use of hypoxia imaging agent 99mTc-HL91 in rat cerebral ischemia models

    International Nuclear Information System (INIS)

    Zhou Ying; Qu Wanying; Li Meng; Chen Fang; Yao Zhiming; Zhu Ming; Zhu Lin

    1999-01-01

    Objective: To explore the possibility of diagnosis for cerebrovascular disease by a novel synthetic hypoxia agent 99m Tc-HL91 used in rat cerebral ischemia models. Methods: Pharmacological experiments of 99m Tc-HL91 were carried out including common properties, radiochemical purity, stability in vitro, anomalous toxicity test and biodistribution in mice. Fifteen cerebral ischemic rat models were established and received 99m Tc-HL91 scintigraphy. Results: 1) HL91 kits were labelled with 99m Tc easily and showed high radiochemical purity and stability. 2) Rapid clearance in blood, heart and lungs and high activity in liver, kidneys and intestines were observed. Relatively low uptake in brain was identified. 3) The radioactivity in ischemic brain tissue increased significantly at 4h postinjection in both rat images and isolated brain images. 4) The radioactivity ratios of lesion to normal brain tissue by drawing ROIs in isolated brain planar images were 0.98 +- 0.06, 0.99 +- 0.05, 1.29 +- 0.03, 1.56 +- 0.14 and 1.66 +- 0.06 at 1,2,4,8 and 12 h postinjection, respectively. There were significant differences among all groups except for 1 h and 2 h, 8 h and 12 h postinjection (P 99m Tc-HL91 in the hypoxic, ischemic brain tissue have been proved. It is appropriate to perform imaging at 4 h postinjection

  5. Attenuation of Cerebral Ischemic Injury in Smad1 Deficient Mice.

    Directory of Open Access Journals (Sweden)

    Jamie K Wong

    Full Text Available Stroke results in brain tissue damage from ischemia and oxidative stress. Molecular regulators of the protective versus deleterious cellular responses after cerebral ischemia remain to be identified. Here, we show that deletion of Smad1, a conserved transcription factor that mediates canonical bone morphogenetic protein (BMP signaling, results in neuroprotection in an ischemia-reperfusion (I/R stroke model. Uninjured mice with conditional deletion of Smad1 in the CNS (Smad1 cKO displayed upregulation of the reactive astrocyte marker GFAP and hypertrophic morphological changes in astrocytes compared to littermate controls. Additionally, cultured Smad1(-/- astrocytes exhibited an enhanced antioxidant capacity. When subjected to I/R injury by transient middle cerebral artery occlusion (tMCAO, Smad1 cKO mice showed enhanced neuronal survival and improved neurological recovery at 7 days post-stroke. This neuroprotective phenotype is associated with attenuated reactive astrocytosis and neuroinflammation, along with reductions in oxidative stress, p53 induction, and apoptosis. Our data suggest that Smad1-mediated signaling pathway is involved in stroke pathophysiology and may present a new potential target for stroke therapy.

  6. Ceftriaxone attenuates hypoxic-ischemic brain injury in neonatal rats

    Directory of Open Access Journals (Sweden)

    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.

  7. Radial extracorporeal shock wave therapy improves cerebral blood flow and neurological function in a rat model of cerebral ischemia.

    Science.gov (United States)

    Kang, Nan; Zhang, Jing; Yu, Xiaotong; Ma, Yuewen

    2017-01-01

    We performed middle cerebral artery occlusion (MCAO) in rats to investigate the effect and some of the underlying mechanisms of radial extracorporeal shock wave therapy (rESWT) in cerebral ischemia rats. We measured neurological function and cerebral blood flow (CBF) using a full-field laser perfusion imager and brain infarct volume on days 3, 12, and 30. Immunofluorescence, western blot, and real-time polymerase chain reaction (PCR) techniques were used to detect the expression of vascular endothelial growth factor (VEGF), neuron-specific enolase (NSE), nestin, Wnt3a, and β-catenin in the ischemic hemisphere. The dose of rESWT used on the head revealed remarkable advantages over sham rESWT, as demonstrated by improved neurological function scores, increased CBF, and reduced brain infarct volume. Furthermore, applying rESWT to the head and limbs enhanced short-term neurological function. Our results confirmed that rESWT can induce VEGF expression over an extended period with a profound effect, which may be the primary reason for CBF recovery. High NSE and nestin expression levels suggest that rESWT enhanced the number of neurons and neural stem cells (NSCs). Wnt3a and β-catenin expression were up-regulated in the ischemic hemisphere, indicating that rESWT promoted NSC proliferation and differentiation via the Wnt/β-catenin pathway. Overall, our findings suggest that an appropriate rESWT dose delivered to the head of rats helps restore neurological function and CBF, and additional application of rESWT to the limbs is more effective than treating the head alone.

  8. Imaging findings and cerebral perfusion in arterial ischemic stroke due to transient cerebral arteriopathy in children; Achados de imagem e perfusao arterial cerebral em acidente vascular cerebral isquemico devido a arteriopatia transitoria em crianca

    Energy Technology Data Exchange (ETDEWEB)

    Barbosa Junior, Alcino Alves, E-mail: alcinojr@uol.com.br [Departamento de Diagnostico por Imagem, Hospital Israelita Albert Einstein - HIAE, Sao Paulo, SP (Brazil); Ellovitch, Saada Resende de Souza [Neuropediatria, Hospital Israelita Albert Einstein - HIAE, Sao Paulo, SP (Brazil); Pincerato, Rita de Cassia Maciel [Hospital Samaritano, Sao Paulo, SP (Brazil)

    2012-04-15

    We report the case of a 4-year-old female child who developed an arterial ischemic stroke in the left middle cerebral artery territory, due to a proximal stenosis of the supraclinoid internal carotid artery, most probably related to transient cerebral arteriopathy of childhood. Computed tomography scan, magnetic resonance imaging, perfusion magnetic resonance and magnetic resonance angiography are presented, as well as follow-up by magnetic resonance and magnetic resonance angiography exams. Changes in cerebral perfusion and diffusion-perfusion mismatch call attention. As far as we know, this is the first report of magnetic resonance perfusion findings in transient cerebral arteriopathy. (author)

  9. Wavelet coherence analysis of dynamic cerebral autoregulation in neonatal hypoxic–ischemic encephalopathy

    Directory of Open Access Journals (Sweden)

    Fenghua Tian

    2016-01-01

    Full Text Available Cerebral autoregulation represents the physiological mechanisms that keep brain perfusion relatively constant in the face of changes in blood pressure and thus plays an essential role in normal brain function. This study assessed cerebral autoregulation in nine newborns with moderate-to-severe hypoxic–ischemic encephalopathy (HIE. These neonates received hypothermic therapy during the first 72 h of life while mean arterial pressure (MAP and cerebral tissue oxygenation saturation (SctO2 were continuously recorded. Wavelet coherence analysis, which is a time-frequency domain approach, was used to characterize the dynamic relationship between spontaneous oscillations in MAP and SctO2. Wavelet-based metrics of phase, coherence and gain were derived for quantitative evaluation of cerebral autoregulation. We found cerebral autoregulation in neonates with HIE was time-scale-dependent in nature. Specifically, the spontaneous changes in MAP and SctO2 had in-phase coherence at time scales of less than 80 min (<0.0002 Hz in frequency, whereas they showed anti-phase coherence at time scales of around 2.5 h (~0.0001 Hz in frequency. Both the in-phase and anti-phase coherence appeared to be related to worse clinical outcomes. These findings suggest the potential clinical use of wavelet coherence analysis to assess dynamic cerebral autoregulation in neonatal HIE during hypothermia.

  10. Neuroprotective Effect of the Ginsenoside Rg1 on Cerebral Ischemic Injury In Vivo and In Vitro Is Mediated by PPARγ-Regulated Antioxidative and Anti-Inflammatory Pathways

    Directory of Open Access Journals (Sweden)

    Yang Li

    2017-01-01

    Full Text Available The ginsenoside Rg1 exerts a neuroprotective effect during cerebral ischemia/reperfusion injury. Rg1 has been previously reported to improve PPARγ expression and signaling, consequently enhancing its regulatory processes. Due to PPARγ’s role in the suppression of oxidative stress and inflammation, Rg1’s PPARγ-normalizing capacity may play a role in the observed neuroprotective action of Rg1 during ischemic brain injury. We utilized a middle cerebral artery ischemia/reperfusion injury model in rats in addition to an oxygen glucose deprivation model in cortical neurons to elucidate the mechanisms underlying the neuroprotective effects of Rg1. We found that Rg1 significantly increased PPARγ expression and reduced multiple indicators of oxidative stress and inflammation. Ultimately, Rg1 treatment improved neurological function and diminished brain edema, indicating that Rg1 may exert its neuroprotective action on cerebral ischemia/reperfusion injury through the activation of PPARγ signaling. In addition, the present findings suggested that Rg1 was a potent PPARγ agonist in that it upregulated PPARγ expression and was inhibited by GW9662, a selective PPARγ antagonist. These findings expand our previous understanding of the molecular basis of the therapeutic action of Rg1 in cerebral ischemic injury, laying the ground work for expanded study and clinical optimization of the compound.

  11. Clinical significance of cerebral microbleeds on MRI : A comprehensive meta-analysis of risk of intracerebral hemorrhage, ischemic stroke, mortality, and dementia in cohort studies (vI)

    NARCIS (Netherlands)

    A. Charidimou (Andreas); S. Shams (Sara); J.R. Romero (Jose Rafael); J. Ding (Jie); R. Veltkamp (Roland); S. Horstmann (Solveig); G. Eiriksdottir (Gudny); M.A. van Buchem (Mark); V. Gudnason (Vilmundur); J.J. Himali (Jayandra); M.E. Gurol (Edip); A. Viswanathan (Anand); T. Imaizumi (Toshio); M.W. Vernooij (Meike); S. Seshadri (Sudha); S.M. Greenberg (Steven); O.R. Benavente (Oscar); L.J. Launer (Lenore); A. Shoamanesh (Ashkan)

    2018-01-01

    markdownabstract__Background:__ Cerebral microbleeds can confer a high risk of intracerebral hemorrhage, ischemic stroke, death and dementia, but estimated risks remain imprecise and often conflicting. We investigated the association between cerebral microbleeds presence and these outcomes in a

  12. Protective Effect of Ischemic Postconditioning against Ischemia Reperfusion-Induced Myocardium Oxidative Injury in IR Rats

    Directory of Open Access Journals (Sweden)

    Jiangwei Ma

    2012-03-01

    Full Text Available Brief episodes of myocardial ischemia-reperfusion (IR employed during reperfusion after a prolonged ischemic insult may attenuate the total ischemia-reperfusion injury. This phenomenon has been termed ischemic postconditioning. In the present study, we studied the possible effect of ischemic postconditioning on an ischemic reperfusion (IR-induced myocardium oxidative injury in rat model. Results showed that ischemic postconditioning could improve arrhythmia cordis, reduce myocardium infarction and serum creatin kinase (CK, lactate dehydrogenase (LDH and aspartate transaminase (AST activities in IR rats. In addition, ischemic postconditioning could still decrease myocardium malondialdehyde (MDA level, and increased myocardium Na+-K+-ATPase, Ca2+-Mg2+-ATPase, superoxide dismutase (SOD, catalase (CAT, glutathione peroxidase (GSH-Px and glutathione reductase (GR activities. It can be concluded that ischemic postconditioning possesses strong protective effects against ischemia reperfusion-induced myocardium oxidative injury in IR rats.

  13. Superselective intra-arterial fibrinolysis for acute cerebral ischemic infarct : usefulness of diffusion weighted MR imaging

    International Nuclear Information System (INIS)

    Byun, Woo Mok; Lee, Se Jin; Kim, Yong Sun; Han, Gun Soo; Bae, Won Kyong

    1999-01-01

    To evaluate the efficacy of superselective intra-arterial fibrinolysis for acute cerebral stroke and the usefulness of pre-and postfibrinolysis diffusion-weighted MRI (DWI). In 41 patients with acute ischemic stroke whose treatment involved intra-arterial fibrinolysis, the occlusion site, degree of recanalization, and clinical results were compared. In 12 patients, diffusion weighted MRI was performed before fibrinolysis, and eight of these also underwent diffusion-weighted MRI after fibrinolysis. Using diffusion-weighted MRI, neurological outcomes were compared with signal intensity ratio (SIR, or the average signal intensity within the region of interest divided by that in the contralateral, nonischemic, homologous region). Twenty patients showed complete recanalization, nine partial recanalization, and in twelve there was no recanalization. Fourteen patients (34%) improved neurologically. No relationship existed between occlusion sites, degree of recanalization, and clinical outcome. Among 12 patients who underwent DWI before fibrinolysis, complete recanalization was noted in eight. Neurological improvement was seen in four patients with low SIR( 1.7), neurological outcome was poor despite complete recanalization. Although superselective intra-arterial fibrinolysis for acute cerebral stroke is a good therapeutic method for recanalization, the clinical outcome can be disappointing. We therefore suggest that in cases of acute cerebral ischemic infaret, SIR-as seen on DWI-might be useful for predicting the benefits of recanalization. In such cases, further investigation of the use of DWI prior to fibrinolysis is therefore needed

  14. 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

  15. 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.

  16. Real-time ischemic condition monitoring in normoglycemic and hyperglycemic rats

    International Nuclear Information System (INIS)

    Choi, Samjin; Kang, Sung Wook; Lee, Gi-Ja; Chae, Su-Jin; Park, Hun-Kuk; Choi, Seok Keun; Chung, Joo-Ho

    2010-01-01

    An increase in excitotoxic amino acid glutamate (GLU) concentration associated with neuronal damage might be the cause of the ischemic damage observed in stroke patients suffering from hyperglycemia. However, the effect has never been investigated by real-time in vivo monitoring. Therefore, this study examined the effects of the functional responses of ischemia-evoked electroencephalography (EEG), cerebral blood flow (%CBF) and ΔGLU in hyperglycemia through real-time in vivo monitoring. Five Sprague-Dawley rats were treated with streptozocin (hyperglycemia) and five normal rats were used as the controls. Global ischemia was induced using an 11-vessel occlusion model. The experimental protocols consisting of 10 min pre-ischemic, 10 min ischemic and 40 min reperfusion periods were applied to both groups. Under these conditions, the responses of the ischemia-evoked EEG, %CBF and ΔGLU were monitored in real time. The EEG showed flat patterns during ischemia followed by poor recovery during reperfusion. The peak reperfusion %CBF was decreased significantly in the hyperglycemia group compared to the control group (p < 0.05, n = 5). The extracellular ΔGLU releases increased significantly during ischemia (p < 0.0001, n = 5) and reperfusion (p < 0.001, n = 5) in the hyperglycemia group compared to the control group. The decrease in reperfusion %CBF during short-term hyperglycemia might be related to the increased plasma osmolality, decreased adenosine levels and swollen endothelial cells with decreased vascular luminal diameters under hyperglycemic conditions. And, the increase in ΔGLU during short-term hyperglycemia might be related to the neurotoxic effects of the high extracellular concentrations of ΔGLU and the inhibition of GLU uptake

  17. Carvacrol Exerts Neuroprotective Effects Via Suppression of the Inflammatory Response in Middle Cerebral Artery Occlusion Rats.

    Science.gov (United States)

    Li, Zhenlan; Hua, Cong; Pan, Xiaoqiang; Fu, Xijia; Wu, Wei

    2016-08-01

    Increasing evidence demonstrates that inflammation plays an important role in cerebral ischemia. Carvacrol, a monoterpenic phenol, is naturally occurring in various plants belonging to the family Lamiaceae and exerts protective effects in a mice model of focal cerebral ischemia/reperfusion injury by reducing infarct volume and decreasing the expression of cleaved caspase-3. However, the anti-inflammatory mechanisms by which carvacrol protect the brain have yet to be fully elucidated. We investigated the effects of carvacrol on inflammatory reaction and inflammatory mediators in middle cerebral artery occlusion rats. The results of the present study showed that carvacrol inhibited the levels of inflammatory cytokines and myeloperoxidase (MPO) activity, as well as the expression of iNOS and COX-2. It also increased SOD activity and decreased MDA level in ischemic cortical tissues. In addition, carvacrol treatment suppressed the ischemia/reperfusion-induced increase in the protein expression of nuclear NF-kB p65. In conclusion, we have shown that carvacrol inhibits the inflammatory response via inhibition of the NF-kB signaling pathway in a rat model of focal cerebral ischemia. Therefore, carvacrol may be a potential therapeutic agent for the treatment of cerebral ischemia injury.

  18. Numerous Fusiform and Saccular Cerebral Aneurysms in Central Nervous System Lupus Presenting with Ischemic Stroke.

    Science.gov (United States)

    Majidi, Shahram; Leon Guerrero, Christopher R; Gandhy, Shreya; Burger, Kathleen M; Sigounas, Dimitri

    2017-07-01

    Central nervous system (CNS) involvement occurs in up to 50% of patients with systemic lupus erythematosus (SLE). Cerebral aneurysm formation is a rare complication of CNS lupus. The majority of these patients present with subarachnoid hemorrhage. We report a patient with an active SLE flare who presented with a recurrent ischemic stroke and was found to have numerous unruptured fusiform and saccular aneurysms in multiple vascular territories. He was treated with high-dose steroid and rituximab along with aspirin and blood pressure control for stroke prevention. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  19. Nicardipine reduces calcium accumulation and electrolyte derangements in regional cerebral ischemia in rats

    International Nuclear Information System (INIS)

    Hadani, M.; Young, W.; Flamm, E.S.

    1988-01-01

    We studied the effects of the calcium channel blocker nicardipine on regional tissue Ca 2+ , Na + , K + , and water shifts in the brains of seven Sprague-Dawley rats after permanent occlusions of the middle cerebral artery. We also assessed the entry of [ 14 C]nicardipine into the brains of five rats; the highest concentrations of [ 14 C]nicardipine were in the infarcted area. Nicardipine treatment significantly reduced Ca 2+ accumulation in the middle cerebral artery territory by 60% compared with six untreated rats 6 hours after arterial occlusion. Eight 125-micrograms/kg boluses of nicardipine given every 30 minutes starting 5 minutes after arterial occlusion also significantly reduced the Na + and K + shifts in the middle cerebral artery territory by 40% and 50%, respectively, 6 hours after arterial occlusion. Nicardipine appears to reduce Ca 2+ accumulation more than it reduces Na + and water accumulation and K + loss. Our results suggest that a calcium channel blocker can protect brain tissues in a model of focal cerebral infarction by directly reducing Ca 2+ entry into ischemic cells

  20. Cerebral blood flow in acute and chronic ischemic stroke using xenon-133 inhalation tomography

    DEFF Research Database (Denmark)

    Vorstrup, S; Paulson, O B; Lassen, N A

    1986-01-01

    Serial measurements of cerebral blood flow (CBF) were performed in 12 patients with acute symptoms of ischemic cerebrovascular disease. CBF was measured by xenon-133 inhalation and single photon emission computer tomography. Six patients had severe strokes and large infarcts on the CT scan....... They showed in the acute phase (Days 1-3) very large low-flow areas, larger than the hypodense areas seen on the CT scan. The cerebral vasoconstrictor and vasodilator capacity was tested in the acute phase following aminophylline and acetazolamide, respectively. A preserved but reduced reactivity was seen...... had occlusion of the relevant internal carotid artery. In all 6 patients, CBF studies at 2 and 6 months resembled the acute phase, showing large areas with reduced flow. At the 6 months follow-up, the vasodilatory stress test was repeated, and all but one showed a preserved but reduced vasoreactivity...

  1. Edaravone, a free radical scavenger, attenuates cerebral infarction and hemorrhagic infarction in rats with hyperglycemia.

    Science.gov (United States)

    Okamura, Koichi; Tsubokawa, Tamiji; Johshita, Hiroo; Miyazaki, Hiroshi; Shiokawa, Yoshiaki

    2014-01-01

    Thrombolysis due to acute ischemic stroke is associated with the risk of hemorrhagic infarction, especially after reperfusion. Recent experimental studies suggest that the main mechanism contributing to hemorrhagic infarction is oxidative stress caused by disruption of the blood-brain barrier. Edaravone, a free radical scavenger, decreases oxidative stress, thereby preventing hemorrhagic infarction during ischemia and reperfusion. In this study, we investigated the effects of edaravone on hemorrhagic infarction in a rat model of hemorrhagic transformation. We used a previously established hemorrhagic transformation model of rats with hyperglycemia. Hyperglycemia was induced by intraperitoneal injection of glucose to all rats (n  =  20). The rats with hyperglycemia showed a high incidence of hemorrhagic infarction. Middle cerebral artery occlusion (MCAO) for 1.5 hours followed by reperfusion for 24 hours was performed in edaravone-treated rats (n  =  10) and control rats (n  =  10). Upon completion of reperfusion, both groups were evaluated for infarct size and hemorrhage volume and the results obtained were compared. Edaravone significantly decreased infarct volume, with the average infarct volume in the edaravone-treated rats (227.6 mm(3)) being significantly lower than that in the control rats (264.0 mm(3)). Edaravone treatment also decreased the postischemic hemorrhage volumes (53.4 mm(3) in edaravone-treated rats vs 176.4 mm(3) in controls). In addition, the ratio of hemorrhage volume to infarct volume was lower in the edaravone-treated rats (23.5%) than in the untreated rats (63.2%). Edaravone attenuates cerebral infarction and hemorrhagic infarction in rats with hyperglycemia.

  2. Electroacupuncture acutely improves cerebral blood flow and attenuates moderate ischemic injury via an endothelial mechanism in mice.

    Directory of Open Access Journals (Sweden)

    Ji Hyun Kim

    Full Text Available Electroacupuncture (EA is a novel therapy based on traditional acupuncture combined with modern eletrotherapy that is currently being investigated as a treatment for acute ischemic stroke. Here, we studied whether acute EA stimulation improves tissue and functional outcome following experimentally induced cerebral ischemia in mice. We hypothesized that endothelial nitric oxide synthase (eNOS-mediated perfusion augmentation was related to the beneficial effects of EA by interventions in acute ischemic injury. EA stimulation at Baihui (GV20 and Dazhui (GV14 increased cerebral perfusion in the cerebral cortex, which was suppressed in eNOS KO, but there was no mean arterial blood pressure (MABP response. The increased perfusion elicited by EA were completely abolished by a muscarinic acetylcholine receptor (mAChR blocker (atropine, but not a β-adrenergic receptor blocker (propranolol, an α-adrenergic receptor blocker (phentolamine, or a nicotinic acetylcholine receptor (nAChR blocker (mecamylamine. In addition, EA increased acetylcholine (ACh release and mAChR M3 expression in the cerebral cortex. Acute EA stimulation after occlusion significantly reduced infarct volume by 34.5% when compared to a control group of mice at 24 h after 60 min-middle cerebral artery occlusion (MCAO (moderate ischemic injury, but not 90-min MCAO (severe ischemic injury. Furthermore, the impact of EA on moderate ischemic injury was totally abolished in eNOS KO. Consistent with a smaller infarct size, acute EA stimulation led to prominent improvement of neurological function and vestibule-motor function. Our results suggest that acute EA stimulation after moderate focal cerebral ischemia, but not severe ischemia improves tissue and functional recovery and ACh/eNOS-mediated perfusion augmentation might be related to these beneficial effects of EA by interventions in acute ischemic injury.

  3. 99mTc-HMPAO Regional Cerebral Blood Flow SPECT in Transient Ischemic Attacks

    International Nuclear Information System (INIS)

    Ahn, Myeong Im; Park, Young Ha; Lee, Sung Yong; Chung, Soo Kyo; Kim, Jong Woo; Bahk, Yong Whee

    1989-01-01

    Transient ischemic attacks (TJAs) is a syndrome resulting from brain ischemia lasting less than 24 hours. The mechanisms of TIAs may be similar to those of cerebral embolism and thrombosis, and thus TIAs may be followed by cerebral infarction. Despite the availability of CT scanning, the diagnosis and management of TIAs continue to be difficult. Recently SPECT has been advocated as a diagnostic imaging modality. We performed 99m Tc-HMPAO regional cerebral blood flow (rCRF) SPECT in 24 patients with the clinical diagnosis of TIAs to assess its ability to detect early changes of rCBF, and determine the diagnostic value. Ten men and fourteen women with an average of 51 years (range; 27-74 years) were included. All but 8 patients had normal brain CT prior to SPECT. The two patients had moderate degree of brain atrophy and the 6 patients nonspecific calcifications. Eighteen of the 24 patients had abnormal 99m Tc-HMPAO rCBF SPECT. Fifteen had unilateral involvement and the other three had bilateral involvements. Seventy-five percents of the defects were found in the left cerebral hemisphere. According to the distribution of the lesions (total number: 34 lesions), fourteen were in the parietal, eight in the temporal, and the remainders were elsewhere. 99m Tc-HMPAO rCHF SPECT is sensitive in detecting rCRF abnormalities in patients with TIAs, and represent the most accurate diagnostic tool available in the diagnosis of TIAs

  4. Sulforaphane exerts neuroprotective effects via suppression of the inflammatory response in a rat model of focal cerebral ischemia.

    Science.gov (United States)

    Ma, Li-Li; Xing, Guo-Ping; Yu, Yin; Liang, Hui; Yu, Tian-Xia; Zheng, Wei-Hong; Lai, Tian-Bao

    2015-01-01

    Inflammatory damage plays an important role in cerebral ischemic pathogenesis and may represent a promising target for treatment. Sulforaphane exerts protective effects in a rat model of focal cerebral ischemia/reperfusion injury by alleviating brain edema. However, the possible mechanisms of sulforaphane after cerebral ischemia/reperfusion injury have not been fully elucidated. Therefore, in the present study, we investigated the effect of sulforaphane on inflammatory reaction and the potential molecular mechanisms in cerebral ischemia rats. We found that sulforaphane significantly attenuated the blood-brain barrier (BBB) disruption; decreased the levels of pro-inflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-1β; reduced the nitric oxide (NO) levels and inducible nitric oxide synthase (iNOS) activity; inhibited the expression of iNOS and cyclooxygenase-2 (COX-2). In addition, sulforaphane inhibits the expression of p-NF-κB p65 after focal cerebral ischemia-reperfusion injury. Taken together, our results suggest that sulforaphane suppresses the inflammatory response via inhibiting the NF-κB signaling pathway in a rat model of focal cerebral ischemia, and sulforaphane may be a potential therapeutic agent for the treatment of cerebral ischemia injury.

  5. (1)H NMR-based metabonomics revealed protective effect of Naodesheng bioactive extract on ischemic stroke rats.

    Science.gov (United States)

    Luo, Lan; Zhen, Lifeng; Xu, Yatao; Yang, Yongxia; Feng, Suxiang; Wang, Shumei; Liang, Shengwang

    2016-06-20

    Stroke is a leading cause of death and disability in the world. However, current therapies are limited. Naodesheng, a widely used traditional Chinese medicine prescription, has shown a good clinical curative effect on ischemic stroke. Also, Naodesheng has been suggested to have neuroprotective effect on focal cerebral ischemia rats, but the underlying molecular mechanism remains unclear. The present study was designed to evaluate the effect of Naodesheng bioactive extract on the metabolic changes in brain tissue, plasma and urine induced by cerebral ischemia perfusion injury, and explore the possible metabolic mechanisms by using a (1)H NMR-based metabonomics approach. A middle cerebral artery occlusion rat model was established and confirmed by the experiments of neurobehavioral abnormality evaluation, brain tissue TTC staining and pathological examination. The metabolic changes in brain tissue, plasma and urine were then assessed by a (1)H NMR technique combined with multivariate statistical analysis method. These NMR data showed that cerebral ischemia reperfusion induced great metabolic disorders in brain tissue, plasma and urine metabolisms. However, Naodesheng bioactive extract could reverse most of the imbalanced metabolites. Meanwhile, it was found that both the medium and high dosages of Naodesheng bioactive extract were more effective on the metabolic changes than the low dosage, consistent with histopathological assessments. These results revealed that Naodesheng had protective effect on ischemic stroke rats and the underlying mechanisms involved multiple metabolic pathways, including energy metabolism, amino acid metabolism, oxidative stress and inflammatory injury. The present study could provide evidence that metabonomics revealed its capacity to evaluate the holistic efficacy of traditional Chinese medicine and explore the underlying mechanisms. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. The Effect of Photoluminescence of Bioceramic Irradiation on Middle Cerebral Arterial Occlusion in Rats

    Directory of Open Access Journals (Sweden)

    Lei Zhang

    2016-01-01

    Full Text Available The purpose of this study is to determine the possible effect of photoluminescence of bioceramic (PLB on ischemic cerebral infarction (stroke, by using an animal model of transient middle cerebral artery occlusion (MCAO. Sprague-Dawley rats were used to induce MCAO to block the origin of the left MCAO; three months later, the positive chronic stroke rats were selected by running tunnel maze; the MCAO rats with significant chronic stroke and neurological defects were used for treadmill experiments with varying speed settings to test their capability for restoration after muscular fatigue under conditions of with and without PLB irradiation. As a result, PLB irradiation could improve exercise completion rate and average running speed during slow and fast treadmill settings. After PLB irradiation, the selected MCAO rats successfully completed all the second-round treadmill exercises at the maximum speed setting, and they had better restoration from muscular fatigue. An in vitro cell study on astrocytes of rats by bioceramic irradiation further demonstrated increased intracellular nitric oxide. To explain these results, we suggest that cortical brain stimulation of microcirculation and enhancement of peripheral muscular activity are the main causes of the improved exercise performance in MCAO rats by PLB.

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

    Directory of Open Access Journals (Sweden)

    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

  8. Progressive Ischemic Stroke due to Thyroid Storm-Associated Cerebral Venous Thrombosis

    Science.gov (United States)

    Tanabe, Natsumi; Hiraoka, Eiji; Hoshino, Masataka; Deshpande, Gautam A.; Sawada, Kana; Norisue, Yasuhiro; Tsukuda, Jumpei; Suzuki, Toshihiko

    2017-01-01

    Patient: Female, 49 Final Diagnosis: Cerebral venous thrombosis Symptoms: Altered mental state • weakness in limbs Medication: — Clinical Procedure: — Specialty: Endocrinology and Metabolic Objective: Rare co-existance of disease or pathology Background: Cerebral venous thrombosis (CVT) is a rare but fatal complication of hyperthyroidism that is induced by the hypercoagulable state of thyrotoxicosis. Although it is frequently difficult to diagnose CVT promptly, it is important to consider it in the differential diagnosis when a hyperthyroid patient presents with atypical neurologic symptoms. Care Report: A 49-year-old Japanese female with unremarkable medical history came in with thyroid storm and multiple progressive ischemic stroke identified at another hospital. Treatment for thyroid storm with beta-blocker, glucocorticoid, and potassium iodide-iodine was started and MR venography was performed on hospital day 3 for further evaluation of her progressive ischemic stroke. The MRI showed CVT, and anticoagulation therapy, in addition to the anti-thyroid agents, was initiated. The patient’s thyroid function was successfully stabilized by hospital day 10 and further progression of CVT was prevented. Conclusions: Physicians should consider CVT when a patient presents with atypical course of stroke or with atypical MRI findings such as high intensity area in apparent diffusion coefficient (ADC) mapping. Not only is an early diagnosis and initiation of anticoagulation important, but identifying and treating the underlying disease is essential to avoid the progression of CVT. PMID:28228636

  9. Lower Serum Caveolin-1 Is Associated with Cerebral Microbleeds in Patients with Acute Ischemic Stroke

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    Jun Zhang

    2016-01-01

    Full Text Available Caveolin-1 (Cav-1 plays pivotal roles in the endothelial damage following stroke. The present study aimed to investigate whether serum Cav-1 level is associated with the presence of cerebral small vessel disease (cSVD in patients with acute ischemic stroke. To this end, 156 patients were consecutively enrolled. Cranial magnetic resonance imaging was analyzed to determine the surrogates of cSVD, including cerebral microbleeds (CMBs, silent lacunar infarcts (SLIs, and white matter hyperintensities (WMHs. After adjusting for potential confounders, patients with low Cav-1 level had a higher risk of CMBs than patients with high Cav-1 level (OR: 4.05, 95% CI: 1.77–9.30. However, there was no relationship between Cav-1 and the presence of SLIs or WMHs. When CMBs were stratified by location and number, a similar association was found in patients with deep or infratentorial CMBs (OR: 4.04, 95% CI: 1.59–10.25 and with multiple CMBs (OR: 3.18, 95% CI: 1.16–8.72. These results suggest lower serum Cav-1 levels may be associated with CMBs, especially those that are multiple and located in deep brain or infratentorial structures, in patients with acute ischemic stroke. Cav-1 may be involved in the pathophysiology of CMBs, and may act as a potential target for treating cSVD.

  10. Progesterone induces neuroprotection following reperfusion-promoted mitochondrial dysfunction after focal cerebral ischemia in rats.

    Science.gov (United States)

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

    2017-06-01

    Organelle damage and increases in mitochondrial permeabilization are key events in the development of cerebral ischemic tissue injury because they cause both modifications in ATP turnover and cellular apoptosis/necrosis. Early restoration of blood flow and improvement of mitochondrial function might reverse the situation and help in recovery following an onset of stroke. Mitochondria and related bioenergetic processes can be effectively used as pharmacological targets. Progesterone (P4), one of the promising neurosteroids, has been found to be neuroprotective in various models of neurological diseases, through a number of mechanisms. This influenced us to investigate the possible role of P4 in the mitochondria-mediated neuroprotective mechanism in an ischemic stroke model of rat. In this study, we have shown the positive effect of P4 administration on behavioral deficits and mitochondrial health in an ischemic stroke injury model of transient middle cerebral artery occlusion (tMCAO). After induction of tMCAO, the rats received an initial intraperitoneal injection of P4 (8 mg/kg body weight) or vehicle at 1 h post-occlusion followed by subcutaneous injections at 6, 12 and 18 h. Behavioral assessment for functional deficits included grip strength, motor coordination and gait analysis. Findings revealed a significant improvement with P4 treatment in tMCAO animals. Staining of isolated brain slices from P4-treated rats with 2,3,5-triphenyltetrazolium chloride (TTC) showed a reduction in the infarct area in comparison to the vehicle group, indicating the presence of an increased number of viable mitochondria. P4 treatment was also able to attenuate mitochondrial reactive oxygen species (ROS) production, as well as block the mitochondrial permeability transition pore (mPTP), in the tMCAO injury model. In addition, it was also able to ameliorate the altered mitochondrial membrane potential and respiration ratio in the ischemic animals, thereby suggesting that P4 has

  11. Serum uric acid levels and cerebral microbleeds in patients with acute ischemic stroke.

    Directory of Open Access Journals (Sweden)

    Wi-Sun Ryu

    Full Text Available Unlike experimental studies indicating a neuroprotective property of uric acid, clinical studies have shown that elevated levels of uric acid are associated with a risk of ischemic stroke. However, the association of uric acid with cerebral hemorrhage has seldom been tested. We aimed to elucidate the association between uric acid and cerebral microbleeds (CMBs, a hemorrhage-prone cerebral microangiopathy. Seven hundred twenty-four patients with ischemic stroke who were consecutively admitted to our hospital were included in this study. We collected demographic, clinical, and laboratory data, including uric acid level, and examined the presence of CMBs using T2*-weighted gradient-echo MRI. We used logistic regression analysis to examine an independent association between uric acid and CMBs. Two-hundred twenty-six patients had CMBs (31.2%. After adjusting for possible confounders, elevated uric acid was independently associated with the presence of CMBs (the highest quartile vs. lowest quartile, adjusted odd ratio [OR], 1.98; 95% confidence interval [CI], 1.16-3.39. This association retained in patients with deep or infratentorial CMBs (with or without lobar CMBs but not among those with lobar CMBs. In addition, this association was robust among patients with hypertension (the highest quartile vs. lowest quartile, adjusted OR, 2.74; 95% CI, 1.43-5.24. In contrast, we did not find the association in patients without hypertension. We demonstrated that serum uric acid is independently associated with the presence of CMBs. In particular, the relation between uric acid and CMBs was robust in hypertensive patients.

  12. Serum uric acid levels and cerebral microbleeds in patients with acute ischemic stroke.

    Science.gov (United States)

    Ryu, Wi-Sun; Kim, Chi Kyung; Kim, Beom Joon; Lee, Seung-Hoon

    2013-01-01

    Unlike experimental studies indicating a neuroprotective property of uric acid, clinical studies have shown that elevated levels of uric acid are associated with a risk of ischemic stroke. However, the association of uric acid with cerebral hemorrhage has seldom been tested. We aimed to elucidate the association between uric acid and cerebral microbleeds (CMBs), a hemorrhage-prone cerebral microangiopathy. Seven hundred twenty-four patients with ischemic stroke who were consecutively admitted to our hospital were included in this study. We collected demographic, clinical, and laboratory data, including uric acid level, and examined the presence of CMBs using T2*-weighted gradient-echo MRI. We used logistic regression analysis to examine an independent association between uric acid and CMBs. Two-hundred twenty-six patients had CMBs (31.2%). After adjusting for possible confounders, elevated uric acid was independently associated with the presence of CMBs (the highest quartile vs. lowest quartile, adjusted odd ratio [OR], 1.98; 95% confidence interval [CI], 1.16-3.39). This association retained in patients with deep or infratentorial CMBs (with or without lobar CMBs) but not among those with lobar CMBs. In addition, this association was robust among patients with hypertension (the highest quartile vs. lowest quartile, adjusted OR, 2.74; 95% CI, 1.43-5.24). In contrast, we did not find the association in patients without hypertension. We demonstrated that serum uric acid is independently associated with the presence of CMBs. In particular, the relation between uric acid and CMBs was robust in hypertensive patients.

  13. [Effect of "Xingnao Kaiqiao Zhenfa" (Acupuncture Technique for Restoring Consciousness) Combined with Rehabilitation Training on Nerve Repair and Expression of Growth-associated Protein-43 of Peri-ischemic Cortex in Ischemic Stroke Rats].

    Science.gov (United States)

    Xu, Lei; Yan, Xing-Zhou; Li, Zhen-Yu; Cao, Xiao-Fang; Wang, Min

    2017-06-25

    To observe the effect of "Xingnao Kaiqiao Zhenfa" (acupuncture technique for restoring consciousness) combined with enriched rehabilitation training on motor function and expression of growth-associated protein-43 (GAP-43) of peri-ischemic cortex in ischemic stroke rats, so as to investigate its mechanism underlying improvement of ischemic stroke. SD rats were randomly divided into sham operation, model, rehabilitation and comprehensive rehabilitation groups, which were further divided into 3 time-points:7, 14 and 21 d ( n =6 in each). Cerebral ischemia(CI) model was established by occlusion of the middle cerebral artery with heat-coagulation. The rehabilitation group was treated by enriched rehabilitation training, once a day. The comprehensive rehabilitation group was treated by acupuncture combined with enriched rehabilitation training. Acupuncture was applied to bilateral "Neiguan"(PC 6) and "Shuigou"(GV 26) for 30 min, once a day. The neurological function score, balance-beam walking test and rotating-rod walking test were evaluated at the end of the corresponding treatment time. The expression of GAP-43 in peri-ischemic cortex was detected by immunohistochemistry. In comparison with the sham operation group, the scores of neurological function, beam walking test and rotating-rod walking test were significantly higher in the model group ( P beam walking and rotating-rod walking tests in the rehabilitation group compared with the model group on day 7 ( P >0.05). Compared with the model group at the other time points, the scores of neurological function, balance-beam walking test and rotating-rod walking test were significantly lower in the rehabilitation and comprehensive rehabilitation groups ( P beam walking test and rotating-rod walking test were significantly lower in the comprehensive rehabilitation group ( P <0.05). In comparison with the sham operation group, the number of GAP-43 positive cells of peri-ischemic cortex was significantly higher in the

  14. Stress test with adenosine in cerebral perfusion imaging for the diagnosis of ischemic cerebrovascular disease

    International Nuclear Information System (INIS)

    Yuan Gengbiao; Kuang Anren; Chen Xuehong; Li Xihuan; Feng Jianzhong

    2004-01-01

    Objective: This study purpose is to evaluate cerebrovascular response and reserve capacity (CVR, CVRC) by stress test with adenosine in cerebral perfusion imaging for the diagnosis of ischemic cerebrovascular diseases. Methods There were 25 patients suffered from transient ischemia attack and 16 patients suffered from occlusive cerebral artery in this study. The rest cerebral perfusion imaging was obtained 30 minutes post-injection of 99mTC-ethylene cysteinate dimmer. After 2-5 days, adenosine stress tests were performed. Adenosine (0.14 mg/kg min) was administered intravenously 3 minutes pre-injection of 99mTC-ECD.Under same condition, the rest and stress tests of cerebral perfusion imaging were performed. By visual and semiquantitative analysis, the results of the rest/stress imaging were divided into the following four patterns: A: The stress imaging showed an expand areas of hypoperfusion, asymmetry index (AI) was decreased; B: Rest imaging was normal but new hypoperfused areas appeared with AI index declining in stress test; C: The hypoperfused areas were decreased or disappeared in size with AI index increasing in stress test; D: No changes showed in cerebral perfusion imaging patterns and Al index between rest and stress tests. AI index was ratio of radio account of interest regions than average radio account of cerebella. Results It was found that A, B, C and D type were 24%,12%,56% and 8% respectively in the group of transient ischemia attack patients, and 31%,44%, 19% and 6% respectively in the group of occlusive cerebrovascular patients. In rest test, of 41 patients of cerebrovascular disease, there were 28 cases decreased of radio uptake, moreover in stress test, there were 38 case decreased of radio uptake, positive rate were 68.29% and 92.68% respectively. Compared to X±SD of AI index of rest/stress test, it is found to increasing and being significant statistics (p<0.01, Spass 8.0 statistics software). Conclusion: Adenosinal-induced vasodilatation

  15. Protective effects of beef decoction rich in carnosine on cerebral ischemia injury by permanent middle cerebral artery occlusion in rats.

    Science.gov (United States)

    Wang, Ai-Hong; Ma, Qian; Wang, Xin; Xu, Gui-Hua

    2018-02-01

    Inflammation has a role in the cerebral injury induced by ischemia and the present study aimed to determine the mechanism of the protective effect of beef decoction (BD) with carnosine against it. A rat model of permanent middle cerebral artery occlusion was established using a suture method in the vehicle and each of the BD groups. In experiment 1, 72 Sprague Dawley (SD) rats were randomly divided into three groups: Sham, vehicle and BD-treated group. Rats in the BD group were given 600 mg/kg BD by oral gavage for 1, 3 and 7 days. The sham and vehicle group rats received an equivalent amount of normal saline. In experiment 2, 60 SD rats were randomly divided into six groups: Sham-operated I, sham-operated II, vehicle, low-dose BD, medium-dose BD and high-dose BD group. Rats in the low-, medium- and high-dose BD groups were given BD at the dose of 200, 400 and 600 mg/kg, respectively, by oral gavage for 7 days. Rats in the sham-operated II group were given 600 mg/kg BD. Rats in the sham-operated I group and vehicle group were given the same volume of normal saline by oral gavage. The body weight, neurological deficits and infarct volume were recorded at 1, 3 and 7 days after the operation. Furthermore, the effect of different doses of BD on interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and interleukin-4 (IL-4) levels in peripheral blood was measured at 7 days. BD-treated rats showed less neurological deficits and a smaller infarct volume at 7 days. BD at 400 and 600 mg/kg significantly decreased the infarct volume in rats. At 600 mg/kg BD, a decline in IL-6, TNF-α, IFN-γ and an increase in IL-4 expression was observed in the BD groups, while no difference in body weight and neurological dysfunction was detected. In conclusion, BD is a neuroprotective agent that may be used as a supplement treatment of ischemic stroke.

  16. Salvia miltiorrhiza Bunge (Danshen) extract attenuates permanent cerebral ischemia through inhibiting platelet activation in rats.

    Science.gov (United States)

    Fei, Yu-Xiang; Wang, Si-Qi; Yang, Li-Jian; Qiu, Yan-Ying; Li, Yi-Ze; Liu, Wen-Yuan; Xi, Tao; Fang, Wei-Rong; Li, Yun-Man

    2017-07-31

    Danshen is a crude herbal drug isolated from dried roots of Salvia miltiorrhiza Bunge. This plant is widely used in oriental medicine for the treatment of cardiovascular and cerebrovascular diseases. The supercritical CO 2 extract from Danshen (SCED) (57.85%, 5.67% and 4.55% for tanshinone IIA, tanshinone I and cryptotanshinone respectively) was studied in this article, whose potential molecular mechanism remains unclear, especially in anti-thrombosis. The present study was designed to observe the protective effect of SCED on ischemic stroke in rats and to explore the underlying anti-thrombosis mechanism. Following induction of cerebral ischemia in rats by permanent middle cerebral artery occlusion (pMCAO). Neurological defect score, cerebral blood flow, infarct size, and brain edema were measured to evaluate the injury. Arteriovenous shunt thrombosis model and adenosine 5'-diphosphate (ADP) induced acute pulmonary embolism model were conducted to estimate the antithrombotic effect of SCED. In order to investigate the effects of SCED on platelet aggregation, rat platelet-rich-plasma (PRP) were incubated with SCED prior to the addition of the stimuli (ADP or 9, 11-dideoxy-11α, 9α-epoxymethanoprostaglandin F2α (U46619)). Aggregation was monitored in a light transmission aggregometer. Inhibitory effect of SCED on thromboxane A2 (TXA 2 ) release was detected by ELISA kit. Phospholipase C (PLC)/ Protein kinase C (PKC) signaling pathway was analyzed by a Western blot technique. The effect of the SCED was also studied in vivo on bleeding time in mice. SCED improved the neurological defect score, increased cerebral blood flow, reduced infarct size and alleviated brain edema in rats exposed to pMCAO. After administration of SCED, thrombosis formation in arteriovenous shunt was inhibited and recovery time in pulmonary embolism was shortened. The inhibitory effect of SCED on platelet activation was further confirmed by TXB 2 ELISA kit and Western blot analysis of PLC

  17. Neuroprotective effect of pretreatment with ganoderma lucidum in cerebral ischemia/reperfusion injury in rat hippocampus

    Science.gov (United States)

    Zhang, Wangxin; Zhang, Quiling; Deng, Wen; Li, Yalu; Xing, Guoqing; Shi, Xinjun; Du, Yifeng

    2014-01-01

    Ganoderma lucidum is a traditional Chinese medicine, which has been shown to have both anti-oxidative and anti-inflammatory effects, and noticeably decreases both the infarct area and neuronal apoptosis of the ischemic cortex. This study aimed to investigate the protective effects and mechanisms of pretreatment with ganoderma lucidum (by intragastric administration) in cerebral ischemia/reperfusion injury in rats. Our results showed that pretreatment with ganoderma lucidum for 3 and 7 days reduced neuronal loss in the hippocampus, diminished the content of malondialdehyde in the hippocampus and serum, decreased the levels of tumor necrosis factor-α and interleukin-8 in the hippocampus, and increased the activity of superoxide dismutase in the hippocampus and serum. These results suggest that pretreatment with ganoderma lucidum was protective against cerebral ischemia/reperfusion injury through its anti-oxidative and anti-inflammatory actions. PMID:25317156

  18. Cerebral Microbleeds Are Not Associated with Long-Term Cognitive Outcome in Patients with Transient Ischemic Attack or Minor Stroke

    NARCIS (Netherlands)

    Brundel, Manon; Kwa, Vincent I. H.; Bouvy, Willem H.; Algra, Ale; Kappelle, L. Jaap; Biessels, Geert Jan; Algra, A.; Kappelle, L. J.; Ramos, L. M. P.; de Schryver, E. L. L. M.; Kwa, V. I. H.; Jöbsis, G. J.; van der Sande, J. J.; Brouwers, P. J. A. M.; Roos, Y. E. B. M.; Stam, J.; Bakker, S. L. M.; Verbiest, H. B. C.; Schoonewille, W. J.; Linn, F. H. H.; Hertzberger, L. I.; van Gemert, H. M. A.; Berntsen, P. J. I. M.

    2014-01-01

    Background: Cerebral microbleeds have been related to cerebrovascular disease and dementia. They occur more frequently in patients with ischemic stroke than in the general population, but their relation to cognition in these patients is uncertain, particularly in the long run. We examined the

  19. Neuroprotective Effect of Xueshuantong for Injection (Lyophilized in Transient and Permanent Rat Cerebral Ischemia Model

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    Xumei Wang

    2015-01-01

    Full Text Available Xueshuantong for Injection (Lyophilized (XST, a Chinese Materia Medica standardized product extracted from Panax notoginseng (Burk., is used extensively for the treatment of cerebrovascular diseases such as acutely cerebral infarction clinically in China. In the present study, we evaluated the acute and extended protective effects of XST in different rat cerebral ischemic model and explored its effect on peroxiredoxin (Prx 6-toll-like receptor (TLR 4 signaling pathway. We found that XST treatment for 3 days could significantly inhibit transient middle cerebral artery occlusion (MCAO induced infarct volume and swelling percent and regulate the mRNA expression of interleukin-1β (IL-1β, IL-17, IL-23p19, tumor necrosis factor-α (TNFα, and inducible nitric oxide synthase (iNOS in brain. Further study demonstrated that treatment with XST suppressed the protein expression of peroxiredoxin (Prx 6-toll-like receptor (TLR 4 and phosphorylation level of p38 and upregulated the phosphorylation level of STAT3. In permanent MCAO rats, XST could reduce the infarct volume and swelling percent. Moreover, our results revealed that XST treatment could increase the rats’ weight and improve a batch of functional outcomes. In conclusion, the present data suggested that XST could protect against ischemia injury in transient and permanent MCAO rats, which might be related to Prx6-TLR4 pathway.

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

    Science.gov (United States)

    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.

  1. Green Tea Extract Ameliorates Learning and Memory Deficits in Ischemic Rats via Its Active Component Polyphenol Epigallocatechin-3-gallate by Modulation of Oxidative Stress and Neuroinflammation

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    Kuo-Jen Wu

    2012-01-01

    Full Text Available Ischemic stroke results in brain damage and behavioral deficits including memory impairment. Protective effects of green tea extract (GTex and its major functional polyphenol (−-epigallocatechin gallate (EGCG on memory were examined in cerebral ischemic rats. GTex and EGCG were administered 1 hr before middle cerebral artery ligation in rats. GTex, EGCG, and pentoxifylline (PTX significantly improved ishemic-induced memory impairment in a Morris water maze test. Malondialdehyde (MDA levels, glutathione (GSH, and superoxide dismutase (SOD activity in the cerebral cortex and hippocampus were increased by long-term treatment with GTex and EGCG. Both compounds were also associated with reduced cerebral infraction breakdown of MDA and GSH in the hippocampus. In in vitro experiments, EGCG had anti-inflammatory effects in BV-2 microglia cells. EGCG inhibited lipopolysaccharide- (LPS- induced nitric oxide production and reduced cyclooxygenase-2 and inducible nitric oxide synthase expression in BV-2 cells. GTex and its active polyphenol EGCG improved learning and memory deficits in a cerebral ischemia animal model and such protection may be due to the reduction of oxidative stress and neuroinflammation.

  2. Transplanted Dental Pulp Stem Cells Migrate to Injured Area and Express Neural Markers in a Rat Model of Cerebral Ischemia.

    Science.gov (United States)

    Zhang, Xuemei; Zhou, Yinglian; Li, Hulun; Wang, Rui; Yang, Dan; Li, Bing; Cao, Xiaofang; Fu, Jin

    2018-01-01

    Ischemic stroke is a major cause of disability and mortality worldwide, while effective restorative treatments are limited at present. Stem cell transplantation holds therapeutic potential for ischemic vascular diseases and may provide an opportunity for neural regeneration. Dental pulp stem cells (DPSCs) origin from neural crest and have neuro-ectodermal features including proliferation and multilineage differentiation potentials. The rat model of middle cerebral artery occlusion (MCAO) was used to evaluate whether intravenous administration of DPSCs can reduce infarct size and to estimate the migration and trans-differentiation into neuron-like cells in focal cerebral ischemia models. Brain tissues were collected at 4 weeks following cell transplantation and analyzed with immunofluorescence, immunohistochemistry and real-time polymerase chain reaction (RT-PCR) methods. Intravenously administration of rat-derived DPSCs were found to migrate into the boundary of ischemic areas and expressed neural specific markers, reducing infarct volume and cerebral edema. These results suggest that DPSCs treatment may serve as a potential therapy for clinical stroke patients in the future. © 2018 The Author(s). Published by S. Karger AG, Basel.

  3. Optimizing Cardiac Out-Put to Increase Cerebral Penumbral Perfusion in Large Middle Cerebral Artery Ischemic Lesion—OPTIMAL Study

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    Hannah Fuhrer

    2017-08-01

    Full Text Available IntroductionIn unsuccessful vessel recanalization, clinical outcome of acute stroke patients depends on early improvement of penumbral perfusion. So far, mean arterial blood pressure (MAP is the target hemodynamic parameter. However, the correlations of MAP to cardiac output (CO and cerebral perfusion are volume state dependent. In severe subarachnoid hemorrhage, optimizing CO leads to a reduction of delayed ischemic neurological deficits and improvement of clinical outcome. This study aims to investigate the effect of standard versus advanced cardiac monitoring with optimization of CO on the clinical outcome in patients with large ischemic stroke.Methods and analysisThe OPTIMAL study is a prospective, multicenter, open, into two arms (1:1 randomized, controlled trial. Sample size estimate: sample sizes of 150 for each treatment group (300 in total ensure an 80% power to detect a difference of 16% of a dichotomized level of functional clinical outcome at 3 months at a significance level of 0.05. Study outcomes: the primary endpoint is the functional outcome at 3 months. The secondary endpoints include functional outcome at 6 months follow-up, and complications related to hemodynamic monitoring and therapies.DiscussionThe results of this trial will provide data on the safety and efficacy of advanced hemodynamic monitoring on clinical outcome.Ethics and disseminationThe trial was approved by the leading ethics committee of Freiburg University, Germany (438/14, 2015 and the local ethics committees of the participating centers. The study is performed in accordance with the Declaration of Helsinki and the guidelines of Good Clinical Practice. It is registered in the German Clinical Trial register (DRKS; DRKS00007805. Dissemination will include submission to peer-reviewed professional journals and presentation at congresses. Hemodynamic monitoring may be altered in a specific stroke patient cohort if the study shows that advanced monitoring is

  4. 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

  5. Sodium phenylbutyrate ameliorates focal cerebral ischemic/reperfusion injury associated with comorbid type 2 diabetes by reducing endoplasmic reticulum stress and DNA fragmentation.

    Science.gov (United States)

    Srinivasan, Krishnamoorthy; Sharma, Shyam S

    2011-11-20

    Endoplasmic reticulum (ER) stress has been postulated to play a crucial role in the pathophysiology of cerebral ischemic/reperfusion (I/R) injury and diabetes. Diabetes is a major risk factor and also common amongst the people who suffer from stroke. In this study, we have investigated the neuroprotective potential of sodium 4-phenylbutyrate (SPB; 30-300mg/kg), a chemical chaperone by targeting ER stress in a rat model of transient focal cerebral ischemia associated with comorbid type 2 diabetes. Intraperitoneal treatment with SPB (100 and 300mg/kg) significantly ameliorated brain I/R damage as evidenced by reduction in cerebral infarct and edema volume. It also significantly improved the functional recovery of various neurobehavioral impairments (neurological deficit score, grip strength and rota rod) evoked by I/R compared with vehicle-treatment. Further, SPB (100mg/kg) significantly reduced the DNA fragmentation as shown by prominent reduction in terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells. This effect was observed concomitantly with significant attenuation in upregulation of 78kDa glucose regulated protein (GRP78), CCAAT/enhancer binding protein homologous protein or growth arrest DNA damage-inducible gene 153 (CHOP/GADD153) and activation of caspase-12, specific markers of ER stress/apoptosis. The neuroprotection observed with SPB was independent of its effect on cerebral blood flow and blood glucose. In conclusion, this study demonstrates the neuroprotective effect of SPB owing to amelioration of ER stress and DNA fragmentation. It also suggest that targeting ER stress might offer a promising therapeutic approach and benefits against ischemic stroke associated with comorbid type 2 diabetes. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. Effect of electroacupuncture on TRPM7 mRNA expression after cerebral ischemia/reperfusion in rats via TrkA pathway.

    Science.gov (United States)

    Zhao, Li; Shi, Jing; Sun, Ning; Tian, Shunlian; Meng, Xianfang; Liu, Xiaochun; Li, Lingli

    2005-01-01

    The effect of electroacupuncture (EA) on TRPM7 mRNA expression of focal cerebral ischemia in rats and further the role of EA in the relationship between TRPM7 and trkA pathway was investigated. Thirty SD rats were randomly divided into 5 groups : normal group, ischemia/reperfusion group, EA treated group (ischemic rats with EA treatment), TE infusion group (ischemic rats with EA treatment and TE buffer infusion), AS-ODN group (ischemic rats with EA treatment and antisense trkA oligonucleotide infusion). The stroke animal model was established by the modified method of middle cerebral artery occlusion. Antisense trkA oligonucleotide that blocked NGFs effects was injected into cerebroventricle before EA. The TRPM7 mRNA was detected by RT-PCR method. The results showed that there were low TRPM7 mRNA levels in cortex and hippocampus in normal group. Compared with normal group, TRPM7 mRNA expression was increased significantly in ischemia/reperfusion group (PPM7 mRNA was found in EA treated group in contrast to ischemia/reperfusion group (P<0.05). The expression of TRPM7 mRNA in AS-ODN group was remarkably increased compared with EA treated group and TE infusion group (P<0.05). The results indicated that TRPM7 channels in the ischemic cortex and hippocampus in rats might play a key role in ischemic brain injury. EA could reverse the overexpression of TRPM7 in cerebral ischemia/reperfusion rats. And the inhibitory effect of EA on TRPM7 channels might be through trkA pathway.

  7. SPECT study of cerebral blood flow reactivity after acetazolamide in patients with transient ischemic attacks

    International Nuclear Information System (INIS)

    Chollet, F.; Celsis, P.; Clanet, M.; Guiraud-Chaumeil, B.; Rascol, A.; Marc-Vergnes, J.P.

    1989-01-01

    We investigated 15 patients with one or more transient ischemic attacks (TIAs) in the internal carotid artery territory within the month following the most recent TIA. Cerebral blood flow (CBF) was measured by single-photon emission computed tomography, using intravenous xenon-133 before and after injection of 1 g acetazolamide. Six patients had severe carotid stenosis or occlusion; the other nine patients had no significant carotid lesions. Twenty age-matched volunteers free of neurologic symptoms or history were used as controls. Mean CBF in the sylvian region was not significantly different between patients and controls. Seven patients exhibited a focal hypoperfusion at rest in the symptomatic hemisphere, and their hypoperfused areas were hyporeactive after administration of acetazolamide. Seven other patients exhibited hyporeactive areas after acetazolamide administration while their CBF tomograms at rest were normal. Thus, CBF abnormalities were detected in 14 of the 15 patients. Our findings suggest that CBF measured early after acetazolamide administration could be useful to confirm the clinical diagnosis of TIA. In the nine patients with no significant lesion of the internal carotid artery, the areas of hypoperfusion were small and were probably related to the focal ischemic event. In the six patients with severe lesions of the internal carotid artery, abnormalities were of variable size and intensity but were often large and pronounced. The discrepancy between these two subgroups of patients could be ascribed to the hemodynamic influence of the internal carotid artery lesions. Moreover, our findings may provide some insight into the pathophysiology of TIAs

  8. 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.

  9. Role of phosphoinositide 3-kinase in ischemic postconditioning-induced attenuation of cerebral ischemia-evoked behavioral deficits in mice.

    Science.gov (United States)

    Rehni, Ashish K; Singh, Nirmal

    2007-01-01

    The present study has been designed to pharmacologically investigate the role of phosphoinositide 3-kinase in ischemic postconditioning-induced reversal of global cerebral ischemia and reperfusion-induced behavioral dysfunction in mice. Bilateral carotid artery occlusion for 10 min followed by reperfusion for 24 h was employed in the present study to produce ischemia and reperfusion-induced cerebral injury in mice. Short-term memory was evaluated using the elevated plus maze test. The inclined beam walking test was employed to assess motor incoordination. Bilateral carotid artery occlusion followed by reperfusion produced impaired short-term memory, motor co-ordination and lateral push response. Three episodes of carotid artery occlusion for a period of 10 s and reperfusion of 10 s (ischemic postconditioning) significantly prevented ischemia-reperfusion-induced behavioral deficit measured in terms of loss of short-term memory, motor coordination and lateral push response. Wortmannin (2 mg/kg, iv), a phosphoinositide 3-kinase inhibitor given 10 min before ischemia attenuated the beneficial effects of ischemic postconditioning. It may be concluded that beneficial effects of ischemic postconditioning on global cerebral ischemia and reperfusion-induced behavioral deficits may involve activation of phosphoinositide 3-kinase-linked pathway.

  10. Niosomes of Ascorbic Acid and α-Tocopherol in the Cerebral Ischemia-Reperfusion Model in Male Rats

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    Jaleh Varshosaz

    2014-01-01

    Full Text Available The objective of the present study was to prepare a stable iv injectable formulation of ascorbic acid and α-tocopherol in preventing the cerebral ischemia. Different niosomal formulations were prepared by Span and Tween mixed with cholesterol. The physicochemical characteristics of niosomal formulations were evaluated in vitro. For in vivo evaluation, the rats were made ischemic by middle cerebral artery occlusion model for 30 min and the selected formulation was used for determining its neuroprotective effect against cerebral ischemia. Neuronal damage was evaluated by optical microscopy and transmission electron microscopy. The encapsulation efficiency of ascorbic acid was increased to more than 84% by remote loading method. The cholesterol content of the niosomes, the hydrophilicity potential of the encapsulated compounds, and the preparation method of niosomes were the main factors affecting the mean volume diameter of the prepared vesicles. High physical stability of the niosomes prepared from Span 40 and Span 60 was demonstrated due to negligible size change of vesicles during 6 months storage at 4–8°C. In vivo studies showed that ST60/Chol 35 : 35 : 30 niosomes had more neuroprotective effects against cerebral ischemic injuries in male rats than free ascorbic acid.

  11. Niosomes of ascorbic acid and α-tocopherol in the cerebral ischemia-reperfusion model in male rats.

    Science.gov (United States)

    Varshosaz, Jaleh; Taymouri, Somayeh; Pardakhty, Abbas; Asadi-Shekaari, Majid; Babaee, Abodolreza

    2014-01-01

    The objective of the present study was to prepare a stable iv injectable formulation of ascorbic acid and α-tocopherol in preventing the cerebral ischemia. Different niosomal formulations were prepared by Span and Tween mixed with cholesterol. The physicochemical characteristics of niosomal formulations were evaluated in vitro. For in vivo evaluation, the rats were made ischemic by middle cerebral artery occlusion model for 30 min and the selected formulation was used for determining its neuroprotective effect against cerebral ischemia. Neuronal damage was evaluated by optical microscopy and transmission electron microscopy. The encapsulation efficiency of ascorbic acid was increased to more than 84% by remote loading method. The cholesterol content of the niosomes, the hydrophilicity potential of the encapsulated compounds, and the preparation method of niosomes were the main factors affecting the mean volume diameter of the prepared vesicles. High physical stability of the niosomes prepared from Span 40 and Span 60 was demonstrated due to negligible size change of vesicles during 6 months storage at 4-8(°)C. In vivo studies showed that ST60/Chol 35 : 35 : 30 niosomes had more neuroprotective effects against cerebral ischemic injuries in male rats than free ascorbic acid.

  12. 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.

  13. PET imaging of cerebral perfusion and oxygen consumption in acute ischemic stroke: Relation to outcome

    International Nuclear Information System (INIS)

    Marchal, G.; Serrati, C.; Rioux, P.; Petit-Taboue, M.C.; Viader, F.; Sayette, V. de la; Doze, F. le; Lonchon, P; Derlon, J.M.; Orgogozo, J.M.; Baron, J.C.

    1993-01-01

    The authors used positron emission tomography (PET) to assess the relation between combined imaging of cerebral blood flow and oxygen consumption 5-18 h after first middle cerebral artery (MCA) stroke and neurological outcome at 2 months. All 18 patients could be classified into three visually defined PET patterns of perfusion and oxygen consumption changes. Pattern 1 suggested extensive irreversible damage and was consistently associated with poor outcome. Pattern 2 suggested continuing ischemia and was associated with variable outcome. Pattern 3 with hyperperfusion and little or no metabolic alteration, was associated with excellent recovery, which suggests that early reperfusion is beneficial. This relation between PET and outcome was highly significant. The results suggest that within 5-18 h of stroke onset, PET is a good predictor of outcome in patterns 1 and 3, for which therapy seems limited. The absence of predictive value for pattern 2 suggests that it is due to a reversible ischemic state that is possibly amenable to therapy. These findings may have important implications for acute MCA stroke management and for patients' selection for therapeutic trials

  14. Characteristics and dynamics of cognitive impairment in patients with primary and recurrent cerebral ischemic hemispheric stroke

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    A. A. Kozyolkin

    2014-08-01

    Full Text Available Acute cerebrovascular disease is a global medical and social problem of the modern angioneurology, occupying leading positions in the structure of morbidity and mortality among adult population of the world. Ischemic stroke – is one of the most common pathology. Today this disease took out the world pandemic. More than 16 million new cases of cerebral infarction recorded in the world each year and it “kills” about 7 million of people. About 111,953 cases of cerebral stroke were registered in 2013 in Ukraine. Cognitive impairment, t hat significantly disrupt daily activities and life of the patient, is one of the most significant post-stroke complications that have social, medical and biological significance. Aim. The purpose of this investigation was to study features and dynamics of cognitive impairments in patients with primary and recurrent cerebral hemispheric ischemic stroke (CHIS in the acute stage of the disease. Materials and methods. To achieve the aim, and the decision of tasks in the clinic of nervous diseases Zaporozhye State Medical University (supervisor - Doctor of Medicine, Professor Kozelkin A. based on the department of acute cerebrovascular disease were performed comparative, prospective cohort study, which included comprehensive clinical and paraclinical examinations of 41 patients (26 men and 15 women aged 45 to 85 years (mean age 66,4 ± 1,4 years with acute left-hemispheric (2 patients and right - hemispheric (39 patients CHIS . First up was a group of 28 patients (19 men and 9 women, mean age 65,6 ± 1,6 years, who suffered from primary CHIS. The second group consisted of 13 patients (7 men and 6 women, mean age 68,1 ± 2,5 years with recurrent CHIS. The groups were matched by age, sex, localization of the lesion and the initial level of neurological deficit. All patients underwent physical examination, neurological examination. Dynamic clinical neurological examination assessing the severity of stroke was conducted

  15. Investigation of redox status in chronic cerebral hypoperfusion-induced neurodegeneration in rats

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    Anil Kumar Saxena

    2015-06-01

    Full Text Available Aging related reduction in cerebral blood flow (CBF has been linked with neurodegenerative disorders including Alzheimer's disease and dementia. Experimentally, a condition of chronic cerebral hypoperfusion due to reduced CBF can be induced by permanent bilateral occlusion of common carotid arteries (2-vessel occlusion, 2VO in rats. Since oxidative stress, leading to neuronal apoptosis and death, is one of the mechanisms, which is thought to play a significant role in chronic degenerative neurological disorders, the present study was planned to assess the ROS status by measuring the levels of anti-oxidant enzymes that might occur during chronic cerebral hypoperfusion. Antioxidant enzymes namely glutathione peroxidase (GPx, superoxide dismutase (SOD, and catalase were measured in the brain tissue at eight weeks of 2VO induction in rats. Results show significantly elevated levels of GPx, SOD, and catalase enzymes as compared with the control group. It is possible that compensatory rise in antioxidant enzymes occurs in response to increased oxidative stress following ischemic insult.

  16. Improvement in regional CBF by L-serine contributes to its neuroprotective effect in rats after focal cerebral ischemia.

    Directory of Open Access Journals (Sweden)

    Tao-Jie Ren

    Full Text Available To investigate the mechanisms underlying the neuroprotective effect of L-serine, permanent focal cerebral ischemia was induced by occlusion of the middle cerebral artery while monitoring cerebral blood flow (CBF. Rats were divided into control and L-serine-treated groups after middle cerebral artery occlusion. The neurological deficit score and brain infarct volume were assessed. Nissl staining was used to quantify the cortical injury. L-serine and D-serine levels in the ischemic cortex were analyzed with high performance liquid chromatography. We found that L-serine treatment: 1 reduced the neurological deficit score, infarct volume and cortical neuron loss in a dose-dependent manner; 2 improved CBF in the cortex, and this effect was inhibited in the presence of apamin plus charybdotoxin while the alleviation of both neurological deficit score and infarct volume was blocked; and 3 increased the amount of L-serine and D-serine in the cortex, and inhibition of the conversion of L-serine into D-serine by aminooxyacetic acid did not affect the reduction of neurological deficit score and infarct volume by L-serine. In conclusion, improvement in regional CBF by L-serine may contribute to its neuroprotective effect on the ischemic brain, potentially through vasodilation which is mediated by the small- and intermediate-conductance Ca(2+-activated K(+ channels on the cerebral blood vessel endothelium.

  17. A comparative study on the efficacy of 10% hypertonic saline and equal volume of 20% mannitol in the treatment of experimentally induced cerebral edema in adult rats

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    Fang Ming

    2010-12-01

    Full Text Available Abstract Background Hypertonic saline and mannitol are commonly used in the treatment of cerebral edema and elevated intracranial pressure (ICP at present. In this connection, 10% hypertonic saline (HS alleviates cerebral edema more effectively than the equal volume of 20% mannitol. However, the exact underlying mechanism for this remains obscure. This study aimed to explore the possible mechanism whereby 10% hypertonic saline can ameliorate cerebral edema more effectively than mannitol. Results Adult male Sprague-Dawley (SD rats were subjected to permanent right-sided middle cerebral artery occlusion (MCAO and treated with a continuous intravenous infusion of 10% HS, 20% mannitol or D-[1-3H(N]-mannitol. Brain water content (BWC as analyzed by wet-to-dry ratios in the ischemic hemisphere of SD rats decreased more significantly after 10% HS treatment compared with 20% mannitol. Concentration of serum Na+ and plasma crystal osmotic pressure of the 10% HS group at 2, 6, 12 and 18 h following permanent MCAO increased significantly when compared with 20% mannitol treated group. Moreover, there was negative correlation between the BWC of the ipsilateral ischemic hemisphere and concentration of serum Na+, plasma crystal osmotic pressure and difference value of concentration of serum Na+ and concentration of brain Na+ in ipsilateral ischemic hemisphere in the 10% HS group at the various time points after MCAO. A remarkable finding was the progressive accumulation of mannitol in the ischemic brain tissue. Conclusions We conclude that 10% HS is more effective in alleviating cerebral edema than the equal volume of 20% mannitol. This is because 10% HS contributes to establish a higher osmotic gradient across BBB and, furthermore, the progressive accumulation of mannitol in the ischemic brain tissue counteracts its therapeutic efficacy on cerebral edema.

  18. Evaluation of hypoxic tissue dynamics with 18F-FMISO PET in a rat model of permanent cerebral ischemia.

    Science.gov (United States)

    Rojas, Santiago; Herance, José Raul; Abad, Sergio; Jiménez, Xavier; Pareto, Deborah; Ruiz, Alba; Torrent, Èlia; Figueiras, Francisca P; Popota, Foteini; Fernández-Soriano, Francisco J; Planas, Anna M; Gispert, Juan D

    2011-06-01

    [¹⁸F]Fluoromisonidazole (¹⁸F-FMISO) is a nitroimidazole derivative that has been proposed as a positron emission tomography (PET) radiotracer to detect hypoxic tissue in vivo. This compound accumulates in hypoxic but viable tissue and may be a good candidate for evaluating the ischemic penumbra. We evaluated the time course of ¹⁸F-FMISO uptake using PET in a rat model of permanent cerebral ischemia and the correlation with histological changes. Rats (n = 14) were subjected to permanent ischemia by intraluminal occlusion of the middle cerebral artery in order to assess by PET the uptake of ¹⁸F-FMISO at various times over 24 h following ischemia. The PET results were compared to histological changes with Nissl and 2,3,5 triphenyltetrazolium chloride staining. Elevated uptake of ¹⁸F-FMISO was detected in the infarcted area up to 8 h after occlusion but was no longer detected at 24 h, a time point coincident with pan necrosis of the tissue. Our findings suggest that salvageable tissue persists for up to 8 h in this rat model of brain ischemia. We propose ¹⁸F-FMISO PET as a tool for evaluating the ischemic penumbra after cerebral ischemia.

  19. The preliminary study of CT cerebral perfusion imaging in transient ischemic attacks

    International Nuclear Information System (INIS)

    Lu Jie; Li Kuncheng; Du Xiangying

    2002-01-01

    Objective: To probe the application of CT cerebral perfusion imaging on transient ischemic attacks (TIA). Methods: Conventional CT and CT cerebral perfusion imaging were performed on 5 normal adults and 20 patients with clinically diagnosed TIA. After regular CT examination, dynamic scans of 40 seconds were performed on selected slice (usually on the basal ganglia slice), while 40 ml non-ionic contrast material were bolus injected through antecubital vein with. These dynamic images were processed with the 'Perfusion CT' software package on a PC based workstation. Cerebral blood flow (CBF) and time to peak (TP) enhancement were measured within specific regions of the brain on CT perfusion images. Quantitative analysis was performed for these images. Results: A gradient of perfusion between gray matter and white matter was showed on cT perfusion images in normal adults and TIA patients. CBF and TP for normal cortical and white matter were 378.2 ml·min -1 ·L -1 , 7.8 s and 112.5 ml·min -1 ·L -1 , 9.9 s, respectively. In 20 cases with TIA, persisting abnormal perfusion changes corresponding to clinical symptoms were found in 15 cases with prolonged TP. Other 5 cases showed normal results. TP of affected side (11.8 +- 4.4) s compared with that of the contralateral side (9.1 +- 3.1) s was significantly prolonged (t = 5.277, P -1 · -1 ] and contralateral side [(229.1 +- 41.4) ml·min -1 ·L -1 ]. Conclusion: Perfusion CT provides valuable hemodynamic information and shows the extent of perfusion disturbances for patients with TIA

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

    Science.gov (United States)

    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.

  1. Consequences of age on ischemic wound healing in rats: altered antioxidant activity and delayed wound closure.

    Science.gov (United States)

    Moor, Andrea N; Tummel, Evan; Prather, Jamie L; Jung, Michelle; Lopez, Jonathan J; Connors, Sarah; Gould, Lisa J

    2014-04-01

    Advertisements targeted at the elderly population suggest that antioxidant therapy will reduce free radicals and promote wound healing, yet few scientific studies substantiate these claims. To better understand the potential utility of supplemental antioxidant therapy for wound healing, we tested the hypothesis that age and tissue ischemia alter the balance of endogenous antioxidant enzymes. Using a bipedicled skin flap model, ischemic and non-ischemic wounds were created on young and aged rats. Wound closure and the balance of the critical antioxidants superoxide dismutase and glutathione in the wound bed were determined. Ischemia delayed wound closure significantly more in aged rats. Lower superoxide dismutase 2 and glutathione in non-ischemic wounds of aged rats indicate a basal deficit due to age alone. Ischemic wounds from aged rats had lower superoxide dismutase 2 protein and activity initially, coupled with decreased ratios of reduced/oxidized glutathione and lower glutathione peroxidase activity. De novo glutathione synthesis, to restore redox balance in aged ischemic wounds, was initiated as evidenced by increased glutamate cysteine ligase. Results demonstrate deficiencies in two antioxidant pathways in aged rats that become exaggerated in ischemic tissue, culminating in profoundly impaired wound healing and prolonged inflammation.

  2. Cerebral Microbleeds are an Independent Predictor of Hemorrhagic Transformation Following Intravenous Alteplase Administration in Acute Ischemic Stroke.

    Science.gov (United States)

    Nagaraja, Nandakumar; Tasneem, Nudrat; Shaban, Amir; Dandapat, Sudeepta; Ahmed, Uzair; Policeni, Bruno; Olalde, Heena; Shim, Hyungsub; Samaniego, Edgar A; Pieper, Connie; Ortega-Gutierrez, Santiago; Leira, Enrique C; Adams, Harold P

    2018-05-01

    Intravenous alteplase (rt-PA) increases the risk of hemorrhagic transformation of acute ischemic stroke. The objective of our study was to evaluate clinical, laboratory, and imaging predictors on forecasting the risk of hemorrhagic transformation following treatment with rt-PA. We also evaluated the factors associated with cerebral microbleeds that increase the risk of hemorrhagic transformation. Consecutive patients with acute ischemic stroke admitted between January 1, 2009 and December 31, 2013 were included in the study if they received IV rt-PA, had magnetic resonance imaging (MRI) of the brain on admission, and computed tomography or MRI of the brain at 24 (18-36) hours later to evaluate for the presence of hemorrhagic transformation. The clinical data, lipid levels, platelet count, MRI, and computed tomography images were retrospectively reviewed. The study included 366 patients, with mean age 67 ± 15 years; 46% were women and 88% were white. The median National Institutes of Health Stroke Scale (NIHSS) score was 6 (interquartile range 3-15). Hemorrhagic transformation was observed in 87 (23.8%) patients and cerebral microbleeds were noted in 95 (25.9%). Patients with hemorrhagic transformation tended to be older, nonwhite, have atrial fibrillation, higher baseline NIHSS score, lower cholesterol and triglyceride levels, and cerebral microbleeds and nonlacunar infarcts. Patients with cerebral microbleeds were more likely to be older, have hypertension, hyperlipidemia, previous history of stroke, and prior use of antithrombotics. On multivariate analysis race, NIHSS score, nonlacunar infarct, and presence of cerebral microbleeds were independently associated with hemorrhagic transformation following treatment with rt-PA. Presence of cerebral microbleeds is an independent predictor of hemorrhagic transformation of acute ischemic stroke following treatment with rt-PA. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights

  3. Cerebral Lactate Concentration in Neonatal Hypoxic-Ischemic Encephalopathy: In Relation to Time, Characteristic of Injury, and Serum Lactate Concentration

    Directory of Open Access Journals (Sweden)

    Tai-Wei Wu

    2018-05-01

    Full Text Available BackgroundCerebral lactate concentration can remain detectable in neonatal hypoxic-ischemic encephalopathy (HIE after hemodynamic stability. The temporal resolution of regional cerebral lactate concentration in relation to the severity or area of injury is unclear. Furthermore, the interplay between serum and cerebral lactate in neonatal HIE has not been well defined. The study aims to describe cerebral lactate concentration in neonatal HIE in relation to time, injury, and serum lactate.Design/methodsFifty-two newborns with HIE undergoing therapeutic hypothermia (TH were enrolled. Magnetic resonance imaging and spectroscopy (MRI + MR spectroscopy were performed during and after TH at 54.6 ± 15.0 and 156 ± 57.6 h of life, respectively. Severity and predominant pattern of injury was scored radiographically. Single-voxel 1H MR spectra were acquired using short-echo (35 ms PRESS sequence localized to the basal ganglia (BG, thalamus (Thal, gray matter (GM, and white matter. Cerebral lactate concentration was quantified by LCModel software. Serum and cerebral lactate concentrations were plotted based on age at time of measurement. Multiple comparisons of regional cerebral lactate concentration based on severity and predominant pattern of injury were performed. Spearman’s Rho was computed to determine correlation between serum lactate and cerebral lactate concentration at the respective regions of interest.ResultsOverall, serum lactate concentration decreased over time. Cerebral lactate concentration remained low for less severe injury and decreased over time for more severe injury. Cerebral lactate remained detectable even after TH. During TH, there was a significant higher concentration of cerebral lactate at the areas of injury and also when injury was more severe. However, these differences were no longer observed after TH. There was a weak correlation between serum lactate and cerebral lactate concentration at the BG (rs

  4. Investigation of cerebral iron deposition in aged patients with ischemic cerebrovascular disease using susceptibility-weighted imaging

    Directory of Open Access Journals (Sweden)

    Liu Y

    2016-08-01

    Full Text Available Yin Liu, Jun Liu, Huanghui Liu, Yunjie Liao, Lu Cao, Bin Ye, Wei Wang Department of Radiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China Objective: The aim of this study was to investigate focal iron deposition level in the brain in patients with ischemic cerebrovascular disease and its correlation with cerebral small vessel disease imaging markers.Patients and methods: Seventy-four patients with first-ever transient ischemic attack (median age: 69 years; 30 males and 44 females and 77 patients with positive ischemic stroke history (median age: 72 years; 43 males and 34 females were studied retrospectively. On phase image of susceptibility-weighted imaging and regions of interest were manually drawn at the bilateral head of the caudate nucleus, lenticular nucleus (LN, thalamus (TH, frontal white matter, and occipital white matter. The correlation between iron deposition level and the clinical and imaging variables was also investigated.Results: Iron deposition level at LN was significantly higher in patients with previous stroke history. It linearly correlated with the presence and number of cerebral microbleeds (CMBs but not with white matter hyperintensity and lacunar infarct. Multiple linear regression analysis showed that deep structure CMBs were the most relevant in terms of iron deposition at LN.Conclusion: Iron deposition at LN may increase in cases of more severe ischemia in aged patients with transient ischemic attack, and it may be an imaging marker for CMB of ischemic origin. Keywords: cerebral microbleed, ischemia, susceptibility-weighted imaging, iron, lenticular nucleus

  5. 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....

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

    DEFF Research Database (Denmark)

    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....

  7. Toward fully automated processing of dynamic susceptibility contrast perfusion MRI for acute ischemic cerebral stroke.

    Science.gov (United States)

    Kim, Jinsuh; Leira, Enrique C; Callison, Richard C; Ludwig, Bryan; Moritani, Toshio; Magnotta, Vincent A; Madsen, Mark T

    2010-05-01

    We developed fully automated software for dynamic susceptibility contrast (DSC) MR perfusion-weighted imaging (PWI) to efficiently and reliably derive critical hemodynamic information for acute stroke treatment decisions. Brain MR PWI was performed in 80 consecutive patients with acute nonlacunar ischemic stroke within 24h after onset of symptom from January 2008 to August 2009. These studies were automatically processed to generate hemodynamic parameters that included cerebral blood flow and cerebral blood volume, and the mean transit time (MTT). To develop reliable software for PWI analysis, we used computationally robust algorithms including the piecewise continuous regression method to determine bolus arrival time (BAT), log-linear curve fitting, arrival time independent deconvolution method and sophisticated motion correction methods. An optimal arterial input function (AIF) search algorithm using a new artery-likelihood metric was also developed. Anatomical locations of the automatically determined AIF were reviewed and validated. The automatically computed BAT values were statistically compared with estimated BAT by a single observer. In addition, gamma-variate curve-fitting errors of AIF and inter-subject variability of AIFs were analyzed. Lastly, two observes independently assessed the quality and area of hypoperfusion mismatched with restricted diffusion area from motion corrected MTT maps and compared that with time-to-peak (TTP) maps using the standard approach. The AIF was identified within an arterial branch and enhanced areas of perfusion deficit were visualized in all evaluated cases. Total processing time was 10.9+/-2.5s (mean+/-s.d.) without motion correction and 267+/-80s (mean+/-s.d.) with motion correction on a standard personal computer. The MTT map produced with our software adequately estimated brain areas with perfusion deficit and was significantly less affected by random noise of the PWI when compared with the TTP map. Results of image

  8. Tissue plasminogen activator; identifying major barriers related to intravenous injection in ischemic acute cerebral infraction

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    Fariborz Khorvash

    2017-01-01

    Full Text Available Background: According to previous publications, in patients with acute ischemic cerebral infarction, thrombolytic therapy using intravenous tissue plasminogen activator (IV-tPA necessitates precise documentation of symptoms' onset. The aim of this study was to identify major barriers related to the IV-tPA injection in such patients. Materials and Methods: Between the year 2014-2015, patients with definitive diagnosis of acute cerebral infarction (n = 180 who attended the neurology ward located at the Isfahan Alzahra Hospital were studied. To investigate barriers related to door to IV-tPA needle time, personal reasons, and criteria for inclusion or exclusion of patients, three questionnaire forms were designed based on the Food and Drug Administration-approved indications or contraindications. Results: The mean age of males versus females was 60 versus 77.5 years (ranged 23–93 vs. 29–70 years, respectively. Out of total population, only 10.7% transferred to hospital in <4.5 h after the onset of symptoms. Regarding to eligibility for IV-tPA, 68.9% of total population have had criteria for such treatment. Concerning to both items such as transferring to hospital in <4.5 h after the onset of symptoms and eligibility for IV-tPA, only 6.6% of total population met the criteria for such management. There was ignorance or inattention to symptoms in 75% of population studied. There was a mean of 195.92 ± 6.65 min (182.8–209.04 min for door to IV-tPA needle time. Conclusion: Despite the international guidelines for IV-tPA injection within 3–4.5 h of ischemic stroke symptoms' onset, the results of this study revealed that falling time due to ignorance of symptoms, literacy, and living alone might need further attention. As a result, to decrease death and disability, educational programs related to the symptoms' onset by consultant neurologist in Isfahan/Iran seem to be advantageous.

  9. 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

  10. Deep cerebral microbleeds are negatively associated with HDL-C in elderly first-time ischemic stroke patients.

    Science.gov (United States)

    Igase, Michiya; Kohara, Katsuhiko; Igase, Keiji; Yamashita, Shiro; Fujisawa, Mutsuo; Katagi, Ryosuke; Miki, Tetsuro

    2013-02-15

    Cerebral microbleeds (CMBs) detected on T2*-weighted MRI gradient-echo have been associated with increased risk of cerebral infarction. We evaluated risk factors for these lesions in a cohort of first-time ischemic stroke patients. Presence of CMBs in consecutive first-time ischemic stroke patients was evaluated. The location of CMBs was classified by cerebral region as strictly lobar (lobar CMBs) and deep or infratentorial (deep CMBs). Logistic regression analysis was performed to determine the contribution of lipid profile to the presence of CMBs. One hundred and sixteen patients with a mean age of 70±10years were recruited. CMBs were present in 74 patients. The deep CMBs group had significantly lower HDL-C levels than those without CMBs. In univariable analysis, advanced periventricular hyperintensity grade (PVH>2) and decreased HDL-C were significantly associated with the deep but not the lobar CMB group. On logistic regression analysis, HDL-C (beta=-0.06, p=0.002) and PVH grade >2 (beta=3.40, p=0.005) were independent determinants of deep CMBs. Low HDL-C may be a risk factor of deep CMBs, including advanced PVH status, in elderly patients with acute ischemic stroke. Management of HDL-C levels might be a therapeutic target for the prevention of recurrence of stroke. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. Pre-Ischemic Treadmill Training for Prevention of Ischemic Brain Injury via Regulation of Glutamate and Its Transporter GLT-1

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    Jingchun Guo

    2012-07-01

    Full Text Available Pre-ischemic treadmill training exerts cerebral protection in the prevention of cerebral ischemia by alleviating neurotoxicity induced by excessive glutamate release following ischemic stroke. However, the underlying mechanism of this process remains unclear. Cerebral ischemia-reperfusion injury was observed in a rat model after 2 weeks of pre-ischemic treadmill training. Cerebrospinal fluid was collected using the microdialysis sampling method, and the concentration of glutamate was determined every 40 min from the beginning of ischemia to 4 h after reperfusion with high-performance liquid chromatography (HPLC-fluorescence detection. At 3, 12, 24, and 48 h after ischemia, the expression of the glutamate transporter-1 (GLT-1 protein in brain tissues was determined by Western blot respectively. The effect of pre-ischemic treadmill training on glutamate concentration and GLT-1 expression after cerebral ischemia in rats along with changes in neurobehavioral score and cerebral infarct volume after 24 h ischemia yields critical information necessary to understand the protection mechanism exhibited by pre-ischemic treadmill training. The results demonstrated that pre-ischemic treadmill training up-regulates GLT-1 expression, decreases extracellular glutamate concentration, reduces cerebral infarct volume, and improves neurobehavioral score. Pre-ischemic treadmill training is likely to induce neuroprotection after cerebral ischemia by regulating GLT-1 expression, which results in re-uptake of excessive glutamate.

  12. Early Cerebral Hemodynamic, Metabolic, and Histological Changes in Hypoxic-Ischemic Fetal Lambs during Postnatal Life.

    Science.gov (United States)

    Rey-Santano, Carmen; Mielgo, Victoria E; Gastiasoro, Elena; Murgia, Xabier; Lafuente, Hector; Ruiz-Del-Yerro, Estibaliz; Valls-I-Soler, Adolf; Hilario, Enrique; Alvarez, Francisco J

    2011-01-01

    The hemodynamic, metabolic, and biochemical changes produced during the transition from fetal to neonatal life may be aggravated if an episode of asphyxia occurs during fetal life. The aim of the study was to examine regional cerebral blood flow (RCBF), histological changes, and cerebral brain metabolism in preterm lambs, and to analyze the role of oxidative stress in the first hours of postnatal life following severe fetal asphyxia. Eighteen chronically instrumented newborn lambs were randomly assigned to either a control group or the hypoxic-ischemic (HI) group, in which case fetal asphyxia was induced just before delivery. All the animals were maintained on intermittent positive pressure ventilation for 3 h after delivery. During the HI insult, the injured group developed acidosis, hypoxia, hypercapnia, lactic acidosis, and tachycardia (relative to the control group), without hypotension. The intermittent positive pressure ventilation transiently improved gas exchange and cardiovascular parameters. After HI injury and during ventilatory support, there continued to be an increased RCBF in inner regions among the HI group, but no significant differences were detected in cortical flow compared to the control group. Also, the magnitude of the increase in TUNEL positive cells (apoptosis) and antioxidant enzymes, and decrease of ATP reserves was significantly greater in the brain regions where the RCBF was not higher. In conclusion, our findings identify early metabolic, histological, and hemodynamic changes involved in brain damage in premature asphyxiated lambs. Such changes have been described in human neonates, so our model could be useful to test the safety and the effectiveness of different neuroprotective or ventilation strategies applied in the first hours after fetal HI injury.

  13. Predictors of cerebral venous thrombosis and arterial ischemic stroke in young Asian women.

    Science.gov (United States)

    Wasay, Mohammad; Saadatnia, Mohammad; Venketasubramanian, Narayanaswamy; Kaul, Subhash; Menon, Bindu; Gunaratne, Padma; Malik, Abdul; Mehmood, Kauser; Ahmed, Shahzad; Awan, Safia; Mehndiratta, M M

    2012-11-01

    The management and outcome of cerebral venous thrombosis (CVT) may be different from that of arterial ischemic stroke (AIS). Clinically differentiating the 2 diseases on clinical grounds may be difficult. The main objective of this study was to identify predictors differentiating CVT from AIS in a large cohort of young Asian women, based on risk factors and investigations. Twelve centers in 8 Asian countries participated. Women aged 15-45 years were included if they had a diagnosis of first-ever symptomatic AIS or CVT confirmed by brain computed tomography scan or magnetic resonance imaging/magnetic resonance venography. Patients with head trauma, cerebral contusions, intracranial hemorrhage, and subarachnoid or subdural hemorrhage were excluded. Data, including demographic data, risk factor assessment, neuroimaging studies, blood tests, and cardiac studies, were collected by retrospective and then prospective chart review between January 2001 and July 2008. Outcome was based on the modified Rankin Scale (mRS) score at admission, discharge, and latest follow-up. A total of 958 patients (204 with CVT and 754 with AIS) were included in the study. Age under 36 years, anemia, pregnancy or postpartum state, and presence of hemorrhagic infarcts on computed tomography scan or magnetic resonance imaging were significant predictors of CVT on univariate analysis. Age over 36 years, diabetes, hypertension, dyslipidemia, recent myocardial infarction, electrocardiogram abnormalities, and blood glucose level >150 mg/dL were strong predictors of AIS. On multivariate analysis, postpartum state and hemorrhagic infarct were the strongest predictors of CVT (P Asian women, predictors of CVT differ from those for AIS. These findings could be useful in the early identification and diagnosis of patients with CVT. Copyright © 2012 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  14. Effect of thuringiensin on adenylate cyclase in rat cerebral cortex

    International Nuclear Information System (INIS)

    Tsai, S.-F.; Yang Chi; Wang, S.-C.; Wang, J.-S.; Hwang, J.-S.; Ho, S.-P.

    2004-01-01

    The purpose of this work is to evaluate the effect of thuringiensin on the adenylate cyclase activity in rat cerebral cortex. The cyclic adenosine 3'5'-monophosphate (cAMP) levels were shown to be dose-dependently elevated 17-450% or 54-377% by thuringiensin at concentrations of 10 μM-100 mM or 0.5-4 mM, due to the activation of basal adenylate cyclase activity of rat cerebral cortical membrane preparation. Thuringiensin also activated basal activity of a commercial adenylate cyclase from Escherichia coli. However, the forskolin-stimulated adenylate cyclase activity in rat cerebral cortex was inhibited by thuringiensin at concentrations of 1-100 μM, thus cAMP production decreased. Furthermore, thuringiensin or adenylate cyclase inhibitor (MDL-12330A) reduced the forskolin (10 μM)-stimulated adenylate cyclase activity at concentrations of 10 μM, 49% or 43% inhibition, respectively. In conclusion, this study demonstrated that thuringiensin could activate basal adenylate cyclase activity and increase cAMP concentrations in rat cerebral cortex or in a commercial adenylate cyclase. Comparing the dose-dependent effects of thuringiensin on the basal and forskolin-stimulated adenylate cyclase activity, thuringiensin can be regarded as a weak activator of adenylate cyclase or an inhibitor of forskolin-stimulated adenylate cyclase

  15. Stimulation of neurotrophic factors and inhibition of proinflammatory cytokines by exogenous application of triiodothyronine in the rat model of ischemic stroke.

    Science.gov (United States)

    Sabbaghziarani, Fatemeh; Mortezaee, Keywan; Akbari, Mohammad; Kashani, Iraj Ragerdi; Soleimani, Mansooreh; Hassanzadeh, Gholamreza; Zendedel, Adib

    2017-01-01

    There is a positive relation between decreases of triiodothyronine (T3) amounts and severity of stroke. The aim of this study was to evaluate the effect of exogenous T3 application on levels of neurogenesis markers in the subventricular zone. Cerebral ischemia was induced by middle cerebral artery occlusion in male Wistar rats. There were 4 experimental groups: sham, ischemic, vehicle, and treatment. Rats were injected with T3 (25 μg/kg, IV injection) at 24 hours after ischemia. Animals were sacrificed at day 7 after ischemia. There were high levels of brain-derived neurotrophic factor, nestin, and Sox2 expressions in gene and protein levels in the T3 treatment group (P ≤ .05 vs ischemic group). Treatment group showed high levels of sera T3 and thyroxine (T4) but low levels of thyrotropin (TSH), tumor necrosis factor-α, and interleukin-6 (P ≤ .05 vs ischemic group) at day 4 after ischemia induction. Findings of this study revealed the effectiveness of exogenous T3 application in the improvement of neurogenesis possibly via regulation of proinflammatory cytokines. Copyright © 2017 John Wiley & Sons, Ltd.

  16. Protective effect of tetraethyl pyrazine against focal cerebral ischemia/reperfusion injury in rats: therapeutic time window and its mechanism.

    Science.gov (United States)

    Jia, Jie; Zhang, Xi; Hu, Yong-Shan; Wu, Yi; Wang, Qing-Zhi; Li, Na-Na; Wu, Cai-Qin; Yu, Hui-Xian; Guo, Qing-Chuan

    2009-03-01

    Tetramethyl pyrazine has been considered an effective agent in treating neurons ischemia/reperfusion injury, but the mechanism of its therapeutic effect remains unclear. This study was to explore the therapeutic time window and mechanism of tetramethyl pyrazine on temporary focal cerebral ischemia/reperfusion injury. Middle cerebral artery occlusion was conducted in male Sprague-Dawley rats and 20 mg/kg of tetramethyl pyrazine was intraperitoneally injected at different time points. At 72 h after reperfusion, all animals' neurologic deficit scores were evaluated. Cerebrums were removed and cerebral infarction volume was measured. The expression of thioredoxin and thioredoxin reductase mRNA was determined at 6 and 24 h after reperfusion. Cerebral infarction volume and neurological deficit scores were significantly decreased in the group with tetramethyl pyrazine treatment. The expression of thioredoxin-1/thioredoxin-2 and thioredoxin reductase-1/thioredoxin reductase-2 was significantly decreased in rats with ischemia/reperfusion injury, while it was increased by tetramethyl pyrazine administration. Treatment with tetramethyl pyrazine, within 4 h after reperfusion, protects the brain from ischemic reperfusion injury in rats. The neuroprotective mechanism of tetramethyl pyrazine treatment is, in part, mediated through the upregulation of thioredoxin transcription.

  17. [Sensitivity and specificity of the cerebral blood flow reactions to acupuncture in the newborn infants presenting with hypoxic ischemic encephalopathy].

    Science.gov (United States)

    Filonenko, A V; Vasilenko, A M; Khan, M A

    2015-01-01

    To evaluate the effects of acupuncture integrated into the standard therapy, the condition of cerebral blood flow, and other syndromes associated with cerebral ischemia in the newborn infants. MATERIAL AND METHODS. A total of 131 pairs of puerperae and newborns with hypoxic ischemic encephalopathy were divided into four treatment groups. 34 children of the first group were given standard therapy (control), in the second group comprised of 33 mothers and children the standard treatment was supplemented by acupuncture, the third group included only 32 mothers given the acupuncture treatment alone, and the fourth group contained only 32 newborn infants treated by acupuncture. Each course of acupuncture treatment consisted of five sessions. Sensitivity and specificity of cerebral blood flow reactions were determined based on the results of the ROC-analysis and the area under the curve before and after the treatment. The treatment with the use of acupuncture greatly improved the cerebrospinal hemodynamics (p newborn babies. The high level of sensitivity (84.4-94.8%) associated with good specificity makes it possible to distinguish between the true positive and true negative cases. Acupuncture integrated into the treatment of "mother-baby" pairs presenting with hypoxic ischemic encephalopathy can be used to improve the initially low level of cerebral blood flow in neonates presenting with this condition.

  18. Curcumin Protects Neuron against Cerebral Ischemia-Induced Inflammation through Improving PPAR-Gamma Function

    OpenAIRE

    Zun-Jing Liu; Wei Liu; Lei Liu; Cheng Xiao; Yu Wang; Jing-Song Jiao

    2013-01-01

    Cerebral ischemia is the most common cerebrovascular disease worldwide. Recent studies have demonstrated that curcumin had beneficial effect to attenuate cerebral ischemic injury. However, it is unclear how curcumin protects against cerebral ischemic injury. In the present study, using rat middle cerebral artery occlusion model, we found that curcumin was a potent PPAR ? agonist in that it upregulated PPAR ? expression and PPAR ? -PPRE binding activity. Administration of curcumin markedly dec...

  19. Damaged Neocortical Perineuronal Nets Due to Experimental Focal Cerebral Ischemia in Mice, Rats and Sheep

    Directory of Open Access Journals (Sweden)

    Wolfgang Härtig

    2017-08-01

    Full Text Available As part of the extracellular matrix (ECM, perineuronal nets (PNs are polyanionic, chondroitin sulfate proteoglycan (CSPG-rich coatings of certain neurons, known to be affected in various neural diseases. Although these structures are considered as important parts of the neurovascular unit (NVU, their role during evolution of acute ischemic stroke and subsequent tissue damage is poorly understood and only a few preclinical studies analyzed PNs after acute ischemic stroke. By employing three models of experimental focal cerebral ischemia, this study was focused on histopathological alterations of PNs and concomitant vascular, glial and neuronal changes according to the NVU concept. We analyzed brain tissues obtained 1 day after ischemia onset from: (a mice after filament-based permanent middle cerebral artery occlusion (pMCAO; (b rats subjected to thromboembolic MACO; and (c sheep at 14 days after electrosurgically induced focal cerebral ischemia. Multiple fluorescence labeling was applied to explore simultaneous alterations of NVU and ECM. Serial mouse sections labeled with the net marker Wisteria floribunda agglutinin (WFA displayed largely decomposed and nearly erased PNs in infarcted neocortical areas that were demarcated by up-regulated immunoreactivity for vascular collagen IV (Coll IV. Subsequent semi-quantitative analyses in mice confirmed significantly decreased WFA-staining along the ischemic border zone and a relative decrease in the directly ischemia-affected neocortex. Triple fluorescence labeling throughout the three animal models revealed up-regulated Coll IV and decomposed PNs accompanied by activated astroglia and altered immunoreactivity for parvalbumin, a calcium-binding protein in fast-firing GABAergic neurons which are predominantly surrounded by neocortical PNs. Furthermore, ischemic neocortical areas in rodents simultaneously displayed less intense staining of WFA, aggrecan, the net components neurocan, versican and the

  20. Agonist of inward rectifier K+ channels enhances the protection of ischemic postconditioning in isolated rat hearts.

    Science.gov (United States)

    Liao, Z; Feng, Z; Long, C

    2014-07-01

    Selective inhibition of inward rectifier K + channels could abolish the protection mediated by ischemic preconditioning, but the roles of these channels in ischemic postconditioning have not been well characterized. Our study aims to evaluate the effect of inward rectifier K + channels on the protection induced by ischemic postconditioning. Langendorff-perfused rat hearts (n=8 per group) were split into four groups: postconditioning hearts (IPO group); ischemic postconditioning with BaCl 2 hearts (PB group); ischemic postconditioning with zacopride hearts (PZ group); and without ischemic postconditioning (CON group). After suffering 30 minutes of global ischemia, groups IPO, PB and PZ went through 10 seconds of ischemic postconditioning with three different perfusates: respectively, Krebs-Henseleit buffer (IPO group); 20 μmol/L BaCl 2 (antagonist of the channel, PB group); 1 μmol/L zacopride (agonist of the channel, PZ group). At the end of reperfusion, the myocardial performance was better preserved in the PZ group than the other three groups. The PB group showed no significant differences from the CON group. Our study has shown that the I K1 channel agonist zacopride is associated with the enhancement of ischemic postconditioning. © The Author(s) 2014.

  1. Relative cerebral blood volume as a marker of durable tissue-at-risk viability in hyperacute ischemic stroke.

    Science.gov (United States)

    Cortijo, Elisa; Calleja, Ana Isabel; García-Bermejo, Pablo; Mulero, Patricia; Pérez-Fernández, Santiago; Reyes, Javier; Muñoz, Ma Fe; Martínez-Galdámez, Mario; Arenillas, Juan Francisco

    2014-01-01

    Selection of best responders to reperfusion therapies could be aided by predicting the duration of tissue-at-risk viability, which may be dependant on collateral circulation status. We aimed to identify the best predictor of good collateral circulation among perfusion computed tomography (PCT) parameters in middle cerebral artery (MCA) ischemic stroke and to analyze how early MCA response to intravenous thrombolysis and PCT-derived markers of good collaterals interact to determine stroke outcome. We prospectively studied patients with acute MCA ischemic stroke treated with intravenous thrombolysis who underwent PCT before treatment showing a target mismatch profile. Collateral status was assessed using a PCT source image-based score. PCT maps were quantitatively analyzed. Cerebral blood volume (CBV), cerebral blood flow, and Tmax were calculated within the hypoperfused volume and in the equivalent region of unaffected hemisphere. Occluded MCAs were monitored by transcranial Duplex to assess early recanalization. Main outcome variables were brain hypodensity volume and modified Rankin scale score at day 90. One hundred patients with MCA ischemic stroke imaged by PCT received intravenous thrombolysis, and 68 met all inclusion criteria. A relative CBV (rCBV) >0.93 emerged as the only predictor of good collaterals (odds ratio, 12.6; 95% confidence interval, 2.9-55.9; P=0.001). Early MCA recanalization was associated with better long-term outcome and lower infarct volume in patients with rCBV<0.93, but not in patients with high rCBV. None of the patients with rCBV<0.93 achieved good outcome in absence of early recanalization. High rCBV was the strongest marker of good collaterals and may characterize durable tissue-at-risk viability in hyperacute MCA ischemic stroke.

  2. Neuroprotective effects of SMADs in a rat model of cerebral ischemia/reperfusion

    Directory of Open Access Journals (Sweden)

    Fang-fang Liu

    2015-01-01

    Full Text Available Previous studies have shown that up-regulation of transforming growth factor β1 results in neuroprotective effects. However, the role of the transforming growth factor β1 downstream molecule, SMAD2/3, following ischemia/reperfusion remains unclear. Here, we investigated the neuroprotective effects of SMAD2/3 by analyzing the relationships between SMAD2/3 expression and cell apoptosis and inflammation in the brain of a rat model of cerebral ischemia/reperfusion. Levels of SMAD2/3 mRNA were up-regulated in the ischemic penumbra 6 hours after cerebral ischemia/reperfusion, reached a peak after 72 hours and were then decreased at 7 days. Phosphorylated SMAD2/3 protein levels at the aforementioned time points were consistent with the mRNA levels. Over-expression of SMAD3 in the brains of the ischemia/reperfusion model rats via delivery of an adeno-associated virus containing the SMAD3 gene could reduce tumor necrosis factor-α and interleukin-1β mRNA levels, down-regulate expression of the pro-apoptotic gene, capase-3, and up-regulate expression of the anti-apoptotic protein, Bcl-2. The SMAD3 protein level was negatively correlated with cell apoptosis. These findings indicate that SMAD3 exhibits neuroprotective effects on the brain after ischemia/reperfusion through anti-inflammatory and anti-apoptotic pathways.

  3. Induction of interleukin-1β mRNA after focal cerebral ischaemia in the rat

    NARCIS (Netherlands)

    Buttini, M.; Sauter, A.; Boddeke, H.W.G.M.

    1994-01-01

    The expression of interleukin-1β (IL-1β) mRNA in the brain in response to cerebral ischaemia in rats was examined using in situ hybridization histochemistry. Focal cerebral ischaemia was induced in spontaneously hypertensive rats by permanent occlusion of the left middle cerebral artery (MCAO).

  4. INDUCTION OF INTERLEUKIN-1-BETA MESSENGER-RNA AFTER FOCAL CEREBRAL-ISCHEMIA IN THE RAT

    NARCIS (Netherlands)

    BUTTINI, M; SAUTER, A; BODDEKE, HWGM

    The expression of interleukin-1beta (IL-1beta) mRNA in the brain in response to cerebral ischaemia in rats was examined using in situ hybridization histochemistry. Focal cerebral ischaemia was induced in spontaneously hypertensive rats by permanent occlusion of the left middle cerebral artery

  5. Anti neuroinflammatory effect of Vildagliptin in ischaemia-reperfusion induced cerebral infarction in normal and STZ induced type-II diabetic rats

    Directory of Open Access Journals (Sweden)

    Kaleru Purnachander

    2016-03-01

    Full Text Available Diabetes is one of the major risk factor for cerebral ischemic stroke. Increased base line levels of oxidative stress in diabetes will lead to cerebral ischemic damage. In pathological conditions such as cerebral ischemia/reperfusion injury, free radicals cause oxidative stress and inflammation leading to increased injury of brain. Inflammation is one of the major pathological mechanisms involved in cerebral ischemia and reperfusion injury. Vildagliptin newer anti-diabetic drug of the class DPP-4 inhibitors is reported to have anti-inflammatory properties apart from its antihyperglycemic activity. Therefore the aim of the present study is to evaluate the anti-inflammatory effect of Vildagliptin against cerebral infarction induced ischemia reperfusion injury in normal and STZ induced diabetic Wistar rats. Cerebral infarction was induced by bilateral common carotid artery occlusion followed by 4 hr reperfusion. Percent infarction, inflammatory markers such as MPO, TNF-α, IL-6 and IL-10 were analysed. Treatment with Vildagliptin for a period of four weeks produced significant reduction in percent cerebral infarct volume. Vildagliptin at 10 mg/kg dose, showed significant reduction in markers like MPO, TNF-α, IL-6 and IL-1β in diabetic group when compared to normal group and in contrast significant increase in anti-inflammatory marker like IL-10 levels. Vildagliptin showed significant cerebroprotective effect by antiinflammatory mechanisms.

  6. Exercise preconditioning improves behavioral functions following transient cerebral ischemia induced by 4-vessel occlusion (4-VO) in rats.

    Science.gov (United States)

    Tahamtan, Mahshid; Allahtavakoli, Mohammad; Abbasnejad, Mehdi; Roohbakhsh, Ali; Taghipour, Zahra; Taghavi, Mohsen; Khodadadi, Hassan; Shamsizadeh, Ali

    2013-12-01

    There is evidence that exercise decreases ischemia/reperfusion injury in rats. Since behavioral deficits are the main outcome in patients after stroke, our study was designed to investigate whether exercise preconditioning improves the acute behavioral functions and also brain inflammatory injury following cerebral ischemia. Male rats weighing 250-300 g were randomly allocated into five experimental groups. Exercise was performed on a treadmill 30min/day for 3 weeks. Ischemia was induced by 4-vessel occlusion method. Recognition memory was assessed by novel object recognition task (NORT) and step-through passive avoidance task. Sensorimotor function and motor movements were evaluated by adhesive removal test and ledged beam-walking test, respectively. Brain inflammatory injury was evaluated by histological assessment. In NORT, the discrimination ratio was decreased after ischemia (P test, a significant reduction in response latency was observed in the ischemic group. Exercise preconditioning significantly decreased the response latency in the ischemic rats (P test, latency to touch and remove the sticky labels from forepaw was increased following induction of ischemia (all P beam-walking test, the slip ratio was increased following ischemia (P < 0.05).  In the ischemia group, marked neuronal injury in hippocampus was observed. These neuropathological changes were attenuated by exercise preconditioning (P < 0.001). Our results showed that exercise preconditioning improves behavioral functions and maintains more viable cells in the dorsal hippocampus of the ischemic brain.

  7. In vivo measurements of cerebral metabolic abnormalities by proton spectroscopy after a transient ischemic attack revealing an internal carotid stenosis > 70%

    International Nuclear Information System (INIS)

    Giroud, M.; Becker, F.; Lemesle, M.; Walker, P.; Guy, F.; Martin, D.; Baudouin, N.; Brunotte, F.; Dumas, R.

    1996-01-01

    Aims: The aim of this work is to look for cerebral metabolic abnormalities within the first 3 days after a transient ischemic attack revealing an internal carotid stenosis > 70 %. Methods: Five patients with a transient ischemic attack lasting between 30 and 180 minutes, affecting sensory and motor brachio-facial territory, with or without aphasia. Were studied. A CT-scan, an EEG, a cervical Doppler ultrasound, a standard arteriography, a magnetic resonance imaging and a proton spectroscopy were performed within the cerebral area affected by the transient ischemic attack. We measured 2 markers: N-acetyl-aspartate, the marker of the neuronal mass, and lactate, the marker of anaerobe metabolism. In each case, a contralateral internal stenosis was diagnosed by cervical Doppler ultrasound and standard arteriography. No cerebral infarction was observed. Results: With the affected cerebral area defined according to clinical and EEG features, proton spectroscopy showed a significant rise of lactate, without any change in N-acetyl-aspartate levels. Conclusions: Within the first 3 days after a transient ischemic attack, there is a significant risk of lactate inside the affected cerebral area. This change may reflect a localized and transient hypoperfusion, but long enough to induce a rise of lactate but not sufficient to produce a cerebral infarct. This area is probably at risk to induce cerebral infarct. This data lead us to study the metabolic change induced by the asymptomatic internal carotid stenosis. (authors). 18 refs

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

    Directory of Open Access Journals (Sweden)

    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

  9. Response of the sensorimotor cortex of cerebral palsy rats receiving transplantation of vascular endothelial growth factor 165-transfected neural stem cells

    Institute of Scientific and Technical Information of China (English)

    Jielu Tan; Xiangrong Zheng; Shanshan Zhang; Yujia Yang; Xia Wang; Xiaohe Yu; Le Zhong

    2014-01-01

    Neural stem cells are characterized by the ability to differentiate and stably express exogenous ge-nes. Vascular endothelial growth factor plays a role in protecting local blood vessels and neurons of newborn rats with hypoxic-ischemic encephalopathy. Transplantation of vascular endothelial growth factor-transfected neural stem cells may be neuroprotective in rats with cerebral palsy. In this study, 7-day-old Sprague-Dawley rats were divided into ifve groups: (1) sham operation (control), (2) cerebral palsy model alone or with (3) phosphate-buffered saline, (4) vascular en-dothelial growth factor 165 + neural stem cells, or (5) neural stem cells alone. hTe cerebral palsy model was established by ligating the letf common carotid artery followed by exposure to hypox-ia. Phosphate-buffered saline, vascular endothelial growth factor + neural stem cells, and neural stem cells alone were administered into the sensorimotor cortex using the stereotaxic instrument and microsyringe. Atfer transplantation, the radial-arm water maze test and holding test were performed. Immunohistochemistry for vascular endothelial growth factor and histology using hematoxylin-eosin were performed on cerebral cortex. Results revealed that the number of vas-cular endothelial growth factor-positive cells in cerebral palsy rats transplanted with vascular endothelial growth factor-transfected neural stem cells was increased, the time for ifnding water and the ifnding repetitions were reduced, the holding time was prolonged, and the degree of cell degeneration or necrosis was reduced. hTese ifndings indicate that the transplantation of vascu-lar endothelial growth factor-transfected neural stem cells alleviates brain damage and cognitive deifcits, and is neuroprotective in neonatal rats with hypoxia ischemic-mediated cerebral palsy.

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

    Science.gov (United States)

    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.

  11. QUANTITATIVE CHANGES IN REGIONAL CEREBRAL BLOOD FLOW INDUCED BY COLD, HEAT AND ISCHEMIC PAIN: A CONTINUOUS ARTERIAL SPIN LABELING STUDY

    Science.gov (United States)

    Frölich, Michael A.; Deshpande, Hrishikesh; Ness, Timothy; Deutsch, Georg

    2012-01-01

    Background The development of arterial spin labeling methods, has allowed measuring regional cerebral blood flow (rCBF) quantitatively and to show the pattern of cerebral activity associated with any state such as a sustained pain state or changes due to a neurotropic drug. Methods We studied the differential effects of three pain conditions in ten healthy subjects on a 3T scanner during resting baseline, heat, cold and ischemic pain using continuous arterial spin labeling. Results Cold pain showed the greatest absolute rCBF increases in left anterior cingulate cortex, left amygdala, left angular gyrus, and Brodmann Area 6, and a significant rCBF decrease in the cerebellum. Changes in rCBF were characteristic of the type of pain condition: cold and heat pain showed increases, while the ischemic condition showed a reduction in mean absolute gray matter flow compared to rest. An association of subjects’ pain tolerance and cerebral blood flow was noted. Conclusions The observation that quantitative rCBF changes are characteristic of the pain task employed and that there is a consistent rCBF change in Brodman area 6, an area responsible for the integration of a motor response to pain, should provide extremely useful information in the quest to develop an imaging biomarker of pain. Conceivably, response in BA6 may serve as an objective measure of analgesic efficacy. PMID:22913924

  12. Quantitative changes in regional cerebral blood flow induced by cold, heat and ischemic pain: a continuous arterial spin labeling study.

    Science.gov (United States)

    Frölich, Michael A; Deshpande, Hrishikesh; Ness, Timothy; Deutsch, Georg

    2012-10-01

    The development of arterial spin labeling methods has allowed measuring regional cerebral blood flow (rCBF) quantitatively and to show the pattern of cerebral activity associated with any state such as a sustained pain state or changes due to a neurotropic drug. The authors studied the differential effects of three pain conditions in 10 healthy subjects on a 3 Tesla scanner during resting baseline, heat, cold, and ischemic pain using continuous arterial spin labeling. Cold pain showed the greatest absolute rCBF increases in left anterior cingulate cortex, left amygdala, left angular gyrus, and Brodmann area 6, and a significant rCBF decrease in the cerebellum. Changes in rCBF were characteristic of the type of pain condition: cold and heat pain showed increases, whereas the ischemic condition showed a reduction in mean absolute gray matter flow compared with rest. An association of subjects' pain tolerance and cerebral blood flow was noted. The observation that quantitative rCBF changes are characteristic of the pain task used and that there is a consistent rCBF change in Brodman area 6, an area responsible for the integration of a motor response to pain, should provide extremely useful information in the quest to develop an imaging biomarker of pain. Conceivably, response in BA6 may serve as an objective measure of analgesic efficacy.

  13. Is elevated SUA associated with a worse outcome in young Chinese patients with acute cerebral ischemic stroke?

    Directory of Open Access Journals (Sweden)

    Zhang Bin

    2010-09-01

    Full Text Available Abstract Background Elevated serum uric acid (SUA levels can enhance its antioxidant prosperities and reduce the occurrence of cerebral infarction. Significantly elevated SUA levels have been associated with a better prognosis in patients with cerebral infarction; however, the results from some studies on the relationship between SUA and the prognosis of patients with cerebral infarction remain controversial. Methods We analyzed the relationship between SUA and clinical prognosis of 585 young Chinese adults with acute ischemic stroke as determined by the modified Rankin Scale at discharge. Using multivariate logistic regression modeling, we explore the relationship between SUA levels and patient's clinical prognosis. Results Lower SUA levels at time of admission were observed more frequently in the lowest quintile for patients with severe stroke (P = 0.02. Patients with cerebral infarction patients caused by small-vessel blockage had higher SUA concentrations (P = 0.01 and the lower mRS scores (P Conclusion Elevated SUA is an independent predictor for good clinical outcome of acute cerebral infarction among young adults.

  14. Prolonged disturbances of regional cerebral blood flow in transient ischemic attacks

    International Nuclear Information System (INIS)

    Hartmann, A.

    1985-01-01

    Regional cerebral blood flow (rCBF) was measured over both hemispheres in 20 patients with unilateral transient ischemic attacks (TIA) of the territory of the internal carotid artery on the day of the TIA. rCBF was estimated with the nontraumatic Xenon 133-inhalation technique using the initial slope index. 13 patients experienced their first TIA, 7 had several attacks. In 14 patients the first rCBF-measurement was performed during the presentation of clinical symptoms. The 2nd rCBF-measurement was done on day 2, the last one on day 7. Scans of the 15 patients studied with CT were normal. On day 1 mean rCBF of the TIA-side was significantly lower than that of the contralateral hemispheres. 22% of all areas showed a significant reduction of flow compared to mean rCBF. Mean rCBF of both the TIA- and the contralateral side was significantly reduced compared to the bi-hemispheric mean rCBF of a control group with no history of TIA or completed strokes but at least 2 risk factors for cerebrovascular disease. Whereas mean rCBF did not change in the contralateral side it increased significantly (+6.9%) in the TIA-side from day 1 to day 2 but not from there to day 7. This is reflected by the increase of the total number of ROI with normal flow from day 1 to day 2. Considering the actual flow and the flow course of that tissue which was believed to be responsible for the clinical symptoms the following regional patterns were observed: normal rCBF in 6 patients; early return to normal concomitant to the clinical course (n = 4)

  15. Analysis of ischemic cerebral lesions using 3.0-T diffusion-weighted imaging and magnetic resonance angiography after revascularization surgery for ischemic disease.

    Science.gov (United States)

    Murai, Yasuo; Mizunari, Takayuki; Takagi, Ryo; Amano, Yasuo; Mizumura, Sunao; Komaba, Yuichi; Okubo, Seiji; Kobayashi, Shiro; Teramoto, Akira

    2013-07-01

    Cerebral revascularization surgery (CRS) is increasingly recognized as an important component in the treatment of complex cerebral vascular disease and tumors. CRS requires that the incidence of perioperative neurological complications should be minimized, because CRS for ischemic disease is often not the goal of treatment, but rather a prophylactic surgery. CRS carries the risk of focal postoperative neurological deficits. Little has been established concerning mechanisms of post-CRS ischemia. We used 3.0-T diffusion-weighted magnetic resonance imaging (DWI) and magnetic resonance angiography (MRA) to analyze the incidence and mechanism of ischemic lesions. We studied the anterior circulation territory after 20 CRS procedures involving 33 vascular anastomosis procedures (13 double anastomoses and 7 single anastomoses) in 12 men and 8 women between June 2007 and October 2011. The operations included single or double superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis to treat internal carotid artery/MCA occlusions or severe MCA stenosis. A combined STA-MCA anastomosis and indirect bypass were performed for moyamoya disease. Postoperative DWI and MRA were obtained in all patients between 24 and 96 h after surgery to detect thromboembolism, hypoperfusion, or procedural ischemic complications and vasospasms of the donor STA. Follow-up DWI and MRA were carried out 1.8±0.6 days after CRS (range, 1-4 days). Temporary occlusion time for anastomoses averaged 18.9 min (range, 16-32 min). Asymptomatic new hyperintensities occurred in the ipsilateral hemisphere of 2 patients on postoperative DWI (10% patients/6.0% anastomoses), and 1 moyamoya patient (5.0% patients/3.0% anastomoses) developed a symptomatic hyperintensity in the ipsilateral occipital lobe in response to the operation. Two abnormal small (3.0-T DWI study of CRS and related clinical events. The incidence of symptomatic postoperative DWI abnormalities was restricted to 1 moyamoya patient

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

    Science.gov (United States)

    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.

  17. Bexarotene reduces blood-brain barrier permeability in cerebral ischemia-reperfusion injured rats.

    Directory of Open Access Journals (Sweden)

    Lu Xu

    Full Text Available Matrix metalloproteinase-9 (MMP-9 over-expression disrupts the blood-brain barrier (BBB in the ischemic brain. The retinoid X receptor agonist bexarotene suppresses MMP-9 expression in endothelial cells and displays neuroprotective effects. Therefore, we hypothesized that bexarotene may have a beneficial effect on I/R-induced BBB dysfunction.A total of 180 rats were randomized into three groups (n = 60 each: (i a sham-operation group, (ii a cerebral ischemia-reperfusion (I/R group, and (iii an I/R+bexarotene group. Brain water content was measured by the dry wet weight method. BBB permeability was analyzed by Evans Blue staining and the magnetic resonance imaging contrast agent Omniscan. MMP-9 mRNA expression, protein expression, and activity were assessed by reverse transcription polymerase chain reaction, Western blotting, and gelatin zymography, respectively. Apolipoprotein E (apoE, claudin-5, and occludin expression were analyzed by Western blotting.After 24 h, 48 h, and 72 h post-I/R, several effects were observed with bexarotene administration: (i brain water content and BBB permeability were significantly reduced; (ii MMP-9 mRNA and protein expression as well as activity were significantly decreased; (iii claudin-5 and occludin expression were significantly increased; and (iv apoE expression was significantly increased.Bexarotene decreases BBB permeability in rats with cerebral I/R injury. This effect may be due in part to bexarotene's upregulation of apoE expression, which has been previously shown to reduce BBB permeability through suppressing MMP-9-mediated degradation of the tight junction proteins claudin-5 and occludin. This work offers insight to aid future development of therapeutic agents for cerebral I/R injury in human patients.

  18. Study of the influence and molecular mechanism of ticagrelor on cerebral ischemia reperfusion injury in rats

    Directory of Open Access Journals (Sweden)

    Gui-Fa Chen

    2017-06-01

    Full Text Available Objective: To study the influence and molecular mechanism of ticagrelor on cerebral ischemia reperfusion injury in rats. Methods: SD rats were selected as experimental animals and divided into control group, model group, ticagrelor group and clopidogrel group, cerebral ischemic reperfusion injury models were made, then ticagrelor group were given intragastric administration of 150 mg ticagrelor, clopidogrel group were given intragastric administration of 90 mg clopidogrel. 1 week after intervention, the brain water content as well as the contents of oxidative stress molecules and inflammatory factors were measured. Results: Water content in brain, MDA, Ox-LDL, NF-kB, TNF-α, IL-1β and IL-6 contents in brain tissue as well as TNF-α, IL-1β and IL-6 contents in serum of model group were significantly higher than those of control group while SOD, GSH-Px and Prdx6 contents in brain tissue were significantly lower than those of control group; water content in brain, MDA, Ox-LDL, NFkB, TNF-α, IL-1β and IL-6 contents in brain tissue as well as TNF-α, IL-1β and IL-6 contents in serum of ticagrelor group and clopidogrel group were significantly lower than those of model group while SOD, GSH-Px and Prdx6 contents in brain tissue were significantly higher than those of model group; water content in brain, MDA, Ox-LDL, NF-kB, TNF-α, IL-1β and IL-6 contents in brain tissue as well as TNF-α, IL-1β and IL-6 contents in serum of ticagrelor group were significantly lower than those of clopidogrel group while SOD, GSHPx and Prdx6 contents in brain tissue were significantly higher than those of clopidogrel group. Conclusion: Ticagrelor can be more effective in inhibiting oxidative stress response and inflammatory response, and reducing the cerebral ischemia reperfusion injury than clopidogrel.

  19. Overview of Experimental and Clinical Findings regarding the Neuroprotective Effects of Cerebral Ischemic Postconditioning

    OpenAIRE

    Ma, Di; Feng, Liangshu; Deng, Fang; Feng, Jia-Chun

    2017-01-01

    Research on attenuating the structural and functional deficits observed following ischemia-reperfusion has become increasingly focused on the therapeutic potential of ischemic postconditioning. In recent years, various methods and animal models of ischemic postconditioning have been utilized. The results of these numerous studies have indicated that the mechanisms underlying the neuroprotective effects of ischemic postconditioning may involve reductions in the generation of free radicals and ...

  20. Double-tracer autoradiographic study of protein synthesis and glucose consumption in rats with focal cerebral ischemia

    DEFF Research Database (Denmark)

    Christensen, Thomas; Balchen, T; Bruhn, T

    1999-01-01

    A double-tracer autoradiographic method for simultaneous measurement of regional glucose utilization (rCMRglc) and regional protein synthesis (PS) in consecutive brain sections is described and applied to study the metabolism of the ischemic penumbra 2 h after occlusion of the middle cerebral...... artery (MCAO) in rats. In halothane anesthesia, the left middle cerebral artery was permanently occluded. Two hours after MCAO an i.v. bolus injection of 14C-deoxyglucose and 3H-leucine was given and circulated for 45 min. Two sets of brain sections were processed for quantitative autoradiography....... Neighboring brain sections exposed an X-ray film (3H-insensitive), and a 3H-sensitive for determination of rCMRglc and PS, respectively. Sections for PS determination were washed in trichloroacetic acid (TCA) prior to film exposure in order to remove 14C-deoxyglucose and unincorporated 3H-leucine. Regional...

  1. Xinnao Shutong Modulates the Neuronal Plasticity Through Regulation of Microglia/Macrophage Polarization Following Chronic Cerebral Hypoperfusion in Rats

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    Liye Wang

    2018-05-01

    Full Text Available Xinnao shutong (XNST capsules have been clinically used in China to treat cerebrovascular diseases. Previous studies have demonstrated that XNST has significant neuroprotective effects against acute cerebral ischemic stroke. The present study investigated the effects and mechanisms of XNST treatment following chronic cerebral hypoperfusion. Thirty-six adult male Sprague-Dawley rats were treated with XNST or vehicle following permanent bilateral common carotid artery (BCCA ligation. Body weight was recorded on days 0, 3, 7, 14, 28, and 42 post-surgery. The Morris water maze (MWM test was used to assess cognitive function in rats. Immunofluorescent staining and western blot were used to assess the severity of neuronal plasticity, white matter injury, and the numbers and/or phenotypic changes incurred to microglia. Protein levels of p-AKT (Thr308 and p-ERK (Thr202/Tyr204 were detected 42 days after BCCA ligation was performed. The results indicate that XNST treatment significantly reduced escape latency, decreased the frequency of platform crossing compared to the vehicle group. Synaptophysin, protein levels improved and white matter injury ameliorated following XNST treatment. Meanwhile, XNST reduced the number of M1 microglia and increased the number of M2 microglia. Furthermore, p-AKT (Thr308 and p-ERK (Thr202/Tyr204 levels were increased 42 days following BCCA ligation. In summary, our results suggest that XNST mitigates memory impairments by restoration of neuronal plasticity and by modulation of microglial polarization following chronic cerebral hypoperfusion in rats.

  2. Expression of glutamic acid decarboxylase and identification of GABAergic cells in the ischemic rat dentate gyrus

    DEFF Research Database (Denmark)

    Müller, Georg Johannes; Dogonowski, Anne-Marie; Finsen, Bente

    2006-01-01

    We have investigated the glutamic acid dexcarboxylase (GAD) mRNA and protein isoforms as markers for ischemic loss of GABAergic neurons in the dentate hilus. Stereological counts of these neurons were performed in rats surviving 8 days after 10 min of transient forebrain ischemia, and in control...

  3. Early segmental changes in ischemic acute tubular necrosis of the rat kidney

    DEFF Research Database (Denmark)

    Faarup, Poul; Nørgaard, Tove; Hegedüs, Viktor

    2004-01-01

    The background and mechanisms of ischemic acute tubular necrosis are still essentially unclarified. Therefore a quantitative morphological technique was applied for evaluation of the early structural changes in different fractions of the proximal convoluted tubule in the rat renal cortex. In male...

  4. Functional response of cerebral blood flow induced by somatosensory stimulation in rats with subarachnoid hemorrhage

    Science.gov (United States)

    Li, Zhiguo; Huang, Qin; Liu, Peng; Li, Pengcheng; Ma, Lianting; Lu, Jinling

    2015-09-01

    Subarachnoid hemorrhage (SAH) is often accompanied by cerebral vasospasm (CVS), which is the phenomenon of narrowing of large cerebral arteries, and then can produce delayed ischemic neurological deficit (DIND) such as lateralized sensory dysfunction. CVS was regarded as a major contributor to DIND in patients with SAH. However, therapy for preventing vasospasm after SAH to improve the outcomes may not work all the time. It is important to find answers to the relationship between CVS and DIND after SAH. How local cerebral blood flow (CBF) is regulated during functional activation after SAH still remains poorly understood, whereas, the regulation of CBF may play an important role in weakening the impact of CVS on cortex function. Therefore, it is worthwhile to evaluate the functional response of CBF in the activated cortex in an SAH animal model. Most evaluation of the effect of SAH is presently carried out by neurological behavioral scales. The functional imaging of cortical activation during sensory stimulation may help to reflect the function of the somatosensory cortex more locally than the behavioral scales do. We investigated the functional response of CBF in the somatosensory cortex induced by an electrical stimulation to contralateral forepaw via laser speckle imaging in a rat SAH model. Nineteen Sprague-Dawley rats from two groups (control group, n=10 and SAH group, n=9) were studied. SAH was induced in rats by double injection of autologous blood into the cisterna magna after CSF aspiration. The same surgical procedure was applied in the control group without CSF aspiration or blood injection. Significant CVS was found in the SAH group. Meanwhile, we observed a delayed peak of CBF response in rats with SAH compared with those in the control group, whereas no significant difference was found in magnitude, duration, and areas under curve of relative CBF changes between the two groups. The results suggest that the regulation function of local CBF during

  5. Enhanced vasomotion of cerebral arterioles in spontaneously hypertensive rats

    Science.gov (United States)

    Lefer, D. J.; Lynch, C. D.; Lapinski, K. C.; Hutchins, P. M.

    1990-01-01

    Intrinsic rhythmic changes in the diameter of pial cerebral arterioles (30-70 microns) in anesthetized normotensive and hypertensive rats were assessed in vivo to determine if any significant differences exist between the two strains. All diameter measurements were analyzed using a traditional graphic analysis technique and a new frequency spectrum analysis technique known as the Prony Spectral Line Estimator. Graphic analysis of the data revealed that spontaneously hypertensive rats (SHR) possess a significantly greater fundamental frequency (5.57 +/- 0.28 cycles/min) of vasomotion compared to the control Wistar-Kyoto normotensive rats (WKY) (1.95 +/- 0.37 cycles/min). Furthermore, the SHR cerebral arterioles exhibited a significantly greater amplitude of vasomotion (10.07 +/- 0.70 microns) when compared to the WKY cerebral arterioles of the same diameter (8.10 +/- 0.70 microns). Diameter measurements processed with the Prony technique revealed that the fundamental frequency of vasomotion in SHR cerebral arterioles (6.14 +/- 0.39 cycles/min) was also significantly greater than that of the WKY cerebral arterioles (2.99 +/- 0.42 cycles/min). The mean amplitudes of vasomotion in the SHR and WKY strains obtained by the Prony analysis were found not to be statistically significant in contrast to the graphic analysis of the vasomotion amplitude of the arterioles. In addition, the Prony system was able to consistently uncover a very low frequency of vasomotion in both strains of rats that was typically less than 1 cycle/min and was not significantly different between the two strains. The amplitude of this slow frequency was also not significantly different between the two strains. The amplitude of the slow frequency of vasomotion (less than 1 cycle/min) was not different from the amplitude of the higher frequency (2-6 cycles/min) vasomotion by Prony or graphic analysis. These data suggest that a fundamental intrinsic defect exists in the spontaneously hypertensive rat

  6. The Protective Effect of Human Umbilical Cord Blood CD34+ Cells and Estradiol against Focal Cerebral Ischemia in Female Ovariectomized Rat: Cerebral MR Imaging and Immunohistochemical Study.

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    Ching-Chung Liang

    Full Text Available Human umbilical cord blood derived CD34+ stem cells are reported to mediate therapeutic effects in stroke animal models. Estrogen was known to protect against ischemic injury. The present study wished to investigate whether the protective effect of CD34+ cells against ischemic injury can be reinforced with complemental estradiol treatment in female ovariectomized rat and its possible mechanism. Experiment 1 was to determine the best optimal timing of CD34+ cell treatment for the neuroprotective effect after 60-min middle cerebral artery occlusion (MCAO. Experiment 2 was to evaluate the adjuvant effect of 17β-estradiol on CD34+ cell neuroprotection after MCAO. Experiment 1 showed intravenous infusion with CD34+ cells before MCAO (pre-treatment caused less infarction size than those infused after MCAO (post-treatment on 7T magnetic resonance T2-weighted images. Experiment 2 revealed infarction size was most significantly reduced after CD34+ + estradiol pre-treatment. When compared with no treatment group, CD34+ + estradiol pre-treatment showed significantly less ADC reduction at 2 h and 2 d, less CBF reduction at 2 h and less hyperperfusion at 2 d. The immunoreactivity of c-Fos, c-Jun and GFAP was attenuated, and BDNF showed significant recovery from 2 h to 2 d after MCAO, especially after CD34+ + estradiol pre-treatment. The present study suggests pre-treatment with CD34+ cells with complemental estradiol can be most protective against ischemic injury, which may act through stabilization of cerebral hemodynamics and normalization of the expressions of immediate early genes and BDNF.

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

    Science.gov (United States)

    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.

  8. The Long-Term Outcome Comparison of Different Time-Delayed Kallikrein Treatments in a Mouse Cerebral Ischemic Model

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    Yaohui Ni

    2018-01-01

    Full Text Available Delayed administration of kallikrein after cerebral infarction can improve neurological function. However, the appropriate kallkrein treatment time after ischemic stroke has not been illuminated. In this study, we compared the long-term outcome among three kallikrein therapeutic regimens starting at different time points following mouse cerebral ischemia. Furthermore, the protective mechanisms involving neurogenesis, angiogenesis, and AKT-GSK3β-VEGF signaling pathway were analyzed. Human tissue kallikrein was injected through the tail vein daily starting at 8 h, 24 h, or 36 h after right middle cerebral artery occlusion (MCAO until the 28th day. Three therapeutic regimens all protected against neurological dysfunction, but kallikrein treatment starting at 8 h after MCAO had the best efficacy. Additionally, kallikrein treatment at 8 h after MCAO significantly enhanced cell proliferation including neural stem cell and induced differentiation of neural stem cell into mature neuron. Kallikrein treatment starting at 8 h also promoted more angiogenesis than other two treatment regimens, which was associated with AKT-GSK3β-VEGF signaling pathway. Thus, we confirm that three delayed kallikrein treatments provide protection against cerebral infarction and furthermore suggest that kallikrein treatment starting at 8 h had a better effect than that at 24 h and 36 h. These findings provide the experimental data contributing to better clinical application of exogenous kallikrein.

  9. Effect of chronic (-)-nicotine treatment on rat cerebral benzodiazepine receptors

    International Nuclear Information System (INIS)

    Magata, Yasuhiro; Kitano, Haruhiro; Shiozaki, Toshiki; Iida, Yasuhiko; Nishizawa, Sadahiko; Saji, Hideo; Konishi, Junji

    2000-01-01

    The purpose of this study was to clarify the effect of (-)-nicotine on cerebral benzodiazepine receptors (BzR) with radiotracer methods. The effect of (-)-nicotine on BzR was examined in in vitro studies using chronic (-)-nicotine-treated rats using 3 H-diazepam. The in vitro radioreceptor assay showed a 14% increase in the maximum number of binding sites of BzR in chronic (-)-nicotine-treated rats in comparison with the control rats. Moreover, a convenient in vivo uptake index of 125 I-iomazenil was calculated and a higher uptake of the radioactivity was observed in the chronic (-)-nicotine-treated group than in the control group. Although further studies of the mechanism of (-)-nicotine on such BzR changes are required, an increase in the amount of BzR in the cerebral cortex was found in rats that underwent chronic (-)-nicotine treatment, and this result contributed to the understanding of the effects of (-)-nicotine and smoking on neural functions

  10. Acupuncture regulates the glucose metabolism in cerebral functional regions in chronic stage ischemic stroke patients---a PET-CT cerebral functional imaging study

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    Huang Yong

    2012-06-01

    Full Text Available Abstract Background Acupuncture has been applied to aid in the recovery of post-stroke patients, but its mechanism is unclear. This study aims to analyze the relationship between acupuncture and glucose metabolism in cerebral functional regions in post-stroke patients using 18 FDG PET-CT techniques. Forty-three ischemic stroke patients were randomly divided into 5 groups: the Waiguan (TE5 needling group, the TE5 sham needling group, the sham point needling group, the sham point sham needling group and the non-needling group. Cerebral functional images of all patients were then acquired using PET-CT scans and processed by SPM2 software. Results Compared with the non-needling group, sham needling at TE5 and needling/sham needling at the sham point did not activate cerebral areas. However, needling at TE5 resulted in the activation of Brodmann Area (BA 30. Needling/sham needling at TE5 and needling at the sham point did not deactivate any cerebral areas, whereas sham needling at the sham point led to deactivation in BA6. Compared with sham needling at TE5, needling at TE5 activated BA13, 19 and 47 and did not deactivate any areas. Compared with needling at the sham point, needling at TE5 had no associated activation but a deactivating effect on BA9. Conclusion Needling at TE5 had a regulating effect on cerebral functional areas shown by PET-CT, and this may relate to its impact on the recovery of post-stroke patients.

  11. MR-angiography allows defining severity grades of cerebral vasospasm in an experimental double blood injection subarachnoid hemorrhage model in rats.

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    Vesna Malinova

    Full Text Available Magnetic resonance (MR imaging has been used for the detection of cerebral vasospasm (VSP related infarction in experimental subarachnoid hemorrhage (eSAH in rats. Conventional angiography is generally used to visualize VSP, which is an invasive technique with a possible increase in morbidity and mortality. In this study we evaluated the validity of MR-angiography (MRA in detecting VSP and its feasibility to define VSP severity grades after eSAH in rats.SAH was induced using the double-hemorrhage model in 12 rats. In two rats, saline solution was injected instead of blood (sham group. MR was performed on day 1, 2 and on day 5. T1-, T2-, T2*-weighted and time-of-flight MR sequences were applied, which were analyzed by two blinded neuroradiologists. Vessel narrowing of 25-50% was defined as mild, 50-75% as moderate and >75% as severe VSP.We performed a total of 34 MRAs in 14 rats. In 14 rats, MRA was performed on day 2 and day 5. In six rats MRA was additionally performed on day1 before the blood injection. A good visualization of cerebral vessels was possible in all cases. No VSP was seen in the sham group neither on day 2 nor on day 5. We found vasospasm on day 2 in 7 of the 14 rats (50% whereas all 7 rats had mild and one rat had additionally moderate and severe vasospasm in one vessel, respectively. On day 5 we found vasospasm in 8 of the 14 rats (60% whereas 4 rats had severe vasospasm, 1 rat had moderate vasospasm and 3 rats demonstrated mild vasospasm. In 4 of the 14 rats (30% an ischemic lesion was detected on day 5. Three of these rats had severe vasospasm and one rat had mild vasospasm. Severe vasospasm on day 5 was statistically significant correlated with the occurrence of ischemic lesions (Fisher's Exact test, OR 19.5, p = 0.03.MRA is a noninvasive diagnostic tool, which allows a good visualization of the cerebral vasculature and provides reproducible results concerning the detection of VSP and the differentiation into three severity

  12. Short-term sleep deprivation stimulates hippocampal neurogenesis in rats following global cerebral ischemia/reperfusion.

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    Oumei Cheng

    Full Text Available Sleep deprivation (SD plays a complex role in central nervous system (CNS diseases. Recent studies indicate that short-term SD can affect the extent of ischemic damage. The aim of this study was to investigate whether short-term SD could stimulate hippocampal neurogenesis in a rat model of global cerebral ischemia/reperfusion (GCIR.One hundred Sprague-Dawley rats were randomly divided into Sham, GCIR and short-term SD groups based on different durations of SD; the short-term SD group was randomly divided into three subgroups: the GCIR+6hSD*3d-treated, GCIR+12hSD-treated and GCIR+12hSD*3d-treated groups. The GCIR rat model was induced via the bilateral occlusion of the common carotid arteries and hemorrhagic hypotension. The rats were sleep-deprived starting at 48 h following GCIR. A Morris water maze test was used to assess learning and memory ability; cell proliferation and differentiation were analyzed via 5-bromodeoxyuridine (BrdU and neuron-specific enolase (NSE, respectively, at 14 and 28 d; the expression of hippocampal BDNF was measured after 7 d.The different durations of short-term SD designed in our experiment exhibited improvement in cognitive function as well as increased hippocampal BDNF expression. Additionally, the short-term SD groups also showed an increased number of BrdU- and BrdU/NSE-positive cells compared with the GCIR group. Of the three short-term SD groups, the GCIR+12hSD*3d-treated group experienced the most substantial beneficial effects.Short-term SD, especially the GCIR+12hSD*3d-treated method, stimulates neurogenesis in the hippocampal dentate gyrus (DG of rats that undergo GCIR, and BDNF may be an underlying mechanism in this process.

  13. The effect of S. pneumoniae bacteremia on cerebral blood flow autoregulation in rats

    DEFF Research Database (Denmark)

    Pedersen, Michael; Brandt, Christian T.; Knudsen, Gitte Moos

    2008-01-01

    during incremental reductions in cerebral perfusion pressure (CPP) by controlled hemorrhage. Autoregulation was preserved in all rats without meningitis (groups A and E) and was lost in 24 of 25 meningitis rats (groups B, C, and D) (P

  14. Docosahexaenoic acid signaling modulates cell survival in experimental ischemic stroke penumbra and initiates long-term repair in young and aged rats.

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    Tiffany N Eady

    Full Text Available Docosahexaenoic acid, a major omega-3 essential fatty acid family member, improves behavioral deficit and reduces infarct volume and edema after experimental focal cerebral ischemia. We hypothesize that DHA elicits neuroprotection by inducing AKT/p70S6K phosphorylation, which in turn leads to cell survival and protects against ischemic stroke in young and aged rats.Rats underwent 2 h of middle cerebral artery occlusion (MCAo. DHA, neuroprotectin D1 (NPD1 or vehicle (saline was administered 3 h after onset of stroke. Neurological function was evaluated on days 1, 2, 3, and 7. DHA treatment improved functional recovery and reduced cortical, subcortical and total infarct volumes 7 days after stroke. DHA also reduced microglia infiltration and increased the number of astrocytes and neurons when compared to vehicle on days 1 and 7. Increases in p473 AKT and p308 AKT phosphorylation/activation were observed in animals treated with DHA 4 h after MCAo. Activation of other members of the AKT signaling pathway were also observed in DHA treated animals including increases in pS6 at 4 h and pGSK at 24 h. DHA or NPD1 remarkably reduced total and cortical infarct in aged rats. Moreover, we show that in young and aged rats DHA treatment after MCAo potentiates NPD1 biosynthesis. The phosphorylation of p308 AKT or pGSK was not different between groups in aged rats. However, pS6 expression was increased with DHA or NPD1 treatment when compared to vehicle.We suggest that DHA induces cell survival, modulates the neuroinflammatory response and triggers long term restoration of synaptic circuits. Both DHA and NPD1 elicited remarkable protection in aged animals. Accordingly, activation of DHA signaling might provide benefits in the management of ischemic stroke both acutely as well as long term to limit ensuing disabilities.

  15. 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

  16. Effects of Remote Ischemic Conditioning Methods on Ischemia-Reperfusion Injury in Muscle Flaps: An Experimental Study in Rats

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    Durdane Keskin

    2017-09-01

    Full Text Available Background The aim of this study was to investigate the effects of remote ischemic conditioning on ischemia-reperfusion injury in rat muscle flaps histopathologically and biochemically. Methods Thirty albino rats were divided into 5 groups. No procedure was performed in the rats in group 1, and only blood samples were taken. A gracilis muscle flap was elevated in all the other groups. Microclamps were applied to the vascular pedicle for 4 hours in order to achieve tissue ischemia. In group 2, no additional procedure was performed. In groups 3, 4, and 5, the right hind limb was used and 3 cycles of ischemia-reperfusion for 5 minutes each (total, 30 minutes was applied with a latex tourniquet (remote ischemic conditioning. In group 3, this procedure was performed before flap elevation (remote ischemic preconditoning. In group 4, the procedure was performed 4 hours after flap ischemia (remote ischemic postconditioning. In group 5, the procedure was performed after the flap was elevated, during the muscle flap ischemia episode (remote ischemic perconditioning. Results The histopathological damage score in all remote conditioning ischemia groups was lower than in the ischemic-reperfusion group. The lowest histopathological damage score was observed in group 5 (remote ischemic perconditioning. Conclusions The nitric oxide levels were higher in the blood samples obtained from the remote ischemic perconditioning group. This study showed the effectiveness of remote ischemic conditioning procedures and compared their usefulness for preventing ischemia-reperfusion injury in muscle flaps.

  17. Effects of Remote Ischemic Conditioning Methods on Ischemia-Reperfusion Injury in Muscle Flaps: An Experimental Study in Rats.

    Science.gov (United States)

    Keskin, Durdane; Unlu, Ramazan Erkin; Orhan, Erkan; Erkilinç, Gamze; Bogdaycioglu, Nihal; Yilmaz, Fatma Meric

    2017-09-01

    The aim of this study was to investigate the effects of remote ischemic conditioning on ischemia-reperfusion injury in rat muscle flaps histopathologically and biochemically. Thirty albino rats were divided into 5 groups. No procedure was performed in the rats in group 1, and only blood samples were taken. A gracilis muscle flap was elevated in all the other groups. Microclamps were applied to the vascular pedicle for 4 hours in order to achieve tissue ischemia. In group 2, no additional procedure was performed. In groups 3, 4, and 5, the right hind limb was used and 3 cycles of ischemia-reperfusion for 5 minutes each (total, 30 minutes) was applied with a latex tourniquet (remote ischemic conditioning). In group 3, this procedure was performed before flap elevation (remote ischemic preconditoning). In group 4, the procedure was performed 4 hours after flap ischemia (remote ischemic postconditioning). In group 5, the procedure was performed after the flap was elevated, during the muscle flap ischemia episode (remote ischemic perconditioning). The histopathological damage score in all remote conditioning ischemia groups was lower than in the ischemic-reperfusion group. The lowest histopathological damage score was observed in group 5 (remote ischemic perconditioning). The nitric oxide levels were higher in the blood samples obtained from the remote ischemic perconditioning group. This study showed the effectiveness of remote ischemic conditioning procedures and compared their usefulness for preventing ischemia-reperfusion injury in muscle flaps.

  18. Computer-aided diagnosis of acute ischemic stroke based on cerebral hypoperfusion using 4D CT angiography

    Science.gov (United States)

    Charbonnier, Jean-Paul; Smit, Ewoud J.; Viergever, Max A.; Velthuis, Birgitta K.; Vos, Pieter C.

    2013-02-01

    The presence of collateral blood flow is found to be a strong predictor of patient outcome after acute ischemic stroke. Collateral blood flow is defined as an alternative way to provide oxygenated blood to ischemic cerebral tissue. Assessment of collateral blood supply is currently performed by visual inspection of a Computed Tomography Angiogram (CTA) which introduces inter-observer variability and depends on the grading scale. Furthermore, variations in the arterial contrast arrival time may lead to underestimation of collateral blood supply in a CTA which exerts a negative influence on the prediction of patient outcome. In this study, the feasibility of a Computer-aided Diagnosis system is investigated capable of objectively predicting patient outcome. We present a novel automatic method for quantitative assessment of cerebral hypoperfusion in timing-invariant (i.e. delay insensitive) CTA (TI-CTA). The proposed Vessel Density Symmetry algorithm automatically generates descriptive maps based on hemispheric asymmetry of blood vessels. Intensity and symmetry based features are extracted from these descriptive maps and subjected to a best-first-search feature selection. Linear Discriminant Analysis is performed to combine selected features into a likelihood of good patient outcome. Receiver operating characteristic (ROC) analysis is conducted to evaluate the diagnostic performance of the CAD by leave-one- patient-out cross validation. A Positive Predicting Value of 1 was obtained at a sensitivity of 25% with an area under the ROC-curve of 0.86. The results show that the CAD is feasible to objectively predict patient outcome. The presented CAD could make an important contribution to acute ischemic stroke diagnosis and treatment.

  19. Is higher body temperature beneficial in ischemic stroke patients with normal admission CT angiography of the cerebral arteries?

    Science.gov (United States)

    Kvistad, Christopher Elnan; Khanevski, Andrej; Nacu, Aliona; Thomassen, Lars; Waje-Andreassen, Ulrike; Naess, Halvor

    2014-01-01

    Low body temperature is considered beneficial in ischemic stroke due to neuroprotective mechanisms, yet some studies suggest that higher temperatures may improve clot lysis and outcomes in stroke patients treated with tissue plasminogen activator (tPA). The effect of increased body temperature in stroke patients treated with tPA and with normal computed tomography angiography (CTA) on admission is unknown. We hypothesized a beneficial effect of higher body temperature in the absence of visible clots on CTA, possibly due to enhanced lysis of small, peripheral clots. Patients with ischemic stroke admitted to our Stroke Unit between February 2006 and April 2013 were prospectively registered in a database (Bergen NORSTROKE Registry). Ischemic stroke patients treated with tPA with normal CTA of the cerebral arteries were included. Outcomes were assessed by the modified Rankin Scale (mRS) after 1 week. An excellent outcome was defined as mRS=0, and a favorable outcome as mRS=0-1. A total of 172 patients were included, of which 48 (27.9%) had an admission body temperature ≥37.0°C, and 124 (72.1%) had a body temperature temperature ≥37.0°C was independently associated with excellent outcomes (odds ratio [OR]: 2.8; 95% confidence interval [CI]: 1.24-6.46; P=0.014) and favorable outcomes (OR: 2.8; 95% CI: 1.13-4.98; P=0.015) when adjusted for confounders. We found an association between higher admission body temperature and improved outcome in tPA-treated stroke patients with normal admission CTA of the cerebral arteries. This may suggest a beneficial effect of higher body temperature on clot lysis in the absence of visible clots on CTA.

  20. Dl-3-n-Butylphthalide Treatment Enhances Hemodynamics and Ameliorates Memory Deficits in Rats with Chronic Cerebral Hypoperfusion

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    Zhilin Xiong

    2017-07-01

    Full Text Available Our previous study has revealed that chronic cerebral hypoperfusion (CCH activates a compensatory vascular mechanism attempting to maintain an optimal cerebral blood flow (CBF. However, this compensation fails to prevent neuronal death and cognitive impairment because neurons die prior to the restoration of normal CBF. Therefore, pharmacological invention may be critical to enhance the CBF for reducing neurodegeneration and memory deficit. Dl-3-n-butylphthalide (NBP is a compound isolated from the seeds of Chinese celery and has been proven to be able to prevent neuronal loss, reduce inflammation and ameliorate memory deficits in acute ischemic animal models and stroke patients. In the present study, we used magnetic resonance imaging (MRI techniques, immunohistochemistry and Morris water maze (MWM to investigate whether NBP can accelerate CBF recovery, reduce neuronal death and improve cognitive deficits in CCH rats after permanent bilateral common carotid artery occlusion (BCCAO. Rats were intravenously injected with NBP (5 mg/kg daily for 14 days beginning the first day after BCCAO. The results showed that NBP shortened recovery time of CBF to pre-occlusion levels at 2 weeks following BCCAO, compared to 4 weeks in the vehicle group, and enhanced hemodynamic compensation through dilation of the vertebral arteries (VAs and increase in angiogenesis. NBP treatment also markedly reduced reactive astrogliosis and cell apoptosis and protected hippocampal neurons against ischemic injury. The escape latency of CCH rats in the MWM was also reduced in response to NBP treatment. These findings demonstrate that NBP can accelerate the recovery of CBF and improve cognitive function in a rat model of CCH, suggesting that NBP is a promising therapy for CCH patients or vascular dementia.

  1. Overview of Experimental and Clinical Findings regarding the Neuroprotective Effects of Cerebral Ischemic Postconditioning.

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    Ma, Di; Feng, Liangshu; Deng, Fang; Feng, Jia-Chun

    2017-01-01

    Research on attenuating the structural and functional deficits observed following ischemia-reperfusion has become increasingly focused on the therapeutic potential of ischemic postconditioning. In recent years, various methods and animal models of ischemic postconditioning have been utilized. The results of these numerous studies have indicated that the mechanisms underlying the neuroprotective effects of ischemic postconditioning may involve reductions in the generation of free radicals and inhibition of calcium overload, as well as the release of endogenous active substances, alterations in membrane channel function, and activation of protein kinases. Here we review the novel discovery, mechanism, key factors, and clinical application of ischemic postconditioning and discuss its implications for future research and problem of clinical practice.

  2. 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.

  3. Correction for Delay and Dispersion Results in More Accurate Cerebral Blood Flow Ischemic Core Measurement in Acute Stroke.

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    Lin, Longting; Bivard, Andrew; Kleinig, Timothy; Spratt, Neil J; Levi, Christopher R; Yang, Qing; Parsons, Mark W

    2018-04-01

    This study aimed to assess how the ischemic core measured by perfusion computed tomography (CTP) was affected by the delay and dispersion effect. Ischemic stroke patients having CTP performed within 6 hours of onset were included. The CTP data were processed twice, generating standard cerebral blood flow (sCBF) and delay- and dispersion-corrected CBF (ddCBF), respectively. Ischemic core measured by the sCBF and ddCBF was then compared at the relative threshold core were used: acute diffusion-weighted imaging or 24-hour diffusion-weighted imaging in patients with complete recanalization. Difference of core volume between CTP and diffusion-weighted imaging was estimated by Mann-Whitney U test and limits of agreement. Patients were also classified into favorable and unfavorable CTP patterns. The imaging pattern classification by sCBF and ddCBF was compared by the χ 2 test; their respective ability to predict good clinical outcome (3-month modified Rankin Scale score) was tested in logistic regression. Fifty-five patients were included in this study. Median sCBF ischemic core volume was 38.5 mL (12.4-61.9 mL), much larger than the median core volume of 17.2 mL measured by ddCBF (interquartile range, 5.5-38.8; P core much closer to diffusion-weighted imaging core references, with the mean volume difference of -0.1 mL (95% limits of agreement, -25.4 to 25.2; P =0.97) and 16.7 mL (95% limits of agreement, -21.7 to 55.2; P core measurement on CTP. © 2018 American Heart Association, Inc.

  4. Hydrogen sulfide intervention in focal cerebral ischemia/reperfusion injury in rats

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    Xin-juan Li

    2015-01-01

    Full Text Available The present study aimed to explore the mechanism underlying the protective effects of hydrogen sulfide against neuronal damage caused by cerebral ischemia/reperfusion. We established the middle cerebral artery occlusion model in rats via the suture method. Ten minutes after middle cerebral artery occlusion, the animals were intraperitoneally injected with hydrogen sulfide donor compound sodium hydrosulfide. Immunofluorescence revealed that the immunoreactivity of P2X 7 in the cerebral cortex and hippocampal CA1 region in rats with cerebral ischemia/reperfusion injury decreased with hydrogen sulfide treatment. Furthermore, treatment of these rats with hydrogen sulfide significantly lowered mortality, the Longa neurological deficit scores, and infarct volume. These results indicate that hydrogen sulfide may be protective in rats with local cerebral ischemia/reperfusion injury by down-regulating the expression of P2X 7 receptors.

  5. Effects of total saponins from Trillium tschonoskii rhizome on grey and white matter injury evaluated by quantitative multiparametric MRI in a rat model of ischemic stroke.

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    Li, Manzhong; Ouyang, Junyao; Zhang, Yi; Cheng, Brian Chi Yan; Zhan, Yu; Yang, Le; Zou, Haiyan; Zhao, Hui

    2018-04-06

    Trillium tschonoskii rhizome (TTR), a medicinal herb, has been traditionally used to treat traumatic brain injury and headache in China. Although the potential neuroprotective efficacy of TTR has gained increasing interest, the pharmacological mechanism remains unclear. Steroid saponins are the main bioactive components of the herb. To investigate the protective and repair-promoting effects of the total saponins from TTR (TSTT) on grey and white matter damages in a rat model of middle cerebral artery occlusion (MCAO) using magnetic resonance imaging (MRI) assay. Ischemic stroke was induced by MCAO. TSTT and Ginaton (positive control) were administered orally to rats 6h after stroke and daily thereafter. After 15 days of treatment, the survival rate of each group was calculated. We then conducted neurological deficit scores and beam walking test to access the neurological function after ischemic stroke. Subsequently, T2-weighted imaging (T2WI) and T2 relaxometry mapping were performed to measure infarct volume and grey and white matter integrity, respectively. Moreover, diffusion tensor imaging (DTI) was carried out to evaluate the grey and white matter microstructural damage. Additionally, arterial spin labelling (ASL) - cerebral blood flow (CBF) and magnetic resonance angiography (MRA) images provided dynamic information about vascular hemodynamic dysfunction after ischemic stroke. Finally, haematoxylin and eosin (HE) staining was carried out to evaluate the stroke-induced pathological changes in the brain. The survival rate and neurological behavioural outcomes (Bederson scores and beam walking tests) were markedly ameliorated by TSTT (65mg/kg) treatment within 15 days after ischemic stroke. Moreover, T2WI and T2 relaxometry mapping showed that TSTT (65mg/kg) significantly reduced infarct volume and attenuated grey and white matter injury, respectively, which was confirmed by histopathological evaluation of brain tissue. The results obtained from DTI showed that

  6. Neuroprotective effect of safranal, an active ingredient of Crocus sativus , in a rat model of transient cerebral ischemia

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    Hamid R. Sadeghnia

    2017-09-01

    Full Text Available Safranal is a monoterpene aldehyde found in saffron (Crocus sativus L. petals. It has been previously reported that safranal has a wide range of activities such as antioxidant and anti-inflammatory effects. In this study, we examined the effect of safranal on brain injuries in a transient model of focal cerebral ischemia. Transient focal cerebral ischemia was induced by middle cerebral artery occlusion for 30 min, followed by 24 h of reperfusion. Safranal in the doses of 72.5 and 145 mg/kg was administered intraperitoneally at 0, 3, and 6 h after reperfusion. Neurobehavioral deficit, infarct volume, hippocampal cell loss and markers of oxidative stress including thiobarbituric acid reactive substances (TBARS, total sulfhydryl (SH content, and antioxidant capacity (using FRAP assay were also assessed. The focal cerebral ischemia induced a significant increase in the neurological score, infarct volume and neuronal cell loss in the ipsilateral hippocampal CA1 and CA3 subfields (p < 0.001 and also oxidative stress markers (p < 0.01. Following safranal administration, the total SH content and antioxidant capacity significantly increased, while marked decreases were observed in the neurological score, infarct volume and hippocampal cell loss, as well as TBARS level. This study concluded that safranal had protective effects on ischemic reperfusion injury in the rat model of stroke. Such effects of safranal may have been exerted mainly by suppressing the production of free radicals and increasing antioxidant activity.

  7. Enhanced post-ischemic neurogenesis in aging rats

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    Yao-Fang Tan

    2010-08-01

    Full Text Available Hippocampal neurogenesis persists in adult mammals, but its rate declines dramatically with age. Evidence indicates that experimentally-reduced levels of neurogenesis (e.g. by irradiation in young rats has profound influence on cognition as determined by learning and memory tests. In the present study we asked whether in middle-aged, 10-13 months old rats, cell production can be restored towards the level present in young rats. To manipulate neurogenesis we induced bilateral carotid occlusion with hypotension. This procedure is known to increase neurogenesis in young rats, presumably in a compensatory manner, but until now, has never been tested in aging rats. Cell production was measured at 10, 35 and 90 days after ischemia. The results indicate that neuronal proliferation and differentiation can be transiently restored in middle-aged rats. Furthermore, the effects are more pronounced in the dorsal as opposed to ventral hippocampus thus restoring the dorso-ventral gradient seen in younger rats. Our results support previous findings showing that some of the essential features of the age-dependent decline in neurogenesis are reversible. Thus, it may be possible to manipulate neurogenesis and improve learning and memory in old age.

  8. High plasma concentrations of asymmetric dimethylarginine inhibit ischemic cardioprotection in hypercholesterolemic rats

    International Nuclear Information System (INIS)

    Landim, M.B.P.; Dourado, P.M.M.; Casella-Filho, A.; Chagas, A.C.P.; Luz, P.L. da

    2013-01-01

    A low concentration of nitric oxide associated with a high concentration of asymmetric dimethylarginine (ADMA) can explain the lack of ischemic cardioprotection observed in the presence of hypercholesterolemia. The objective of the present study was to evaluate the effect of hypercholesterolemia on ischemic pre- and postconditioning and its correlation with plasma concentrations of ADMA. Male Wistar rats (6-8 weeks old) fed a 2% cholesterol diet (n = 21) for 8 weeks were compared to controls (n = 25) and were subjected to experimental myocardial infarction and reperfusion, with ischemic pre- and postconditioning. Total cholesterol and ADMA were measured in plasma before the experimental infarct and the infarct area was quantified. Weight, total cholesterol and plasma ADMA (means ± SE; 1.20 ± 0.06, 1.27 ± 0.08 and 1.20 ± 0.08 vs 0.97 ± 0.04, 0.93 ± 0.05 and 0.97 ± 0.04 µM) were higher in animals on the hypercholesterolemic diet than in controls, respectively. Cardioprotection did not reduce infarct size in the hypercholesterolemic animals (pre: 13.55% and post: 8% compared to 7.95% observed in the group subjected only to ischemia and reperfusion), whereas infarct size was reduced in the animals on a normocholesterolemic diet (pre: 8.25% and post: 6.10% compared to 12.31%). Hypercholesterolemia elevated ADMA and eliminated the cardioprotective effects of ischemic pre- and postconditioning in rats

  9. High plasma concentrations of asymmetric dimethylarginine inhibit ischemic cardioprotection in hypercholesterolemic rats

    Energy Technology Data Exchange (ETDEWEB)

    Landim, M.B.P.; Dourado, P.M.M.; Casella-Filho, A.; Chagas, A.C.P.; Luz, P.L. da [Unidade de Aterosclerose, Instituto do Coração, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil)

    2013-05-10

    A low concentration of nitric oxide associated with a high concentration of asymmetric dimethylarginine (ADMA) can explain the lack of ischemic cardioprotection observed in the presence of hypercholesterolemia. The objective of the present study was to evaluate the effect of hypercholesterolemia on ischemic pre- and postconditioning and its correlation with plasma concentrations of ADMA. Male Wistar rats (6-8 weeks old) fed a 2% cholesterol diet (n = 21) for 8 weeks were compared to controls (n = 25) and were subjected to experimental myocardial infarction and reperfusion, with ischemic pre- and postconditioning. Total cholesterol and ADMA were measured in plasma before the experimental infarct and the infarct area was quantified. Weight, total cholesterol and plasma ADMA (means ± SE; 1.20 ± 0.06, 1.27 ± 0.08 and 1.20 ± 0.08 vs 0.97 ± 0.04, 0.93 ± 0.05 and 0.97 ± 0.04 µM) were higher in animals on the hypercholesterolemic diet than in controls, respectively. Cardioprotection did not reduce infarct size in the hypercholesterolemic animals (pre: 13.55% and post: 8% compared to 7.95% observed in the group subjected only to ischemia and reperfusion), whereas infarct size was reduced in the animals on a normocholesterolemic diet (pre: 8.25% and post: 6.10% compared to 12.31%). Hypercholesterolemia elevated ADMA and eliminated the cardioprotective effects of ischemic pre- and postconditioning in rats.

  10. Pilocarpine-induced status epilepticus in rats involves ischemic and excitotoxic mechanisms.

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    Paolo Francesco Fabene

    Full Text Available The neuron loss characteristic of hippocampal sclerosis in temporal lobe epilepsy patients is thought to be the result of excitotoxic, rather than ischemic, injury. In this study, we assessed changes in vascular structure, gene expression, and the time course of neuronal degeneration in the cerebral cortex during the acute period after onset of pilocarpine-induced status epilepticus (SE. Immediately after 2 hr SE, the subgranular layers of somatosensory cortex exhibited a reduced vascular perfusion indicative of ischemia, whereas the immediately adjacent supragranular layers exhibited increased perfusion. Subgranular layers exhibited necrotic pathology, whereas the supergranular layers were characterized by a delayed (24 h after SE degeneration apparently via programmed cell death. These results indicate that both excitotoxic and ischemic injuries occur during pilocarpine-induced SE. Both of these degenerative pathways, as well as the widespread and severe brain damage observed, should be considered when animal model-based data are compared to human pathology.

  11. Effects of CDP-choline on neurologic deficits and cerebral glucose metabolism in a rat model of cerebral ischemia

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    Kakihana, M.; Fukuda, N.; Suno, M.; Nagaoka, A.

    1988-02-01

    The effects of cytidine 5'-diphosphocholine (CDP-choline) on neurologic deficits and cerebral glucose metabolism were studied in a rat model of transient cerebral ischemia. Cerebral ischemia was induced by occluding both common carotid arteries for 20 or 30 minutes 24 hours after the vertebral arteries were permanently occluded by electrocautery. CDP-choline was administered intraperitoneally twice daily for 4 days after reestablishing carotid blood flow. CDP-choline at two dosages (50 and 250 mg/kg) shortened the time required for recovery of spontaneous motor activity in a dose-related manner; recovery time was measured early after reperfusion. Neurologic signs were observed for 10 days. High-dose CDP-choline improved neurologic signs in the rats within 20-30 minutes of ischemia. When cerebral glucose metabolism was assessed on Day 4, increases in the levels of glucose and pyruvate were accompanied by decreases in the synthesis of labeled acetylcholine from uniformly labeled (/sup 14/C)glucose measured in the cerebral cortex of rats with 30 minutes of ischemia. High-dose CDP-choline also attenuated changes in these variables. CDP-(1,2-/sup 14/C)choline injected intravenously 10 minutes after reperfusion was used for membrane lipid biosynthesis. These results indicate that CDP-choline has beneficial effects on brain dysfunction induced by cerebral ischemia, which may be due in part to the restorative effects of CDP-choline on disturbed cerebral glucose metabolism, probably by stimulating phospholipid biosynthesis.

  12. Effects of CDP-choline on neurologic deficits and cerebral glucose metabolism in a rat model of cerebral ischemia

    International Nuclear Information System (INIS)

    Kakihana, M.; Fukuda, N.; Suno, M.; Nagaoka, A.

    1988-01-01

    The effects of cytidine 5'-diphosphocholine (CDP-choline) on neurologic deficits and cerebral glucose metabolism were studied in a rat model of transient cerebral ischemia. Cerebral ischemia was induced by occluding both common carotid arteries for 20 or 30 minutes 24 hours after the vertebral arteries were permanently occluded by electrocautery. CDP-choline was administered intraperitoneally twice daily for 4 days after reestablishing carotid blood flow. CDP-choline at two dosages (50 and 250 mg/kg) shortened the time required for recovery of spontaneous motor activity in a dose-related manner; recovery time was measured early after reperfusion. Neurologic signs were observed for 10 days. High-dose CDP-choline improved neurologic signs in the rats within 20-30 minutes of ischemia. When cerebral glucose metabolism was assessed on Day 4, increases in the levels of glucose and pyruvate were accompanied by decreases in the synthesis of labeled acetylcholine from uniformly labeled [ 14 C]glucose measured in the cerebral cortex of rats with 30 minutes of ischemia. High-dose CDP-choline also attenuated changes in these variables. CDP-[1,2- 14 C]choline injected intravenously 10 minutes after reperfusion was used for membrane lipid biosynthesis. These results indicate that CDP-choline has beneficial effects on brain dysfunction induced by cerebral ischemia, which may be due in part to the restorative effects of CDP-choline on disturbed cerebral glucose metabolism, probably by stimulating phospholipid biosynthesis

  13. Expression of S100 protein and protective effect of arundic acid on the rat brain in chronic cerebral hypoperfusion.

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    Ohtani, Ryo; Tomimoto, Hidekazu; Wakita, Hideaki; Kitaguchi, Hiroshi; Nakaji, Kayoko; Takahashi, Ryosuke

    2007-03-02

    S100 protein is expressed primarily by astroglia in the brain, and accumulates in and around the ischemic lesions. Arundic acid, a novel astroglia-modulating agent, is neuroprotective in acute cerebral infarction, whereas the protective effects remain unknown during chronic cerebral hypoperfusion. Rats undergoing chronic cerebral hypoperfusion were subjected to a bilateral ligation of the common carotid arteries, and were allowed to survive for 3, 7 and 14 days. The animals received a daily intraperitoneal injection of 5.0, 10.0 or 20.0 mg/kg of arundic acid, or vehicle, for 14 days. Alternatively, other groups of rats received a delayed intraperitoneal injection of 20.0 mg/kg of arundic acid or vehicle, which started from 1, 3 or 7 days after ligation and continued to 14 days. The degree of white matter (WM) lesions and the numerical density of S100 protein-immunoreactive astroglia were estimated. In the WM of rats with vehicle injections, the number of S100 protein-immunoreactive astroglia increased significantly after chronic cerebral hypoperfusion as compared to the sham-operation. A dosage of 10.0 and 20.0 mg/kg of arundic acid suppressed the numerical increase in S100 protein-immunoreactive astroglia and the WM lesions. These pathological changes were suppressed with delayed treatment up to 7 days in terms of astroglial activation, and up to 3 days in terms of the WM lesions. The protective effects of arundic acid against WM lesions were demonstrated in a dose-dependent manner, and even after postischemic treatments. These results suggest the potential usefulness of arundic acid in the treatment of cerebrovascular WM lesions.

  14. Cerebral microbleeds are not associated with long-term cognitive outcome in patients with transient ischemic attack or minor stroke.

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    Brundel, Manon; Kwa, Vincent I H; Bouvy, Willem H; Algra, Ale; Kappelle, L Jaap; Biessels, Geert Jan

    2014-01-01

    Cerebral microbleeds have been related to cerebrovascular disease and dementia. They occur more frequently in patients with ischemic stroke than in the general population, but their relation to cognition in these patients is uncertain, particularly in the long run. We examined the relationship between microbleeds in patients with a transient ischemic attack (TIA) or minor ischemic stroke, and cognitive performance 4 years later. Participants were recruited from a prospective multicenter cohort of patients with a TIA or minor ischemic stroke (n=397). They underwent magnetic resonance imaging (MRI), including a T2*-weighted sequence, within 3 months after their ischemic event. Microbleeds, atrophy, lacunae and white matter hyperintensities (WMH) were rated visually. Cognitive status was examined in 94% of all patients who were still alive after a mean interval of 3.8 years by the Dutch version of the Telephone Interview for Cognitive Status (TICS; n=280) or by an Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) obtained from a close relative if a TICS could not be obtained (n=48). The relationship between presence of microbleeds and TICS or IQCODE score was assessed with linear regression analyses adjusted for age, sex, educational level and time interval between MRI and cognitive evaluation. The mean age was 65±12 years at inclusion. The vascular event at inclusion was a TIA in 170 patients (52%) and a minor ischemic stroke in 155 patients (47%). Microbleeds were present in 11.6% of the patients. Patients with microbleeds were significantly older than patients without microbleeds (70±9 vs. 64±12 years), more often had hypertension, and had more cerebral atrophy, WMH and lacunae on MRI (all pTICS score was 35.3±5.9 for patients with microbleeds (n=29) and 34.6±5.2 for patients without microbleeds (n=251); the adjusted mean difference (95% CI) was 1.69 (-0.01 to 3.38). The total IQCODE score was 66.0±10.8 for patients with microbleeds (n=9

  15. 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.

  16. Antrodia camphorata Potentiates Neuroprotection against Cerebral Ischemia in Rats via Downregulation of iNOS/HO-1/Bax and Activated Caspase-3 and Inhibition of Hydroxyl Radical Formation

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    Po-Sheng Yang

    2015-01-01

    Full Text Available Antrodia camphorata (A. camphorata is a fungus generally used in Chinese folk medicine for treatment of viral hepatitis and cancer. Our previous study found A. camphorata has neuroprotective properties and could reduce stroke injury in cerebral ischemia animal models. In this study, we sought to investigate the molecular mechanisms of neuroprotective effects of A. camphorata in middle cerebral artery occlusion (MCAO rats. A selective occlusion of the middle cerebral artery (MCA with whole blood clots was used to induce ischemic stroke in rats and they were orally treated with A. camphorata (0.25 and 0.75 g/kg/day alone or combined with aspirin (5 mg/kg/day. To provide insight into the functions of A. camphorata mediated neuroprotection, the expression of Bax, inducible nitric oxide synthase (iNOS, haem oxygenase-1 (HO-1, and activated caspase-3 was determined by Western blot assay. Treatment of aspirin alone significantly reduced the expressions of HO-1 (P<0.001, iNOS (P<0.001, and Bax (P<0.01 in ischemic regions. The reduction of these expressions was more potentiated when rats treated by aspirin combined with A. camphorata (0.75 g/kg/day. Combination treatment also reduced apoptosis as measured by a significant reduction in active caspase-3 expression in the ischemic brain compared to MCAO group (P<0.01. Moreover, treatment of A. camphorata significantly (P<0.05 reduced fenton reaction-induced hydroxyl radical (OH• formation at a dose of 40 mg/mL. Taken together, A. camphorata has shown neuroprotective effects in embolic rats, and the molecular mechanisms may correlate with the downregulation of Bax, iNOS, HO-1, and activated caspase-3 and the inhibition of OH• signals.

  17. Neurotherapeutic activity of the recombinant heat shock protein Hsp70 in a model of focal cerebral ischemia in rats

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    Shevtsov MA

    2014-05-01

    Full Text Available Maxim A Shevtsov,1,2 Boris P Nikolaev,3 Ludmila Y Yakovleva,3 Anatolii V Dobrodumov,4 Anastasiy S Dayneko,5 Alexey A Shmonin,5,6 Timur D Vlasov,5 Elena V Melnikova,5 Alexander D Vilisov,4,5 Irina V Guzhova,1 Alexander M Ischenko,3 Anastasiya L Mikhrina,7 Oleg V Galibin,5 Igor V Yakovenko,2 Boris A Margulis1 1Institute of Cytology of the Russian Academy of Sciences (RAS, St Petersburg, Russia; 2AL Polenov Russian Research Scientific Institute of Neurosurgery, St Petersburg, Russia; 3Research Institute of Highly Pure Biopreparations, St Petersburg, Russia; 4Institute of Macromolecular Compounds of the Russian Academy of Sciences (RAS, St Petersburg, Russia; 5First St Petersburg IP Pavlov State Medical University, St Petersburg, Russia; 6Federal Almazov Medical Research Centre, St Petersburg, Russia; 7IM Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences (RAS, St Petersburg, Russia Abstract: Recombinant 70 kDa heat shock protein (Hsp70 is an antiapoptotic protein that has a cell protective activity in stress stimuli and thus could be a useful therapeutic agent in the management of patients with acute ischemic stroke. The neuroprotective and neurotherapeutic activity of recombinant Hsp70 was explored in a model of experimental stroke in rats. Ischemia was produced by the occlusion of the middle cerebral artery for 45 minutes. To assess its neuroprotective capacity, Hsp70, at various concentrations, was intravenously injected 20 minutes prior to ischemia. Forty-eight hours after ischemia, rats were sacrificed and brain tissue sections were stained with 2% triphenyl tetrazolium chloride. Preliminary treatment with Hsp70 significantly reduced the ischemic zone (optimal response at 2.5 mg/kg. To assess Hsp70’s neurotherapeutic activity, we intravenously administered Hsp70 via the tail vein 2 hours after reperfusion (2 hours and 45 minutes after ischemia. Rats were then kept alive for 72 hours. The

  18. 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

  19. High-Frequency Repetitive Transcranial Magnetic Stimulation (rTMS Improves Functional Recovery by Enhancing Neurogenesis and Activating BDNF/TrkB Signaling in Ischemic Rats

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    Jing Luo

    2017-02-01

    Full Text Available Repetitive transcranial magnetic stimulation (rTMS has rapidly become an attractive therapeutic approach for stroke. However, the mechanisms underlying this remain elusive. This study aimed to investigate whether high-frequency rTMS improves functional recovery mediated by enhanced neurogenesis and activation of brain-derived neurotrophic factor (BDNF/tropomyosin-related kinase B (TrkB pathway and to compare the effect of conventional 20 Hz rTMS and intermittent theta burst stimulation (iTBS on ischemic rats. Rats after rTMS were sacrificed seven and 14 days after middle cerebral artery occlusion (MCAO, following evaluation of neurological function. Neurogenesis was measured using specific markers: Ki67, Nestin, doublecortin (DCX, NeuN and glial fibrillary acidic protein (GFAP, and the expression levels of BDNF were visualized by Western blotting and RT-PCR analysis. Both high-frequency rTMS methods significantly improved neurological function and reduced infarct volume. Moreover, 20 Hz rTMS and iTBS significantly promoted neurogenesis, shown by an increase of Ki67/DCX, Ki67/Nestin, and Ki67/NeuN-positive cells in the peri-infarct striatum. These beneficial effects were accompanied by elevated protein levels of BDNF and phosphorylated-TrkB. In conclusion, high-frequency rTMS improves functional recovery possibly by enhancing neurogenesis and activating BDNF/TrkB signaling pathway and conventional 20 Hz rTMS is better than iTBS at enhancing neurogenesis in ischemic rats.

  20. A microarray study of gene and protein regulation in human and rat brain following middle cerebral artery occlusion

    Science.gov (United States)

    Mitsios, Nick; Saka, Mohamad; Krupinski, Jerzy; Pennucci, Roberta; Sanfeliu, Coral; Wang, Qiuyu; Rubio, Francisco; Gaffney, John; Kumar, Pat; Kumar, Shant; Sullivan, Matthew; Slevin, Mark

    2007-01-01

    Background Altered gene expression is an important feature of ischemic cerebral injury and affects proteins of many functional classes. We have used microarrays to investigate the changes in gene expression at various times after middle cerebral artery occlusion in human and rat brain. Results Our results demonstrated a significant difference in the number of genes affected and the time-course of expression between the two cases. The total number of deregulated genes in the rat was 335 versus 126 in the human, while, of 393 overlapping genes between the two array sets, 184 were changed only in the rat and 36 in the human with a total of 41 genes deregulated in both cases. Interestingly, the mean fold changes were much higher in the human. The expression of novel genes, including p21-activated kinase 1 (PAK1), matrix metalloproteinase 11 (MMP11) and integrase interactor 1, was further analyzed by RT-PCR, Western blotting and immunohistochemistry. Strong neuronal staining was seen for PAK1 and MMP11. Conclusion Our findings confirmed previous studies reporting that gene expression screening can detect known and unknown transcriptional features of stroke and highlight the importance of research using human brain tissue in the search for novel therapeutic agents. PMID:17997827

  1. Alpha-Tocopherol Reduces Brain Edema and Protects Blood-Brain Barrier Integrity following Focal Cerebral Ischemia in Rats.

    Science.gov (United States)

    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.

  2. MRI of cerebral ischaemia in rats with occlusion of the middle cerebral artery

    International Nuclear Information System (INIS)

    Thuomas, K.AA.; Kotwica, Z.; Bergstroem, K.; Bolander, H.; Hillered, L.; Olsson, Y.; Ponten, U.; Persson, L.

    1991-01-01

    The development of ischaemic brain oedema caused by middle cerebral artery (MCA) occlusion was studied by serial magnetic resonance imaging (MRI) in rats. Multiple spin echo sequences were used with TR = 1500 ms and TE = 30-240 ms (8 echos). Substraction images were obtained by subtracting the last three echos from the first echo. Fourteen rats were studied 3, 6, and 12 h and 1, 1.5, 3, 4, 6, and 8 days after MCA occlusion, and 2 of them also 3 and 6 weeks later. Two T2 components could be separated, a fast one representing bound water and a slow one representing free bulk water. MR showed T2 prolongation even on the first examination, and the highest values were observed 24 h after occlusion. The subsequent examinations showed a slow reduction in oedema. MR studies 3 and 6 weeks after occlusion revealed an area of very long T2, which correlated well with infarction shown by histology. The substraction images demonstrated both the infarct location and the oedematous changes in the surrounding uninfarcted tissue. MRI imaging employing T2 components and subtraction images appears to be a valuable method for observing the time course of the development and resolution of oedema in cerebral infarction. (orig.)

  3. Regional cerebral blood flow in acute stage with ischemic cerebrovascular disease by xenon-133 inhalation and single photon emission computerized tomography

    Energy Technology Data Exchange (ETDEWEB)

    Kurokawa, Hiroyuki; Iino, Katsuro; Kojima, Hisashi; Saito, Hitoshi; Suzuki, Mikio; Watanabe, Kazuo; Kato, Toshiro

    1987-05-01

    Single photon emission computed tomography (SPECT) with xenon-133 inhalation method was undertaken within 48 hr after the onset in 68 patients with ischemic cerebrovascular disease. The results for regional cerebral blood flow (rCBF) were compared with concurrently available computed tomography (CT) scans. In patients with cerebral infarction, SPECT detected ischemic lesions earlier than CT, with the detectability being 92 %. The area with a decreased blood flow, as seen on SPECT, was more extensive than the low density area on CT, with a concomitant decrease in blood flow in the contralateral cerebral hemisphere. Crossed cerebellar diaschisis was associated with stenosis of the internal carotid artery in 50 % (7/14), and with stenosis of the middle cerebral artery in 35 % (9/26). Abnormal SPECT findings were seen in 47 % (8/17) of the patients with transient ischemic attack (TIA). Five TIA patients had a decreased rCBF on SPECT, which was not provided by CT scans. On the contrary, small infarct lesions in the cerebral basal ganglia, as observed in 4 patients, was not detected by SPECT, but detected by CT. This may imply the limitations of SPECT in the detection of deep-seated lesions of the cerebrum. The results led to the conclusion that SPECT can be performed safely even in acute, seriously ill patients to know changes in rCBF because it is noninvasive and is capable of being repeated in a short time. (Namekawa, K.).

  4. Increased radiosensitivity of cerebral capillaries in neonatal Gunn rats as compared to Sprague-Dawley rats

    International Nuclear Information System (INIS)

    Landolt, R.; Arn, D.

    1979-01-01

    The extent of petechial haemorrhages of the cerebral cortex examined between 14 hours and 4 days after X-irradiation to the head was compared in Sprague-Dawley and homozygous Gunn rats with congenital hyperbilirubinaemia. Animals 1 to 2 days old received single doses of either 250, 500 or 750 rad. By means of a special scoring scale the degree of the damage to the micro vasculature was semi-quantitatively estimated. In both strains a significant difference in effect was obtained between 250 and 500 rad, but not between 500 and 750 rad. The shape of the dose-effect curve in Gunn rats was similar to that of Sprague-Dawley rats, but displaced upwards. In Gunn rats the effect of 250 rad was greater that that of 750 rad in Sprague-Dawley rats. Possible radiosensitizing mechanisms are discussed with reference to the literature and these results. (author)

  5. Resistance to Reperfusion Injury Following Short Term Postischemic Administration of Natural Honey in Globally Ischemic Isolated Rat Heart

    OpenAIRE

    Haleh Vaez; Mehrban Samadzadeh; Fahimeh Zahednezhad; Moslem Najafi

    2012-01-01

    Purpose: Results of our previous study revealed that preischemic perfusion of honey before zero flow global ischemia had cardioprotective effects in rat. The present study investigated potential resistance to reperfusion injury following short term postischemic administration of natural honey in globally ischemic isolated rat heart. Methods: Male Wistar rats were divided into five groups (n=10-13). The rat hearts were isolated, mounted on a Langendorff apparatus, allowed to equilibra...

  6. Increased Expression Of Toll-Like Receptor 2 Mrna Following Permanent Middle Cerebral Artery Occlusion In Rat: Role Of TRPV1 Receptors

    Directory of Open Access Journals (Sweden)

    Amir Moghadam Ahmadi

    2017-02-01

    Full Text Available Background: Stroke is a major cause of mortality and long term disability in adults. TRPV1 has a pivotal role in neuroinflammation. Among TLRs, TLR2 significantly participate in induction of inflammation in brain. In this study, the effect of TRPV1 receptor agonist and antagonist on outcome and gene expression of TLR2 in a rat model of permanent middle cerebral artery occlusion (MCAO was investigated. Methods: Forty male rats were assigned to the following groups: sham, vehicle stroke, AMG9810 (selective TRPV1 antagonist, 0.5 mg/kg; 3 h after stroke, and capsaicin (1 mg/kg; 3 h after stroke. Stroke was induced by permanent middle cerebral artery occlusion and behavioral functions were assessed 1, 3, and 7 days after stroke. Infarct volume, brain edema and mRNA expression of TLR2 were also evaluated at the end of the study. Results: While stroke animals showed infarctions and behavioral functions, we did not observe any cerebral infarction and behavioral functions in sham-operated animals. AMG9810 decreased neurological deficits 7 days after cerebral ischemia (P<0.01. In the ledged beam-walking test, the slip ratio was increased following ischemia (*P < 0.05. AMG9810 improved this index in animals undergone stroke. However, capsaicin enhanced the slip ratio 3 and 7 days after cerebral ischemia (#P<0.05. TLR2 P<0.05(mRNA expression was elevated in ischemic rats.   Conclusion: Our data indicate that pharmacological blockade of TRPV1 by AMG9810 attenuates behavioral function and mRNA expression of TLR2. Therefore, it might be useful as a potential target for the treatment of ischemic stroke.

  7. Effect of growth hormone on glycogenesis in rat cerebral cortical slices

    International Nuclear Information System (INIS)

    Visweswaran, P.; Binod Kumar; Azad, V.S.S.; Brahamchari, A.K.; Singh, S.P.

    1994-01-01

    Incubation of cerebral cortical slices of growth hormone treated diabetic and normal rats with U- 14 C glucose showed a two-fold increase in glycogenesis in diabetic rats. Glucose-6-phosphatase activity was lowered while the activities of phosphoglucomutase and phosphorylase were elevated in the cerebral cortex of diabetic rats treated with growth hormone. However, glycogen synthetase activity was slightly depressed. (author). 13 refs., 2 tabs

  8. EEG indices in patients with high risk of ischemic stroke as predictors of initial disturbed cerebral circulation

    Directory of Open Access Journals (Sweden)

    N. A. Isaeva

    2014-01-01

    Full Text Available Abnormal changes were detected in EEG in patients with high risk of ischemic stroke (higher level than in the population. These changes show the disturbances in forming mechanisms of functional condition of cerebrum during the calm wakeful period. Changes were represented by: the registration of EEG IV- type (the E.A. Zhirmunsky type which was characterized by disorganization of alpha activity and of slow waves; the instability of pattern during the record of background activity; the paroxysmal activity in form of flashes of the bilateral synchronized waves; the strengthening of low-frequency and high-amplitude β-activity. Revealed changes in EEG show the presence of initial disturbed cerebral circulation and can be recommended as predictors of these disturbances.

  9. Activation-induced resetting of cerebral oxygen and glucose uptake in the rat

    DEFF Research Database (Denmark)

    Madsen, P L; Linde, R; Hasselbalch, S G

    1998-01-01

    In the clinical setting it has been shown that activation will increase cerebral glucose uptake in excess of cerebral oxygen uptake. To study this phenomenon further, this study presents an experimental setup that enables precise determination of the ratio between cerebral uptake of glucose...... and oxygen in the awake rat. Global CBF was measured by the Kety-Schmidt technique, and the ratio between cerebral uptake rates for oxygen, glucose, and lactate was calculated from cerebral arterial-venous differences. During baseline conditions, rats were kept in a closed box designed to minimize...... interference. During baseline conditions CBF was 1.08 +/- 0.25 mL x g(-1) x minute(-1), and the cerebral oxygen to glucose uptake ratio was 5.5. Activation was induced by opening the sheltering box for 6 minutes. Activation increased CBF to 1.81 mL x g(-1) x minute(-1). During activation cerebral glucose...

  10. LONG-TERM CLINICAL OUTCOME IN NORMAL VOLUNTEERS AND PATIENTS WITH CEREBRAL TRANSIENT ISCHEMIC ATTACKS

    Directory of Open Access Journals (Sweden)

    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.

  11. Constraint-induced movement therapy promotes motor function recovery and downregulates phosphorylated extracellular regulated protein kinase expression in ischemic brain tissue of rats

    Directory of Open Access Journals (Sweden)

    Bei Zhang

    2015-01-01

    Full Text Available Motor function impairment is a common outcome of stroke. Constraint-induced movement therapy (CIMT involving intensive use of the impaired limb while restraining the unaffected limb is widely used to overcome the effects of ′learned non-use′ and improve limb function after stroke. However, the underlying mechanism of CIMT remains unclear. In the present study, rats were randomly divided into a middle cerebral artery occlusion (model group, a CIMT + model (CIMT group, or a sham group. Restriction of the affected limb by plaster cast was performed in the CIMT and sham groups. Compared with the model group, CIMT significantly improved the forelimb functional performance in rats. By western blot assay, the expression of phosphorylated extracellular regulated protein kinase in the bilateral cortex and hippocampi of cerebral ischemic rats in the CIMT group was significantly lower than that in the model group, and was similar to sham group levels. These data suggest that functional recovery after CIMT may be related to decreased expression of phosphorylated extracellular regulated protein kinase in the bilateral cortex and hippocampi.

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Regulatory T cells are strong promoters of acute ischemic stroke in mice by inducing dysfunction of the cerebral microvasculature.

    Science.gov (United States)

    Kleinschnitz, Christoph; Kraft, Peter; Dreykluft, Angela; Hagedorn, Ina; Göbel, Kerstin; Schuhmann, Michael K; Langhauser, Friederike; Helluy, Xavier; Schwarz, Tobias; Bittner, Stefan; Mayer, Christian T; Brede, Marc; Varallyay, Csanad; Pham, Mirko; Bendszus, Martin; Jakob, Peter; Magnus, Tim; Meuth, Sven G; Iwakura, Yoichiro; Zernecke, Alma; Sparwasser, Tim; Nieswandt, Bernhard; Stoll, Guido; Wiendl, Heinz

    2013-01-24

    We have recently identified T cells as important mediators of ischemic brain damage, but the contribution of the different T-cell subsets is unclear. Forkhead box P3 (FoxP3)-positive regulatory T cells (Tregs) are generally regarded as prototypic anti-inflammatory cells that maintain immune tolerance and counteract tissue damage in a variety of immune-mediated disorders. In the present study, we examined the role of Tregs after experimental brain ischemia/reperfusion injury. Selective depletion of Tregs in the DEREG mouse model dramatically reduced infarct size and improved neurologic function 24 hours after stroke and this protective effect was preserved at later stages of infarct development. The specificity of this detrimental Treg effect was confirmed by adoptive transfer experiments in wild-type mice and in Rag1(-/-) mice lacking lymphocytes. Mechanistically, Tregs induced microvascular dysfunction in vivo by increased interaction with the ischemic brain endothelium via the LFA-1/ICAM-1 pathway and platelets and these findings were confirmed in vitro. Ablation of Tregs reduced microvascular thrombus formation and improved cerebral reperfusion on stroke, as revealed by ultra-high-field magnetic resonance imaging at 17.6 Tesla. In contrast, established immunoregulatory characteristics of Tregs had no functional relevance. We define herein a novel and unexpected role of Tregs in a primary nonimmunologic disease state.

  14. 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.

    Directory of Open Access Journals (Sweden)

    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.

  15. 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

    Science.gov (United States)

    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

  16. Nrdp1 Increases Ischemia Induced Primary Rat Cerebral Cortical Neurons and Pheochromocytoma Cells Apoptosis Via Downregulation of HIF-1α Protein

    Directory of Open Access Journals (Sweden)

    Yuan Zhang

    2017-09-01

    Full Text Available Neuregulin receptor degradation protein-1 (Nrdp1 is an E3 ubiquitin ligase that targets proteins for degradation and regulates cell growth, apoptosis and oxidative stress in various cell types. We have previously shown that Nrdp1 is implicated in ischemic cardiomyocyte death. In this study, we investigated the change of Nrdp1 expression in ischemic neurons and its role in ischemic neuronal injury. Primary rat cerebral cortical neurons and pheochromocytoma (PC12 cells were infected with adenoviral constructs expressing Nrdp1 gene or its siRNA before exposing to oxygen-glucose deprivation (OGD treatment. Our data showed that Nrdp1 was upregulated in ischemic brain tissue 3 h after middle cerebral artery occlusion (MCAO and in OGD-treated neurons. Of note, Nrdp1 overexpression by Ad-Nrdp1 enhanced OGD-induced neuron apoptosis, while knockdown of Nrdp1 with siRNA attenuated this effect, implicating a role of Nrdp1 in ischemic neuron injury. Moreover, Nrdp1 upregulation is accompanied by increased protein ubiquitylation and decreased protein levels of ubiquitin-specific protease 8 (USP8 in OGD-treated neurons, which led to a suppressed interaction between USP8 and HIF-1α and subsequently a reduction in HIF-1α protein accumulation in neurons under OGD conditions. In conclusion, our data support an important role of Nrdp1 upregulation in ischemic neuronal death, and suppressing the interaction between USP8 and HIF-1α and consequently the hypoxic adaptive response of neurons may account for this detrimental effect.

  17. Alpha-MSH decreases core and brain temperature during global cerebral ischemia in rats

    DEFF Research Database (Denmark)

    Spulber, S.; Moldovan, Mihai; Oprica, M.

    2005-01-01

    -vessel occlusion forebrain ischemia on core temperature (CT) and brain temperature (BT), respectively. After 10 min cerebral ischemia, BT was lower in alpha-MSH- than in saline-injected animals. After 10 min reperfusion, both CT and BT were lower than the corresponding pre-ischemic levels after injection of alpha...

  18. Relaxation along a fictitious field (RAFF and Z-spectroscopy using alternating-phase irradiation (ZAPI in permanent focal cerebral ischemia in rat.

    Directory of Open Access Journals (Sweden)

    Kimmo T Jokivarsi

    Full Text Available Cerebral ischemia alters the molecular dynamics and content of water in brain tissue, which is reflected in NMR relaxation, diffusion and magnetization transfer (MT parameters. In this study, the behavior of two new MRI contrasts, Relaxation Along a Fictitious Field (RAFF and Z-spectroscopy using Alternating-Phase Irradiation (ZAPI, were quantified together with conventional relaxation parameters (T1, T2 and T1ρ and MT ratios in acute cerebral ischemia in rat. The right middle cerebral artery was permanently occluded and quantitative MRI data was acquired sequentially for the above parameters for up to 6 hours. The following conclusions were drawn: 1 Time-dependent changes in RAFF and T1ρ relaxation are not coupled to those in MT. 2 RAFF relaxation evolves more like transverse, rather than longitudinal relaxation. 3 MT measured with ZAPI is less sensitive to ischemia than conventional MT. 4 ZAPI data suggest alterations in the T2 distribution of macromolecules in acute cerebral ischemia. It was shown that both RAFF and ZAPI provide complementary MRI information from acute ischemic brain tissue. The presented multiparametric MRI data may aid in the assessment of brain tissue status early in ischemic stroke.

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

    Directory of Open Access Journals (Sweden)

    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.

  20. The usefulness of percutaneous transluminal angioplasty of the middle cerebral artery stenosis in patients with transient ischemic attack

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Young Chul; Lim, Hyo Soon; Kim, Jae Kyu; Seo, Jeong Jin; Jeong, Gwang Woo; Kang, Heoung Keun [Chonnam National Univ. Medical School, Kwangju (Korea, Republic of)

    2001-06-01

    To determine the effectiveness of percutaneous transluminal angioplasty(PTA) of atherosclerotic middle cerebral artery(MCA) stenosis in patients with transient ischemic attack (TIA). Ten patients with TIA who had undergone PTA were retrospectively investigated. In all ten, angiography revealed stenosis of the MCA. Mechanical dilatation was performed at the stenotic portion, and the angiographic findings after PTA, as well as peri/post-angioplastic complications, were evaluated. Four to 64 (mean, 23.5) months later, neurologic symptoms and the nature and timing of recurrent attacks were also assessed. The degree of stenosis before PTA was 50-75% in six patients and greater than 75% in four. Complete or partial angiographic recanalization of the stenotic segment occurred in nine patients (90%). During follow-up, seven patients recovered without recurrent TIA or cerebral stroke; one reported a tingling sensation and one experienced vertebrobasilar insufficiency. Motor aphasia developed in one patient after PTA, but after systemic heparinization, improved within 24 hours. One patient who suffered intracranial hemorrhage due to vascular rupture during PTA did three days later. PTA for atherosclerotic MCA stenosis in patients with TIA is an effective therapeutic method.

  1. Preliminary experience on early mechanical recanalization of middle cerebral artery for acute ischemic stroke and literature review

    International Nuclear Information System (INIS)

    Bai Weixing; Li Tianxiao; Zhu Liangfu; Xue Jiangyu; Wang Ziliang

    2012-01-01

    Objective: To evaluate the feasibility,efficacy and complication of early middle cerebral artery (MCA) mechanical recanalization (MER) for treatment of acute ischemic stroke. Methods: Seven cases undergone MER of MCA for the treatment of acute cerebral infarct were retrospectively reviewed and analyzed, including the etiology, mechanism, Qureshi grading scale, location and size of infarcts, NIHSS score of pre and post procedure, endovascular technique and complications. Referring to the literature, the indications of MCA recanalization were further identified. Results: A total of 7 cases with mean age of 48 yrs were reviewed, which included 3 cases of atherosclerotic thrombosis and 4 embolic cases with pre NIHSS score ranging from 3 to 22. Mechanical recanalization succeeded in 6 cases, but 2 cases of cardiogenic embolism died of intracranial hemorrhage postoperatively. Favorable clinical outcomes were achieved in 4 cases whereas 1 deteriorated. Overall complications seemed to be consistent with literatures reviewed. Conclusions: Early MER of MCA may benefit to a certain subset of acute ischemia stroke patients, however, embolic cases, elder patients and those with severe neurologic deficits are often accompanied by higher complications and unfavorable outcome. (authors)

  2. The usefulness of percutaneous transluminal angioplasty of the middle cerebral artery stenosis in patients with transient ischemic attack

    International Nuclear Information System (INIS)

    Lee, Young Chul; Lim, Hyo Soon; Kim, Jae Kyu; Seo, Jeong Jin; Jeong, Gwang Woo; Kang, Heoung Keun

    2001-01-01

    To determine the effectiveness of percutaneous transluminal angioplasty(PTA) of atherosclerotic middle cerebral artery(MCA) stenosis in patients with transient ischemic attack (TIA). Ten patients with TIA who had undergone PTA were retrospectively investigated. In all ten, angiography revealed stenosis of the MCA. Mechanical dilatation was performed at the stenotic portion, and the angiographic findings after PTA, as well as peri/post-angioplastic complications, were evaluated. Four to 64 (mean, 23.5) months later, neurologic symptoms and the nature and timing of recurrent attacks were also assessed. The degree of stenosis before PTA was 50-75% in six patients and greater than 75% in four. Complete or partial angiographic recanalization of the stenotic segment occurred in nine patients (90%). During follow-up, seven patients recovered without recurrent TIA or cerebral stroke; one reported a tingling sensation and one experienced vertebrobasilar insufficiency. Motor aphasia developed in one patient after PTA, but after systemic heparinization, improved within 24 hours. One patient who suffered intracranial hemorrhage due to vascular rupture during PTA did three days later. PTA for atherosclerotic MCA stenosis in patients with TIA is an effective therapeutic method

  3. Cerebral ischemic lesions detected with diffusion-weighted magnetic resonance imaging after carotid artery stenting. Comparison of several anti-embolic protection devices

    International Nuclear Information System (INIS)

    Taha, M.M.; Maeda, Masayuki; Sakaida, Hiroshi

    2009-01-01

    Distal embolism is an important periprocedural technical complication with carotid angioplasty and carotid artery stenting (CAS). We evaluated the safety and efficacy of protection devices used during CAS by detecting new cerebral ischemic lesions using diffusion-weighted magnetic resonance imaging in 95 patients who underwent 98 CAS procedures: 34 using single PercuSurge GuardWire, 31 using double balloon protection, 15 using proximal flow reverse protection devices, 14 using Naviballoon, and 4 using filter anti-embolic devices. Diffusion-weighted imaging was performed preoperatively and postoperatively to evaluate the presence of any new embolic cerebral lesions. Postoperative diffusion-weighted imaging revealed 117 new ischemic lesions. Three patients had new ischemic stroke, two minor and one major, all ipsilateral to the treated carotid artery. The remaining patients had clinically silent ischemia. The incidence of new embolic lesions was lower using the proximal flow reverse protection device than with the double balloon protection (33% vs. 48.4%), but the volume of ipsilateral new ischemic lesions per patient was 136.6 mm 3 vs. 86.9 mm 3 , respectively. Neuroprotection with Naviballoon yielded ipsilateral lesions of large volume (86.6 mm 3 ) and higher number (5.7 lesions per patient) than using the filter anti-embolic device (34.8 mm 3 and 1 lesion per patient). New cerebral ischemic lesions after neuroprotected CAS are usually silent. The lower incidence of distal ischemia using proximal flow reverse and double balloon protection devices is limited by the larger volume and higher number of ischemic lesions. (author)

  4. Cerebral ischemic lesions detected with diffusion-weighted magnetic resonance imaging after carotid artery stenting: Comparison of several anti-embolic protection devices.

    Science.gov (United States)

    Taha, Mahmoud M; Maeda, Masayuki; Sakaida, Hiroshi; Kawaguchi, Kenji; Toma, Naoki; Yamamoto, Akitaka; Hirose, Tomofumi; Miura, Youichi; Fujimoto, Masashi; Matsushima, Satoshi; Taki, Waro

    2009-09-01

    Distal embolism is an important periprocedural technical complication with carotid angioplasty and carotid artery stenting (CAS). We evaluated the safety and efficacy of protection devices used during CAS by detecting new cerebral ischemic lesions using diffusion-weighted magnetic resonance imaging in 95 patients who underwent 98 CAS procedures: 34 using single PercuSurge GuardWire, 31 using double balloon protection, 15 using proximal flow reverse protection devices, 14 using Naviballoon, and 4 using filter anti-embolic devices. Diffusion-weighted imaging was performed preoperatively and postoperatively to evaluate the presence of any new embolic cerebral lesions. Postoperative diffusion-weighted imaging revealed 117 new ischemic lesions. Three patients had new ischemic stroke, two minor and one major, all ipsilateral to the treated carotid artery. The remaining patients had clinically silent ischemia. The incidence of new embolic lesions was lower using the proximal flow reverse protection device than with the double balloon protection (33% vs. 48.4%), but the volume of ipsilateral new ischemic lesions per patient was 136.6 mm(3) vs. 86.9 mm(3), respectively. Neuroprotection with Naviballoon yielded ipsilateral lesions of large volume (86.6 mm(3)) and higher number (5.7 lesions per patient) than using the filter anti-embolic device (34.8 mm(3) and 1 lesion per patient). New cerebral ischemic lesions after neuroprotected CAS are usually silent. The lower incidence of distal ischemia using proximal flow reverse and double balloon protection devices is limited by the larger volume and higher number of ischemic lesions.

  5. Repeated exposure to methamphetamine induces sex-dependent hypersensitivity to ischemic injury in the adult rat heart.

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    Boyd R Rorabaugh

    Full Text Available We previously reported that adult female, but not male rats that were prenatally exposed to methamphetamine exhibit myocardial hypersensitivity to ischemic injury. However, it is unknown whether hypersensitivity to ischemic injury develops when rats are exposed to methamphetamine during adulthood. The goal of this study was to determine whether methamphetamine exposure during adulthood sensitizes the heart to ischemic injury.Adult male and female rats received daily injections of methamphetamine (5 mg/kg or saline for 10 days. Their hearts were isolated on day 11 and subjected to a 20 min ischemic insult on a Langendorff isolated heart apparatus. Cardiac contractile function was measured by an intraventricular balloon, and infarct size was measured by triphenyltetrazolium chloride staining.Hearts from methamphetamine-treated females exhibited significantly larger infarcts and suppressed postischemic recovery of contractile function compared to hearts from saline-treated females. In contrast, methamphetamine had no effect on infarct size or contractile recovery in male hearts. Subsequent experiments demonstrated that hypersensitivity to ischemic injury persisted in female hearts following a 1 month period of abstinence from methamphetamine. Myocardial protein kinase C-ε expression, Akt phosphorylation, and ERK phosphorylation were unaffected by adult exposure to methamphetamine.Exposure of adult rats to methamphetamine sex-dependently increases the extent of myocardial injury following an ischemic insult. These data suggest that women who have a heart attack might be at risk of more extensive myocardial injury if they have a recent history of methamphetamine abuse.

  6. Repeated exposure to methamphetamine induces sex-dependent hypersensitivity to ischemic injury in the adult rat heart

    Science.gov (United States)

    Seeley, Sarah L.; Stoops, Thorne S.; D’Souza, Manoranjan S.

    2017-01-01

    Background We previously reported that adult female, but not male rats that were prenatally exposed to methamphetamine exhibit myocardial hypersensitivity to ischemic injury. However, it is unknown whether hypersensitivity to ischemic injury develops when rats are exposed to methamphetamine during adulthood. The goal of this study was to determine whether methamphetamine exposure during adulthood sensitizes the heart to ischemic injury. Methods Adult male and female rats received daily injections of methamphetamine (5 mg/kg) or saline for 10 days. Their hearts were isolated on day 11 and subjected to a 20 min ischemic insult on a Langendorff isolated heart apparatus. Cardiac contractile function was measured by an intraventricular balloon, and infarct size was measured by triphenyltetrazolium chloride staining. Results Hearts from methamphetamine-treated females exhibited significantly larger infarcts and suppressed postischemic recovery of contractile function compared to hearts from saline-treated females. In contrast, methamphetamine had no effect on infarct size or contractile recovery in male hearts. Subsequent experiments demonstrated that hypersensitivity to ischemic injury persisted in female hearts following a 1 month period of abstinence from methamphetamine. Myocardial protein kinase C-ε expression, Akt phosphorylation, and ERK phosphorylation were unaffected by adult exposure to methamphetamine. Conclusions Exposure of adult rats to methamphetamine sex-dependently increases the extent of myocardial injury following an ischemic insult. These data suggest that women who have a heart attack might be at risk of more extensive myocardial injury if they have a recent history of methamphetamine abuse. PMID:28575091

  7. The effect of atorvastatin on survival of rat ischemic flap

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    Jian-Xun Chen

    2013-04-01

    Full Text Available Management of skin avulsion with tissue exposure is a challenge for plastic surgeons. Clinical observations have suggested that longer survival of skin flap prevents further contamination and infection. Less well known is the role of atorvastatin in avulsion skin flap. Therefore, we attempted to determine whether atorvastatin could alleviate avulsion skin flap in a rat model. Twenty male Sprague–Dawley rats were randomized into two groups: the atorvastatin group and the control. Before operation, each rat received an initial blood perfusion scan as baseline data. Then, each rat received an operation of skin flap incision, elevation, and resuturing to the original position under general anesthesia. Another blood perfusion scan was performed on each rat 30 minutes, 4 days, and 7 days postoperatively. On the 7th postoperative day, the necrotic area of skin flap was measured as the skin flap viability. The skin flap tissues at 2.5 and 5 cm distal to the skin flap base were collected for histopathological analysis, as well as measurement of vascular endothelial growth factor (VEGF mRNA expression, and vascular density. Compared with 30 minutes postoperation, there was a significant increase in the ratio of skin flap blood perfusion on the 4th and 7th days postoperation in both control and atorvastatin groups (p<0.05. Compared with the control group, there was a significant decrease in necrotic area, significant increase in ratio of skin flap blood perfusion on postoperation days 4 and 7, and significant increase in vascular density under high field at 2.5 cm distal to the base of skin flap in the atorvastatin group (p<0.05. The VEGF121 and VEGF165 mRNA expression at 2.5 cm distal to the base of skin flap differed significantly between the two groups (p<0.05. Compared with the control group, atorvastatin treatment improved skin flap blood perfusion, vascular density, and necrotic area dependent on VEGF mRNA expression.

  8. Ultrastructure of rat cerebral vessels 4 months after gamma irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Iwanowski, L; Ostenda, M

    1975-01-01

    The purpose of this paper was to check the current opinion that one of the late postirradiation changes is early senility (Maxwell, Kruger, 1964). The postirradiation changes of the brain parenchyma are well known from the literature; therefore our investigation is limited to brain capillaries and their closest vicinity. This paper constitutes a fragment of a larger work on the role of connective tissue in the aging brain. Six Wistar male rats of the same brood, about 3 months old, were irradiated over the whole body with gamma rays. Three rats were exposed to a dose of 400 R and three to 800 R. The chosen doses were the lowest and the highest, provoking brain edema but still not lethal. Four months after the exposure the rats were perfused with 4% glutaraldehyde intracardiacly and decapitated. Brain specimens were taken from frontoparietal cortex, lateral ventricle wall, from corpus callosum and griseum pontis. The samples were routinely handled for ultrastructural studies. Observations were performed under electron microscopes showed that the cerebral vessels of both groups of animals were similar.

  9. Pharmacological and molecular comparison of K(ATP) channels in rat basilar and middle cerebral arteries

    DEFF Research Database (Denmark)

    Ploug, Kenneth Beri; Edvinsson, Lars; Olesen, Jes

    2006-01-01

    , we studied the possible involvement of endothelial K(ATP) channels by pressurized arteriography after luminal administration of synthetic K(ATP) channel openers to rat basilar and middle cerebral arteries. Furthermore, we examined the mRNA and protein expression profile of K(ATP) channels to rat...... basilar and middle cerebral arteries using quantitative real-time PCR (Polymerase Chain Reaction) and Western blotting, respectively. In the perfusion system, we found no significant responses after luminal application of three K(ATP) channel openers to rat basilar and middle cerebral arteries...

  10. Neuroprotective effect of Buddleja officinalis extract on transient middle cerebral artery occlusion in rats.

    Science.gov (United States)

    Lee, Dae-Hee; Ha, Nina; Bu, Yung-Min; Choi, Hyoung Il; Park, Yoo Guen; Kim, Yoon Bum; Kim, Mi-Yeon; Kim, Hocheol

    2006-08-01

    The flower buds of Buddleja officinalis MAXIM (Loganiaceae) are used to treat headache and inflammatory diseases in traditional Korean medicine. In the present study, the neuroprotective effects of the methanolic extract of B. officinalis (BOME) and of its hexane fraction (BOHF) were investigated in a middle cerebral artery occlusion (MCAo, 120 min occlusion, 24 h reperfusion) Sprague-Dawley rat model. BOME or BOHF (100 mg/kg, p.o.) was twice administered 30 min before the onset of MCAo and 2 h after reperfusion. BOME and BOHF treated groups showed infarct volumes reduced by 33.9% and 68.2%, respectively, at 2 h occlusion. In BOHF treated animals, cyclooxygenase-2 and iNOS inductions were inhibited in ischemic hemispheres at both the mRNA and protein levels. Furthermore, in vitro studies showed that BOME and BOHF both inhibited LPS-induced nitric oxide production in BV-2 mouse microglial cells. These results suggest that the anti-inflammatory and the microglial activation inhibitory effects of B. officinalis extract may contribute to its neuroprotective effects in brain ischemia.

  11. Demethylation of Circulating Estrogen Receptor Alpha Gene in Cerebral Ischemic Stroke.

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    Hsiu-Fen Lin

    Full Text Available Estrogen is involved in neuron plasticity and can promote neuronal survival in stroke. Its actions are mostly exerted via estrogen receptor alpha (ERα. Previous animal studies have shown that ERα is upregulated by DNA demethylation following ischemic injury. This study investigated the methylation levels in the ERα promoter in the peripheral blood of ischemic stroke patients.The study included 201 ischemic stroke patients, and 217 age- and sex-comparable healthy controls. The quantitative methylation level in the 14 CpG sites of the ERα promoter was measured by pyrosequencing in each participant. Multivariate regression model was used to adjust for stroke traditional risk factors. Stroke subtypes and sex-specific analysis were also conducted.The results demonstrated that the stroke cases had a lower ERα methylation level than controls in all 14 CpG sites, and site 13 and site 14 had significant adjusted p-values of 0.035 and 0.026, respectively. Stroke subtypes analysis showed that large-artery atherosclerosis and cardio-embolic subtypes had significantly lower methylation levels than the healthy controls at CpG site 5, site 9, site 12, site 13 and site 14 with adjusted p = 0.039, 0.009, 0.025, 0.046 and 0.027 respectively. However, the methylation level for the patients with small vessel subtype was not significant. We combined the methylation data from the above five sites for further sex-specific analysis. The results showed that the significant association only existed in women (adjusted p = 0.011, but not in men (adjusted p = 0.300.Female stroke cases have lower ERα methylation levels than those in the controls, especially in large-artery and cardio-embolic stroke subtypes. The study implies that women suffering from ischemic stroke of specific subtype may undergo different protective mechanisms to reduce the brain injury.

  12. Retinal ischemic injury rescued by sodium 4-phenylbutyrate in a rat model.

    Science.gov (United States)

    Jeng, Yung-Yue; Lin, Nien-Ting; Chang, Pen-Heng; Huang, Yuan-Ping; Pang, Victor Fei; Liu, Chen-Hsuan; Lin, Chung-Tien

    2007-03-01

    Retinal ischemia is a common cause of visual impairment for humans and animals. Herein, the neuroprotective effects of phenylbutyrate (PBA) upon retinal ischemic injury were investigated using a rat model. Retinal ganglion cells (RGCs) were retrograde labeled with the fluorescent tracer fluorogold (FG) applied to the superior collicoli of test Sprague-Dawley rats. High intraocular pressure and retinal ischemia were induced seven days subsequent to such FG labeling. A dose of either 100 or 400 mg/kg PBA was administered intraperitoneally to test rats at two time points, namely 30 min prior to the induction of retinal ischemia and 1 h subsequent to the cessation of the procedure inducing retinal ischemia. The test-rat retinas were collected seven days subsequent to the induction of retinal ischemia, and densities of surviving RGCs were estimated by counting FG-labeled RGCs within the retina. Histological analysis revealed that ischemic injury caused the loss of retinal RGCs and a net decrease in retinal thickness. For PBA-treated groups, almost 100% of the RGCs were preserved by a pre-ischemia treatment with PBA (at a dose of either 100 or 400 mg/kg), while post-ischemia treatment of RGCs with PBA did not lead to the preservation of RGCs from ischemic injury by PBA as determined by the counting of whole-mount retinas. Pre-ischemia treatment of RGCs with PBA (at a dose of either 100 or 400 mg/kg) significantly reduced the level of ischemia-associated loss of thickness of the total retina, especially the inner retina, and the inner plexiform layer of retina. Besides, PBA treatment significantly reduced the ischemia-induced loss of cells in the ganglion-cell layer of the retina. Taken together, these results suggest that PBA demonstrates a marked neuroprotective effect upon high intraocular pressure-induced retinal ischemia when the PBA is administered prior to ischemia induction.

  13. Very Low Cerebral Blood Volume Predicts Parenchymal Hematoma in Acute Ischemic Stroke

    DEFF Research Database (Denmark)

    Hermitte, Laure; Cho, Tae-Hee; Ozenne, Brice

    2013-01-01

    BACKGROUND AND PURPOSE: Parenchymal hematoma (PH) may worsen the outcome of patients with stroke. The aim of our study was to confirm the relationship between the volume of very low cerebral blood volume (CBV) and PH using a European multicenter database (I-KNOW). A secondary objective was to exp......BACKGROUND AND PURPOSE: Parenchymal hematoma (PH) may worsen the outcome of patients with stroke. The aim of our study was to confirm the relationship between the volume of very low cerebral blood volume (CBV) and PH using a European multicenter database (I-KNOW). A secondary objective...

  14. Frequency and determinants for hemorrhagic transformation of posterior cerebral stroke : Posterior ischemic stroke and hemorrhagic transformation.

    Science.gov (United States)

    Valentino, Francesca; Gentile, Luana; Terruso, Valeria; Mastrilli, Sergio; Aridon, Paolo; Ragonese, Paolo; Sarno, Caterina; Savettieri, Giovanni; D'Amelio, Marco

    2017-11-13

    hemorrhagic transformation is a threatening ischemic stroke complication. Frequency of hemorrhagic transformation differs greatly among studies, and its risk factors have been usually studied in patients with anterior ischemic stroke who received thrombolytic therapy. We evaluated, in a hospital-based series of patients with posterior ischemic stroke not treated with thrombolysis, frequency and risk factors of hemorrhagic transformation. Patients with posterior circulation stroke were seen in our Department during the period January 2004 to December 2009. Demographic and clinical information were collected. We estimated risk for spontaneous hemorrhagic transformation by means of uni- and multivariate logistic regression analyses. 119 consecutive patients were included (73 males, 61.3%). Hemorrhagic transformation was observed in 7 patients (5.9%). Only clinical worsening was significantly associated with hemorrhagic transformation (OR 6.8, 95% CI 1.3-34.5). Our findings indicate that patients with posterior have a low risk of spontaneous hemorrhagic transformation, suggesting that these patients might have greater advantage from intravenous thrombolysis.

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

    Directory of Open Access Journals (Sweden)

    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.

  16. Characterization of α2-adrenergic receptors in rat cerebral cortex

    International Nuclear Information System (INIS)

    Nasseri, A.

    1987-01-01

    The properties of 3 H-RX 781094 binding sites and the receptors inhibiting norepinephrine (NE) release and cyclic AMP accumulation in rat cerebral cortex were compared. 3 H-RX 781094, a new α 2 -adrenergic receptor antagonist radioligand, labelled a homogeneous population of binding sites at 37 0 C with the pharmacological specificity expected of α 2 -adrenergic receptors. Gpp(NH)p and NaCl decreased the potencies of agonists at 3 H-RX 781094 binding sites 3-22 fold. Antagonists blocked the inhibition of potassium-evoked tritium release from cortical slices preloaded with 3 H-NE by exogenous NE with potencies similar to those observed in competition for specific 3 H-RX 781094 binding sites. EEDQ, an irreversible α 2 -adrenergic receptors and determine whether there was a receptor reserve for the inhibition of tritium release

  17. Ischemic Cardiomyopathy and Cerebral Infarction in a Young Patient Associated with Khat Chewing

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    T. J. Meulman

    2015-01-01

    Full Text Available Khat is a stimulating agent used by many people in the Horn of Africa and the Arabian peninsula. Khat chewing is a known cardiovascular risk factor and is thought to cause vasoconstriction, systemic hypertension, and thrombogenicity. A 33-year-old Somalian man initially presented with loss of neurological function of the left arm, hazy vision, and headache. He smokes tobacco and chews two bundles of khat a week for more than 10 years. His ECG on admission showed a Q wave in V1 and V2 and 2 mm ST-elevations in V1, V2, and V3 and a terminal negative T wave in I, aVL, V2, V3, and V4, consistent with a recent, evolving anterior infarction. A noncontrast enhanced CT of the brain showed ischemia in the right middle cerebral artery vascular territory. An MRI showed recent ischemia in the vascular territory of the posterior division of the right middle cerebral artery. Coronary angiography showed a 70% stenosis with haziness of the proximal left anterior descending artery. Diagnostic tests and imaging are consistent with recent myocardial infarction in the LAD vascular territory because of coronary spasm and cerebral infarction in the middle cerebral artery vascular territory probably related to khat chewing.

  18. Hyperdense middle cerebral artery sign and outcome after intravenous thrombolysis for acute ischemic stroke

    NARCIS (Netherlands)

    Aries, M J H; Uyttenboogaart, M; Koopman, K; Rödiger, L A; Vroomen, P C; De Keyser, J; Luijckx, G J

    2009-01-01

    Background: The presence of a hyperdense middle cerebral artery sign (HMCAS) on baseline brain CT is associated with poor clinical outcome in stroke patients treated with intravenous recombinant tissue plasminogen activator (tPA). It remains uncertain whether the presence of HMCAS is associated with

  19. Preliminary evaluation of [1-11C]octanoate as a PET tracer for studying cerebral ischemia. A PET study in rat and canine models of focal cerebral ischemia

    International Nuclear Information System (INIS)

    Kuge, Yuji; Kawashima, Hidefumi; Hashimoto, Tadatoshi

    2000-01-01

    Octanoate is taken up into the brain and is converted in astrocytes to glutamine through the tricarboxylic acid (TCA) cycle after β-oxidation. We speculate that [1- 11 C]octanoate may be used as a tracer for astroglial functions and/or fatty acid metabolism in the brain and may be useful for studying cerebral ischemia. In the present study we investigated brain distribution of [1- 11 C]octanoate and compared it with cerebral blood flow (CBF) by using rat and canine models of middle cerebral artery (MCA) occlusion and a high resolution PET. In rats brain distribution of [ 15 O]H 2 O measured 1-2 h and 5-6 h after insult was compared with that of [1- 11 C]octanoate measured 3-4 h after insult. Radioactivity ratios of lesioned to normal hemispheres determined with [ 15 O]H 2 O were lower than those determined with [1- 11 C]octanoate. These results were confirmed by a study on a canine model of MCA-occlusion. Twenty-four hours after insult, CBF decreased in the MCA-territory of the occluded hemisphere, whereas normal or higher accumulation of [1- 11 C]octanoate was observed in the ischemic regions. The uptake of [1- 11 C]octanoate-derived radioactivity therefore increased relative to CBF in the ischemic regions, indicating that [1- 11 C]octanoate provides functional information different from CBF. In conclusion, we found that [1- 11 C]octanoate is a potential radiopharmaceutical for studying the pathophysiology of cerebral ischemia. (author)

  20. Electroacupuncture modulates stromal cell-derived factor-1α expression and mobilization of bone marrow endothelial progenitor cells in focal cerebral ischemia/reperfusion model rats.

    Science.gov (United States)

    Xie, Chenchen; Gao, Xiang; Luo, Yong; Pang, Yueshan; Li, Man

    2016-10-01

    Stromal cell-derived factor-1α(SDF-1α) plays a crucial role in regulating the mobilization, migration and homing of endothelial progenitor cells(EPCs). Electroacupuncture(EA), a modern version of Traditional Chinese Medicine, can improve neurological recovery and angiogenesis in cerebral ischemic area. This study aimed to investigate the effects of electroacupuncture(EA) on the mobilization and migration of bone marrow EPCs and neurological functional recovery in rats model after focal cerebral ischemia/reperfusion and the potentially involved mechanisms. Sprague-Dawley rats received filament occlusion of the right middle cerebral artery for 2h followed by reperfusion for 12h, 1d, 2d, 3d, 7d respectively. Rats were randomly divided into sham group, model group and EA group. After 2h of the reperfusion, EA was given at the "Baihui" (GV 20)/Siguan ("Hegu" (LI 4)/"Taichong" (LR 3)) acupoints in the EA group. Modified neurological severity score (mNSS) was used to assess the neurological functional recovery. EPCs number and SDF-1α level in bone marrow(BM) and peripheral blood(PB) were detected by using fluorescence-activated cell sorting (FACS) analysis and quantitative real time polymerase chain reaction (qRT-PCR) respectively. An mNSS test showed that EA treatment significantly improved the neurological functional outcome. EPCs number in PB and BM were obviously increased in the EA group. After cerebral ischemia, the SDF-1α level was decreased in BM while it was increased in PB, which implied a gradient of SDF-1α among BM and PB after ischemia. It suggested that the forming of SDF-1α concentration gradient can induce the mobilization and homing of EPCs. Eletroacupuncture as a treatment can accelerate and increase the forming of SDF-1α concentration gradient to further induce the mobilization of EPCs and angiogenesis in ischemic brain and improve the neurological function recovery. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Effect of baicalin on the autophagy and Beclin-1 expression in rats with cerebral ischemia

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    Xiang-Long Hong

    2016-07-01

    Full Text Available Objective: To explore the effect of baicalin on the autophagy and Beclin-1 expression in rats with cerebral ischemia, and the role of autophagy in the cerebral ischemia injury. Methods: The healthy male SD rats were randomized into the sham operation group, the ischemia model group, baicalin treatment group (100 mg/kg, and 3MA group (15 mg/kg, with 10 rats in each group. Transient focal cerebral ischemia injury model in rats was induced by occlusion of middle cerebral artery (MCA for 180 min. The rats were given the corresponding drugs through the tail veins 30 min before molding. Half of the specimens were used for TTC staining to analyze the cerebral infarction volume. The others were used to determine the expression of Beclin-1 in the brain tissues by Western-blot. Results: When compared with the ischemia model group, the cerebral infarction volume in 3MA group was significantly increased, while that in baicalin treatment group was significantly reduced, and the comparison among the groups was statistically significant. When compared with the ischemia model group, Beclin-1 expression level in baicalin treatment group was significantly elevated, while Beclin-1 expression level in 3MA group was significantly higher than that in the sham-operation group but lower than that in the ischemia model group. Conclusions: The autophagy level of brain tissues in normal rats is low. The cerebral ischemia can activate autophagy. The activated autophagy is probably involved in the neuroprotection of cerebral ischemia injury. Application of 3MA to inhibit the occurrence of autophagy can aggravate the cerebral injury. Baicalin can significantly improve the cerebral ischemia injury and promote the occurrence of autophagy, whose mechanism is probably associated with the up-regulation of Beclin-1 expression to promote the activation of type III PI3K signal transduction pathway.

  2. Anti-inflammatory and neuroprotective effects of sanguinarine following cerebral ischemia in rats

    OpenAIRE

    Wang, Qin; Dai, Peng; Bao, Han; Liang, Ping; Wang, Wei; Xing, An; Sun, Jianbin

    2016-01-01

    Stroke is one of the leading causes of mortality worldwide. Protective agents that can diminish injuries caused by cerebral ischemia-reperfusion (I/R) are important in alleviating the harmful outcomes of stroke. The aim of the present study was to investigate the protective role of sanguinarine in cerebral I/R injury. A rat middle cerebral artery occlusion model was used to assess the clinical effect of sanguinarine, and inflammatory cytokines in the serum were detected by ELISA. Western blot...

  3. Ecto-ATPase inhibition: ATP and adenosine release under physiological and ischemic in vivo conditions in the rat striatum.

    Science.gov (United States)

    Melani, Alessia; Corti, Francesca; Stephan, Holger; Müller, Christa E; Donati, Chiara; Bruni, Paola; Vannucchi, Maria Giuliana; Pedata, Felicita

    2012-01-01

    In the central nervous system (CNS) ATP and adenosine act as transmitters and neuromodulators on their own receptors but it is still unknown which part of extracellular adenosine derives per se from cells and which part is formed from the hydrolysis of released ATP. In this study extracellular concentrations of adenosine and ATP from the rat striatum were estimated by the microdialysis technique under in vivo physiological conditions and after focal ischemia induced by medial cerebral artery occlusion. Under physiological conditions, adenosine and ATP concentrations were in the range of 130 nmol/L and 40 nmol/L, respectively. In the presence of the novel ecto-ATPase inhibitor, PV4 (100 nmol/L), the extracellular concentration of ATP increased 12-fold to ~360 nmol/L but the adenosine concentration was not altered. This demonstrates that, under physiological conditions, adenosine is not a product of extracellular ATP. In the first 4h after ischemia, adenosine increased to ~690 nmol/L and ATP to ~50 nmol/L. In the presence of PV4 the extracellular concentration of ATP was in the range of 450 nmol/L and a significant decrease in extracellular adenosine (to ~270 nmol/L) was measured. The contribution of extracellular ATP to extracellular adenosine was maximal in the first 20 min after ischemia onset. Furthermore we demonstrated, by immunoelectron microscopy, the presence of the concentrative nucleoside transporter CNT2 on plasma and vesicle membranes isolated from the rat striatum. These results are in favor that adenosine is transported in vesicles and is released in an excitation-secretion manner under in vivo physiological conditions. Early after ischemia, extracellular ATP is hydrolyzed by ecto-nucleotidases which significantly contribute to the increase in extracellular adenosine. To establish the contribution of extracellular ATP to adenosine might constitute the basis for devising a correct putative purinergic strategy aimed at protection from ischemic damage

  4. Reduction of cerebral injury in stroke-prone spontaneously hypertensive rats by amlodipine

    NARCIS (Netherlands)

    Blezer, E.L.A.; Nicolaij, K.; Goldschmeding, R.C.; Koomans, H.A.; Joles, Jaap

    2002-01-01

    Dihydropyridine Ca2+ channel antagonists, initiated together with high salt intake, prevent the development of hypertension and subsequent cerebral damage in stroke-prone spontaneously hypertensive rats (SHRSP). We hypothesized that the dihydropyridine Ca2+ channel antagonist amlodipine

  5. Expression of tumor necrosis factor alpha after focal cerebral ischaemia in the rat

    NARCIS (Netherlands)

    Buttini, M; Appel, K; Sauter, A; GebickeHaerter, PJ; Boddeke, HWGM

    Induction of tumor necrosis factor alpha was studied in the brain of rats after focal cerebral ischaemia by occlusion of the left middle cerebral artery. Using a specific antisense riboprobe for in situ hybridization histochemistry, cells positive for tumor necrosis factor alpha messenger RNA were

  6. Microangiographic study of the normal anatomy of the cerebral venous system in rats

    International Nuclear Information System (INIS)

    Schumacher, M.

    1984-01-01

    Microangiographic serial cuts were performed in 20 Sprague-Dawley rats for a systematic study of the normal anatomy of the cerebral veins. The draining pathways of the cerebral and cerebellar cortex, basal ganglia, hypothalamus, hippocampus and the midbrain are described and discussed with regard to their different functions. (orig.)

  7. [Effects of exogenous high mobility group protein box 1 on angiogenesis in ischemic zone of early scald wounds of rats].

    Science.gov (United States)

    Dai, L; Guo, X; Huang, H J; Liao, X M; Luo, X Q; Li, D; Zhou, H; Gao, X C; Tan, M Y

    2018-04-20

    Objective: To observe effects of exogenous high mobility group protein box 1 (HMGB1) on angiogenesis in ischemic zone of early scald wounds of rats. Methods: Thirty-six Sprague-Dawley rats were divided into HMGB1 group and simple scald (SS) group according to the random number table, with 18 rats in each group. Comb-like copper mould was placed on the back of rats for 20 s after being immersed in 100 ℃ hot water for 3 to 5 min to make three ischemic zones of wound. Immediately after scald, rats in HMGB1 group were subcutaneously injected with 0.4 μg HMGB1 and 0.1 mL phosphate buffer solution (PBS), and rats in SS group were subcutaneously injected with 0.1 mL PBS from boarders of ischemic zone of scald wound. At post scald hour (PSH) 24, 48, and 72, 6 rats in each group were collected. Protein expressions of vascular endothelial growth factor (VEGF) in ischemic zone of wound at PSH 24, 48, and 72 and protein expressions of CD31 in ischemic zone of wound at PSH 48 and 72 were detected by immunohistochemistry. The number of microvessel in CD31 immunohistochemical sections of ischemic zone of wound at PSH 48 and 72 was calculated after observing by the microscope. The mRNA expressions of VEGF and CD31 in ischemic zone of wound were detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction at PSH 24, 48, and 72. Data were processed with analysis of variance of factorial design, t test, and Bonferroni correction. Results: (1) At PSH 24, 48, and 72, protein expressions of VEGF in ischemic zone of wound of rats in HMGB1 group were significantly higher than those of rats in SS group ( t =7.496, 4.437, 5.402, P zone of wound of rats in HMGB1 group were 0.038 8±0.007 9 and 0.057 7±0.001 2 respectively, significantly higher than 0.013 4±0.004 9 and 0.030 3±0.004 0 of rats in SS group ( t =10.257, 15.055, P zone of wound of rats in HMGB1 group was obviously more than that of rats in SS group ( t =3.536, 4.000, P zone of wound of

  8. Electroacupuncture ameliorates post-stroke learning and memory through minimizing ultrastructural brain damage and inhibiting the expression of MMP-2 and MMP-9 in cerebral ischemia-reperfusion injured rats.

    Science.gov (United States)

    Lin, Ruhui; Yu, Kunqiang; Li, Xiaojie; Tao, Jing; Lin, Yukun; Zhao, Congkuai; Li, Chunyan; Chen, Li-Dian

    2016-07-01

    The aim of the present study was to investigate the potential neuroprotective effects of electroacupuncture (EA) in the treatment of cerebral ischemia/reperfusion (I/R) injury, and to elucidate the association between this neuroprotective effect and brain ultrastructure and expression of matrix metalloproteinase (MMP)‑2 and 9. Rats underwent focal cerebral I/R injury by arterial ligation and received in vivo therapeutic EA at the Baihui (DU20) and Shenting (DU24) acupoints. The therapeutic efficacy was then evaluated following the surgery. The results of the current study demonstrated that EA treatment significantly ameliorated neurological deficits and reduced cerebral infarct volume compared with I/R injured rats. Furthermore, EA improved the learning and memory ability of rats following I/R injury, inhibited blood brain barrier breakdown and reduced neuronal damage in the ischemic penumbra. Furthermore, EA attenuated ultrastructural changes in the brain tissue following ischemia and inhibited MMP‑2/MMP‑9 expression in cerebral I/R injured rats. The results suggest that EA ameliorates anatomical deterioration, and learning and memory deficits in rats with cerebral I/R injury.

  9. Neuronal apoptosis and synaptic density in the dentate gyrus of ischemic rats' response to chronic mild stress and the effects of Notch signaling.

    Directory of Open Access Journals (Sweden)

    Shaohua Wang

    Full Text Available Our previous research highlighted an inconsistency with Notch1 signaling-related compensatory neurogenesis after chronic mild stress (CMS in rodents suffering from cerebral ischemia, which continue to display post-stroke depressive symptoms. Here, we hypothesize that CMS aggrandized ischemia-related apoptosis injury and worsened synaptic integrity via gamma secretase-meditated Notch1 signaling. Adult rats were exposed to a CMS paradigm after left middle cerebral artery occlusion (MCAO. Open-field and sucrose consumption testing were employed to assess depression-like behavior. Gene expression of pro-apoptotic Bax, anti-apoptotic Bcl-2, and synaptic density-related synaptophysin were measured by western blotting and real-time PCR on Day 28 after MCAO surgery. CMS induced depressive behaviors in ischemic rats, which was accompanied by an elevation in Bax/bcl-2 ratio, TUNEL staining in neurons and reduced synaptophysin expression in the dentate gyrus. These collective effects were reversed by the gamma-secretase inhibitor DAPT (N-[N-(3,5-difluorophenacetyl-L-alanyl]-S-phenyl-glycine t-butyl ester. We found that post-stroke stressors made neurons in the dentate gyrus vulnerable to apoptosis, which supports a putative role for Notch signaling in neural integrity, potentially in newborn cells' synaptic deficit with regard to preexisting cells. These findings suggest that post-stroke depression therapeutically benefits from blocking gamma secretase mediated Notch signaling, and whether this signaling pathway could be a therapeutic target needs to be further investigated.

  10. [Results of thrombolyses procedures in acute ischemic cerebral stroke realized in Kraków 2004-2007--Grant Ministry of Science and Information].

    Science.gov (United States)

    Popiela, Tadeusz J; Urbanik, Andrzej; Słowik, Agnieszka

    2010-01-01

    To lower the number of complications of acute cerebral ischemic stroke and to reduce the time of rehabilitation in these patients it is necessary to induce treatment within the first 3 hours of the onset of the stroke. Early intervention however, is possible only in cases with the confirm localized ischemic focus visualized in one of the diagnostic imaging methods. The most widespread is CT, hovewer the first symptoms of ischemic stroke can be seen not beforel2 hours of the onset. The study evaluated the effectiveness of early diagnostics of ischemic stroke using perfusion CT (pCT) with subsequent intravenous or intra-arterial thrombolysis. The patients with ischemic stroke confirmed by pCT and qualified to thrombolysis in the first 3 hours of the onset of the stroke were randomly selected to intravenous or intra-arterial thrmobolysis. Those, who were 3 to 6 hours of the onset of the stroke were qualified to intra-arterial thrombolysis. A study group consisted of 377 patients hospitalized due to ischemic stroke. Of these pCT was performed in 76 cases, intravenous thrombolysis in 4 and intra-arterial thrombolysis in 2. Clinical condition substantially improved in 3 patients. Obtained results indicate the necessity to introduce pCT to the routine diagnostics of the acute ischemic stroke. A small number of patients eligible for thrombolysis does not allow to compare the effectiveness of intra-arterial and intravenous thrombolysis, however the project allowed to work out the efficient system of diagnostics and treatment of the acute ischemic stroke in the area of Krakow based on the standards used in the European countries.

  11. Regional cerebral blood flow using sup 133 Xenon intra-venous technique, 2; Evaluation of regional cerebral blood flow in patients with cerebrovascular ischemic disease

    Energy Technology Data Exchange (ETDEWEB)

    Yonekura, Masahiro; Teramoto, Shigeyoshi; Moriyama, Tadayoshi (Nagasaki Chuo National Hospital (Japan))

    1990-12-01

    Using the {sup 133}Xenon venous method, we have studied the regional cerebral blood flow (rCBF) in 947 patients with cerebrovascular ischemic disease. In 116 stroke or TIA patients with internal carotid artery occlusion or severe stenosis, their rCBF revealed 48.9 ml/100 g/min on average in the group of one side occlusion, 46.7 ml/100 g/min in the group of both sides occlusion. These values reduced approximately 12%, 16% and 15% of the rCBF in healthy volunteers of same age, respectively. In 28 patients with moya moya disease, their rCBF tended to be higher in younger cases and lower with advanced age. In the majority of the cases, their rCBF was age-dependent with 20{similar to}25 ml/100 g/min below the curve of age-matched rCBF of healthy volunteers. The reduction of rCBF was observed in 69 (48.3%) of 143 cases clinically diagnosed as small vessel disease, in 58 (41.4%) of 140 cases with vertebro-basilar insufficiency and in 23 (44.2%) of 52 cases with syncopal attack compared with the rCBF of healthy volunteers. (author).

  12. Evaluation of asymmetries of blood flow rate and of circulation time by intravenous radionuclide cerebral angiography in patients with ischemic completed stroke.

    Science.gov (United States)

    Bartolini, A; Primavera, A; Gasparetto, B

    1984-12-01

    155 patients with ischemic completed stroke of varying severity and outcome have been evaluated by radionuclide cerebral angiography with analysis of regional time-activity curves. Two parameters have been evaluated: area under the upslope of the curve (Aup) reflecting regional blood flow rate and moment of the whole curve reflecting tracer circulation time (rABCT) Combination of these two methods ensured increased detection of perfusion asymmetries.

  13. [Retrospective analysis of risk factors in 900 patients with ischemic cerebral stroke of wind-phlegm collateral obstruction syndrome and qi deficiency blood stasis syndrome in Wuhan District].

    Science.gov (United States)

    Qiu, Xin; Wang, Kai-xin; Chen, Guo-hua

    2011-11-01

    To analyze the correlation between risk factors and ischemic cerebral stroke of wind-phlegm collateral obstruction syndrome and qi deficiency blood stasis syndrome. Totally 900 patients of the two syndrome types were recruited. Risk factors correlated to ischemic cerebral stroke such as gender, age, time of onset, site of infarction, tongue proper, tongue fur, pulse picture, hypertension, diabetes, past stroke history, hyperlipidemia, hematocrit, smoking, drinking, genetic factor, blood type, complications were analyzed using Chi-square test and non-conditional Logistic regression analysis. Statistical significance existed between the two syndrome types in age (X2 = 8.2392, P = 0.0413), hyperlipidemia (X2 = 4.8386, P = 0.0278), tongue proper (X2 = 7.9470, P = 0.0048), and tongue fur (X2 = 4.3298, P = 0.0375). Statistical significance existed between the two syndrome types in hyperlipidemia, tongue proper, and tongue fur, and their OR value was 0.699 (P = 0.0282), 0.332 (P =0.0071), and 0.667 (P = 0.0382) respectively. The OR value of the past stroke history was 3.226 (P = 0.0314), that of complications 0.203 (P = 0.0705), and that of anterior circulation infarction 0.214 (P = 0.0098). Among different ages groups, the constituent ratio of qi deficiency blood stasis syndrome was obviously higher than that of wind-phlegm collateral obstruction syndrome. Besides, patients of qi deficiency blood stasis syndrome were liable to suffer from hyperlipidemia, anterior circulation infarction, and complications. The age, blood lipid levels, site of infarction, complications are closely correlated with Chinese syndrome types of ischemic cerebral stroke, which can provide objective indices for typing ischemic cerebral stroke.

  14. Thrombolytic treatment for acute ischemic cerebral stroke: intraarterial urokinase infusion vs. intravenous heparin and urokinase infusion

    International Nuclear Information System (INIS)

    Ko, Gi Young; Suh, Dae Chul; Lee, Jae Hong; Kim, Jun Hyoung; Choi, Choong Gon; Lee, Ho Kyu; Lee, Myoung Chong

    1996-01-01

    To evaluate the efficacy and limitation of intra-arterial urokinase (IAUK) infusion for treatment of acute cerebral stroke. Twenty-seven acute cerebral stroke patients treated with IAUK infusion within six hours of stroke onset were reviewed. All patients showed normal initial brain findings on CT. In 21 patients, urokinase(5-15 x 10 5 IU) was administered through a microcatheter placed into or proximal to occluded segment. Mechanical disruption of thrombus by guidewire was performed in 17 patients. Angiographic and clinical responses and complications after IAUK infusion, were evaluated and the results were compared with those of intravenous heparin(N=19) and urokinase infusion(N=19). Complete or partial angiographic recanalization of occluded segment was found in 18 patients (67%), and neurologic improvement was followed in 14 patients(52%). The degree of improvement on the stroke scale score after IAUK infusion was statistically more significant(p<0.05) than that shown after intravenous heparin and urokinase infusion. Complications after IAUK infusion were large(15%) and small amount intracerebral hemorrhage(15%), contrast leakage into brain parenchyma(11%), and gastrointestinal bleeding(4%). Between the IAVK and the intravenous urokinase infusion group, differences in extent and types of complications were statistically insignificant, but were significantly higher in those two groups than in the intravenous heparin infusion group. IAUK infusion may be effective for the treatment of acute cerebral stroke

  15. Effects of Ischemic Postconditioning on the Hemodynamic Parameters and Heart Nitric Oxide Levels of Hypothyroid Rats

    International Nuclear Information System (INIS)

    Jeddi, Sajad; Zaman, Jalal; Ghasemi, Asghar

    2015-01-01

    Ischemic postconditioning (IPost) is a method of protecting the heart against ischemia-reperfusion (IR) injury. However, the effectiveness of IPost in cases of ischemic heart disease accompanied by co-morbidities such as hypothyroidism remains unclear. The aim of this study was to determine the effect of IPost on myocardial IR injury in hypothyroid male rats. Propylthiouracil in drinking water (500 mg/L) was administered to male rats for 21 days to induce hypothyroidism. The hearts from control and hypothyroid rats were perfused in a Langendorff apparatus and exposed to 30 min of global ischemia, followed by 120 min of reperfusion. IPost was induced immediately following ischemia. Hypothyroidism and IPost significantly improved the left ventricular developed pressure (LVDP) and peak rates of positive and negative changes in left ventricular pressure (±dp/dt) during reperfusion in control rats (p < 0.05). However, IPost had no add-on effect on the recovery of LVDP and ±dp/dt in hypothyroid rats. Furthermore, hypothyroidism significantly decreased the basal NO metabolite (NO x ) levels of the serum (72.5 ± 4.2 vs. 102.8 ± 3.7 μmol/L; p < 0.05) and heart (7.9 ± 1.6 vs. 18.8 ± 3.2 μmol/L; p < 0.05). Heart NO x concentration in the hypothyroid groups did not change after IR and IPost, whereas these were significantly (p < 0.05) higher and lower after IR and IPost, respectively, in the control groups. Hypothyroidism protects the heart from IR injury, which may be due to a decrease in basal nitric oxide (NO) levels in the serum and heart and a decrease in NO after IR. IPost did not decrease the NO level and did not provide further cardioprotection in the hypothyroid group

  16. Effects of Ischemic Postconditioning on the Hemodynamic Parameters and Heart Nitric Oxide Levels of Hypothyroid Rats

    Energy Technology Data Exchange (ETDEWEB)

    Jeddi, Sajad; Zaman, Jalal; Ghasemi, Asghar, E-mail: ghasemi@endocrine.ac.ir [Endocrine Physiology Research Center - Research Institute for Endocrine Sciences - Shahid Beheshti University of Medical Sciences, Tehran (Iran, Islamic Republic of); Endocrine Research Center - Research Institute for Endocrine Sciences - Shahid Beheshti University of Medical Sciences, Tehran (Iran, Islamic Republic of)

    2015-02-15

    Ischemic postconditioning (IPost) is a method of protecting the heart against ischemia-reperfusion (IR) injury. However, the effectiveness of IPost in cases of ischemic heart disease accompanied by co-morbidities such as hypothyroidism remains unclear. The aim of this study was to determine the effect of IPost on myocardial IR injury in hypothyroid male rats. Propylthiouracil in drinking water (500 mg/L) was administered to male rats for 21 days to induce hypothyroidism. The hearts from control and hypothyroid rats were perfused in a Langendorff apparatus and exposed to 30 min of global ischemia, followed by 120 min of reperfusion. IPost was induced immediately following ischemia. Hypothyroidism and IPost significantly improved the left ventricular developed pressure (LVDP) and peak rates of positive and negative changes in left ventricular pressure (±dp/dt) during reperfusion in control rats (p < 0.05). However, IPost had no add-on effect on the recovery of LVDP and ±dp/dt in hypothyroid rats. Furthermore, hypothyroidism significantly decreased the basal NO metabolite (NO{sub x}) levels of the serum (72.5 ± 4.2 vs. 102.8 ± 3.7 μmol/L; p < 0.05) and heart (7.9 ± 1.6 vs. 18.8 ± 3.2 μmol/L; p < 0.05). Heart NO{sub x} concentration in the hypothyroid groups did not change after IR and IPost, whereas these were significantly (p < 0.05) higher and lower after IR and IPost, respectively, in the control groups. Hypothyroidism protects the heart from IR injury, which may be due to a decrease in basal nitric oxide (NO) levels in the serum and heart and a decrease in NO after IR. IPost did not decrease the NO level and did not provide further cardioprotection in the hypothyroid group.

  17. Rutin protects against cognitive deficits and brain damage in rats with chronic cerebral hypoperfusion.

    Science.gov (United States)

    Qu, Jie; Zhou, Qiong; Du, Ying; Zhang, Wei; Bai, Miao; Zhang, Zhuo; Xi, Ye; Li, Zhuyi; Miao, Jianting

    2014-08-01

    Chronic cerebral hypoperfusion is a critical causative factor for the development of cognitive decline and dementia in the elderly, which involves many pathophysiological processes. Consequently, inhibition of several pathophysiological pathways is an attractive therapeutic strategy for this disorder. Rutin, a biologically active flavonoid, protects the brain against several insults through its antioxidant and anti-inflammatory properties, but its effect on cognitive deficits and brain damage caused by chronic cerebral hypoperfusion remains unknown. Here, we investigated the neuroprotective effect of rutin on cognitive impairments and the potential mechanisms underlying its action in rats with chronic cerebral hypoperfusion. We used Sprague-Dawley rats with permanent bilateral common carotid artery occlusion (BCCAO), a well-established model of chronic cerebral hypoperfusion. After rutin treatment for 12 weeks, the neuroprotective effect of rutin in rats was evaluated by behavioural tests, biochemical and histopathological analyses. BCCAO rats showed marked cognitive deficits, which were improved by rutin treatment. Moreover, BCCAO rats exhibited central cholinergic dysfunction, oxidative damage, inflammatory responses and neuronal damage in the cerebral cortex and hippocampus, compared with sham-operated rats. All these effects were significantly alleviated by treatment with rutin. Our results provide new insights into the pharmacological actions of rutin and suggest that rutin has multi-targeted therapeutical potential on cognitive deficits associated with conditions with chronic cerebral hypoperfusion such as vascular dementia and Alzheimer's disease. © 2014 The British Pharmacological Society.

  18. Proteomic analysis of rat cerebral cortex following subchronic acrolein toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Rashedinia, Marzieh; Lari, Parisa [Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad (Iran, Islamic Republic of); Abnous, Khalil, E-mail: Abnouskh@mums.ac.r [Pharmaceutical Research Center, Department of Medicinal Chemistry, Mashhad University of Medical Sciences, Mashhad (Iran, Islamic Republic of); Hosseinzadeh, Hossein, E-mail: Hosseinzadehh@mums.ac.ir [Pharmaceutical Research Center, Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad (Iran, Islamic Republic of)

    2013-10-01

    Acrolein, a member of reactive α,β-unsaturated aldehydes, is a major environmental pollutant. Acrolein is also produced endogenously as a toxic by-product of lipid peroxidation. Because of high reactivity, acrolein may mediate oxidative damages to cells and tissues. It has been shown to be involved in a wide variety of pathological states including pulmonary, atherosclerosis and neurodegenerative diseases. In this study we employed proteomics approach to investigate the effects of subchronic oral exposures to 3 mg/kg of acrolein on protein expression profile in the brain of rats. Moreover effects of acrolein on malondialdehyde (MDA) levels and reduced glutathione (GSH) content were investigated. Our results revealed that treatment with acrolein changed levels of several proteins in diverse physiological process including energy metabolism, cell communication and transport, response to stimulus and metabolic process. Interestingly, several differentially over-expressed proteins, including β-synuclein, enolase and calcineurin, are known to be associated with human neurodegenerative diseases. Changes in the levels of some proteins were confirmed by Western blot. Moreover, acrolein increases the level of MDA, as a lipid peroxidation biomarker and decreased GSH concentrations, as a non-enzyme antioxidant in the brain of acrolein treated rats. These findings suggested that acrolein induces the oxidative stress and lipid peroxidation in the brain, and so that may contribute to the pathophysiology of neurological disorders. - Highlights: • Acrolein intoxication increased lipid peroxidation and deplete GSH in rat brain. • Effect of acrolein on protein levels of cerebral cortex was analyzed by 2DE-PAGE. • Levels of a number of proteins with different biological functions were increased.

  19. Proteomic analysis of rat cerebral cortex following subchronic acrolein toxicity

    International Nuclear Information System (INIS)

    Rashedinia, Marzieh; Lari, Parisa; Abnous, Khalil; Hosseinzadeh, Hossein

    2013-01-01

    Acrolein, a member of reactive α,β-unsaturated aldehydes, is a major environmental pollutant. Acrolein is also produced endogenously as a toxic by-product of lipid peroxidation. Because of high reactivity, acrolein may mediate oxidative damages to cells and tissues. It has been shown to be involved in a wide variety of pathological states including pulmonary, atherosclerosis and neurodegenerative diseases. In this study we employed proteomics approach to investigate the effects of subchronic oral exposures to 3 mg/kg of acrolein on protein expression profile in the brain of rats. Moreover effects of acrolein on malondialdehyde (MDA) levels and reduced glutathione (GSH) content were investigated. Our results revealed that treatment with acrolein changed levels of several proteins in diverse physiological process including energy metabolism, cell communication and transport, response to stimulus and metabolic process. Interestingly, several differentially over-expressed proteins, including β-synuclein, enolase and calcineurin, are known to be associated with human neurodegenerative diseases. Changes in the levels of some proteins were confirmed by Western blot. Moreover, acrolein increases the level of MDA, as a lipid peroxidation biomarker and decreased GSH concentrations, as a non-enzyme antioxidant in the brain of acrolein treated rats. These findings suggested that acrolein induces the oxidative stress and lipid peroxidation in the brain, and so that may contribute to the pathophysiology of neurological disorders. - Highlights: • Acrolein intoxication increased lipid peroxidation and deplete GSH in rat brain. • Effect of acrolein on protein levels of cerebral cortex was analyzed by 2DE-PAGE. • Levels of a number of proteins with different biological functions were increased

  20. Novel resveratrol analogues attenuate renal ischemic injury in rats

    Science.gov (United States)

    Khader, Adam; Yang, Weng-Lang; Kuncewitch, Michael; Prince, Jose M.; Marambaud, Philippe; Nicastro, Jeffrey; Coppa, Gene F.; Wang, Ping

    2014-01-01

    Background Renal ischemia-reperfusion (I/R) is a severe clinical complication with no specific treatment. Resveratrol has been shown as a promising experimental agent in renal I/R due to its effect on cellular energy metabolism, oxidative stress, and inflammation. Recently, we identified two biologically active resveratrol analogues (RSVAs), RSVA405 and RSVA314. We hypothesized that both RSAVs would attenuate I/R-induced renal injury. Methods Adult male rats were subjected to renal I/R through bilateral renal pedicle clamping for 60 min, followed by reperfusion. RSVA405 (3 mg/kg BW), RSVA314 (3 mg/kg BW), or vehicle (10% DMSO and 33% Solutol in PBS) was administered by intraperitoneal injection 1 h prior to ischemia. Blood and renal tissues were collected 24 h after I/R for evaluation. Results Administration of RSVA405 and RSVA314 significantly reduced the serum levels of renal dysfunction and injury markers, including creatinine, blood urea nitrogen, aspartate aminotransferase, and lactate dehydrogenase, compared to vehicle. The protective effect of RSVA405 and RSVA314 was also reflected on histologic evaluation. Both RSVAs reduced the number of apoptotic cells by more than 60% as determined by TUNEL assay, compared to vehicle. The renal ATP levels of the vehicle group was decreased to 52.4% of control, while those of the RSVA405 and RSVA314 groups were restored to 72.3% and 79.6% of control, respectively. Both RSVAs significantly reduced the protein expression of inducible nitric oxide synthase and nitrotyrosine, and the mRNA levels of TNF-α, IL-6 and IL-1β. Conclusions RSVA405 and RSVA314 attenuate I/R-induced renal injury through the modulation of energy metabolism, oxidative stress, and inflammation. PMID:25214260

  1. High dose infusion of activated protein C (rhAPC) fails to improve neuronal damage and cognitive deficit after global cerebral ischemia in rats.

    Science.gov (United States)

    Brückner, Melanie; Lasarzik, Irina; Jahn-Eimermacher, Antje; Peetz, Dirk; Werner, Christian; Engelhard, Kristin; Thal, Serge C

    2013-09-13

    Recent studies demonstrated anticoagulatory, antiinflammatory, antiapoptotic, and neuroprotective properties of activated protein C (APC) in rodent models of acute neurodegenerative diseases, suggesting APC as promising broad acting therapeutic agent. Unfortunately, continuous infusion of recombinant human APC (rhAPC) failed to improve brain damage following cardiac arrest in rats. The present study was designed to investigate the neuroprotective effect after global cerebral ischemia (GI) with an optimized infusion protocol. Rats were subjected to bilateral clip occlusion of the common carotid arteries (BCAO) and controlled hemorrhagic hypotension to 40 mm Hg for 14 min and a subsequent 5h-infusion of rhAPC (2mg/kg bolus+6 mg/kg/h continuous IV) or vehicle (0.9% NaCl). The dosage was calculated to maintain plasma hAPC activity at 150%. Cerebral inflammation, apoptosis and neuronal survival was determined at day 10. rhAPC infusion did not influence cortical cerebral perfusion during reperfusion and failed to reduce neuronal cell loss, microglia activation, and caspase 3 activity. Even an optimized rhAPC infusion protocol designed to maintain a high level of APC plasma activity failed to improve the sequels following GI. Despite positive reports about protective effects of APC following, e.g., ischemic stroke, the present study supports the notion that infusion of APC during the early reperfusion phase does not result in sustained neuroprotection and fails to improve outcome after global cerebral ischemia. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  2. Experimental Focal Cerebral Ischemia

    DEFF Research Database (Denmark)

    Christensen, Thomas

    2007-01-01

    Focal cerebral ischemia due to occlusion of a major cerebral artery is the cause of ischemic stroke which is a major reason of mortality, morbidity and disability in the populations of the developed countries. In the seven studies summarized in the thesis focal ischemia in rats induced by occlusion...... in the penumbra is recruited in the infarction process leading to a progressive growth of the infarct. The penumbra hence constitutes an important target for pharmacological treatment because of the existence of a therapeutic time window during which treatment with neuroprotective compounds may prevent...

  3. Vildagliptin reduces cardiac ischemic-reperfusion injury in obese orchiectomized rats.

    Science.gov (United States)

    Pongkan, Wanpitak; Pintana, Hiranya; Jaiwongkam, Thidarat; Kredphoo, Sasiwan; Sivasinprasasn, Sivaporn; Chattipakorn, Siriporn C; Chattipakorn, Nipon

    2016-10-01

    Obesity and testosterone deprivation are associated with coronary artery disease. Testosterone and vildagliptin (dipeptidyl peptidase-4 inhibitors) exert cardioprotection during ischemic-reperfusion (I/R) injury. However, the effect of these drugs on I/R heart in a testosterone-deprived, obese, insulin-resistant model is unclear. This study investigated the effects of testosterone and vildagliptin on cardiac function, arrhythmias and the infarct size in I/R heart of testosterone-deprived rats with obese insulin resistance. Orchiectomized (O) or sham operated (S) male Wistar rats were divided into 2 groups to receive normal diet (ND) or high-fat diet (HFD) for 12 weeks. Orchiectomized rats in each diet were divided to receive testosterone (2 mg/kg), vildagliptin (3 mg/kg) or the vehicle daily for 4 weeks. Then, I/R was performed by a 30-min left anterior descending coronary artery ligation, followed by a 120-min reperfusion. LV function, arrhythmia scores, infarct size and cardiac mitochondrial function were determined. HFD groups developed insulin resistance at week 12. At week 16, cardiac function was impaired in NDO, HFO and HFS rats, but was restored in all testosterone- and vildagliptin-treated rats. During I/R injury, arrhythmia scores, infarct size and cardiac mitochondrial dysfunction were prominently increased in NDO, HFO and HFS rats, compared with those in NDS rats. Treatment with either testosterone or vildagliptin similarly attenuated these impairments during I/R injury. These finding suggest that both testosterone replacement and vildagliptin share similar efficacy for cardioprotection during I/R injury by decreasing the infarct size and attenuating cardiac mitochondrial dysfunction caused by I/R injury in testosterone-deprived rats with obese insulin resistance. © 2016 Society for Endocrinology.

  4. Antiplatelet Treatment After Transient Ischemic Attack and Ischemic Stroke in Patients With Cerebral Microbleeds in 2 Large Cohorts and an Updated Systematic Review.

    Science.gov (United States)

    Lau, Kui Kai; Lovelock, Caroline E; Li, Linxin; Simoni, Michela; Gutnikov, Sergei; Küker, Wilhelm; Mak, Henry Ka Fung; Rothwell, Peter M

    2018-06-01

    In patients with transient ischemic attack/ischemic stroke, microbleed burden predicts intracerebral hemorrhage (ICH), and ischemic stroke, but implications for antiplatelet treatment are uncertain. Previous cohort studies have had insufficient follow-up to assess the time course of risks, have not stratified risks by antithrombotic use, and have not reported extracranial bleeds or functional outcome of ICH versus ischemic stroke. In 2 independent prospective cohorts with transient ischemic attack/ischemic stroke (Oxford Vascular Study/mainly white; University of Hong Kong/mainly Chinese), antiplatelet treatment was started routinely irrespective of microbleed burden. Risks, time course and outcome of ICH, extracranial bleeds, and recurrent ischemic events were determined and stratified by microbleed burden (0 versus 1, 2-4, and ≥5), adjusting for age, sex, and vascular risk factors. Microbleeds were more frequent in the Chinese cohort (450 of 1003 versus 165 of 1080; P <0.0001), but risk associations were similar during 7433 patient-years of follow-up. Among 1811 patients on antiplatelet drugs, risk of major extracranial bleeds was unrelated to microbleed burden ( P trend =0.87), but the 5-year risk of ICH was steeply related ( P trend <0.0001), with 11 of 15 (73%) of ICH in 140 of 1811 (7.7%) patients with ≥5 microbleeds. However, risk of ischemic stroke also increased with microbleed burden ( P trend =0.013), such that risk of ischemic stroke and coronary events exceeded ICH and major extracranial bleeds during the first year, even among patients with ≥5 microbleeds (11.6% versus 3.9%). However, this ratio changed over time, with risk of hemorrhage (11.2%) matching that of ischemic events (12.0%) after 1 year. Moreover, whereas the association between microbleed burden and risk of ischemic stroke was due mainly to nondisabling events ( P trend =0.007), the association with ICH was accounted for ( P trend <0.0001) by disabling/fatal events (≥5 microbleeds

  5. Therapeutic time window and underlying therapeutic mechanism of breviscapine injection against cerebral ischemia/reperfusion injury in rats.

    Science.gov (United States)

    Guo, Chao; Zhu, Yanrong; Weng, Yan; Wang, Shiquan; Guan, Yue; Wei, Guo; Yin, Ying; Xi, Miaomaio; Wen, Aidong

    2014-01-01

    Breviscapine injection is a Chinese herbal medicine standardized product extracted from Erigeron breviscapus (Vant.) Hand.-Mazz. It has been widely used for treating cardiovascular and cerebrovascular diseases. However, the therapeutic time window and the action mechanism of breviscapine are still unclear. The present study was designed to investigate the therapeutic time window and underlying therapeutic mechanism of breviscapine injection against cerebral ischemic/reperfusion injury. Sprague-Dawley rats were subjected to middle cerebral artery occlusion for 2h followed by 24h of reperfusion. Experiment part 1 was used to investigate the therapeutic time window of breviscapine. Rats were injected intravenously with 50mg/kg breviscapine at different time-points of reperfusion. After 24h of reperfusion, neurologic score, infarct volume, brain water content and serum level of neuron specific enolase (NSE) were measured in a masked fashion. Part 2 was used to explore the therapeutic mechanism of breviscapine. 4-Hydroxy-2-nonenal (4-HNE), 8-hydroxyl-2'- deoxyguanosine (8-OHdG) and the antioxidant capacity of ischemia cortex were measured by ELISA and ferric-reducing antioxidant power (FRAP) assay, respectively. Immunofluorescence and western blot analysis were used to analyze the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). Part 1: breviscapine injection significantly ameliorated neurologic deficit, reduced infarct volume and water content, and suppressed the levels of NSE in a time-dependent manner. Part 2: breviscapine inhibited the increased levels of 4-HNE and 8-OHdG, and enhanced the antioxidant capacity of cortex tissue. Moreover, breviscapine obviously raised the expression of Nrf2 and HO-1 proteins after 24h of reperfusion. The therapeutic time window of breviscapine injection for cerebral ischemia/reperfusion injury seemed to be within 5h after reperfusion. By up-regulating the expression of Nrf2/HO-1 pathway

  6. 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...

  7. 31P nuclear magnetic resonance surface coil study of ischemic preconditioned isolated perfused rat heart

    International Nuclear Information System (INIS)

    Yan Yongbin; Luo Xuechun; Zhang Riqing; Wang Xiaoyin; Zuo Lin; Liu Wei

    2000-01-01

    ischemic preconditioning (IPC) will protect the heart from the damage caused by a subsequent long ischemia period. 31 P spectra of isolated perfused rat heart measured by the nuclear magnetic resonance (NMR) surface coil technique can be used to continually, dynamically and noninvasively obtain metabolism information. This paper explores the IPC mechanisms by NMR. This study shows that IPC has no effect on enhancing the ATP and PCr levels during reperfusion but makes significantly slows and smooths the changes of intracellular pH and ATP during ischemia periods. The ATP and PCr recovery rate of the IPC group after ischemia is significantly higher than that of the control group. In conclusion, the above results support that IPC can protect the rat heart by reducing damage during the ischemia period

  8. Neuroprotective Effect of Matricaria chamomilla Extract on Motor Dysfunction Induced by Transient Global Cerebral Ischemia and Reperfusion in Rat

    Directory of Open Access Journals (Sweden)

    Azam Moshfegh

    2017-09-01

    Full Text Available Background Stroke can cause paralysis, muscle weakness, and loss of balance that may affect walking and routine activities. Objectives The aim of this study was to evaluate the effect of ethyl alcohol extract of Matricaria chamomilla on cerebral ischemia-induced motor dysfunctions in rats. Methods In this experimental study, forty two male Wistar rats were divided into 6 groups consisting of control group, sham group, ischemia/reperfusion group and three treatment groups [treated with 50, 100, and 200 mg/kg doses of M. chamomilla extract and undergoing ischemia/reperfusion(I/R]. Motor coordination and balance were evaluated using Rotarod test. Total antioxidant capacity, malondialdehyde (MDA, and nitric oxide (NO levels of serum and brain were also determined. Results The extract of M. chamomilla significantly improved I/R-induced motor dysfunction. Induction of I/R led to increase serum MDA, while the extract of M, chamomlla significantly reduced it. Administration all doses of M. chamomilla extract to the ischemic rats did not reduce the hippocampus MDA levels (P > 0.05. The extract of M. chamomilla at dose of 200 mg/kg slightly decreased cortex MDA (P > 0.01. It had no significant effects on the total antioxidant capacity of the brain (hippocampus and cortex and serum. Injection of Matricaria chamomilla extract also did not change serum NO level. Conclusions Our findings suggested that the Matricaria chamomilla extract could improve motor dysfunction.

  9. Region-specific effects on brain metabolites of hypoxia and hyperoxia overlaid on cerebral ischemia in young and old rats: a quantitative proton magnetic resonance spectroscopy study

    Directory of Open Access Journals (Sweden)

    Giuliani Patricia

    2010-02-01

    Full Text Available Abstract Background Both hypoxia and hyperoxia, deregulating the oxidative balance, may play a role in the pathology of neurodegenerative disorders underlain by cerebral ischemia. In the present study, quantitative proton magnetic resonance spectroscopy was used to evaluate regional metabolic alterations, following a 24-hour hypoxic or hyperoxic exposure on the background of ischemic brain insult, in two contrasting age-groups of rats: young - 3 months old and aged - 24 months old. Methods Cerebral ischemia was induced by ligation of the right common carotid artery. Concentrations of eight metabolites (alanine, choline-containing compounds, total creatine, γ-aminobutyric acid, glutamate, lactate, myo-inositol and N-acetylaspartate were quantified from extracts in three different brain regions (fronto-parietal and occipital cortices and the hippocampus from both hemispheres. Results In the control normoxic condition, there were significant increases in lactate and myo-inositol concentrations in the hippocampus of the aged rats, compared with the respective values in the young ones. In the ischemia-hypoxia condition, the most prevalent changes in the brain metabolites were found in the hippocampal regions of both young and aged rats; but the effects were more evident in the aged animals. The ischemia-hyperoxia procedure caused less dedicated changes in the brain metabolites, which may reflect more limited tissue damage. Conclusions We conclude that the hippocampus turns out to be particularly susceptible to hypoxia overlaid on cerebral ischemia and that old age further increases this susceptibility.

  10. Dragon's blood dropping pills have protective effects on focal cerebral ischemia rats model.

    Science.gov (United States)

    Xin, Nian; Yang, Fang-Ju; Li, Yan; Li, Yu-Juan; Dai, Rong-Ji; Meng, Wei-Wei; Chen, Yan; Deng, Yu-Lin

    2013-12-15

    Dragon's blood is a bright red resin obtained from Dracaena cochinchinensis (Lour.) S.C.Chen (Yunnan, China). As a traditional Chinese medicinal herb, it has great traditional medicinal value and is used for wound healing and to stop bleeding. Its main biological activity comes from phenolic compounds. In this study, phenolic compounds were made into dropping pills and their protective effects were examined by establishing focal cerebral ischemia rats model used method of Middle Cerebral Artery Occlusion (MCAO), and by investigating indexes of neurological scores, infarct volume, cerebral index, cerebral water content and oxidation stress. Compared to model group, high, middle and low groups of Dragon's blood dropping pills could improve the neurological function significantly (ppills had protective effects on focal cerebral ischemia rats. Copyright © 2013 Elsevier GmbH. All rights reserved.

  11. Hyperintensity on diffusion weighted image along ipsilateral cortical spinal tract after cerebral ischemic stroke: A diffusion tensor analysis

    International Nuclear Information System (INIS)

    Liu Xiang; Tian Wei; Li Lilin; Kolar, Balasubramanya; Qiu Xing; Chen, Feng; Dogra, Vikram S.

    2012-01-01

    Purpose: Hyperintensity along the ipsilateral cortical spinal tract (CST) on a diffusion weighted imaging (DWI) has been reported to may be associated with motor disability after brain infarction and can be misdiagnosed as a new infarction. However, the underlying patho-physiology related to this finding is not clear. The goal of our study was to analyze the diffusion tensor imaging (DTI) changes in patients with this hyperintensity. Materials and methods: Eight patients (50 ± 10 years) who exhibited hyperintensity on DWI along ipsilateral CST from 3 to 21 days after stroke onset were reviewed as positive group, including 5 patients with serial DTI examinations. Twelve patients without hyperintensity during the matched examination time were classified as reference group. The apparent diffusion coefficient (ADC), fractional anisotropy (FA), and eigenvalues and their ratios (ipsilateral/contralateral value) in cerebral peduncle were measured, their correlation with motor function scale at eight months after stroke onset were evaluated. Results: The serial examinations showed that hyperintensity could eventually disappear. Both the ipsilateral ADC and FA values were significantly decreased (p < 0.05) compared to the contralateral side. The ipsilateral FA significantly correlated with motor function scale in both groups (r = 0.875, 0.738; p = 0.004, 0.006 respectively). Conclusions: The hyperintensity on DWI is a transient pathological process of Wallerian degeneration after ischemic stroke, its diffusion characteristics include concurrent significant decrease of ipsilateral ADC and FA. The ipsilateral FA value has the potential to predict neurological motor function outcome in such patients.

  12. CT and MRI findings of cerebral ischemic lesions in the cortical and perforating arterial system

    Energy Technology Data Exchange (ETDEWEB)

    Kameyama, Masakuni; Udaka, Fukashi; Nishinaka, Kazuto; Kodama, Mitsuo; Urushidani, Makoto; Kawamura, Kazuyuki; Inoue, Haruhisa; Kageyama, Taku [Sumitomo Hospital, Osaka (Japan)

    1995-07-01

    It is clinically useful to divide the location of infarction into the cortical and perforating arterial system. Computerized tomography (CT) and magnetic resonance imaging (MRI) now make the point of infarction a simple and useful task in daily practice. The diagnostic modality has also demonstrated that risk factors and clinical manifestations are different for infarction in the cortical as opposed to the perforating system. In this paper, we present various aspects of images of cerebral ischemia according to CT and/or MRI findings. With the advance of imaging mechanics, diagnostic capability of CT or/and MRI for cerebral infarction has markedly been improved. We must consider these points on evaluating the previously reported results. In addition, we always consider the pathological background of these image-findings for the precise interpretation of their clinical significance. In some instances, dynamic study such as PET or SPECT is needed for real interpretations of CT and/or MRI images. We paid special reference to lacunar stroke and striatocapsular infarct. In addition, `branch atheromatous disease (Caplan)` was considered, in particular, for their specific clinical significances. Large striatocapsular infarcts frequently show cortical signs and symptoms such as aphasia or agnosia in spite of their subcortical localization. These facts, although have previously been known, should be re-considered for their pathoanatomical mechanism. (author).

  13. CT and MRI findings of cerebral ischemic lesions in the cortical and perforating arterial system

    International Nuclear Information System (INIS)

    Kameyama, Masakuni; Udaka, Fukashi; Nishinaka, Kazuto; Kodama, Mitsuo; Urushidani, Makoto; Kawamura, Kazuyuki; Inoue, Haruhisa; Kageyama, Taku

    1995-01-01

    It is clinically useful to divide the location of infarction into the cortical and perforating arterial system. Computerized tomography (CT) and magnetic resonance imaging (MRI) now make the point of infarction a simple and useful task in daily practice. The diagnostic modality has also demonstrated that risk factors and clinical manifestations are different for infarction in the cortical as opposed to the perforating system. In this paper, we present various aspects of images of cerebral ischemia according to CT and/or MRI findings. With the advance of imaging mechanics, diagnostic capability of CT or/and MRI for cerebral infarction has markedly been improved. We must consider these points on evaluating the previously reported results. In addition, we always consider the pathological background of these image-findings for the precise interpretation of their clinical significance. In some instances, dynamic study such as PET or SPECT is needed for real interpretations of CT and/or MRI images. We paid special reference to lacunar stroke and striatocapsular infarct. In addition, 'branch atheromatous disease (Caplan)' was considered, in particular, for their specific clinical significances. Large striatocapsular infarcts frequently show cortical signs and symptoms such as aphasia or agnosia in spite of their subcortical localization. These facts, although have previously been known, should be re-considered for their pathoanatomical mechanism. (author)

  14. Doppler Ultrasonographic Parameters for Predicting Cerebral Vascular Reserve in Patients with Acute Ischemic Stroke

    International Nuclear Information System (INIS)

    Jung, Han Young; Lee, Hui Joong; Kim, Hye Jung; Kim, Yong Sun; Kang, Duk Sik

    2006-01-01

    We investigated Doppler ultrasonographic (US) parameters of patients with acute stroke to predict the cerebral vascular reserve (CVR) measured by SPECT. We reviewed the flow velocity and cross-sectional area of the circular vessel at the common, external, and internal carotid arteries (ICA) and the vertebral arteries (VA) in 109 acute stroke patients who underwent SPECT. Flow volume (FV) of each artery was calculated as the product of the angle-corrected time averaged flow velocity and cross-sectional area of the circular vessel. Total cerebral FV (TCBFV) was determined as the sum of the FVs of the right and left ICA and VA. We compared the Doppler US parameters between 44 cases of preserved and 65 cases of impaired CVR. In the preserved CVR group, ICA FV, anterior circulating FV (ACFV) and TCBFV were higher than in the impaired CVR group (p < 0.05, independent t-test). In the impaired CVR group, the ROC curves showed ACFV and TCBFV were suitable parameters to predict CVR (p < 0.05). Doppler US was helpful for understanding the hemodynamic state of acute stroke. FV measurement by Doppler US was useful for predicting CVR

  15. Cerebral Hypoperfusion in Posterior Reversible Encephalopathy Syndrome is Different from Transient Ischemic Attack on CT Perfusion.

    Science.gov (United States)

    Vanacker, Peter; Matias, Gonçalo; Hagmann, Patric; Michel, Patrik

    2015-01-01

    PRES is a reversible neurotoxic state presenting with headache, altered mental status, visual loss, and seizures. Delayed diagnosis can be avoided if radiological patterns could distinguish PRES from cerebral ischemia. Clinical and radiological data were collected on all hospitalized patients who had (1) discharge diagnosis of PRES and (2) acute CTP/CTA. Data were compared with 10 TIA patients with proven cytotoxic edema on MRI. Of the four PRES patients found, three were correlated with acute blood pressure and one with chemotherapy. At the radiological level, quantitative analyses of the CTP parameters showed that 2 out of 4 patients had bilaterally reduced CBF-values (23.2-47.1 ml/100g/min) in occipital regions, as seen in the pathological regions of TIA patients (27.3 ± 13.5 ml/100g/min). When compared with TIA patients, the pathological ROI's demonstrated decreased CBV-values (3.4-5.6 ml/100g). Vasogenic edema on MRI FLAIR imaging was seen in only one PRES patient, and cytotoxic edema on DWI-imaging was never found. CT angiography showed in one PRES patient a vasospasm-like unilateral posterior cerebral artery. If confirmed by other groups, CTP and CTA imaging in patients with acute visual loss and confusion may help to distinguish PRES from bi-occipital ischemia. These radiological parameters may identify PRES patients at risk for additional tissue infarction. Copyright © 2014 by the American Society of Neuroimaging.

  16. Effects of Mercury Chloride on the Cerebral Cortex of Adult Wistar Rats

    African Journals Online (AJOL)

    Mercury is among the heavy metals that have been reported to cause devastating health problem worldwide. The primary site of action of mercury chloride is the central nervous system. This study investigated the effect of mercury chloride on the cerebral cortex of adult wistar rats. Twenty-four (24) adult wistar rats were used ...

  17. Comparative studies of D2 receptors and cerebral blood flow in hemi-Parkinsonism rats

    International Nuclear Information System (INIS)

    Lin Yansong; Lin Xiangtong

    2000-01-01

    Objective: To study the relationship between dopamine D 2 receptors and cerebral blood flow in hemi-Parkinsonism rats. Methods: Hemi-Parkinsonism rats were made by stereotaxic 6-hydroxy dopamine (6-OH-DA) lesions in substantia nigra and ventral tegmental area, apomorphine (Apo) which could induce the successful model rat to rotate toward the intact side was used to select the rat models, 125 I-IBZM in vivo autoradiography and 99 Tc m -HMPAO regional cerebral biodistribution analysis were used to study D 2 receptors and cerebral blood flow. The HPLC-ECD was used to measure striatum DA and its metabolite content . Results: the lesioned side striatum DA and its metabolites homovanillic acid (HVA) 3,4-dihyroxy-phenylacetic acid (DOPAC) reduced significantly than that of the intact side and pseudo-operated group, striatum/cerebellum 125 I-IBZM uptake ratio was 8.04 +- 0.71 in lesioned side of hemi-Parkinsonism rats, significantly increased compared with the intact side and the pseudo-operated group (P 0.05). Conclusions: the 6-OH-DA lesioned side DA content decreased significantly and thus induced a compensative up-regulation of striatum D 2 receptor binding sites in hemi-Parkinsonism rats, which show good correlation with rotation behavior induced by Apo. Comparing with cerebral blood flow, D 2 receptor reflected by IBZM seems to be more specific and earlier to detect the cerebral functional impairment in experimental hemi-Parkinsonism

  18. Preliminary EEG study of protective effects of Tebonin in transient global cerebral ischemia in rats

    DEFF Research Database (Denmark)

    Zagrean, L; Vatasescu, R; Munteanu, A M

    2000-01-01

    and metabolism. The objective of this study was to investigate the effects of preventive treatment with Ginkgo biloba extract (EGb 761--Tebonin) in cerebral global ischemia and reperfusion in rats using computerized EEG analysis. Ginkgo biloba extract, known to be, in vitro, a free radicals scavanger and a PAF......--antagonist, was administrated in dose of 100 mg/kg over 24 hours, for 5 days before and 5 days after cerebral ischemia--reperfusion. The apparition of isoelectric EEG (flat-line) following 4-vessel occlusion was observed after a mean time of 25 sec. in Ginkgo biloba treated rats and after 18 sec. in control rats (p

  19. Distribution of catecholamines and serotonin in the rat cerebral cortex:

    International Nuclear Information System (INIS)

    Reader, T.A.

    1981-01-01

    The rat cerebral cortex was dissected in five regions and analyzed for the catecholamines noradrenaline, adrenaline and dopamine, and for the indoleamine seroton in using sensitive radioenzymatic assay methods with thin-layer-chromatography. The noradrenaline concentration was highest in the ventral cortex, lateral to the hypothalamus, had intermediate values for the prefrontal, frontal and parietal cortical areas and was lowest in the occipital cortex. Dopamine levels were also highest in the cortex lateral to the hypothalamus, and moderate in the prefrontal and frontal cortical areas, with the lowest values measured for the occipital cortex. The ratios dopamine/noradrenaline further support the hypothesis that they are independent transmitters. Traces of adrenaline were measured in all regions examined. The serotonin distribution was found to be non-homogeneous, with the highest values for the prefrontal cortex and ventral cortex lateral to the hypothalamus. The functional significance of these amines and their ratios are discussed in relation to their role as putative modulators of cortical neuronal excitability. (author)

  20. Intravenous grafts of amniotic fluid-derived stem cells induce endogenous cell proliferation and attenuate behavioral deficits in ischemic stroke rats.

    Directory of Open Access Journals (Sweden)

    Naoki Tajiri

    Full Text Available We recently reported isolation of viable rat amniotic fluid-derived stem (AFS cells [1]. Here, we tested the therapeutic benefits of AFS cells in a rodent model of ischemic stroke. Adult male Sprague-Dawley rats received a 60-minute middle cerebral artery occlusion (MCAo. Thirty-five days later, animals exhibiting significant motor deficits received intravenous transplants of rat AFS cells or vehicle. At days 60-63 post-MCAo, significant recovery of motor and cognitive function was seen in stroke animals transplanted with AFS cells compared to vehicle-infused stroke animals. Infarct volume, as revealed by hematoxylin and eosin (H&E staining, was significantly reduced, coupled with significant increments in the cell proliferation marker, Ki67, and the neuronal marker, MAP2, in the dentate gyrus (DG [2] and the subventricular zone (SVZ of AFS cell-transplanted stroke animals compared to vehicle-infused stroke animals. A significantly higher number of double-labeled Ki67/MAP2-positive cells and a similar trend towards increased Ki67/MAP2 double-labeling were observed in the DG and SVZ of AFS cell-transplanted stroke animals, respectively, compared to vehicle-infused stroke animals. This study reports the therapeutic potential of AFS cell transplantation in stroke animals, possibly via enhancement of endogenous repair mechanisms.

  1. [Effect of Electroacupuncture on Cerebro-cortex Caspase-3 Expression and Blood Lipid Levels in Hyperlipemia Rats with Cerebral Ischemia].

    Science.gov (United States)

    Wang, Zhuo-Yu; Ma, Jia-Jia; Guan, Han-Yu; Tian, Yao; Ren, Xiu-Jun; Ma, Hui-Fang

    2017-04-25

    as Caspase-3 immunoactivity level were significantly increased in the model group( P 0.05). H.E. staining showed a reduction of the apoptotic cells and inflammatory cells in both EA group I and Ⅱ. Both EA and EA+MA interventions can improve neurological function in HL-CI rats,which may be related to their effects in adjusting the levels of serum lipids and down-regulating the expression of cell apoptosis-related Caspase-3 protein in the ischemic cortex. Moreover, the cerebral ischemia injury may be lightened by EA-lowering hyperlipemia first.

  2. [Focal cerebral ischemia in rats with estrogen deficiency and endothelial dysfunction].

    Science.gov (United States)

    Litvinov, A A; Volotova, E V; Kurkin, D V; Logvinova, E O; Darmanyan, A P; Tyurenkov, I N

    2017-01-01

    To assess an effect of ovariectomy (OE) on the cerebral blood flow, endothelium-dependent vasodilation, neurological, cognitive and locomotor deficit as markers of brain damage after focal ischemia in rats. The study was conducted in 48 female Wistar rats. Ovariectomy was performed with ovaries and uterine body extirpation, cerebral ischemia was performed by middle cerebral artery occlusion (MCAO) in rats. To assess brain damage, Combs and Garcia scores, 'open field' test (OFT), 'extrapolatory escape test' (EET), 'passive avoidance test' (PAT), 'beam-walking test' were used. Cerebral blood flow was measured using ultrasonic flowmetry. After 7 days of MCAO, the cerebral blood flow in ovarioectomized animals was reduced by 20% compared to sham-ovariectomized animals. Ovariectomized animals with MCAO showed a three-fold endothelium-dependent vasodilation reduction (the reaction of cerebral vessels to the introduction of acetylcholine and N-L-arginine), indicating the presence of severe endothelial dysfunction. In ovarioectomized animals, the cerebral blood flow was reduced by 34% compared to sham-operated animals. MCAO and OE taken together resulted in more than 2-fold increase in neurological, motor disturbances, 3-fold decrease in motor activity of the animals in the OP test. Focal ischemia in ovarioectomized animals with endothelial dysfunction led to memory decrease by 1/5 fold in PAT and by 2-fold in EET.

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

    Science.gov (United States)

    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.

  4. 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.

    Science.gov (United States)

    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.

  5. Differentiation of the infarct core from ischemic penumbra within the first 4.5 hours, using diffusion tensor imaging-derived metrics: A rat model

    Energy Technology Data Exchange (ETDEWEB)

    Kuo, Duen Pang [Dept. of Electrical Engineering, National Taiwan University, Taipei (China); Lu, Chia Feng [Research Center of Translational Imaging, College of Medicine, Taipei Medical University, Taipei (China); Chen, Yung Chieh [Dept. of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei (China); Liou, Michelle [Institute of Statistical Science, Academia Sinica, Taipei (China); Chung, Hsiao Wen [Graduate Institute of Biomedical Electrics and Bioinformatics, National Taiwan University, Taipei (China)

    2017-04-15

    To investigate whether the diffusion tensor imaging-derived metrics are capable of differentiating the ischemic penumbra (IP) from the infarct core (IC), and determining stroke onset within the first 4.5 hours. All procedures were approved by the local animal care committee. Eight of the eleven rats having permanent middle cerebral artery occlusion were included for analyses. Using a 7 tesla magnetic resonance system, the relative cerebral blood flow and apparent diffusion coefficient maps were generated to define IP and IC, half hour after surgery and then every hour, up to 6.5 hours. Relative fractional anisotropy, pure anisotropy (rq) and diffusion magnitude (rL) maps were obtained. One-way analysis of variance, receiver operating characteristic curve and nonlinear regression analyses were performed. The evolutions of tensor metrics were different in ischemic regions (IC and IP) and topographic subtypes (cortical, subcortical gray matter, and white matter). The rL had a significant drop of 40% at 0.5 hour, and remained stagnant up to 6.5 hours. Significant differences (p < 0.05) in rL values were found between IP, IC, and normal tissue for all topographic subtypes. Optimal rL threshold in discriminating IP from IC was about -29%. The evolution of rq showed an exponential decrease in cortical IC, from -26.9% to -47.6%; an rq reduction smaller than 44.6% can be used to predict an acute stroke onset in less than 4.5 hours. Diffusion tensor metrics may potentially help discriminate IP from IC and determine the acute stroke age within the therapeutic time window.

  6. CaMKII and MEK1/2 inhibition time-dependently modify inflammatory signaling in rat cerebral arteries during organ culture

    DEFF Research Database (Denmark)

    Waldsee, Roya; Eftekhari, Sajedeh; Ahnstedt, Hilda

    2014-01-01

    MKII) II and extracellular signal-regulated kinase1/2 (ERK1/2) on inflammatory mediators in rat cerebral arteries using organ culture as a method for inducing ischemic-like vascular wall changes. METHODS: Rat basilar arteries were cultured in serum-free medium for 0, 3, 6 or 24 hours in the presence...... of phosphorylated c-Jun N-terminal kinase and p-p38, as evaluated by immunohistochemistry. KN93 affected the increase in caspase-3 mRNA expression only when given at the start of incubation, while U0126 had an inhibitory effect when given up to six hours later. Tumor necrosis factor receptor 1 was elevated after...

  7. Protective effects of geniposide and ginsenoside Rg1 combination treatment on rats following cerebral ischemia are mediated via microglial microRNA‑155‑5p inhibition.

    Science.gov (United States)

    Wang, Jun; Li, Dan; Hou, Jincai; Lei, Hongtao

    2018-02-01

    Geniposide, an active component of Gardenia, has been reported to protect against cerebral ischemia in animals. Ginsenoside Rg1, a component of Panax notoginseng, is usually administered in combination with Gardenia for the treatment of acute ischemic stroke; however, there are unknown effects of ginsenoside Rg1 that require further investigation. In the present study, the effects of geniposide and ginsensoide Rg1 combination treatment on focal cerebral ischemic stroke were investigated. For in vivo analysis, male rats were separated into three groups, including the (control), model and geniposide + ginsenoside Rg1 groups (n=8 per group). A middle cerebral artery occlusion model was established as the model group. The treatment group was treated with geniposide (30 mg/kg, tail vein injection) + ginsenoside Rg1 (6 mg/kg, tail vein injection), and the model group received saline instead. Neurobehavioral deficits, infarct volume, brain edema, and the expression of microRNA (miR)‑155‑5p and CD11b by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and immunohistochemistry, were assessed following 24 h of ischemia. For in vitro analysis, BV2 mouse microglial cells were cultured and exposed to geniposide (40 µg/ml) + ginsenoside Rg1 (8 µg/ml) during various durations of oxygen‑glucose deprivation (OGD). The expression levels of miR‑155‑5p, pri‑miR‑155 and pre‑miR‑155 were detected by RT‑qPCR. The results demonstrated that increases in brain infarct volume, edema volume, CD11b‑positive cells and miR‑155‑5p levels were alleviated following geniposide + ginsenoside administration in rats exposed to ischemia. Furthermore, geniposide + ginsenoside Rg1 treatment suppressed the miR‑155‑5p, pri‑miR‑155 and pre‑miR‑155 expression levels in OGD‑injured BV2 microglial cells. The results of the present study demonstrated that tail vein administration of geniposide in combination with ginsenoside Rg1

  8. Role of fractalkine/CX3CR1 signaling pathway in the recovery of neurological function after early ischemic stroke in a rat model.

    Science.gov (United States)

    Liu, Yan-Zhi; Wang, Chun; Wang, Qian; Lin, Yong-Zhong; Ge, Yu-Song; Li, Dong-Mei; Mao, Geng-Sheng

    2017-09-01

    This study aims to explore the role of fractalkine/CX3C chemokine receptor 1 (CX3CR1) signaling pathway in the recovery of neurological functioning after an early ischemic stroke in rats. After establishment of permanent middle cerebral artery occlusion (pMCAO) models, 50 rats were divided into blank, sham, model, positive control and CX3CR1 inhibitor groups. Neurological impairment, walking and grip abilities, and cortical and hippocampal infarctions were evaluated by Zea Longa scoring criterion, beam-walking assay and grip strength test, and diffusion-weighted magnetic resonance imaging. qRT-PCR and Western blotting were performed to detect mRNA and protein expressions. ELISA was conducted to measure concentration of sFractalkine (sFkn), interleukin-1β (IL-1β) and TNF-α. The recovery rate of neurological functioning impairment and reduced walking and grip abilities was faster in the positive control and CX3CR1 inhibitor groups than the model group. The model, positive control and CX3CR1 inhibitor groups showed increased mRNA and protein expression of chemokine C-X3-C motif ligand 1 (CX3CL1) and CX3CR1, concentration of sFkn, IL-1β and TNF-α, and size of cortical and cerebral infarctions while decreased expression of NGF and BDNF compared with the blank and sham groups. Compared with the model group, the mRNA and protein expression of CX3CL1 and CX3CR1, concentration of sFkn, IL-1β and TNF-α, and size of cortical and cerebral infarctions decreased while expression of NGF and BDNF increased in the positive control and CX3CR1 inhibitor groups. Thus, the study suggests that inhibition of fractalkine/CX3CR1 signaling pathway promotes the recovery of neurological functioning after the occurrence of an early ischemic stroke. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Reduction of superoxide dismutase activity correlates with visualization of edema by T[sub 2]-weighted MR imaging in focal ischemic rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Imaizumi, Shigeki; Chang, LeeHong; Cohen, Yoram; Chan, P H; Weinstein, P R; James, T L [California Univ., San Francisco, CA (United States); Yoshimoto, Takashi

    1994-01-01

    This study investigated the correlation between in vivo serial T[sub 2]-weighted magnetic resonance (MR) imaging and changes in superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, and water, sodium ion (Na[sup +]), and potassium ion (K[sup +]) 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[sub 2] signal intensity of the injured right cortex increased with time compared to that of the contralateral cortex. Increased Na[sup +] and water and decreased K[sup +] contents occurred in the injured cortex, indicating that serial T[sub 2]-weighted MR imaging reflects the changes in water content and Na[sup +] and K[sup +] 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).

  10. 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)

  11. Early Recurrence and Cerebral Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation: Effect of Anticoagulation and Its Timing: The RAF Study.

    Science.gov (United States)

    Paciaroni, Maurizio; Agnelli, Giancarlo; Falocci, Nicola; Caso, Valeria; Becattini, Cecilia; Marcheselli, Simona; Rueckert, Christina; Pezzini, Alessandro; Poli, Loris; Padovani, Alessandro; Csiba, Laszló; Szabó, Lilla; Sohn, Sung-Il; Tassinari, Tiziana; Abdul-Rahim, Azmil H; Michel, Patrik; Cordier, Maria; Vanacker, Peter; Remillard, Suzette; Alberti, Andrea; Venti, Michele; Scoditti, Umberto; Denti, Licia; Orlandi, Giovanni; Chiti, Alberto; Gialdini, Gino; Bovi, Paolo; Carletti, Monica; Rigatelli, Alberto; Putaala, Jukka; Tatlisumak, Turgut; Masotti, Luca; Lorenzini, Gianni; Tassi, Rossana; Guideri, Francesca; Martini, Giuseppe; Tsivgoulis, Georgios; Vadikolias, Kostantinos; Liantinioti, Chrissoula; Corea, Francesco; Del Sette, Massimo; Ageno, Walter; De Lodovici, Maria Luisa; Bono, Giorgio; Baldi, Antonio; D'Anna, Sebastiano; Sacco, Simona; Carolei, Antonio; Tiseo, Cindy; Acciarresi, Monica; D'Amore, Cataldo; Imberti, Davide; Zabzuni, Dorjan; Doronin, Boris; Volodina, Vera; Consoli, Domenico; Galati, Franco; Pieroni, Alessio; Toni, Danilo; Monaco, Serena; Baronello, Mario Maimone; Barlinn, Kristian; Pallesen, Lars-Peder; Kepplinger, Jessica; Bodechtel, Ulf; Gerber, Johannes; Deleu, Dirk; Melikyan, Gayane; Ibrahim, Faisal; Akhtar, Naveed; Mosconi, Maria Giulia; Bubba, Valentina; Silvestri, Ilenia; Lees, Kennedy R

    2015-08-01

    The best time for administering anticoagulation therapy in acute cardioembolic stroke remains unclear. This prospective cohort study of patients with acute stroke and atrial fibrillation, evaluated (1) the risk of recurrent ischemic event and severe bleeding; (2) the risk factors for recurrence and bleeding; and (3) the risks of recurrence and bleeding associated with anticoagulant therapy and its starting time after the acute stroke. The primary outcome of this multicenter study was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding within 90 days from acute stroke. Of the 1029 patients enrolled, 123 had 128 events (12.6%): 77 (7.6%) ischemic stroke or transient ischemic attack or systemic embolism, 37 (3.6%) symptomatic cerebral bleeding, and 14 (1.4%) major extracranial bleeding. At 90 days, 50% of the patients were either deceased or disabled (modified Rankin score ≥3), and 10.9% were deceased. High CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesion and type of anticoagulant were predictive factors for primary study outcome. At adjusted Cox regression analysis, initiating anticoagulants 4 to 14 days from stroke onset was associated with a significant reduction in primary study outcome, compared with initiating treatment before 4 or after 14 days: hazard ratio 0.53 (95% confidence interval 0.30-0.93). About 7% of the patients treated with oral anticoagulants alone had an outcome event compared with 16.8% and 12.3% of the patients treated with low molecular weight heparins alone or followed by oral anticoagulants, respectively (P=0.003). Acute stroke in atrial fibrillation patients is associated with high rates of ischemic recurrence and major bleeding at 90 days. This study has observed that high CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesions, and type of anticoagulant administered

  12. Protein metabolism in the rat cerebral cortex in vivo and in vitro as affected by the acquisition enhancing drug piracetam

    NARCIS (Netherlands)

    Nickolson, V.J.; Wolthuis, O.L.

    1976-01-01

    The effect of Piracetam on rat cerebral protein metabolism in vivo and in vitro was studied. It was found that the drug stimulates the uptake of labelled leucine by cerebral cortex slices, has no effect on the incorporation of leucine into cerebral protein, neither in slices nor in vivo, but

  13. Role of thalamic diffusion for disease differentiation between multiple sclerosis and ischemic cerebral small vessel disease

    International Nuclear Information System (INIS)

    Oeztoprak, Bilge; Oeztoprak, Ibrahim; Salk, Ismail; Topalkara, Kamil; Erkoc, Mustafa F.

    2015-01-01

    Cerebral small vessel disease (CSVD) and multiple sclerosis (MS) both harbor multiple, T2-hyperintense white matter lesions on conventional magnetic resonance imaging (MRI).We aimed to determine the microstructural changes via diffusion-weighted imaging (DWI) in normal appearing thalami. We hypothesized that the apparent diffusion coefficient (ADC) values would be different in CSVD and MS, since the extent of arterial involvement is different in these two diseases. DWI was performed for 50 patients with CSVD and 35 patients with MS along with gender- and age-matched controls whose conventional MRI revealed normal findings. DWI was done with 1.5 Tesla MR devices using echo planar imaging (EPI) for b = 0, 1000 s/mm 2 . ADC values were obtained from the thalami which appeared normal on T2-weighted and FLAIR images. Standard oval regions of interest (ROIs) of 0.5 cm 2 which were oriented parallel to the long axis of the thalamus were used for this purpose. The mean ADC value of the thalamus was (0.99 ± 0.16) x 10 -3 mm 2 /s in patients with CSVD, whereas the mean ADC value was (0.78 ± 0.06) x 10 -3 mm 2 /s in the control group. The mean ADC value was significantly higher in patients with CSVD compared to the controls (p < 0.001). The mean ADC values of the thalamus were (0.78 ± 0.08) x 10 -3 mm 2 /s in MS patients, and (0.75 ± 0.08) x 10 -3 mm 2 /s in the control group, which are not significantly different (p > 0.05). Our study revealed a difference in the diffusion of the thalami between CSVD and MS. DWI may aid in the radiological disease differentiation. (orig.)

  14. Role of thalamic diffusion for disease differentiation between multiple sclerosis and ischemic cerebral small vessel disease

    Energy Technology Data Exchange (ETDEWEB)

    Oeztoprak, Bilge; Oeztoprak, Ibrahim; Salk, Ismail [Cumhuriyet University School of Medicine, Department of Radiology, Sivas (Turkey); Topalkara, Kamil [Bayindir Hospital, Department of Neurology, Ankara (Turkey); Erkoc, Mustafa F. [Bozok University School of Medicine, Department of Radiology, Yozgat (Turkey)

    2015-04-01

    Cerebral small vessel disease (CSVD) and multiple sclerosis (MS) both harbor multiple, T2-hyperintense white matter lesions on conventional magnetic resonance imaging (MRI).We aimed to determine the microstructural changes via diffusion-weighted imaging (DWI) in normal appearing thalami. We hypothesized that the apparent diffusion coefficient (ADC) values would be different in CSVD and MS, since the extent of arterial involvement is different in these two diseases. DWI was performed for 50 patients with CSVD and 35 patients with MS along with gender- and age-matched controls whose conventional MRI revealed normal findings. DWI was done with 1.5 Tesla MR devices using echo planar imaging (EPI) for b = 0, 1000 s/mm{sup 2}. ADC values were obtained from the thalami which appeared normal on T2-weighted and FLAIR images. Standard oval regions of interest (ROIs) of 0.5 cm{sup 2} which were oriented parallel to the long axis of the thalamus were used for this purpose. The mean ADC value of the thalamus was (0.99 ± 0.16) x 10{sup -3} mm{sup 2}/s in patients with CSVD, whereas the mean ADC value was (0.78 ± 0.06) x 10{sup -3} mm{sup 2}/s in the control group. The mean ADC value was significantly higher in patients with CSVD compared to the controls (p < 0.001). The mean ADC values of the thalamus were (0.78 ± 0.08) x 10{sup -3} mm{sup 2}/s in MS patients, and (0.75 ± 0.08) x 10{sup -3} mm{sup 2}/s in the control group, which are not significantly different (p > 0.05). Our study revealed a difference in the diffusion of the thalami between CSVD and MS. DWI may aid in the radiological disease differentiation. (orig.)

  15. Bone marrow mesenchymal stem cells overexpressing human basic fibroblast growth factor increase vasculogenesis in ischemic rats

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, J.C. [Department of Vascular Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou (China); Zheng, G.F. [Department of Vascular Surgery, The People' s Hospital of Ganzhou, Ganzhou (China); Wu, L.; Ou Yang, L.Y.; Li, W.X. [Department of Vascular Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou (China)

    2014-08-08

    Administration or expression of growth factors, as well as implantation of autologous bone marrow cells, promote in vivo angiogenesis. This study investigated the angiogenic potential of combining both approaches through the allogenic transplantation of bone marrow-derived mesenchymal stem cells (MSCs) expressing human basic fibroblast growth factor (hbFGF). After establishing a hind limb ischemia model in Sprague Dawley rats, the animals were randomly divided into four treatment groups: MSCs expressing green fluorescent protein (GFP-MSC), MSCs expressing hbFGF (hbFGF-MSC), MSC controls, and phosphate-buffered saline (PBS) controls. After 2 weeks, MSC survival and differentiation, hbFGF and vascular endothelial growth factor (VEGF) expression, and microvessel density of ischemic muscles were determined. Stable hbFGF expression was observed in the hbFGF-MSC group after 2 weeks. More hbFGF-MSCs than GFP-MSCs survived and differentiated into vascular endothelial cells (P<0.001); however, their differentiation rates were similar. Moreover, allogenic transplantation of hbFGF-MSCs increased VEGF expression (P=0.008) and microvessel density (P<0.001). Transplantation of hbFGF-expressing MSCs promoted angiogenesis in an in vivo hind limb ischemia model by increasing the survival of transplanted cells that subsequently differentiated into vascular endothelial cells. This study showed the therapeutic potential of combining cell-based therapy with gene therapy to treat ischemic disease.

  16. Bone marrow mesenchymal stem cells overexpressing human basic fibroblast growth factor increase vasculogenesis in ischemic rats

    Directory of Open Access Journals (Sweden)

    J.C. Zhang

    2014-10-01

    Full Text Available Administration or expression of growth factors, as well as implantation of autologous bone marrow cells, promote in vivo angiogenesis. This study investigated the angiogenic potential of combining both approaches through the allogenic transplantation of bone marrow-derived mesenchymal stem cells (MSCs expressing human basic fibroblast growth factor (hbFGF. After establishing a hind limb ischemia model in Sprague Dawley rats, the animals were randomly divided into four treatment groups: MSCs expressing green fluorescent protein (GFP-MSC, MSCs expressing hbFGF (hbFGF-MSC, MSC controls, and phosphate-buffered saline (PBS controls. After 2 weeks, MSC survival and differentiation, hbFGF and vascular endothelial growth factor (VEGF expression, and microvessel density of ischemic muscles were determined. Stable hbFGF expression was observed in the hbFGF-MSC group after 2 weeks. More hbFGF-MSCs than GFP-MSCs survived and differentiated into vascular endothelial cells (P<0.001; however, their differentiation rates were similar. Moreover, allogenic transplantation of hbFGF-MSCs increased VEGF expression (P=0.008 and microvessel density (P<0.001. Transplantation of hbFGF-expressing MSCs promoted angiogenesis in an in vivo hind limb ischemia model by increasing the survival of transplanted cells that subsequently differentiated into vascular endothelial cells. This study showed the therapeutic potential of combining cell-based therapy with gene therapy to treat ischemic disease.

  17. Regional cerebral blood flow and oxygen metabolism in patients with ischemic stroke studied with high resolution pet and the O-15 labelled gas steady-state method

    International Nuclear Information System (INIS)

    Uemura, K.; Shishido, F.; Inugami, A.; Yamaguchi, T.; Ogawa, T.; Murakami, M.; Kanno, I.; Tagawa, K.; Yasui, N.

    1986-01-01

    Although regional cerebral blood flow (rCBF) studies have considerably increased pathophysiological knowledge in ischemic cerebrovascular disease, sometimes the results of such studies do not correlate with neurological abnormalities observed in the subjects being examined. Because regional neuronal activities always couple to the regional energy metabolism of brain tissue, simultaneous observation of rCBF and regional energy metabolism, such as regional oxygen consumption (rCMRO/sub 2/) and regional glucose consumption (rCMRG1), will provide greater understanding of the pathophysiology of the disease than rCBF study alone. Positron emission tomography (PET) using the 0-15 labelled gas steady-state method offers simultaneous measurement of rCBF and rCMRO/sub 2/ in vivo, and demonstrates imbalance between rCBF and rCMRO/sub 2/ in an ischemic lesion in a human brain. However, clinical PET studies in ischemic cerebrovascular disease reported previously, have been carried out using low resolution (more than 15 mm in the full width at half maximum; FWHM) PET. This report presents preliminary results using a high resolution tomograph; Headtome III and 0-15 labelled gas steady state method to investigate ischemic cerebrovascular disease

  18. Protective effect of estrogen in endothelin-induced middle cerebral artery occlusion in female rats

    OpenAIRE

    Glendenning, Michele L.; Lovekamp-Swan, Tara; Schreihofer, Derek A.

    2008-01-01

    Estrogen is a powerful endogenous and exogenous neuroprotective agent in animal models of brain injury, including focal cerebral ischemia. Although this protection has been demonstrated in several different treatment and injury paradigms, it has not been demonstrated in focal cerebral ischemia induced by intraparenchymal endothelin-1 injection, a model with many advantages over other models of experimental focal ischemia. Reproductively mature female Sprague-Dawley rats were ovariectomized an...

  19. Long-term evolution of cerebral hemodynamics after brain irradiation in the rat

    International Nuclear Information System (INIS)

    Keyeux, A.; Ochrymowicz-Bemelmans, D.

    1985-01-01

    Long-term evolution of radioisotope indices, evaluating respectively the cerebral blood flow (CBF), the cerebral blood volume (CBV) and the cephalic specific distribution space of iodoantipyrine (ΔIAP) of rat, was studied after brain irradiation at 20 Gy. Radioinduced hemodynamic alterations evidenced by this approach are biphasic and support the prominent role of circulation impairment in the genesis of delayed brain radionecrosis [fr

  20. Neuroprotective effects of electro acupuncture on hypoxic-ischemic encephalopathy in newborn rats Ass.

    Science.gov (United States)

    Xu, Tao; Li, Wenjie; Liang, Yiqun; Yang, Zhonghua; Liu, Jingdong; Wang, Yejun; Su, Nailun

    2014-11-01

    Hypoxic-ischemic encephalopathy (HIE) is a common and potentially devastating condition in the neonate, associated with high mortality and morbidity. Effective treatment options are limited and therefore alternative therapies such as acupuncture are increasingly used. Previous studies have shown that electro acupuncture promoted proliferation of neural progenitor cell and increased expression of neurotrophic factor in HIE. However, effects of electro acupuncture on downstream signaling pathways have been rarely researched. So, in the present study, we aimed to evaluate the neuroprotective effects of electro acupuncture on HIE and to further investigate the role of GDNF family receptor member RET and its key downstream PI3-K/Akt pathway in the process. A rat HIE model was constructed by the left common carotid artery (LCCA) ligation method in combination with hypoxic treatment. Considering that Baihui (GV20), Dazhui (GV14), Quchi (LI11) and Yongquan (KI1) are commonly used in clinics for stroke treatment and are easy to locate, we chose the above four acupoints as the combination for electro acupuncture treatment which was performed once a day for different time periods. Hematoxylin-eosin (HE) staining and transmission electron microscopy results showed that electro acupuncture could ameliorate neurologic damage and alleviate the degenerative changes of ultra structure of cortical neurons in rats subjected to HIE. And the longer acupuncture treatment lasted, the better its therapeutic effect would be. This was accompanied by gradually increased expression of GDNF family receptor RET at the mRNA level and its downstream signaling Akt at the protein level in the ischemic cortex. These findings suggest that electro acupuncture shows neuroprotective effects in HIE, which at least in part is attributed to activation of PI3-K/Akt signaling pathway.

  1. Protection of Ischemic and Reperfused Rat Heart by Aqueous Extract of Urtica Dioica

    Directory of Open Access Journals (Sweden)

    D Shackebaei

    2010-09-01

    Full Text Available Background: Urtica dioica (U.D has widely been used in traditional medicine for its hypotensive and vasodilatory effects. The objective of this study was to clarify the effects of aqueous extract of Urtica dioica on isolated ischemia- reperfused heart.Methods: The heart of male wistar rats were isolated and perfused according to langendorff method. In the control group (n = 13 the hearts were subjected to three steps of stabilization (30 min, normothermic global ischemia (40 min and reperfusion (45 min. In addition, before and after ischemia, the aqueous extract of U.D (200 mg/ml was added to perfusion solution in the test group (n=14. Different cardiac variables including left ventricular pressure, heart rate and coronary flow were measured and rate pressure product was calculated.Results: Results showed that left ventricular pressure (59.11±4.7 and rate pressure product (13680±1136 in 45th minute of reperfusion in the test group were significantly (P=0.0187 and 0.0321 respectively greater than the control group (39.1±6.0, 9480±1480 respectively. These findings indicated decreased cardiac damage following ischemia in the test group, compared with that of control group.Conclusion: Results of the present study showed that the aqueous extract of U.D, increased the tolerance of isolated rat hearts against ischemic damage. This effect can be explained by potent antioxidant activity of the U.D extract, suggesting its clinical use in ischemic heart disease.

  2. [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.

  3. Neuroprotective effect of TAT-14-3-3ε fusion protein against cerebral ischemia/reperfusion injury in rats.

    Directory of Open Access Journals (Sweden)

    Yuanjun Zhu

    Full Text Available Stroke is the major cause of death and disability worldwide, and the thrombolytic therapy currently available was unsatisfactory. 14-3-3ε is a well characterized member of 14-3-3 family, and has been reported to protect neurons against apoptosis in cerebral ischemia. However, it cannot transverse blood brain barrier (BBB due to its large size. A protein transduction domain (PTD of HIV TAT protein, is capable of delivering a large variety of proteins into the brain. In this study, we generated a fusion protein TAT-14-3-3ε, and evaluated its potential neuroprotective effect in rat focal ischemia/reperfusion (I/R model. Western blot analysis validated the efficient transduction of TAT-14-3-3ε fusion protein into brain via a route of intravenous injection. TAT-14-3-3ε pre-treatment 2 h before ischemia significantly reduced cerebral infarction volume and improved neurologic score, while post-treatment 2 h after ischemia was less effective. Importantly, pre- or post-ischemic treatment with TAT-14-3-3ε significantly increased the number of surviving neurons as determined by Nissl staining, and attenuated I/R-induced neuronal apoptosis as showed by the decrease in apoptotic cell numbers and the inhibition of caspase-3 activity. Moreover, the introduction of 14-3-3ε into brain by TAT-mediated delivering reduced the formation of autophagosome, attenuated LC3B-II upregulation and reversed p62 downregulation induced by ischemic injury. Such inhibition of autophagy was reversed by treatment with an autophagy inducer rapamycin (RAP, which also attenuated the neuroprotective effect of TAT-14-3-3ε. Conversely, autophagy inhibitor 3-methyladenine (3-MA inhibited I/R-induced the increase in autophagic activity, and attenuated I/R-induced brain infarct. These results suggest that TAT-14-3-3ε can be efficiently transduced into brain and exert significantly protective effect against brain ischemic injury through inhibiting neuronal apoptosis and autophagic

  4. Anti-inflammatory and neuroprotective effects of sanguinarine following cerebral ischemia in rats.

    Science.gov (United States)

    Wang, Qin; Dai, Peng; Bao, Han; Liang, Ping; Wang, Wei; Xing, An; Sun, Jianbin

    2017-01-01

    Stroke is one of the leading causes of mortality worldwide. Protective agents that can diminish injuries caused by cerebral ischemia-reperfusion (I/R) are important in alleviating the harmful outcomes of stroke. The aim of the present study was to investigate the protective role of sanguinarine in cerebral I/R injury. A rat middle cerebral artery occlusion model was used to assess the clinical effect of sanguinarine, and inflammatory cytokines in the serum were detected by ELISA. Western blotting was performed to examine the change in levels of apoptosis-associated proteins in the injured brains. The results suggested that sanguinarine, an anti-inflammatory agent derived from the roots of Sanguinaria canadensis , improved the state of cerebral ischemia in a rat model. The data demonstrated that when rats were treated with sanguinarine prior to middle cerebral artery occlusion, the infarct volume was reduced significantly. The inflammatory factors tumor necrosis factor-α, interleukin (IL)-6 and IL-1β were measured in sanguinarine and vehicle-treated groups using an enzyme-linked immunosorbent assay, and the expression levels of the three factors were significantly reduced following treatment with sanguinarine (Pprotective effect in cerebral ischemia, and that this effect is associated with the anti-inflammatory and anti-apoptotic properties of sanguinarine.

  5. Noninvasive quantitative assessment of cerebral blood flow (CBF) using Tc-99m ECD SPECT with adjunctive radionuclide angiography in ischemic stroke

    International Nuclear Information System (INIS)

    Yim, Jun Sung; Choi, Yun Young; Kim, Seung Hyun; Kim, Myung Ho; Cho, Suk Shin

    1999-01-01

    Quantitative CBF measurements are essential for diagnosing ischemic lesion, evaluating the therapeutic effects and predicting the prognosis of cerebral ischemia. Even though several methods have been introduced, these techniques are too cumbersome and invasive to be applied to routine studies. In this study, a non-invasive simple method for the quantitative angiography. Fifteen normal controls and 27 patients with unilateral carotid ischemic stoke were selected. Brain perfusion index (BPI) of each hemisphere was measured in each subject by acquisition of serial radionuclide angiography after injection of 20mCi of Tc-99m ECD. With Lassen's correction algorithm of curve-linear relationship between the brain activity and blood flow, rCBF on transaxial SPECT slice corresponding with MRI lesion sites (ischemic core, border zone and contralateral mirror locus) were calculated. BPI values for normal controls showed a significant negative correlation with advantage age (r=-0.64, p=0.021) and hemisphric BPI were 11.02±1.6 and 7.8±1.4 for normal controls and patient, respectively. Significant differences were observed between two groups (p=0.0012). rCBF obtained from core zone (12±2.5 ml/100/min), boneder zone (29.2±8.1) and contralateral mirror locus (52.1±15.1) were clearly defined in each subject of patient group. Measurement of BPI and rCBF using Tc-99m ECD SPECT with adjunctive radionuclide angiography could be an useful, simple and non-invasive method in evaluation of the cerebral flood in the ischemic stroke

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

    Science.gov (United States)

    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.

  7. Characterization of beta-adrenergic receptors in synaptic membranes from rat cerebral cortex and cerebellum

    International Nuclear Information System (INIS)

    Lautens, L.

    1986-01-01

    Beta-adrenergic receptor ligand binding sites have been characterized in synaptic membranes from rat cerebral cortex and cerebellum using radioligand binding techniques. The equilibrium and kinetic properties of binding were assessed. The binding sites were non-interacting and exhibited two states of agonist binding which were sensitive to guanyl nucleotide. Synaptic membranes from cerebral cortex contained an equal number of beta 1 - and beta 2 -receptors; membranes from cerebellum possessed more beta 2 -than beta 1 -receptors. Photoaffinity labeling experiments revealed two different beta-adrenergic receptor polypeptides, R 1 and R 2 (and possibly a third, R 3 ) in synaptic membranes. The ratios of incorporation of photoaffinity label into R 1 : 2 were approximately 1:1 (cerebral cortex) and 5:1 (cerebellum). Photoaffinity labeling of R 1 and R 2 was inhibited equally well by both agonist and antagonist in synaptic membranes from cerebellum; whereas agonist was a less potent inhibitor in membranes from cerebral cortex. Both subtypes of beta-adrenergic receptors exhibited the same apparent molecular weight in synaptic membranes from cerebral cortex. The beta-adrenergic receptors in synaptic membranes from cerebral cortex and cerebellum were glycoproteins which exhibited the same apparent molecular weight after exposure to endoglycosidase F. The partial proteolytic digest maps of photoaffinity labeled beta-adrenergic receptors from rat cerebral cortex, cerebellum, lung and heart were compared

  8. Acute treatment with docosahexaenoic acid complexed to albumin reduces injury after a permanent focal cerebral ischemia in rats.

    Directory of Open Access Journals (Sweden)

    Tiffany N Eady

    Full Text Available Docosahexaenoic acid complexed to albumin (DHA-Alb is highly neuroprotective after temporary middle cerebral artery occlusion (MCAo, but whether a similar effect occurs in permanent MCAo is unknown. Male Sprague-Dawley rats (270-330 g underwent permanent MCAo. Neurological function was evaluated on days 1, 2 and 3 after MCAo. We studied six groups: DHA (5 mg/kg, Alb (0.63 or 1.25 g/kg, DHA-Alb (5 mg/kg+0.63 g/kg or 5 mg/kg+1.25 g/kg or saline. Treatment was administered i.v. at 3 h after onset of stroke (n = 7-10 per group. Ex vivo imaging of brains and histopathology were conducted on day 3. Saline- and Alb-treated rats developed severe neurological deficits but were not significantly different from one another. In contrast, rats treated with low and moderate doses of DHA-Alb showed improved neurological score compared to corresponding Alb groups on days 2 and 3. Total, cortical and subcortical lesion volumes computed from T2 weighted images were reduced following a moderate dose of DHA-Alb (1.25 g/kg by 25%, 22%, 34%, respectively, compared to the Alb group. The total corrected, cortical and subcortical infarct volumes were reduced by low (by 36-40% and moderate doses (by 34-42% of DHA-Alb treatment compared to the Alb groups. In conclusion, DHA-Alb therapy is highly neuroprotective in permanent MCAo in rats. This treatment can provide the basis for future therapeutics for patients suffering from ischemic stroke.

  9. Tetramethylpyrazine analogue CXC195 protects against cerebral ischemia/reperfusion-induced apoptosis through PI3K/Akt/GSK3β pathway in rats.

    Science.gov (United States)

    Chen, Lin; Wei, Xinbing; Hou, Yunfeng; Liu, Xiaoqian; Li, Senpeng; Sun, Baozhu; Liu, Xinyong; Liu, Huiqing

    2014-01-01

    CXC195 showed strongest protective effects among the ligustrazine derivatives in cells and prevented apoptosis induced by H2O2 injury. We recently demonstrated that CXC195 protected against cerebral ischemia/reperfusion (I/R) injury by its antioxidant activity. However, whether the anti-apoptotic action of CXC195 is involved in cerebral I/R injury is unknown. Here, we investigated the role of CXC195 in apoptotic processes induced by cerebral I/R and the possible signaling pathways. Male Wistar rats were submitted to transient middle cerebral artery occlusion for 2h, followed by 24h reperfusion. CXC195 was injected intraperitoneally at 2h and 12h after the onset of ischemia. The number of apoptotic cells was measured by TUNEL assay, apoptosis-related protein cleaved caspase-3, Bcl-2, Bax and the phosphorylation levels of Akt and GSK3β in ischemic penumbra were assayed by western blot. The results showed that administration of CXC195 at the doses of 3mg/kg and 10mg/kg significantly inhibited the apoptosis by decreasing the number of apoptotic cells, decreasing the level of cleaved caspase-3 and Bax, and increasing the level of Bcl-2 in rats subjected to I/R injury. Simultaneously, CXC195 treatment markedly increased the phosphorylation of Akt and GSK3β. Blockade of PI3K activity by wortmannin, dramatically abolished its anti-apoptotic effect and lowered both Akt and GSK3β phosphorylation levels. Our study firstly demonstrated that CXC195 protected against cerebral I/R injury by reducing apoptosis in vivo and PI3K/Akt/GSK3β pathway involved in the anti-apoptotic effect. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

  10. Electroacupuncture ameliorates cognitive impairment through inhibition of NF-κB-mediated neuronal cell apoptosis in cerebral ischemia-reperfusion injured rats.

    Science.gov (United States)

    Feng, Xiaodong; Yang, Shanli; Liu, Jiao; Huang, Jia; Peng, Jun; Lin, Jiumao; Tao, Jing; Chen, Lidian

    2013-05-01

    Cognitive impairment is a serious mental deficit following stroke that severely affects the quality of life of stroke survivors. Nuclear factor‑κB (NF-κB)-mediated neuronal cell apoptosis is involved in the development of post-stroke cognitive impairment; therefore, it has become a promising target for the treatment of impaired cognition. Acupuncture at the Baihui (DU20) and Shenting (DU24) acupoints is commonly used in China to clinically treat post‑stroke cognitive impairment; however, the precise mechanism of its action is largely unknown. In the present study, we evaluated the therapeutic efficacy of electroacupuncture against post-stroke cognitive impairment and investigated the underlying molecular mechanisms using a rat model of focal cerebral ischemia-reperfusion (I/R) injury. Electroacupuncture at Baihui and Shenting was identified to significantly ameliorate neurological deficits and reduce cerebral infarct volume. Additionally, electroacupuncture improved learning and memory ability in cerebral I/R injured rats, demonstrating its therapeutic efficacy against post-stroke cognitive impairment. Furthermore, electroacupuncture significantly suppressed the I/R-induced activation of NF-κB signaling in ischemic cerebral tissues. The inhibitory effect of electroacupuncture on NF-κB activation led to the inhibition of cerebral cell apoptosis. Finally, electroacupuncture markedly downregulated the expression of pro-apoptotic Bax and Fas, two critical downstream target genes of the NF-κB pathway. Collectively, our findings suggest that inhibition of NF-κB‑mediated neuronal cell apoptosis may be one mechanism via which electroacupuncture at Baihui and Shenting exerts a therapeutic effect on post-stroke cognitive impairment.

  11. 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.

  12. Central vestibular syndrome in a red fox (Vulpes vulpes) with presumptive right caudal cerebral artery ischemic infarct and prevalent midbrain involvement.

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    Ricciardi, Mario; Gernone, Floriana; Simone, Antonio De; Giannuzzi, Pasquale

    2017-01-01

    A wild young male red fox ( Vulpes vulpes ) was found in the mountainous hinterland of Rome (Italy) with a heavily depressed mental status and unresponsive to the surrounding environment. Neurological examination revealed depression, left circling, right head tilt, ventromedial positional strabismus and decreased postural reactions on the left side. Neurological abnormalities were suggestive of central vestibular syndrome. Two consecutive MRIs performed with 30 days interval were compatible with lacunar ischemic infarct in the territory of right caudal cerebral artery and its collateral branches. The lesion epicentre was in the right periaqueductal portion of the rostral mesencephalic tegmentum. Neuroanatomical and neurophysiological correlation between lesion localization and clinical presentation are discussed.

  13. Central vestibular syndrome in a red fox (Vulpes vulpes with presumptive right caudal cerebral artery ischemic infarct and prevalent midbrain involvement

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    Mario Ricciardi

    2017-06-01

    Full Text Available A wild young male red fox (Vulpes vulpes was found in the mountainous hinterland of Rome (Italy with a heavily depressed mental status and unresponsive to the surrounding environment. Neurological examination revealed depression, left circling, right head tilt, ventromedial positional strabismus and decreased postural reactions on the left side. Neurological abnormalities were suggestive of central vestibular syndrome. Two consecutive MRIs performed with 30 days interval were compatible with lacunar ischemic infarct in the territory of right caudal cerebral artery and its collateral branches. The lesion epicentre was in the right periaqueductal portion of the rostral mesencephalic tegmentum. Neuroanatomical and neurophysiological correlation between lesion localization and clinical presentation are discussed.

  14. The hemorrhagic transformation index score: a prediction tool in middle cerebral artery ischemic stroke.

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    Kalinin, Mikhail N; Khasanova, Dina R; Ibatullin, Murat M

    2017-09-07

    We aimed to develop a tool, the hemorrhagic transformation (HT) index (HTI), to predict any HT within 14 days after middle cerebral artery (MCA) stroke onset regardless of the intravenous recombinant tissue plasminogen activator (IV rtPA) use. That is especially important in the light of missing evidence-based data concerning the timing of anticoagulant resumption after stroke in patients with atrial fibrillation (AF). We retrospectively analyzed 783 consecutive MCA stroke patients. Clinical and brain imaging data at admission were recorded. A follow-up period was 2 weeks after admission. The patients were divided into derivation (DC) and validation (VC) cohorts by generating Bernoulli variates with probability parameter 0.7. Univariate/multivariate logistic regression, and factor analysis were used to extract independent predictors. Validation was performed with internal consistency reliability and receiver operating characteristic (ROC) analysis. Bootstrapping was used to reduce bias. The HTI was composed of 4 items: Alberta Stroke Program Early CT score (ASPECTS), National Institutes of Health Stroke Scale (NIHSS), hyperdense MCA (HMCA) sign, and AF on electrocardiogram (ECG) at admission. According to the predicted probability (PP) range, scores were allocated to ASPECTS as follows: 10-7 = 0; 6-5 = 1; 4-3 = 2; 2-0 = 3; to NIHSS: 0-11 = 0; 12-17 = 1; 18-23 = 2; >23 = 3; to HMCA sign: yes = 1; to AF on ECG: yes = 1. The HTI score varied from 0 to 8. For each score, adjusted PP of any HT with 95% confidence intervals (CI) was as follows: 0 = 0.027 (0.011-0.042); 1 = 0.07 (0.043-0.098); 2 = 0.169 (0.125-0.213); 3 = 0.346 (0.275-0.417); 4 = 0.571 (0.474-0.668); 5 = 0.768 (0.676-0.861); 6 = 0.893 (0.829-0.957); 7 = 0.956 (0.92-0.992); 8 = 0.983 (0.965-1.0). The optimal cutpoint score to differentiate between HT-positive and negative groups was 2 (95% normal-based CI, 1-3) for the DC and VC alike. ROC area

  15. TRPV1 receptor-mediated expression of Toll-like receptors 2 and 4 following permanent middle cerebral artery occlusion in rats

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    Elham Hakimizadeh

    2017-08-01

    Full Text Available Objective(s: Stroke is known as a main cause of mortality and prolonged disability in adults. Both transient receptor potential V1 (TRPV1 channels and toll-like receptors (TLRs are involved in mediating the inflammatory responses. In the present study, the effects of TRPV1 receptor activation and blockade on stroke outcome and gene expression of TLR2 and TLR4 were assessed following permanent middle cerebral artery occlusion in rats Materials and Methods: Eighty male Wistar rats were divided into four groups as follows: sham, vehicle, AMG9810 (TRPV1 antagonist -treated and capsaicin (TRPV1 agonist -treated. For Stroke induction, the middle cerebral artery was permanently occluded and then behavioral functions were evaluated 1, 3 and 7 days after stroke. Results: TRPV1 antagonism significantly reduced the infarct volume compared to the stroke group. Also, neurological deficits were decreased by AMG9810 seven days after cerebral ischemia. In the ledged beam-walking test, the slip ratio was enhanced following ischemia. AMG9810 decreased this index in stroke animals. However, capsaicin improved the ratio 3 and 7 days after cerebral ischemia. Compared to the sham group, the mRNA expression of TLR2 and TLR4 was significantly increased in the stroke rats. AMG9810 Administration significantly reduced the mRNA expression of TLR2 and TLR4. However, capsaicin did not significantly affect the gene expression of TLR2 and TLR4. Conclusion: Our results demonstrated that TRPV1 antagonism by AMG9810 attenuates behavioral function and mRNA expression of TLR2 and TLR4. Thus, it might be useful to shed light on future therapeutic strategies for the treatment of ischemic stroke.

  16. TRPV1 receptor-mediated expression of Toll-like receptors 2 and 4 following permanent middle cerebral artery occlusion in rats

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    Hakimizadeh, Elham; Shamsizadeh, Ali; Roohbakhsh, Ali; Arababadi, Mohammad Kazemi; Hajizadeh, Mohammad Reza; Shariati, Mehdi; Fatemi, Iman; Moghadam-ahmadi, Amir; Bazmandegan, Gholamreza; Rezazadeh, Hossein; Allahtavakoli, Mohammad

    2017-01-01

    Objective(s): Stroke is known as a main cause of mortality and prolonged disability in adults. Both transient receptor potential V1 (TRPV1) channels and toll-like receptors (TLRs) are involved in mediating the inflammatory responses. In the present study, the effects of TRPV1 receptor activation and blockade on stroke outcome and gene expression of TLR2 and TLR4 were assessed following permanent middle cerebral artery occlusion in rats Materials and Methods: Eighty male Wistar rats were divided into four groups as follows: sham, vehicle, AMG9810 (TRPV1 antagonist) -treated and capsaicin (TRPV1 agonist) -treated. For Stroke induction, the middle cerebral artery was permanently occluded and then behavioral functions were evaluated 1, 3 and 7 days after stroke. Results: TRPV1 antagonism significantly reduced the infarct volume compared to the stroke group. Also, neurological deficits were decreased by AMG9810 seven days after cerebral ischemia. In the ledged beam-walking test, the slip ratio was enhanced following ischemia. AMG9810 decreased this index in stroke animals. However, capsaicin improved the ratio 3 and 7 days after cerebral ischemia. Compared to the sham group, the mRNA expression of TLR2 and TLR4 was significantly increased in the stroke rats. AMG9810 Administration significantly reduced the mRNA expression of TLR2 and TLR4. However, capsaicin did not significantly affect the gene expression of TLR2 and TLR4. Conclusion: Our results demonstrated that TRPV1 antagonism by AMG9810 attenuates behavioral function and mRNA expression of TLR2 and TLR4. Thus, it might be useful to shed light on future therapeutic strategies for the treatment of ischemic stroke. PMID:29085577

  17. Enhanced cerebrovascular expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 via the MEK/ERK pathway during cerebral ischemia in the rat

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    Maddahi Aida

    2009-06-01

    Full Text Available Abstract Background Cerebral ischemia is usually characterized by a reduction in local blood flow and metabolism and by disruption of the blood-brain barrier in the infarct region. The formation of oedema and opening of the blood-brain barrier in stroke is associated with enhanced expression of metalloproteinase-9 (MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1. Results Here, we found an infarct volume of 24.8 ± 2% and a reduced neurological function after two hours of middle cerebral artery occlusion (MCAO, followed by 48 hours of recirculation in rat. Immunocytochemistry and confocal microscopy revealed enhanced expression of MMP-9, TIMP-1, and phosphorylated ERK1/2 in the smooth muscle cells of the ischemic MCA and associated intracerebral microvessels. The specific MEK1/2 inhibitor U0126, given intraperitoneal zero or 6 hours after the ischemic event, reduced the infarct volume significantly (11.8 ± 2% and 14.6 ± 3%, respectively; P Conclusion These data are the first to show that the elevated vascular expression of MMP-9 and TIMP-1, associated with breakdown of the blood-brain barrier following focal ischemia, are transcriptionally regulated via the MEK/ERK pathway.

  18. Morphologic changes of cerebral veins in hypertensive rats: venous collagenosis is associated with hypertension.

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    Zhou, Min; Mao, Lijuan; Wang, Ying; Wang, Qian; Yang, Zhiyun; Li, Shurong; Li, Ling

    2015-03-01

    The aims of this study were to determine whether arterial hypertension could affect the venous system of brain and to find out the consequent pathologic changes of cerebral veins. Thirty male Sprague-Dawley rats were divided into 2 groups: a sham-clipped group and a stroke-prone renovascular hypertensive rat group. A 2-kidney 2-clip rat model was used to induce renovascular hypertension in the hypertensive group. Systolic blood pressure was measured by tail cuff once each week. Susceptibility-weighted imaging (SWI) was performed at 12, 16, and 20 weeks after surgery. All the rats were sacrificed after the SWI examination at 20 weeks after surgery. The brains were extracted and embedded in paraffin for histologic examination. Masson trichrome staining was performed to identify venous collagenosis. The sham group demonstrated less prominence of cerebral veins compared with hypertensive groups (P veins on SWI as a sign of venous hypertension and the thickened cerebral venous walls (venous collagenosis), which may play a role in cerebral ischemia and/or infarction, are both consequences of long-term hypertension in hypertensive rats. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  19. Exercise preconditioning exhibits neuroprotective effects on hippocampal CA1 neuronal damage after cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Nabi Shamsaei; Mehdi Khaksari; Sohaila Erfani; Hamid Rajabi; Nahid Aboutaleb

    2015-01-01

    Recent evidence has suggested the neuroprotective effects of physical exercise on cerebral isch-emic injury. However, the role of physical exercise in cerebral ischemia-induced hippocampal damage remains controversial. The aim of the present study was to evaluate the effects of pre-ischemia treadmill training on hippocampal CA1 neuronal damage after cerebral ischemia. Male adult rats were randomly divided into control, ischemia and exercise + ischemia groups. In the exercise + ischemia group, rats were subjected to running on a treadmill in a designated time schedule (5 days per week for 4 weeks). Then rats underwent cerebral ischemia induction th rough occlusion of common carotids followed by reperfusion. At 4 days after cerebral ischemia, rat learning and memory abilities were evaluated using passive avoidance memory test and rat hippocampal neuronal damage was detected using Nissl and TUNEL staining. Pre-ischemic ex-ercise signiifcantly reduced the number of TUNEL-positive cells and necrotic cell death in the hippocampal CA1 region as compared to the ischemia group. Moreover, pre-ischemic exercise significantly prevented ischemia-induced memory dysfunction. Pre-ischemic exercise mighct prevent memory deficits after cerebral ischemia through rescuing hippocampal CA1 neurons from ischemia-induced degeneration.

  20. CCD-camera-based diffuse optical tomography to study ischemic stroke in preclinical rat models

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    Lin, Zi-Jing; Niu, Haijing; Liu, Yueming; Su, Jianzhong; Liu, Hanli

    2011-02-01

    Stroke, due to ischemia or hemorrhage, is the neurological deficit of cerebrovasculature and is the third leading cause of death in the United States. More than 80 percent of stroke patients are ischemic stroke due to blockage of artery in the brain by thrombosis or arterial embolism. Hence, development of an imaging technique to image or monitor the cerebral ischemia and effect of anti-stoke therapy is more than necessary. Near infrared (NIR) optical tomographic technique has a great potential to be utilized as a non-invasive image tool (due to its low cost and portability) to image the embedded abnormal tissue, such as a dysfunctional area caused by ischemia. Moreover, NIR tomographic techniques have been successively demonstrated in the studies of cerebro-vascular hemodynamics and brain injury. As compared to a fiberbased diffuse optical tomographic system, a CCD-camera-based system is more suitable for pre-clinical animal studies due to its simpler setup and lower cost. In this study, we have utilized the CCD-camera-based technique to image the embedded inclusions based on tissue-phantom experimental data. Then, we are able to obtain good reconstructed images by two recently developed algorithms: (1) depth compensation algorithm (DCA) and (2) globally convergent method (GCM). In this study, we will demonstrate the volumetric tomographic reconstructed results taken from tissuephantom; the latter has a great potential to determine and monitor the effect of anti-stroke therapies.

  1. Protective effect of remote limb ischemic perconditioning on the liver grafts of rats with a novel model.

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    Junjun Jia

    Full Text Available Remote ischemic conditioning (RIC is a known manual conditioning to decrease ischemic reperfusion injury (IRI but not increase ischemic time. Here we tried to establish a rat RIC model of liver transplantation (LT, optimize the applicable protocols and investigate the protective mechanism.The RIC model was developed by a standard tourniquet. Sprague-Dawley rats were assigned randomly to the sham operated control (N, standard rat liver transplantation (OLT and RIC groups. According to the different protocols, RIC group was divided into 3 subgroups (10 min×3, n = 6; 5 min×3, n = 6; 1 min×3, n = 6 respectively. Serum transaminases (ALT, AST, creatine kinase (CK, histopathologic changes, malondialdehyde (MDA, myeloperoxidase (MPO and expressions of p-Akt were evaluated.Compared with the OLT group, the grafts subjected to RIC 5min*3 algorithm showed significant reduction of morphological damage and improved the graft function. Also, production of reactive oxygen species (MDA and neutrophil accumulation (MPO were markedly depressed and p-Akt was upregulated.In conclusion, we successfully established a novel model of RIC in rat LT, the optimal RIC 5min*3 algorithm seemed to be more efficient to alleviate IRI of the liver graft in both functional and morphological categories, which due to its antioxidative, anti-inflammation activities and activating PI3K Akt pathway.

  2. Reduced microvascular volume and hemispherically deficient vasoreactivity to hypercapnia in acute ischemia: MRI study using permanent middle cerebral artery occlusion rat model.

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    Suh, J Y; Shim, Woo H; Cho, Gyunggoo; Fan, Xiang; Kwon, Seon J; Kim, Jeong K; Dai, George; Wang, Xiaoying; Kim, Young R

    2015-06-01

    Vasoreactivity to hypercapnia has been used for assessing cerebrovascular tone and control altered by ischemic stroke. Despite the high prognostic potential, traits of hypercapnia-induced hemodynamic changes have not been fully characterized in relation with baseline vascular states and brain tissue damage. To monitor cerebrovascular responses, T2- and T2*-weighted magnetic resonance imaging (MRI) images were acquired alternatively using spin- and gradient-echo echo plannar imaging (GESE EPI) sequence with 5% CO2 gas inhalation in normal (n=5) and acute stroke rats (n=10). Dynamic relative changes in cerebrovascular volume (CBV), microvascular volume (MVV), and vascular size index (VSI) were assessed from regions of interest (ROIs) delineated by the percent decrease of apparent diffusion coefficient (ADC). The baseline CBV was not affected by middle cerebral artery occlusion (MCAO) whereas the baseline MVV in ischemic areas was significantly lower than that in the rest of the brain and correlated with ADC. Vasoreactivity to hypercapnic challenge was considerably attenuated in the entire ipsilesional hemisphere including normal ADC regions, in which unsolicited, spreading depression-associated increases of CBV and MVV were observed. The lesion-dependent inhomogeneity in baseline MVV indicates the effective perfusion reserve for accurately delineating the true ischemic damage while the cascade of neuronal depolarization is probably responsible for the hemispherically lateralized changes in overall neurovascular physiology.

  3. Effects of Mild Blast Traumatic Brain Injury on Cerebral Vascular, Histopathological, and Behavioral Outcomes in Rats

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    Zeng, Yaping; Deyo, Donald; Parsley, Margaret A.; Hawkins, Bridget E.; Prough, Donald S.; DeWitt, Douglas S.

    2018-01-01

    Abstract To determine the effects of mild blast-induced traumatic brain injury (bTBI), several groups of rats were subjected to blast injury or sham injury in a compressed air-driven shock tube. The effects of bTBI on relative cerebral perfusion (laser Doppler flowmetry [LDF]), and mean arterial blood pressure (MAP) cerebral vascular resistance were measured for 2 h post-bTBI. Dilator responses to reduced intravascular pressure were measured in isolated middle cerebral arterial (MCA) segments, ex vivo, 30 and 60 min post-bTBI. Neuronal injury was assessed (Fluoro-Jade C [FJC]) 24 and 48 h post-bTBI. Neurological outcomes (beam balance and walking tests) and working memory (Morris water maze [MWM]) were assessed 2 weeks post-bTBI. Because impact TBI (i.e., non-blast TBI) is often associated with reduced cerebral perfusion and impaired cerebrovascular function in part because of the generation of reactive oxygen and nitrogen species such as peroxynitrite (ONOO−), the effects of the administration of the ONOO− scavenger, penicillamine methyl ester (PenME), on cerebral perfusion and cerebral vascular resistance were measured for 2 h post-bTBI. Mild bTBI resulted in reduced relative cerebral perfusion and MCA dilator responses to reduced intravascular pressure, increases in cerebral vascular resistance and in the numbers of FJC-positive cells in the brain, and significantly impaired working memory. PenME administration resulted in significant reductions in cerebral vascular resistance and a trend toward increased cerebral perfusion, suggesting that ONOO− may contribute to blast-induced cerebral vascular dysfunction. PMID:29160141

  4. Effect of hyperbaric oxygenation on mitochondrial function of neuronal cells in the cortex of neonatal rats after hypoxic-ischemic brain damage

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    L. Yang

    2016-01-01

    Full Text Available The timing and mechanisms of protection by hyperbaric oxygenation (HBO in hypoxic-ischemic brain damage (HIBD have only been partially elucidated. We monitored the effect of HBO on the mitochondrial function of neuronal cells in the cerebral cortex of neonatal rats after HIBD. Neonatal Sprague-Dawley rats (total of 360 of both genders were randomly divided into normal control, HIBD, and HIBD+HBO groups. The HBO treatment began immediately after hypoxia-ischemia (HI and continued once a day for 7 consecutive days. Animals were euthanized 0, 2, 4, 6, and 12 h post-HI to monitor the changes in mitochondrial membrane potential (ΔΨm occurring soon after a single dose of HBO treatment, as well as 2, 3, 4, 5, 6, and 7 days post-HI to study ΔΨm changes after a series of HBO treatments. Fluctuations in ΔΨm were observed in the ipsilateral cortex in both HIBD and HIBD+HBO groups. Within 2 to 12 h after HI insult, the ΔΨm of the HIBD and HIBD+HBO groups recovered to some extent. A secondary drop in ΔΨm was observed in both groups during the 1-4 days post-HI period, but was more severe in the HIBD+HBO group. There was a secondary recovery of ΔΨm observed in the HIBD+HBO group, but not in the HIBD group, during the 5-7 days period after HI insult. HBO therapy may not lead to improvement of neural cell mitochondrial function in the cerebral cortex in the early stage post-HI, but may improve it in the sub-acute stage post-HI.

  5. Investigation of the role of non-selective calcium channel blocker (flunarizine) on cerebral ischemic-reperfusion associated cognitive dysfunction in aged mice.

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    Gulati, Puja; Muthuraman, Arunachalam; Kaur, Parneet

    2015-04-01

    The present study was designed to investigate the role of flunarizine (a non-selective calcium channel blocker) on cerebral ischemic-reperfusion associated cognitive dysfunction in aged mice. Bilateral carotid artery occlusion of 12min followed by reperfusion for 24h was given to induce cerebral injury in male Swiss mice. The assessment of learning & memory was performed by Morris water maze test; motor in-coordination was evaluated by rota rod, lateral push and inclined beam walking tests; cerebral infarct size was quantified by triphenyltetrazolium chloride staining. In addition, reduced glutathione (GSH), total calcium and acetylcholinesterase (AChE) activity were also estimated in aged brain tissue. Donepezil treated group served as a positive control in this study. Ischemia reperfusion (I/R) injury produced significant increase in cerebral infarct size. A significant loss of memory along with impairment of motor performance was also noted. Further, I/R injury also produced significant increase in levels of total calcium, AChE activity and decrease in GSH levels. Pretreatment of flunarizine significantly attenuated I/R induced infarct size, behavioral and biochemical changes. Hence, it may be concluded that, a non-selective calcium channel blocker can be useful in I/R associated cognitive dysfunction due to its anti-oxidant, anti-infarct and modulatory actions of neurotransmitters & calcium channels. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Homocysteine Aggravates Cortical Neural Cell Injury through Neuronal Autophagy Overactivation following Rat Cerebral Ischemia-Reperfusion

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    Yaqian Zhao

    2016-07-01

    Full Text Available Elevated homocysteine (Hcy levels have been reported to be involved in neurotoxicity after ischemic stroke. However, the underlying mechanisms remain incompletely understood to date. In the current study, we hypothesized that neuronal autophagy activation may be involved in the toxic effect of Hcy on cortical neurons following cerebral ischemia. Brain cell injury was determined by hematoxylin-eosin (HE staining and TdT-mediated dUTP Nick-End Labeling (TUNEL staining. The level and localization of autophagy were detected by transmission electron microscopy, western blot and immunofluorescence double labeling. The oxidative DNA damage was revealed by immunofluorescence of 8-Hydroxy-2′-deoxyguanosine (8-OHdG. Hcy treatment aggravated neuronal cell death, significantly increased the formation of autophagosomes and the expression of LC3B and Beclin-1 in the brain cortex after middle cerebral artery occlusion-reperfusion (MCAO. Immunofluorescence analysis of LC3B and Beclin-1 distribution indicated that their expression occurred mainly in neurons (NeuN-positive and hardly in astrocytes (GFAP-positive. 8-OHdG expression was also increased in the ischemic cortex of Hcy-treated animals. Conversely, LC3B and Beclin-1 overexpression and autophagosome accumulation caused by Hcy were partially blocked by the autophagy inhibitor 3-methyladenine (3-MA. Hcy administration enhanced neuronal autophagy, which contributes to cell death following cerebral ischemia. The oxidative damage-mediated autophagy may be a molecular mechanism underlying neuronal cell toxicity of elevated Hcy level.

  7. Possible involvement of caveolin in attenuation of cardioprotective effect of ischemic preconditioning in diabetic rat heart

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    Singh Manjeet

    2011-07-01

    Full Text Available Abstract Background Nitric oxide (NO has been noted to produce ischemic preconditioning (IPC-mediated cardioprotection. Caveolin is a negative regulator of NO, which inhibits endothelial nitric oxide synthase (eNOS by making caveolin-eNOS complex. The expression of caveolin is increased during diabetes mellitus (DM. The present study was designed to investigate the involvement of caveolin in attenuation of the cardioprotective effect of IPC during DM in rat. Methods Experimental DM was induced by single dose of streptozotocin (50 mg/Kg, i.p, and animals were used for experiments four weeks later. Isolated heart was mounted on Langendorff's apparatus, and was subjected to 30 min of global ischemia and 120 min of reperfusion. IPC was given by four cycles of 5 min of ischemia and 5 min of reperfusion with Kreb's-Henseleit solution (K-H. Extent of injury was measured in terms of infarct size by triphenyltetrazolium chloride (TTC staining, and release of lactate dehydrogenase (LDH and creatin kinase-MB (CK-MB in coronary effluent. The cardiac release of NO was noted by measuring the level of nitrite in coronary effluent. Results IPC- induced cardioprotection and release of NO was significantly decreased in diabetic rat heart. Pre-treatment of diabetic rat with daidzein (DDZ a caveolin inhibitor (0.2 mg/Kg/s.c, for one week, significantly increased the release of NO and restored the attenuated cardioprotective effect of IPC. Also perfusion of sodium nitrite (10 μM/L, a precursor of NO, significantly restored the lost effect of IPC, similar to daidzein in diabetic rat. Administration of 5-hydroxy deaconate (5-HD, a mito KATP channel blocker, significantly abolished the observed IPC-induced cardioprotection in normal rat or daidzein and sodium nitrite perfused diabetic rat heart alone or in combination. Conclusions Thus, it is suggested that attenuation of the cardioprotection in diabetic heart may be due to decrease the IPC mediated release of NO in

  8. Protective effects of traditional Chinese medicine formula NaoShuanTong capsule on haemorheology and cerebral energy metabolism disorders in rats with blood stasis.

    Science.gov (United States)

    Liu, Hong; Peng, Yao-Yao; Liang, Feng-Yin; Chen, Si; Li, Pei-Bo; Peng, Wei; Liu, Zhong-Zheng; Xie, Cheng-Shi; Long, Chao-Feng; Su, Wei-Wei

    2014-01-02

    NaoShuanTong capsule (NSTC), an oral traditional Chinese medicine formula, is composed of Pollen Typhae , Radix Paeoniae Rubra , Rhizoma Gastrodiae , Radix Rhapontici and Radix Curcumae . It has been widely used to treat ischemic stroke in clinic for many years in China. In addition to neuronal apoptosis, haemorheology and cerebral energy metabolism disorders also play an important role in the pathogenesis and development of ischemic stroke. The present study was designed to evaluate the in vivo protective effects of NSTC on haemorheology and cerebral energy metabolism disorders in rats with blood stasis. Sixty specific pathogen-free sprague-dawley rats, male only, were randomly divided into six groups (control group, model group, aspirin (100 mg/kg/d) group, NSTC low-dose (400 mg/kg/d) group, NSTC intermediate-dose (800 mg/kg/d) group, NSTC high-dose (1600 mg/kg/d) group) with 10 animals in each. The rats except those in the control group were placed in ice-cold water (0-4 °C) for 5 min during the time interval (4 h) of two adrenaline hydrochloride injections (0.8 mg/kg) to induce blood stasis. After treatment, whole blood viscosity at three shear rates, plasma viscosity and erythrocyte sedimentation rate significantly decreased in NSTC intermediate- and high-dose groups; erythrocyte aggregation index and red corpuscle electrophoresis index significantly decreased in all the three dose NSTC groups. Moreover, treatment with high-dose NSTC could significantly improve Na + -K + adenosine triphosphatase (ATPase) and Ca 2+ ATPase activity, as well as lower lactic acid level in brain tissues. These results demonstrated the protective effects of NSTC on haemorheology and cerebral energy metabolism disorders, which may provide scientific information for the further understanding of mechanism(s) of NSTC as a clinical treatment for ischemic stroke. Furthermore, the protective effects of activating blood circulation as observed in this study might create valuable

  9. Neuronal precursor cell proliferation in the hippocampus after transient cerebral ischemia: a comparative study of two rat strains using stereological tools.

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    Kelsen, Jesper; Larsen, Marianne H; Sørensen, Jens Christian; Møller, Arne; Frøkiaer, Jørgen; Nielsen, Søren; Nyengaard, Jens R; Mikkelsen, Jens D; Rønn, Lars Christian B

    2010-04-06

    We are currently investigating microglial activation and neuronal precursor cell (NPC) proliferation after transient middle cerebral artery occlusion (tMCAo) in rats. This study aimed: (1) to investigate differences in hippocampal NPC proliferation in outbred male spontaneously hypertensive rats (SHRs) and Sprague-Dawley rats (SDs) one week after tMCAo; (2) to present the practical use of the optical fractionator and 2D nucleator in stereological brain tissue analyses; and (3) to report our experiences with an intraluminal tMCAo model where the occluding filament is advanced 22 mm beyond the carotid bifurcation and the common carotid artery is clamped during tMCAo. Twenty-three SDs and twenty SHRs were randomized into four groups subjected to 90 minutes tMCAo or sham. BrdU (50 mg/kg) was administered intraperitoneally twice daily on Day 4 to 7 after surgery. On Day 8 all animals were euthanized. NeuN-stained tissue sections were used for brain and infarct volume estimation with the 2D nucleator and Cavalieri principle. Brains were studied for the presence of activated microglia (ED-1) and hippocampal BrdU incorporation using the optical fractionator. We found no significant difference or increase in post-ischemic NPC proliferation between the two strains. However, the response to remote ischemia may differ between SDs and SHRs. In three animals increased post-stroke NPC proliferation was associated with hippocampal ischemic injury. The mean infarct volume was 89.2 +/- 76.1 mm3 in SHRs and 16.9 +/- 22.7 mm3 in SDs (p < 0.005). Eight out of eleven SHRs had ischemic neocortical damage in contrast to only one out of 12 SDs. We observed involvement of the anterior choroidal and hypothalamic arteries in several animals from both strains and the anterior cerebral artery in two SHRs. We found no evidence of an early hippocampal NPC proliferation one week after tMCAo in both strains. Infarction within the anterior choroidal artery could induce hippocampal ischemia and

  10. Delayed perfusion phenomenon in a rat stroke model at 1.5 T MR: An imaging sign parallel to spontaneous reperfusion and ischemic penumbra?

    Energy Technology Data Exchange (ETDEWEB)

    Chen Feng [Department of Radiology, University Hospitals, Catholic University of Leuven, Herestraat 49, B-3000 Leuven (Belgium); Department of Radiology, Zhong Da Hospital, Southeast University, 87 Ding Jia Qiao Road, Nanjing 210009, Jiangsu Province (China); Suzuki, Yasuhiro [Department of Molecular and Cellular Medicine, Faculty of Medicine, Catholic University of Leuven, Herestraat 49, B-3000 Leuven (Belgium); Department of Pharmacology, Hamamatsu University School of Medicine, 1-20-1 Handayama, 431-3192 Hamamatsu (Japan); Nagai, Nobuo [Department of Molecular and Cellular Medicine, Faculty of Medicine, Catholic University of Leuven, Herestraat 49, B-3000 Leuven (Belgium); Sun Xihe [Department of Radiology, University Hospitals, Catholic University of Leuven, Herestraat 49, B-3000 Leuven (Belgium); Department of Radiology, the Affiliated Hospital of Weifang Medical University, Weifang 261031, Shandong Province (China); Coudyzer, Walter [Department of Radiology, University Hospitals, Catholic University of Leuven, Herestraat 49, B-3000 Leuven (Belgium); Yu Jie [Department of Radiology, University Hospitals, Catholic University of Leuven, Herestraat 49, B-3000 Leuven (Belgium); Marchal, Guy [Department of Radiology, University Hospitals, Catholic University of Leuven, Herestraat 49, B-3000 Leuven (Belgium); Ni Yicheng [Department of Radiology, University Hospitals, Catholic University of Leuven, Herestraat 49, B-3000 Leuven (Belgium)]. E-mail: Yicheng.Ni@med.kuleuven.ac.be

    2007-01-15

    Introduction: Delayed perfusion (DP) sign at MR imaging was reported in stroke patients. We sought to experimentally elucidate its relation to spontaneous reperfusion and ischemic penumbra. Methods: Stroke was induced by photothrombotic occlusion of middle cerebral artery in eight rats and studied up to 72 h using a 1.5 T MR scanner with T2 weighted imaging (T2WI), diffusion weighted imaging (DWI), and dynamic susceptibility contrast-enhanced perfusion weighted imaging (DSC-PWI). Relative signal intensity (rSI), relative lesion volume (rLV), relative cerebral blood flow (rCBF), PWI{sub rLV}-DWI{sub rLV} mismatch (penumbra) and DP{sub rLV} were quantified and correlated with neurological deficit score (NDS), triphenyl tetrazolium chloride (TTC) staining, microangiography (MA) and histopathology. Results: The rSI and rLV characterized this stroke model on different MRI sequences and time points. DSC-PWI reproduced cortical DP in all rats, where rCBF evolved from 88.9% at 1 h through 64.9% at 6 h to 136.3% at 72 h. The PWI{sub rLV}-DWI{sub rLV} mismatch reached 10 {+-} 5.4% at 1 h, remained positive through 12 h and decreased to -3.3 {+-} 4.5% at 72 h. The incidence and rLV of the DP were well correlated with those of the penumbra (p < 0.01, r {sup 2} = 0.85 and p < 0.0001, r {sup 2} = 0.96, respectively). Shorter DP durations and more collateral arterioles occurred in rats without (n = 4) than with (n = 4) cortex involvement (p < 0.05). Rats without cortex involvement tended to earlier reperfusion and a lower NDS. Microscopy confirmed MRI, MA and TTC findings. Conclusions: In this rat stroke model, we reproduced clinically observed DP on DSC-PWI, confirmed spontaneous reperfusion, and identified the penumbra extending to 12 h post-ischemia, which appeared interrelated.

  11. Asymmetry in the brain influenced the neurological deficits and infarction volume following the middle cerebral artery occlusion in rats

    OpenAIRE

    Zhang Meizeng; Gao Huanmin

    2008-01-01

    Abstract Background Paw preference in rats is similar to human handedness, which may result from dominant hemisphere of rat brain. However, given that lateralization is the uniqueness of the humans, many researchers neglect the differences between the left and right hemispheres when selecting the middle cerebral artery occlusion (MCAO) in rats. The aim of this study was to evaluate the effect of ischemia in the dominant hemisphere on neurobehavioral function and on the cerebral infarction vol...

  12. VIP/PACAP receptors in cerebral arteries of rat

    DEFF Research Database (Denmark)

    Erdling, André; Sheykhzade, Majid; Maddahi, Aida

    2013-01-01

    BACKGROUND: Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating peptide (PACAP)-containing nerves surround cerebral blood vessels. The peptides have potent vasodilator properties via smooth muscle cell receptors and activation of adenylate cyclase. The purpose of this s......BACKGROUND: Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating peptide (PACAP)-containing nerves surround cerebral blood vessels. The peptides have potent vasodilator properties via smooth muscle cell receptors and activation of adenylate cyclase. The purpose...

  13. Prediction of early neurological deterioration using diffusion- and perfusion-weighted imaging in hyperacute middle cerebral artery ischemic stroke.

    Science.gov (United States)

    Arenillas, Juan F; Rovira, Alex; Molina, Carlos A; Grivé, Elisenda; Montaner, Joan; Alvarez-Sabín, José

    2002-09-01

    Early neurological deterioration (END) occurs in approximately one third of all ischemic stroke patients and is associated with a poor outcome. Our study sought to assess the value of ultra-early MRI in the prediction of END in stroke patients. Between August 1999 and November 2001, 38 stroke patients with a proven middle cerebral artery (MCA) or intracranial internal carotid artery (ICA) occlusion on MR angiography underwent perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI) within 6 hours after onset, and 30 fulfilled all inclusion criteria. Control DWI and MR angiography were performed between days 3 and 5. Cranial CT was performed to rule out hemorrhagic transformation. Vascular risk factors, temperature, blood pressure, glycemia, and blood count were assessed on admission. National Institutes of Health Stroke Scale (NIHSS) scores were obtained at baseline and at 6, 12, 24, and 48 hours. At the same time points, transcranial Doppler (TCD) examinations were conducted to assess arterial recanalization. END was defined as an increase in the NIHSS score >4. A logistic regression model was applied to detect independent predictors of END. The Kruskal-Wallis test was used to evaluate the relationship between infarct growth and duration of vessel occlusion. Initial MR angiography showed an occlusion of intracranial ICA in 7 patients (23.3%), of proximal MCA in 14 (46.6%), and of distal MCA in the remaining 9 (30%). A PWI-DWI mismatch >20% was observed in 28 patients (93.3%). END occurred in 7 patients (23.3%). Baseline NIHSS score (P=0.05), proximal site of occlusion (P=0.002), initial DWI (P=0.002) and PWI (P=0.003) volumes, and reduced PWI-DWI mismatch (P=0.038) were associated with END in the univariate analysis. Only hyperacute DWI volume remained as a predictor of END when a logistic regression model was applied (odds ratio, 11.5; 95% CI, 2.31 to 57.10; P=0.0028). A receiver operator characteristic curve identified a cutoff point of DWI >89 cm(3

  14. Comparative studies of D2 receptors and cerebral blood flow in hemi-parkinsonism rats

    International Nuclear Information System (INIS)

    Lin, Y.; Lin, X.

    2000-01-01

    To study the relationship between dopamine (DA) D 2 receptors and cerebral blood flow in hemiparkinsonism rats. Hemi-parkinsonism rats were made by stereotaxic 6-hydroxy dopamine (6-OH-DA) lesions in substantia nigra and ventral tegmental area, apomorphine (Apo) which could induce the successful model rat rotates toward the intact side was used to screen that rats, 125 I-IBZM in vivo autoradiography and 99m Tc-HM-PAO regional brain biodistribution were used to study D 2 receptors and cerebral blood flow. The HPLC-ECD were used to measure the concentration of DA and it metabolites homovanillic acid (HVA), 3,4-dehydroxyphenyl acetic acid (DOPAC) in bilateral striatum (ST). The lesioned side ST DA and its metabolites HVA DOPAC reduced significantly than that of the intact side and pseudo-operated control group, ST/cerebellum (CB) 125 I-IBZM uptake ratio was 8.04 ±0.71 in lesioned side of hemi-parkinsonism rats, significantly increased compared with the intact side and the pseudo-operated group (p 99m Tc 30.1±4.53% enhancement as compared to the intact side, and also show good correlation with 30 min Apo induced rotation numbers (r=0.98), the regional cerebral blood flow study didn't show significant difference between bilateral brain cortex area (p>0.05). The DA content decreased significantly and induced an up-regulation of ST D 2 receptor binding sites in 6-OH-DA lesioned side in hemi-parkinsonism rats, the increased percentage of lesioned-intact side ST/CB 125 I-IBZM uptake ratio showed good correlation with rotation behavior induced by Apo. Compare with cerebral blood flow, D 2 receptor reflected by IBZM seems to be more specific and earlier to detect the cerebral functional impairment in experimental hemi-parkinsonism

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

    Directory of Open Access Journals (Sweden)

    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.

  16. Chronic exposure to zinc oxide nanoparticles increases ischemic-reperfusion injuries in isolated rat hearts

    Energy Technology Data Exchange (ETDEWEB)

    Milivojević, Tamara; Drobne, Damjana; Romih, Tea; Mali, Lilijana Bizjak [University of Ljubljana, Department of Biology, Biotechnical Faculty (Slovenia); Marin, Irena; Lunder, Mojca; Drevenšek, Gorazd, E-mail: gorazd.drevensek@mf.uni-lj.si [University of Ljubljana, Institute of Pharmacology and Experimental Toxicology, Faculty of Medicine (Slovenia)

    2016-10-15

    The use of zinc oxide nanoparticles (ZnO NPs) in numerous products is increasing, although possible negative implications of their long-term consumption are not known yet. Our aim was to evaluate the chronic, 6-week oral exposure to two different concentrations of ZnO NPs on isolated rat hearts exposed to ischemic-reperfusion injury and on small intestine morphology. Wistar rats of both sexes (n = 18) were randomly divided into three groups: (1) 4 mg/kg ZnO NPs, (2) 40 mg/kg ZnO NPs, and (3) control. After 6 weeks of treatment, the hearts were isolated, the left ventricular pressure (LVP), the coronary flow (CF), the duration of arrhythmias and the lactate dehydrogenase release rate (LDH) were measured. A histological investigation of the small intestine was performed. Chronic exposure to ZnO NPs acted cardiotoxic dose-dependently. ZnO NPs in dosage 40 mg/kg maximally decreased LVP (3.3-fold) and CF (2.5-fold) and increased the duration of ventricular tachycardia (all P < 0.01) compared to control, whereas ZnO NPs in dosage 4 mg/kg acted less cardiotoxic. Goblet cells in the small intestine epithelium of rats, treated with 40 mg ZnO NPs/kg, were enlarged, swollen and numerous, the intestinal epithelium width was increased. Unexpectedly, ZnO NPs in both dosages significantly decreased LDH. A 6-week oral exposure to ZnO NPs dose-dependently increased heart injuries and caused irritation of the intestinal mucosa. A prolonged exposure to ZnO NPs might cause functional damage to the heart even with exposures to the recommended daily doses, which should be tested in future studies.

  17. Higher density of serotonin-1A receptors in the hippocampus and cerebral cortex of alcohol-preferring P rats

    International Nuclear Information System (INIS)

    Wong, D.T.; Threlkeld, P.G.; Lumeng, L.; Li, Ting-Kai

    1990-01-01

    Saturable [ 3 H]-80HDPAT binding to 5HT-1A receptors in membranes prepared from hippocampus and frontal cerebral cortex of alcohol-preferring (P) rats and of alcohol-nonpreferring (NP) rats has been compared. The B max values or densities of recognition sites for 5HT-1A receptors in both brain areas of the P rats are 38 and 44 percent lower in the P rats than in the NP rats. The corresponding K D values are 38 and 44 percent lower in the P rats than in the NP rats, indicating higher affinities of the recognition sites for the 5HT-1A receptors in hippocampus and cerebral cortex of the P rats. These findings indicate either an enrichment of 5HT-1A receptor density during selective breeding for alcohol preference or an upregulation of 5HT-1A receptors of 5HT found in these brain areas of P rats as compared with the NP rats

  18. Co-60 and Ca-45 autoradiography in cerebral ischemia in the rat

    NARCIS (Netherlands)

    Stevens, H; Krop-van Gastel, W; Korf, J

    1998-01-01

    Radioisotopes of divalent Co (Co-57 in Single photon emission tomography (SPECT)and Co-55 in positron emission tomography (PET) have clinically been applied to visualize Ca related brain damage. The cerebral uptake of Ca-45 and Co-60 in a unilateral stroke model in the rat was compared; 100 mu Ci

  19. CRYOPRESERVATION OF FRESHLY ISOLATED SYNAPTOSOMES PREPARED FROM THE CEREBRAL-CORTEX OF RATS

    NARCIS (Netherlands)

    GLEITZ, J; BEILE, A; WILFFERT, B; TEGTMEIER, F

    In the present study, we established a cryopreservation method for freshly isolated synaptosomes prepared from the cerebral cortex of rats. Freshly prepared synaptosomes were either shock-frozen or frozen under temperature-controlled conditions using a programmable temperature controller. Each group

  20. Proteinuria precedes cerebral edema in stroke-prone rats : a magnetic resonance imaging study

    NARCIS (Netherlands)

    Blezer, E.L.A.; Schurink, M.; Nicolaij, K.; Dop Bär, P.R.; Jansen, G.H.; Koomans, H.A.; Joles, Jaap

    1998-01-01

    Background and Purpose: Stroke-prone spontaneously hypertensive rats (SHRSP) subjected to high sodium intake develop severe hypertension, cerebral edema, and proteinuria, culminating in organ damage and early death. MRI, which can be applied serially, provides the unique opportunity to study

  1. Gene expression and molecular changes in cerebral arteries following subarachnoid hemorrhage in the rat

    DEFF Research Database (Denmark)

    Vikman, Petter; Beg, Saema; Khurana, Tejvir S

    2006-01-01

    OBJECT: The authors investigated early changes in the cerebral arteries of rats that occur after subarachnoid hemorrhage (SAH). METHODS: Messenger RNA was investigated by performing microarray and quantitative real-time polymerase chain reaction (PCR) analyses, and protein expression was shown...

  2. Brain scan in cerebral ischemia. An experimental model in the rat

    International Nuclear Information System (INIS)

    Turner, J.H.

    1975-01-01

    A rapid embolic method for consistent induction of stroke in the rat is described. Brain scans were performed using a micro-pinhole collimator system, and the value of the model for studies in localization of radiopharmaceuticals in cerebral ischemia is demonstrated

  3. Nimodipine Effects on Cerebral Microvessels and Sciatic Nerve in Aging Rats

    NARCIS (Netherlands)

    de Jong, Giena; Jansen, Arthur; Horvath, E.; Gispen, W.H.; Luiten, P.G.M.

    1992-01-01

    At the ultrastructural level different anomalies of the cerebral microvasculature were encountered in the brains of aged rats. These aberrations can either be attributed to degeneration processes or to the perivascular deposition of, e.g., collagen fibrils and other, unidentified, proteinous debris.

  4. Manejo da hipertensão arterial na isquemia cerebral aguda Management of arterial hypertension in patients with acute ischemic stroke

    Directory of Open Access Journals (Sweden)

    WALTER JOSÉ FAGUNDES-PEREYRA

    1999-12-01

    Full Text Available OBJETIVO: Avaliar o nível de conhecimento dos médicos, através de sua conduta, em paciente com quadro de hipertensão arterial na fase aguda da isquemia cerebral. Também comentamos as principais condutas nesta fase, com ênfase na tensão arterial (TA. MÉTODO: Foram entrevistados 120 médicos da clínica médica e da cirurgia geral, em dez dos maiores Hospitais de Belo Horizonte, em 1997. Todos responderam a um questionário contendo um caso clínico de paciente hipertenso leve, admitido com quadro de isquemia cerebral e tensão arterial de 186x110 mmHg. Os profissionais deveriam optar por reduzir, aumentar ou manter a TA. RESULTADOS: Dos entrevistados, 38 (31,7% responderam que reduziriam os níveis tensionais, 82 (68,3% optaram pela manutenção e nenhum aumentaria (pPURPOSE: We aimed with study to assess the current clinical practice about the management of high blood pressure in patients in the acute phase of ischemic stroke. We also comment some topics of ischemic stroke treatment. METHODS: A case report of a patient admitted 8 hours after onset of ischemic stroke and with blood pressure of 186x110 mmHg was presented to 120 surgeons and clinician. They were asked to decide the best therapeutic option: to increase, decrease or maintenance blood pressure. RESULTS: Thirty-eight physicians (31,7% considered decreasing blood pressure the best therapeutics, 82 (68,3% considered maintenance and none decided to increase it (p < 0.05. There was no difference between the two specialties conduct. The physicians, with more than 10 years of graduation, had a tendency to decrease the blood pressure (p <0.05. CONCLUSION: The maintenance of blood pressure may present a sufficient blood support to compensate brain flow. A high percentage of the physicians (31,7% do not know about the current concepts of therapeutics considering hypertension in acute ischemic stroke. The development on special units to treat these patients ("stroke units" may eventually

  5. Correlation between synaptic plasticity, associated proteins, and rehabilitation training in a rat model of cerebral infarction

    Institute of Scientific and Technical Information of China (English)

    Dan Yang; Qian Yu

    2008-01-01

    All motions provide sensory, motoric, and reflexive input to the central nervous system, as well as playing an important role in cerebral functional plasticity and compensation. Cerebral plasticity has become the theoretical basis of neurorehabilitation. Studies of cerebrovascular disease, in particular, demonstrate that regeneration is accompanied by multiple forms of plasticity, such as functional and structural, in different phases of stroke rehabilitation. This study was designed to measure synaptic plasticity and expression of associated proteins to analyze the effect of rehabilitation training on learning and memory in a rat model of cerebral infarction. Results suggest that rehabilitation training increases expression of nerve growth factor associated protein 43, brain-derived neurotrophic factor, and neural cell adhesion molecules, and also promotes cerebral functional plasticity.

  6. Effects of MK-801 upon local cerebral glucose utilization in conscious rats and in rats anaesthetised with halothane

    International Nuclear Information System (INIS)

    Kurumaji, A.; McCulloch, J.

    1989-01-01

    The effects of MK-801 (0.5 mg/kg i.v.), a non-competitive N-methyl-D-aspartate (NMDA) antagonist, upon local cerebral glucose utilization were examined in conscious, lightly restrained rats and in rats anaesthetised with halothane in nitrous oxide by means of the quantitative autoradiographic [14C]-2-deoxyglucose technique. In the conscious rats, MK-801 produced a heterogenous pattern of altered cerebral glucose utilization with significant increases being observed in 12 of the 28 regions of gray matter examined and significant decreases in 6 of the 28 regions. Pronounced increases in glucose use were observed after MK-801 in the olfactory areas and in a number of brain areas in the limbic system (e.g., hippocampus molecular layer, dentate gyrus, subicular complex, posterior cingulate cortex, and mammillary body). In the cerebral cortices, large reductions in glucose use were observed after administration of MK-801, whereas in the extrapyramidal and sensory-motor areas, glucose use remained unchanged after MK-801 administration in conscious rats. In the halothane-anaesthetised rats, the pattern of altered glucose use after MK-801 differed qualitatively and quantitatively from that observed in conscious rats. In anaesthetised rats, significant reductions in glucose use were noted after MK-801 in 10 of the 28 regions examined, with no area displaying significantly increased glucose use after administration of the drug. In halothane-anaesthetised rats, MK-801 failed to change the rates of glucose use in the olfactory areas, the hippocampus molecular layer, and the dentate gyrus

  7. Hemorrhagic Transformation After Large Cerebral Infarction in Rats Pretreated With Dabigatran or Warfarin.

    Science.gov (United States)

    Kwon, Il; An, Sunho; Kim, Jayoung; Yang, Seung-Hee; Yoo, Joonsang; Baek, Jang-Hyun; Nam, Hyo Suk; Kim, Young Dae; Lee, Hye Sun; Choi, Hyun-Jung; Heo, Ji Hoe

    2017-10-01

    It is uncertain whether hemorrhagic transformation (HT) after large cerebral infarction is less frequent in dabigatran users than warfarin users. We compared the occurrence of HT after large cerebral infarction among rats pretreated with dabigatran, warfarin, or placebo. This was a triple-blind, randomized, and placebo-controlled experiment. After treatment with warfarin (0.2 mg/kg), dabigatran (20 mg/kg), or saline for 7 days, Wistar rats were subjected to transient middle cerebral artery occlusion. As the primary outcome, HT was determined by gradient-recalled echo imaging. For the secondary outcome, intracranial hemorrhage was assessed via gradient-recalled echo imaging in surviving rats and via autopsy for dead rats. Of 62 rats, there were 33 deaths (53.2%, 17 technical reasons). Of the intention-to-treat population, 33 rats underwent brain imaging. HT was less frequent in the dabigatran group than the warfarin group (placebo 2/14 [14%], dabigatran 0/10 [0%], and warfarin 9/9 [100%]; dabigatran versus warfarin; P warfarin group (19/29 [65.5%]; P =0.003), but not in the dabigatran group (6/19 [31.6%]; P =0.420). Mortality was significantly higher in the warfarin group than the dabigatran group (79.3% versus 47.4%; P =0.022), but not related to the hemorrhage frequency. The risk of HT after a large cerebral infarction was significantly increased in rats pretreated with warfarin than those with dabigatran. However, the results here may not have an exact clinical translation. © 2017 American Heart Association, Inc.

  8. Cerebroprotective Actions of Triticum aestivum Linn Powder and Bauhinia purpurea Flower Powder in Surgically Induced Cerebral Infraction in Rats.

    Science.gov (United States)

    Annapurna, Akula; Vishala, Thonangi C; Bitra, Veera R; Rapaka, Deepthi; Shaik, Asmath

    2018-01-01

    The prime objective of this study is to evaluate the cerebroprotective actions of Triticum aestivum (wheatgrass) powder and Bauhinia purpurea flower (dev kanchan) powder against the experimentally induced global ischemia reperfusion injury in rats. In the first phase of the studies, 1 h before the surgical procedure, the Wistar rats were orally served with varied doses of wheatgrass powder (5, 10, 30, and 100 μg/kg) and Bauhinia flower powder (30, 100, 200, and 300 μg/kg), respectively. The ischemia was induced by 30-min bilateral carotid artery occlusion in succession to reperfusion for 4 h. It was proved that the wheatgrass powder and Bauhinia flower powder yielded a significant, dose-dependent cerebroprotection in terms of reduction in cerebral infarct size when compared with the control group. Coming to the second phase of the studies, a certain potential dose of 10 μg/kg of wheatgrass and 200 μg/kg of Bauhinia flower powders was selected keeping the protective action in view, and the animals were treated for 15 days. The major findings of the study are that wheatgrass and Bauhinia flower powders significantly augmented the magnitude of the antioxidant enzymes, viz., super oxide dismutase and catalase, and further reduced the levels of lipid peroxidation. The present study clearly showed that the wheatgrass powder and Bauhinia flower powder possess significant antioxidant properties that may act as a key ingredient in various ayurvedic preparations for the treatment of various diseases like cerebral ischemic reperfusion injury. The wheat grass contains high amount of bioflavonoids, alkaloids, SOD etc which are responsible for anti oxidant activity.The Bauhinia purpurea contains glycosides, flavonoids and also plays a major role in DPPH activity which is responsible for anti oxidant activity.The wheat grass (10 mg/kg) and bauhinia (200 mg/kg) significantly(P bauhinia (200 mg/kg) significantly (P <0.0001) reduced the lipid peroxidation (MDA) and increased SOD

  9. Monitoring of cerebral haemodynamics in newborn infants

    DEFF Research Database (Denmark)

    Liem, K Djien; Greisen, Gorm

    2010-01-01

    The most important cerebrovascular injuries in newborn infants, particularly in preterm infants, are cerebral haemorrhage and ischemic injury. The typical cerebral vascular anatomy and the disturbance of cerebral haemodynamics play important roles in the pathophysiology. The term 'cerebral haemod...

  10. Effects of Electroacupuncture Combined with Repetitive Transcranial Magnetic Stimulation on the Expression of Nestin in Neural Stem Cell after Focal Cerebral Ischemia in Adult Rats

    Institute of Scientific and Technical Information of China (English)

    HUANG Guofu; HUANG Xiaolin; CHEN Hong; HAY Xiaohua

    2009-01-01

    Objective: To investigate the influence of electroacupuncture (EA) combined with repetitive transeranial magnetic stimulation(rTMS) on the temporal profile of nestin expression after induction of focal cerebral isehemia in adult rats and to explore the mechanism of EA combined with rTMS in treating ischemic brain injury. Method: The model of transient focal ischemia was produced by occlusion of middle cerebral artery. Seventy-five Wistar rats were randomly divided into normal group, model group, EA group, rTMS group and EA +rTMS group. The neurologic impairment rating and ability of learning and memory were observed at the 7th、14th and 28th d after infarction respectively. Meanwhile, Western blotting was used to observe the number of nestin expression positive cells. Result: Nestin-positive cells were found in cortex, subgranular zone (SGZ), subventricular zone (SVZ) of the ipsilateral side at different time points after cerebral isehemia. The number of nestin-positive cells peaked at the 7th d, began to decrease at the 14th d and was significantly higher in EA+rTMS group than that in model group (P<0.05), then almost reached normal at the 28th d. The improvement of neural motor function deficits as well as the indexes of learning and memory were more obvious in EA+rTMS group compared with model group (P<0.01, P<0.05). These effects were most obvious in EA+rTMS group compared with the EA and rTMS group (P<0.05). Conclusion: EA and rTMS possess the potency of building up and can increase the number of nestin-positive cells in some brain regions after focal cerebral ischemia, which might be one of the important mechanisms of EA combined with rTMS in treating ischemia brain injury.

  11. Combined administration of hyperbaric oxygen and hydroxocobalamin improves cerebral metabolism after acute cyanide poisoning in rats

    DEFF Research Database (Denmark)

    Hansen, M B; Olsen, Niels Vidiendal; Hyldegaard, O

    2013-01-01

    -to-pyruvate ratio in rat brain by means of microdialysis during acute CN poisoning. Anesthetized rats were allocated to three groups: 1) vehicle (1.2 ml isotonic NaCl intra-arterially); 2) potassium CN (5.4 mg/kg intra-arterially); 3) potassium CN, OHCob (100 mg/kg intra-arterially) and subsequent HBOT (284 k......Pa in 90 min). OHCob and HBOT significantly attenuated the acute surges in interstitial cerebral lactate, glucose, and glycerol concentrations compared with the intoxicated rats given no treatment. Furthermore, the combined treatment resulted in consistent low lactate, glucose, and glycerol concentrations...

  12. Cerebral ischemia produced by four-vessel occlusion in the rat: a quantitative evaluation of cerebral blood flow

    International Nuclear Information System (INIS)

    Furlow, T.W. Jr.

    1982-01-01

    Cerebral ischemia was produced in the rat by simultaneous occlusion of the vertebral and carotid arteries according to the method of Pulsinelli and Brierley (Stroke 10: 267, 1979). Local cerebral blood flow (CBF) was determined by polarographic and autoradiographic techniques. Hydrogen-clearance measurements showed that mean CBF fell in four monitored regions of the hemispheres to between 0.11 and 0.18 ml/g/min, being least in deep rostal gray, intermediate in superficial gray, and greatest in deep caudal gray. However, individual animals had local CBF in excess of 0.20 and even 0.30 ml/g/min, and no animal showed zero CBF. When animals were rendered hypotensive (MABP of 50 Torr) during vascular occlusion, mean CBF ranged between 0.03 and 0.10 ml/g/min in the same regional order. With hypotension, total arrest of flow occurred. Autoradiographic data confirmed the above findings and indicated adequate CBF to the lower brainstem. During vascular occlusion, sufficient CBF may be present ot sustain cerebral tissue as in animals with a well developed spinal circulation or an inadvertently patent vertebral artery

  13. Ilexonin A Promotes Neuronal Proliferation and Regeneration via Activation of the Canonical Wnt Signaling Pathway after Cerebral Ischemia Reperfusion in Rats

    Directory of Open Access Journals (Sweden)

    Bi-Qin Zhang

    2016-01-01

    Full Text Available Aims. Ilexonin A (IA, a component of the Chinese medicine Ilex pubescens, has been shown to be neuroprotective during ischemic injury. However, the specific mechanism underlying this neuroprotective effect remains unclear. Methods. In this study, we employed a combination of immunofluorescence staining, western blotting, RT-PCR, and behavioral tests, to investigate the molecular mechanisms involved in IA regulation of neuronal proliferation and regeneration after cerebral ischemia and reperfusion in rodents. Results. Increases in β-catenin protein and LEF1 mRNA and decreases in GSK3β protein and Axin mRNA observed in IA-treated compared to control rodents implicated the canonical Wnt pathway as a key signaling mechanism activated by IA treatment. Furthermore, rodents in the IA treatment group showed less neurologic impairment and a corresponding increase in the number of Brdu/nestin and Brdu/NeuN double positive neurons in the parenchymal ischemia tissue following middle cerebral artery occlusion compared to matched controls. Conclusion. Altogether, our data indicate that IA can significantly diminish neurological deficits associated with cerebral ischemia reperfusion in rats as a result of increased neuronal survival via modulation of the canonical Wnt pathway.

  14. Remote ischemic preconditioning differentially attenuates post-ischemic cardiac arrhythmia in streptozotocin-induced diabetic versus nondiabetic rats.

    Science.gov (United States)

    Hu, Zhaoyang; Chen, Mou; Zhang, Ping; Liu, Jin; Abbott, Geoffrey W

    2017-04-26

    Sudden cardiac death (SCD), a leading cause of global mortality, most commonly arises from a substrate of cardiac ischemia, but requires an additional trigger. Diabetes mellitus (DM) predisposes to SCD even after adjusting for other DM-linked cardiovascular pathology such as coronary artery disease. We previously showed that remote liver ischemia preconditioning (RLIPC) is highly protective against cardiac ischemia reperfusion injury (IRI) linked ventricular arrhythmias and myocardial infarction, via induction of the cardioprotective RISK pathway, and specifically, inhibitory phosphorylation of GSK-3β (Ser 9). We evaluated the impact of acute streptozotocin-induced DM on coronary artery ligation IRI-linked ventricular arrhythmogenesis and RLIPC therapy in rats. Post-IRI arrhythmia induction was similar in nondiabetic and DM rats, but, unexpectedly, DM rats exhibited lower incidence of SCD during reperfusion (41 vs. 100%), suggesting uncontrolled hyperglycemia does not acutely predispose to SCD. RLIPC was highly effective in both nondiabetic and DM rats at reducing incidence and duration of, and increasing latency to, all classes of ventricular tachyarrhythmias. In contrast, atrioventricular block (AVB) was highly responsive to RLIPC in nondiabetic rats (incidence reduced from 72 to 18%) but unresponsive in DM rats. RISK pathway induction was similar in nondiabetic and DM rats, thus not explaining the DM-specific resistance of AVB to therapy. Our findings uncover important acute DM-specific differences in responsiveness to remote preconditioning for ventricular tachyarrhythmias versus AVB, which may have clinical significance given that AVB is a malignant arrhythmia twofold more common in human diabetics than nondiabetics, and correlated to plasma glucose levels >10 mmol/L.

  15. Alterations in the Cerebral Microvascular Proteome Expression Profile After Transient Global Cerebral Ischemia in Rat

    DEFF Research Database (Denmark)

    Spray, Stine; Johansson, Sara E; Edwards, Alistair V G

    2017-01-01

    . The proteomic profile of the isolated cerebral microvasculature 72 h after GCI (compared to sham) indicated that the main expressional changes could be divided into nine categories: (1) cellular respiration, (2) remodelling of the extracellular matrix, (3) decreased contractile phenotype, (4) clathrin...

  16. Age-Specific Associations of Renal Impairment With Magnetic Resonance Imaging Markers of Cerebral Small Vessel Disease in Transient Ischemic Attack and Stroke.

    Science.gov (United States)

    Liu, Bian; Lau, Kui Kai; Li, Linxin; Lovelock, Caroline; Liu, Ming; Kuker, Wilhelm; Rothwell, Peter M

    2018-04-01

    It has been hypothesized that cerebral small vessel disease (SVD) and chronic renal impairment may be part of a multisystem small-vessel disorder, but their association may simply be as a result of shared risk factors (eg, hypertension) rather than to a systemic susceptibility to premature SVD. However, most previous studies were hospital based, most had inadequate adjustment for hypertension, many were confined to patients with lacunar stroke, and none stratified by age. In a population-based study of transient ischemic attack and ischemic stroke (OXVASC [Oxford Vascular Study]), we evaluated the magnetic resonance imaging markers of cerebral SVD, including lacunes, white matter hyperintensities, cerebral microbleeds, and enlarged perivascular space. We studied the age-specific associations of renal impairment (estimated glomerular filtration rate <60 mL/min per 1.73 m 2 ) and total SVD burden (total SVD score) adjusting for age, sex, vascular risk factors, and premorbid blood pressure (mean blood pressure during 15 years preevent). Of 1080 consecutive patients, 1028 (95.2%) had complete magnetic resonance imaging protocol and creatinine measured at baseline. Renal impairment was associated with total SVD score (odds ratio [OR], 2.16; 95% confidence interval [CI], 1.69-2.75; P <0.001), but only at age <60 years (<60 years: OR, 3.97; 95% CI, 1.69-9.32; P =0.002; 60-79 years: OR, 1.01; 95% CI, 0.72-1.41; P =0.963; ≥80 years: OR, 0.95; 95% CI, 0.59-1.54; P =0.832). The overall association of renal impairment and total SVD score was also attenuated after adjustment for age, sex, history of hypertension, diabetes mellitus, and premorbid average systolic blood pressure (adjusted OR, 0.76; 95% CI, 0.56-1.02; P =0.067), but the independent association of renal impairment and total SVD score at age <60 years was maintained (adjusted OR, 3.11; 95% CI, 1.21-7.98; P =0.018). Associations of renal impairment and SVD were consistent for each SVD marker at age <60 years but

  17. Neuroprotective effect of curcumin on transient focal cerebral ischemia in rats.

    Science.gov (United States)

    Zhao, Jing; Zhao, Yong; Zheng, Weiping; Lu, Yuyu; Feng, Gang; Yu, Shanshan

    2008-09-10

    Curcumin, a member of the curcuminoid family of compounds, is a yellow colored phenolic pigment obtained from the powdered rhizome of C. longa Linn. Recent studies have demonstrated that curcumin has protective effects against cerebral ischemia/reperfusion injury. However, little is known about its mechanism. Hence, in the present study the neuroprotective potential of curcumin was investigated in middle cerebral artery occlusion (MCAO) induced focal cerebral IR injury. Administration of curcumin 100 and 300 mg/kg i.p. 60 min after MCAO significantly diminished infarct volume, and improved neurological deficit in a dose-dependent manner. Nissl staining showed that the neuronal injury was significantly improved after being treated with curcumin. Curcumin significantly decreased the expression of caspase-3 protein. A higher number of TUNEL-positive cells were found in the vehicle group, but they were significantly decreased in the treated group. Taken together, these results suggest that the neuroprotective potentials of curcumin against focal cerebral ischemic injury are, at least in part, ascribed to its anti-apoptotic effects.

  18. Pomegranate extract protects against cerebral ischemia/reperfusion injury and preserves brain DNA integrity in rats.

    Science.gov (United States)

    Ahmed, Maha A E; El Morsy, Engy M; Ahmed, Amany A E

    2014-08-21

    Interruption to blood flow causes ischemia and infarction of brain tissues with consequent neuronal damage and brain dysfunction. Pomegranate extract is well tolerated, and safely consumed all over the world. Interestingly, pomegranate extract has shown remarkable antioxidant and anti-inflammatory effects in experimental models. Many investigators consider natural extracts as novel therapies for neurodegenerative disorders. Therefore, this study was carried out to investigate the protective effects of standardized pomegranate extract against cerebral ischemia/reperfusion-induced brain injury in rats. Adult male albino rats were randomly divided into sham-operated control group, ischemia/reperfusion (I/R) group, and two other groups that received standardized pomegranate extract at two dose levels (250, 500 mg/kg) for 15 days prior to ischemia/reperfusion (PMG250+I/R, and PMG500+I/R groups). After I/R or sham operation, all rats were sacrificed and brains were harvested for subsequent biochemical analysis. Results showed reduction in brain contents of MDA (malondialdehyde), and NO (nitric oxide), in addition to enhancement of SOD (superoxide dismutase), GPX (glutathione peroxidase), and GRD (glutathione reductase) activities in rats treated with pomegranate extract prior to cerebral I/R. Moreover, pomegranate extract decreased brain levels of NF-κB p65 (nuclear factor kappa B p65), TNF-α (tumor necrosis factor-alpha), caspase-3 and increased brain levels of IL-10 (interleukin-10), and cerebral ATP (adenosine triphosphate) production. Comet assay showed less brain DNA (deoxyribonucleic acid) damage in rats protected with pomegranate extract. The present study showed, for the first time, that pre-administration of pomegranate extract to rats, can offer a significant dose-dependent neuroprotective activity against cerebral I/R brain injury and DNA damage via antioxidant, anti-inflammatory, anti-apoptotic and ATP-replenishing effects. Copyright © 2014 Elsevier Inc

  19. Local cerebral blood flow (1CBF) and oxygen consumption (1CMRO2) in evolving irreversible ischemic infarction: a study with positron tomography and oxygen-15

    International Nuclear Information System (INIS)

    Baron, J.C.; Rougemont, D.; Lebrun-Grandie, P.; Comar, D.; Bousser, M.G.; Bories, J.; Castaigne, P.; Cabanis, E.

    1982-09-01

    In 25 patients suffering from cerebral ischemia set up in the area of the internal carotid artery the local cerebral blood flow (lCBF) and local cerebral oxygen consumption (lCMRO 2 ) were measured by the method of continuous inhalation of oxygen 15-labelled gas combined with positron emission tomography. These two local parameters and their ratio, the local oxygen extraction rate (lO 2 E), were studied inside the brain region tending spontaneously towards ischemic necrosis, a zone defined by means of repeated tomodensitometric examinations. The essential facts observed are the variability of the lCBF and the lO 2 E values, from extremely low to extremely high, whereas the collapse of the lCMRO 2 is constant. Consequently this last parameter alone would be a good prognostic index, an lCMRO 2 decrease to a level below about 70% of the controlateral value indicating that the necrosis is spontaneously irreparable. These results are discussed in the light of published data

  20. 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.

    Directory of Open Access Journals (Sweden)

    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.

  1. Cerebral energy metabolism in streptozotocin-diabetic rats

    NARCIS (Netherlands)

    Biessels, G.J.; Braun, K.P.J.; Graaf, de R.A.; Eijsden, van P.; Gispen, W.H.; Nicolaij, K.

    2001-01-01

    Aims/hypothesis. It is increasingly evident that the brain is another site of diabetic end-organ damage. The pathogenesis has not been fully explained, but seems to involve an interplay between aberrant glucose metabolism and vascular changes. Vascular changes, such as deficits in cerebral blood

  2. Protective effect of estrogen in endothelin-induced middle cerebral artery occlusion in female rats.

    Science.gov (United States)

    Glendenning, Michele L; Lovekamp-Swan, Tara; Schreihofer, Derek A

    2008-11-14

    Estrogen is a powerful endogenous and exogenous neuroprotective agent in animal models of brain injury, including focal cerebral ischemia. Although this protection has been demonstrated in several different treatment and injury paradigms, it has not been demonstrated in focal cerebral ischemia induced by intraparenchymal endothelin-1 injection, a model with many advantages over other models of experimental focal ischemia. Reproductively mature female Sprague-Dawley rats were ovariectomized and divided into placebo and estradiol-treated groups. Two weeks later, halothane-anesthetized rats underwent middle cerebral artery (MCA) occlusion by interparenchymal stereotactic injection of the potent vasoconstrictor endothelin 1 (180pmoles/2microl) near the middle cerebral artery. Laser-Doppler flowmetry (LDF) revealed similar reductions in cerebral blood flow in both groups. Animals were behaviorally evaluated before, and 2 days after, stroke induction, and infarct size was evaluated. In agreement with other models, estrogen treatment significantly reduced infarct size evaluated by both TTC and Fluoro-Jade staining and behavioral deficits associated with stroke. Stroke size was significantly correlated with LDF in both groups, suggesting that cranial perfusion measures can enhance success in this model.

  3. Multi-site laser Doppler flowmetry for assessing collateral flow in experimental ischemic stroke: Validation of outcome prediction with acute MRI.

    Science.gov (United States)

    Cuccione, Elisa; Versace, Alessandro; Cho, Tae-Hee; Carone, Davide; Berner, Lise-Prune; Ong, Elodie; Rousseau, David; Cai, Ruiyao; Monza, Laura; Ferrarese, Carlo; Sganzerla, Erik P; Berthezène, Yves; Nighoghossian, Norbert; Wiart, Marlène; Beretta, Simone; Chauveau, Fabien

    2017-06-01

    High variability in infarct size is common in experimental stroke models and affects statistical power and validity of neuroprotection trials. The aim of this study was to explore cerebral collateral flow as a stratification factor for the prediction of ischemic outcome. Transient intraluminal occlusion of the middle cerebral artery was induced for 90 min in 18 Wistar rats. Cerebral collateral flow was assessed intra-procedurally using multi-site laser Doppler flowmetry monitoring in both the lateral middle cerebral artery territory and the borderzone territory between middle cerebral artery and anterior cerebral artery. Multi-modal magnetic resonance imaging was used to assess acute ischemic lesion (diffusion-weighted imaging, DWI), acute perfusion deficit (time-to-peak, TTP), and final ischemic lesion at 24 h. Infarct volumes and typology at 24 h (large hemispheric versus basal ganglia infarcts) were predicted by both intra-ischemic collateral perfusion and acute DWI lesion volume. Collateral flow assessed by multi-site laser Doppler flowmetry correlated with the corresponding acute perfusion deficit using TTP maps. Multi-site laser Doppler flowmetry monitoring was able to predict ischemic outcome and perfusion deficit in good agreement with acute MRI. Our results support the additional value of cerebral collateral flow monitoring for outcome prediction in experimental ischemic stroke, especially when acute MRI facilities are not available.

  4. Chronic photoperiod disruption does not increase vulnerability to focal cerebral ischemia in young normotensive rats.

    Science.gov (United States)

    Ku Mohd Noor, Ku Mastura; Wyse, Cathy; Roy, Lisa A; Biello, Stephany M; McCabe, Christopher; Dewar, Deborah

    2017-11-01

    Photoperiod disruption, which occurs during shift work, is associated with changes in metabolism or physiology (e.g. hypertension and hyperglycaemia) that have the potential to adversely affect stroke outcome. We sought to investigate if photoperiod disruption affects vulnerability to stroke by determining the impact of photoperiod disruption on infarct size following permanent middle cerebral artery occlusion. Adult male Wistar rats (210-290 g) were housed singly under two different light/dark cycle conditions ( n = 12 each). Controls were maintained on a standard 12:12 light/dark cycle for nine weeks. For rats exposed to photoperiod disruption, every three days for nine weeks, the lights were switched on 6 h earlier than in the previous photoperiod. T 2 -weighted magnetic resonance imaging was performed at 48 h after middle cerebral artery occlusion. Disruption of photoperiod in young healthy rats for nine weeks did not alter key physiological variables that can impact on ischaemic damage, e.g. blood pressure and blood glucose immediately prior to middle cerebral artery occlusion. There was no effect of photoperiod disruption on infarct size after middle cerebral artery occlusion. We conclude that any potentially adverse effect of photoperiod disruption on stroke outcome may require additional factors such as high fat/high sugar diet or pre-existing co-morbidities.

  5. Subarachnoid hemorrhage enhances endothelin receptor expression and function in rat cerebral arteries

    DEFF Research Database (Denmark)

    Hansen-Schwartz, Jacob; Hoel, Natalie Løvland; Zhou, Mingfang

    2003-01-01

    OBJECTIVE: Inspired by organ culture-induced changes in the vascular endothelin (ET) receptor population, we investigated whether such changes occur in cerebral arteries in a rat subarachnoid hemorrhage (SAH) model. METHODS: SAH was induced with injection of 250 microl of blood into the prechiasm......OBJECTIVE: Inspired by organ culture-induced changes in the vascular endothelin (ET) receptor population, we investigated whether such changes occur in cerebral arteries in a rat subarachnoid hemorrhage (SAH) model. METHODS: SAH was induced with injection of 250 microl of blood...... into the prechiasmatic cistern. After 2 days, the middle cerebral artery, basilar artery, and posterior communicating artery were harvested. Pharmacological studies were performed in vitro, and levels of messenger ribonucleic acid (mRNA) were quantified in real-time reverse transcriptase-polymerase chain reaction assays....... RESULTS: In the middle cerebral artery and basilar artery from rats with induced SAH, enhanced biphasic responses to ET-1 were observed. The -log(50% effective concentration) value for the high-affinity phase was approximately 12, compared with approximately 8.5 for sham-operated animals...

  6. NEUROPROTECTIVE EFFICACY OF SUBCUTANEOUS INSULIN-LIKE GROWTH FACTOR-I ADMINISTRATION IN NORMOTENSIVE AND HYPERTENSIVE RATS WITH AN ISCHEMIC STROKE

    NARCIS (Netherlands)

    de Geyter, D.; Stoop, W.; Sarre, S.; de Keyser, J.; Kooijman, R.

    2013-01-01

    The aim of this study was to test the insulin-like growth factor-I (IGF-I) as a neuroprotective agent in a rat model for ischemic stroke and to compare its neuroprotective effects in conscious normotensive and spontaneously hypertensive rats. The effects of subcutaneous IGF-I injection were

  7. Dynamics of enhanced mitochondrial respiration in female compared with male rat cerebral arteries.

    Science.gov (United States)

    Rutkai, Ibolya; Dutta, Somhrita; Katakam, Prasad V; Busija, David W

    2015-11-01

    Mitochondrial respiration has never been directly examined in intact cerebral arteries. We tested the hypothesis that mitochondrial energetics of large cerebral arteries ex vivo are sex dependent. The Seahorse XFe24 analyzer was used to examine mitochondrial respiration in isolated cerebral arteries from adult male and female Sprague-Dawley rats. We examined the role of nitric oxide (NO) on mitochondrial respiration under basal conditions, using N(ω)-nitro-l-arginine methyl ester, and following pharmacological challenge using diazoxide (DZ), and also determined levels of mitochondrial and nonmitochondrial proteins using Western blot, and vascular diameter responses to DZ. The components of mitochondrial respiration including basal respiration, ATP production, proton leak, maximal respiration, and spare respiratory capacity were elevated in females compared with males, but increased in both male and female arteries in the presence of the NOS inhibitor. Although acute DZ treatment had little effect on mitochondrial respiration of male arteries, it decreased the respiration in female arteries. Levels of mitochondrial proteins in Complexes I-V and the voltage-dependent anion channel protein were elevated in female compared with male cerebral arteries. The DZ-induced vasodilation was greater in females than in males. Our findings show that substantial sex differences in mitochondrial respiratory dynamics exist in large cerebral arteries and may provide the mechanistic basis for observations that the female cerebral vasculature is more adaptable after injury. Copyright © 2015 the American Physiological Society.

  8. Effects of captopril on cerebral blood flow in normotensive and hypertensive rats

    International Nuclear Information System (INIS)

    Barry, D.I.; Paulson, O.B.; Jarden, J.O.; Juhler, M.; Graham, D.I.; Strandgaard, S.

    1984-01-01

    Cerebrovascular effects of the angiotensin converting enzyme inhibitor captopril were examined in normotensive and hypertensive rats. Cerebral blood flow was measured with the intracarotid 133 xenon injection method in halothane-anesthetized animals. The blood-brain barrier permeability of captopril (determined with an integral-uptake method) was negligible, the permeability-surface area product in most brain regions being 1 X 10(-5) cm3/g per second, that is, three to four times lower than that of sodium ion. When administered into the cerebral ventricles to bypass the blood-brain barrier, captopril had no effect on cerebral blood flow: furthermore, cerebral blood flow autoregulation (studied by raising and lowering blood pressure) was identical to that in controls. In contrast, when given intravenously, captopril had a marked effect on cerebral blood flow autoregulation--both the lower and upper limits of autoregulation being shifted to a lower pressure (by about 20 to 30 and 50 to 60 mm Hg, respectively), and the autoregulatory range was shortened by about 40 mm Hg. This effect may be ascribed to inhibition of converting enzyme in the cerebral blood vessels rather than within the brain

  9. Cerebral microangiopathies

    International Nuclear Information System (INIS)

    Linn, Jennifer

    2011-01-01

    Cerebral microangiopathies are a very heterogenous group of diseases characterized by pathological changes of the small cerebral vessels. They account for 20 - 30 % of all ischemic strokes. Degenerative microangiopathy and sporadic cerebral amyloid angiography represent the typical acquired cerebral microangiopathies, which are found in over 90 % of cases. Besides, a wide variety of rare, hereditary microangiopathy exists, as e.g. CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy), Fabrys disease and MELAS syndrome (Mitochondrial myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like episodes). (orig.)

  10. Impaired cardiac ischemic tolerance in spontaneously hypertensive rats is attenuated by adaptation to chronic and acute stress.

    Science.gov (United States)

    Ravingerová, T; Bernátová, I; Matejíková, J; Ledvényiová, V; Nemčeková, M; Pecháňová, O; Tribulová, N; Slezák, J

    2011-01-01

    Chronic hypertension may have a negative impact on the myocardial response to ischemia. On the other hand, intrinsic ischemic tolerance may persist even in the pathologically altered hearts of hypertensive animals, and may be modified by short- or long-term adaptation to different stressful conditions. The effects of long-term limitation of living space (ie, crowding stress [CS]) and brief ischemia-induced stress on cardiac response to ischemia/reperfusion (I/R) injury are not yet fully characterized in hypertensive subjects. The present study was designed to test the influence of chronic and acute stress on the myocardial response to I/R in spontaneously hypertensive rats (SHR) compared with their effects in normotensive counterparts. In both groups, chronic, eight-week CS was induced by caging five rats per cage in cages designed for two rats (200 cm(2)/rat), while controls (C) were housed four to a cage in cages designed for six animals (480 cm(2)/rat). Acute stress was evoked by one cycle of I/R (5 min each, ischemic preconditioning) before sustained I/R in isolated Langendorff-perfused hearts of normotensive and SHR rats. At baseline conditions, the effects of CS were manifested only as a further increase in blood pressure in SHR, and by marked limitation of coronary perfusion in normotensive animals, while no changes in heart mechanical function were observed in any of the groups. Postischemic recovery of contractile function, severity of ventricular arrhythmias and lethal injury (infarction size) were worsened in the hypertrophied hearts of C-SHR compared with normotensive C. However, myo-cardial stunning and reperfusion-induced ventricular arrhythmias were attenuated by CS in SHR, which was different from deterioration of I/R injury in the hearts of normotensive animals. In contrast, ischemic preconditioning conferred an effective protection against I/R in both groups, although the extent of anti-infarct and anti-arrhythmic effects was lower in SHR. Both

  11. Curcumin Protects Neuron against Cerebral Ischemia-Induced Inflammation through Improving PPAR-Gamma Function

    Directory of Open Access Journals (Sweden)

    Zun-Jing Liu

    2013-01-01

    Full Text Available Cerebral ischemia is the most common cerebrovascular disease worldwide. Recent studies have demonstrated that curcumin had beneficial effect to attenuate cerebral ischemic injury. However, it is unclear how curcumin protects against cerebral ischemic injury. In the present study, using rat middle cerebral artery occlusion model, we found that curcumin was a potent PPARγ agonist in that it upregulated PPARγ expression and PPARγ-PPRE binding activity. Administration of curcumin markedly decreased the infarct volume, improved neurological deficits, and reduced neuronal damage of rats. In addition, curcumin suppressed neuroinflammatory response by decreasing inflammatory mediators, such as IL-1β, TNF-α, PGE2, NO, COX-2, and iNOS induced by cerebral ischemia of rats. Furthermore, curcumin suppressed IκB degradation that was caused by cerebral ischemia. The present data also showed that PPARγ interacted with NF-κB-p65 and thus inhibited NF-κB activation. All the above protective effects of curcumin on cerebral ischemic injury were markedly attenuated by GW9662, an inhibitor of PPARγ. Our results as described above suggested that PPARγ induced by curcumin may play a critical role in protecting against brain injury through suppression of inflammatory response. It also highlights the potential of curcumin as a therapeutic agent against cerebral ischemia.

  12. Effects of Edaravone, a Free Radical Scavenger, on Photochemically Induced Cerebral Infarction in a Rat Hemiplegic Model

    OpenAIRE

    Ikeda, Satoshi; Harada, Katsuhiro; Ohwatashi, Akihiko; Kamikawa, Yurie

    2013-01-01

    Edaravone is a free radical scavenger that protects the adjacent cortex during cerebral infarction. We created a hemiparetic model of cerebral thrombosis from a photochemically induced infarction with the photosensitive dye, rose bengal, in rats. We examined the effects of edaravone on recovery in the model. A total of 36 adult Wistar rats were used. The right sensorimotor area was irradiated with green light with a wavelength of 533?nm (10?mm diameter), and the rose bengal was injected intra...

  13. Behavioural inflexibility in a comorbid rat model of striatal ischemic injury and mutant hAPP overexpression.

    Science.gov (United States)

    Levit, Alexander; Regis, Aaron M; Garabon, Jessica R; Oh, Seung-Hun; Desai, Sagar J; Rajakumar, Nagalingam; Hachinski, Vladimir; Agca, Yuksel; Agca, Cansu; Whitehead, Shawn N; Allman, Brian L

    2017-08-30

    Alzheimer disease (AD) and stroke coexist and interact; yet how they interact is not sufficiently understood. Both AD and basal ganglia stroke can impair behavioural flexibility, which can be reliably modeled in rats using an established operant based set-shifting test. Transgenic Fischer 344-APP21 rats (TgF344) overexpress pathogenic human amyloid precursor protein (hAPP) but do not spontaneously develop overt pathology, hence TgF344 rats can be used to model the effect of vascular injury in the prodromal stages of Alzheimer disease. We demonstrate that the injection of endothelin-1 (ET1) into the dorsal striatum of TgF344 rats (Tg-ET1) produced an exacerbation of behavioural inflexibility with a behavioural phenotype that was distinct from saline-injected wildtype & TgF344 rats as well as ET1-injected wildtype rats (Wt-ET1). In addition to profiling the types of errors made, interpolative modeling using logistic exposure-response regression provided an informative analysis of the timing and efficiency of behavioural flexibility. During set-shifting, Tg-ET1 committed fewer perseverative errors than Wt-ET1. However, Tg-ET1 committed significantly more regressive errors and had a less efficient strategy change than all other groups. Thus, behavioural flexibility was more vulnerable to striatal ischemic injury in TgF344 rats. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. [Effect of Scalp-acupuncture Stimulation on Neurological Function and Expression of ASIC 1 a and ASIC 2 b of Hippocampal CA 1 Region in Cerebral Ischemia