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Sample records for accelerated cerebral ischemic

  1. Simvastatin Reduces Lipopolysaccharides-Accelerated Cerebral Ischemic Injury via Inhibition of Nuclear Factor-kappa B Activity

    PubMed Central

    Anthony Jalin, Angela M. A.; Lee, Jae-Chul; Cho, Geum-Sil; Kim, Chunsook; Ju, Chung; Pahk, Kisoo; Song, Hwa Young; Kim, Won-Ki

    2015-01-01

    Preceding infection or inflammation such as bacterial meningitis has been associated with poor outcomes after stroke. Previously, we reported that intracorpus callosum microinjection of lipopolysaccharides (LPS) strongly accelerated the ischemia/reperfusion-evoked brain tissue damage via recruiting inflammatory cells into the ischemic lesion. Simvastatin, 3-hydroxy-3-methylgultaryl (HMG)-CoA reductase inhibitor, has been shown to reduce inflammatory responses in vascular diseases. Thus, we investigated whether simvastatin could reduce the LPS-accelerated ischemic injury. Simvastatin (20 mg/kg) was orally administered to rats prior to cerebral ischemic insults (4 times at 72, 48, 25, and 1-h pre-ischemia). LPS was microinjected into rat corpus callosum 1 day before the ischemic injury. Treatment of simvastatin reduced the LPS-accelerated infarct size by 73%, and decreased the ischemia/reperfusion-induced expressions of pro-inflammatory mediators such as iNOS, COX-2 and IL-1β in LPS-injected rat brains. However, simvastatin did not reduce the infiltration of microglial/macrophageal cells into the LPS-pretreated brain lesion. In vitro migration assay also showed that simvastatin did not inhibit the monocyte chemoattractant protein-1-evoked migration of microglial/macrophageal cells. Instead, simvastatin inhibited the nuclear translocation of NF-κB, a key signaling event in expressions of various proinflammatory mediators, by decreasing the degradation of IκB. The present results indicate that simvastatin may be beneficial particularly to the accelerated cerebral ischemic injury under inflammatory or infectious conditions. PMID:26535078

  2. Cerebral ischemic stroke: is gender important?

    PubMed Central

    Gibson, Claire L

    2013-01-01

    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. PMID:23756694

  3. [Cerebral infarction and transient ischemic attack].

    PubMed

    Sahara, Noriyuki; Kuwashiro, Takahiro; Okada, Yasushi

    2016-04-01

    Japanese Guidelines for the Management of Stroke 2015 was published. Here, we describe several points revised from the 2009 edition about "Cerebral infarction and transient ischemic attack (TIA)". The revision points are as follows; 1. Extension of possible time window of intravenous recombinant tissue-plasminogen activator treatment (from within 3 hours to within 4.5 hours); 2. Antiplatelet therapy in acute stage (dual antiplatelet therapy (DAPT) for non-cardioembolic ischemic stroke or TIA); 3. Endovascular recanalization therapy in acute stage; 4. Antiplatelet therapy in chronic stage (Cilostazol is recommended similar to aspirin or clopidogrel); 5. Non-vitamin K antagonist oral anticoagulants (NOACs) for non-valvular atrial fibrillation (NVAF) stroke or TIA patients; 6. Management of TIA. We explain the revised points of the guideline in the text.

  4. [Cerebral infarction and transient ischemic attack].

    PubMed

    Sahara, Noriyuki; Kuwashiro, Takahiro; Okada, Yasushi

    2016-04-01

    Japanese Guidelines for the Management of Stroke 2015 was published. Here, we describe several points revised from the 2009 edition about "Cerebral infarction and transient ischemic attack (TIA)". The revision points are as follows; 1. Extension of possible time window of intravenous recombinant tissue-plasminogen activator treatment (from within 3 hours to within 4.5 hours); 2. Antiplatelet therapy in acute stage (dual antiplatelet therapy (DAPT) for non-cardioembolic ischemic stroke or TIA); 3. Endovascular recanalization therapy in acute stage; 4. Antiplatelet therapy in chronic stage (Cilostazol is recommended similar to aspirin or clopidogrel); 5. Non-vitamin K antagonist oral anticoagulants (NOACs) for non-valvular atrial fibrillation (NVAF) stroke or TIA patients; 6. Management of TIA. We explain the revised points of the guideline in the text. PMID:27333757

  5. Bone Fracture Exacerbates Murine Ischemic Cerebral Injury

    PubMed Central

    Degos, Vincent; Maze, Mervyn; Vacas, Susana; Hirsch, Jan; Guo, Yi; Shen, Fanxia; Jun, Kristine; van Rooijen, Nico; Gressens, Pierre; Young, William L.; Su, Hua

    2014-01-01

    Background Bone fracture increases alarmins and pro-inflammatory cytokines in the blood, and provokes macrophage infiltration and pro-inflammatory cytokine expression in the hippocampus. We recently reported that stroke is an independent risk factor after bone surgery for adverse outcome, the impact of bone fracture on stroke outcome is unknown. We tested the hypothesis that bone fracture, shortly after ischemic stroke, enhances stroke-related injuries by augmenting the neuroinflammatory response. Methods Tibia fracture (bone fracture) was induced in mice one day after permanent occlusion of the distal middle cerebral artery (stroke). High-mobility-group box chromosomal protein-1 (HMGB1) was tested to mimic the bone fracture effects. HMGB1 neutralizing antibody and clodrolip (macrophage depletion) were tested to attenuate the bone fracture effects. Neurobehavioral function (n=10), infarct volume, neuronal death, and macrophages/microglia-infiltration (n=6–7) were analyzed three days after. Results We found that mice with both stroke and bone fracture had larger infarct volumes (mean percentage of ipsilateral hemisphere±SD: 30±7% vs. 12±3%, n=6, P<0.001) more severe neurobehavioral dysfunction, and more macrophages/microglia in the peri-infarct region than mice with stroke only. Intraperitoneal injection of HMGB1 mimicked, whereas neutralizing HMGB1 attenuated, the bone fracture effects and the macrophage/microglia infiltration. Depleting macrophages with clodrolip also attenuated the aggravating effects of bone fracture on stroke lesion and behavioral dysfunction. Conclusions These novel findings suggest that bone fracture shortly after stroke enhances stroke injury via augmented inflammation through HMGB1 and macrophage/microglia infiltration. Interventions to modulate early macrophage/microglia activation could be therapeutic goals to limit the adverse consequences of bone fracture after stroke. PMID:23438676

  6. Imaging findings and cerebral perfusion in arterial ischemic stroke due to transient cerebral arteriopathy in children.

    PubMed

    Barbosa Junior, Alcino Alves; Ellovitch, Saada Resende de Souza; Pincerato, Rita de Cassia Maciel

    2012-01-01

    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.

  7. Effects of ischemic stroke on dynamics of cerebral autoregulation

    NASA Astrophysics Data System (ADS)

    Chen, Zhi; Ivanov, Plamen Ch; Hu, Kun; Stanley, Eugene; Novak, Vera

    2004-03-01

    Cerebral vasoregulation involves several complex mechanisms adapting blood flow to fluctuations of systemic blood pressure (BP). Autonomic BP and metabolic vasoregulation are impaired after stroke and cerebral blood flow depends on systemic BP. To probe the mechanisms of cerebral autoregulation we study levels of nonlinear synchronization between cerebral blood flow velocity (BFV) and peripheral BP. We quantify the instantaneous phase of each signal employing analytic signal approach and Hilbert transform. As a marker of synchronization, we introduce a measure of cross-correlation between the instantaneous phase increments of the BFV and BP signals at different time lags. We have studied 12 subjects with minor chronic ischemic stroke and 11 matched normotensive controls (age<65years). BFV and BP of these subjects are continuously recorded during supine baseline, head-up tilt, hyperventilation and CO2 rebreathing. For control subjects we find significant synchronization between cerebral BFV and peripheral BP only for short time lags of up to 5-6 seconds, suggesting a rapid return to a steady cerebral blood flow after initial blood pressure perturbations. In contrast, for stroke subjects BFV/BP we find enhanced synchronization over longer time lags of up to 20 seconds, suggesting entrainment of cerebral blood flow velocity by slow vasomotor rhythms. These findings suggest that cerebral vasoregulation is impaired and cerebral blood flow follows the fluctuations of systemic BP in a synchronous manner. Our analysis shows that cerebral autoregulation is impaired in 10 out of the 12 stroke subjects, which is typically difficult to diagnose with conventional methods. Thus, our novel synchronization approach offers a new tool sensitive for evaluation of changes in the dynamics of cerebral autoregulation under stroke.

  8. Bone Fracture Pre-Ischemic Stroke Exacerbates Ischemic Cerebral Injury in Mice

    PubMed Central

    Zou, Dingquan; Zhan, Lei; Li, Zhengxi; Zhu, Wan; Su, Hua

    2016-01-01

    Ischemic stroke is a devastating complication of bone fracture. Bone fracture shortly after stroke enhances stroke injury by augmenting inflammation. We hypothesize that bone fracture shortly before ischemic stroke also exacerbates ischemic cerebral injury. Tibia fracture was performed 6 or 24 hours before permanent middle cerebral artery occlusion (pMCAO) on C57BL/6J mice or Ccr2RFP/+Cx3cr1GFP/+ mice that have the RFP gene knocked into one allele of Ccr2 gene and GFP gene knocked into one allele of Cx3cr1 gene. Behavior was tested 3 days after pMCAO. Infarct volume, the number of CD68+ cells, apoptotic neurons, bone marrow-derived macrophages (RFP+), and microgila (GFP+) in the peri-infarct region were quantified. Compared to mice subjected to pMCAO only, bone fracture 6 or 24 hours before pMCAO increased behavioral deficits, the infarct volume, and the number of CD68+ cells and apoptotic neurons in the peri-infarct area. Both bone marrow-derived macrophages (CCR2+) and microglia (CX3CR1+) increased in the peri-infarct regions of mice subjected to bone fracture before pMCAO compared to stroke-only mice. The mice subjected to bone fracture 6 hours before pMCAO had more severe injury than mice that had bone fracture 24 hours before pMCAO. Our data showed that bone fracture shortly before stroke also increases neuroinflammation and exacerbates ischemic cerebral injury. Our findings suggest that inhibition of neuroinflammation or management of stroke risk factors before major bone surgery would be beneficial for patients who are likely to suffer from stroke. PMID:27089041

  9. Motor performance improved by exercises in cerebral ischemic rats.

    PubMed

    Yang, Yea-Ru; Chang, Heng-Chih; Wang, Paulus S; Wang, Ray-Yau

    2012-01-01

    Physical exercise may induce neuroprotective effects against brain damage after stroke. The authors aimed to investigate the effects of various exercises on motor function, striatal angiogenesis, and infarct volume in cerebral ischemic rats. Adult male Sprague Dawley rats were subjected to middle cerebral artery occlusion and randomly assigned to 1 of the 4 groups: Rota-rod training, lower speed treadmill training, higher speed treadmill training, or no exercise control. Motor function, striatal angiogenesis, and infarct volume were evaluated before or after motor training. After training, motor function and striatal angiogenesis changed significantly in Rota-rod and higher speed treadmill training groups as compared with the control group. Improvement in motor function significantly correlated with striatal angiogenesis after motor training. Infarct volumes were significantly decreased in lower and higher speed treadmill training groups. The results indicated that both motor training procedures can be used as effective training programs in stroke rehabilitation.

  10. Effects of cervical-lymphatic blockade on brain edema and infarction volume in cerebral ischemic rats.

    PubMed

    Si, Jinchao; Chen, Lianbi; Xia, Zuoli

    2006-10-31

    To observe the effects of cervical-lymphatic blockade (CLB) on brain edema and infarction volume of ischemic (MCAO) rat, we examined changes in cerebral water content, Ca2+ and glutamate concentrations, cerebral infarction volume and mRNA expression levels of N-methyl-D-aspartame receptor 1 (NMDA receptor 1) in the ischemic (left) hemisphere. The present results demonstrated that all the above indices in rats with middle cerebral artery occlusion plus cervical lymphatic blockade (MCAO+CLB) were markedly higher than those with only middle cerebral artery occlusion (MCAO) at different time points. These results indicated [corrected] that CLB can aggravate cerebral ischemia by increasing brain edema and infarction volume.

  11. εPKC confers acute tolerance to cerebral ischemic reperfusion injury

    PubMed Central

    Bright, Rachel; Sun, Guo-Hua; Yenari, Midori A.; Steinberg, Gary K.; Mochly-Rosen, Daria

    2008-01-01

    In response to mild ischemic stress, the brain elicits endogenous survival mechanisms to protect cells against a subsequent lethal ischemic stress, referred to as ischemic tolerance. The molecular signals that mediate this protection are thought to involve the expression and activation of multiple kinases, including protein kinase C (PKC). Here we demonstrate that εPKC mediates cerebral ischemic tolerance in vivo. Systemic delivery of ψεRACK, an εPKC-selective peptide activator, confers neuroprotection against a subsequent cerebral ischemic event when delivered immediately prior to stroke. In addition, activation of εPKC by ψεRACK treatment decreases vascular tone in vivo, as demonstrated by a reduction in microvascular cerebral blood flow. Here we demonstrate the role of acute and transient εPKC in early cerebral tolerance in vivo and suggest that extra-parenchymal mechanisms, such as vasoconstriction, may contribute to the conferred protection. PMID:18586397

  12. Remote ischemic preconditioning improves post resuscitation cerebral function via overexpressing neuroglobin after cardiac arrest in rats.

    PubMed

    Fan, Ran; Yu, Tao; Lin, Jia-Li; Ren, Guang-Dong; Li, Yi; Liao, Xiao-Xing; Huang, Zi-Tong; Jiang, Chong-Hui

    2016-10-01

    In this study, we investigated the effects of remote ischemic preconditioning on post resuscitation cerebral function in a rat model of cardiac arrest and resuscitation. The animals were randomized into six groups: 1) sham operation, 2) lateral ventricle injection and sham operation, 3) cardiac arrest induced by ventricular fibrillation, 4) lateral ventricle injection and cardiac arrest, 5) remote ischemic preconditioning initiated 90min before induction of ventricular fibrillation, and 6) lateral ventricle injection and remote ischemic preconditioning before cardiac arrest. Reagent of Lateral ventricle injection is neuroglobin antisense oligodeoxynucleotides which initiated 24h before sham operation, cardiac arrest or remote ischemic preconditioning. Remote ischemic preconditioning was induced by four cycles of 5min of limb ischemia, followed by 5min of reperfusion. Ventricular fibrillation was induced by current and lasted for 6min. Defibrillation was attempted after 6min of cardiopulmonary resuscitation. The animals were then monitored for 2h and observed for an additionally maximum 70h. Post resuscitation cerebral function was evaluated by neurologic deficit score at 72h after return of spontaneous circulation. Results showed that remote ischemic preconditioning increased neurologic deficit scores. To investigate the neuroprotective effects of remote ischemic preconditioning, we observed neuronal injury at 48 and 72h after return of spontaneous circulation and found that remote ischemic preconditioning significantly decreased the occurrence of neuronal apoptosis and necrosis. To further comprehend mechanism of neuroprotection induced by remote ischemic preconditioning, we found expression of neuroglobin at 24h after return of spontaneous circulation was enhanced. Furthermore, administration of neuroglobin antisense oligodeoxynucleotides before induction of remote ischemic preconditioning showed that the level of neuroglobin was decreased then partly abrogated

  13. Radon inhalation protects against transient global cerebral ischemic injury in gerbils.

    PubMed

    Kataoka, Takahiro; Etani, Reo; Takata, Yuji; Nishiyama, Yuichi; Kawabe, Atsushi; Kumashiro, Masayuki; Taguchi, Takehito; Yamaoka, Kiyonori

    2014-10-01

    Although brain disorders are not the main indication for radon therapy, our previous study suggested that radon inhalation therapy might mitigate brain disorders. In this study, we assessed whether radon inhalation protects against transient global cerebral ischemic injury in gerbils. Gerbils were treated with inhaled radon at a concentration of 2,000 Bq/m(3) for 24 h. After radon inhalation, transient global cerebral ischemia was induced by bilateral occlusion of the common carotid artery. Results showed that transient global cerebral ischemia induced neuronal damage in hippocampal CA1, and the number of damaged neurons was significantly increased compared with control. However, radon treatment inhibited ischemic damage. Superoxide dismutase (SOD) activity in the radon-treated gerbil brain was significantly higher than that in sham-operated gerbils. These findings suggested that radon inhalation activates antioxidative function, especially SOD, thereby inhibiting transient global cerebral ischemic injury in gerbils.

  14. Cilostazol: therapeutic potential against focal cerebral ischemic damage.

    PubMed

    Hong, Ki Whan; Lee, Jeong Hyun; Kima, Ki Young; Park, So Youn; Lee, Won Suk

    2006-01-01

    Cilostazol was developed as a selective inhibitor of cyclic nucleotide phosphodiesterase 3 (PDE3). The anti-platelet and vasodilator properties of cilostazol have been extensively characterized and considered to contribute to the variety of clinical effects such as intermittent claudication and recurrent stroke. In this review, the novel action mechanism (s) of cilostazol are overviewed with the focus on the action of cilostazol in in vitro and in vivo studies as a maxi-K channel opener targeting anti-apoptotic signaling pathways. Under treatment with cilostazol (10 mg/kg intravenously or 30 mg/kg orally), a significant reduction in cerebral infarct area was evident in rats subjected to ischemia/reperfusion. Increase in cyclic AMP and decrease in TNF-alpha levels were identified in the ipsilateral cortex under treatment with cilostazol accompanied by decreased Bax formation and cytochrome c release with increased Bcl-2 production in the penumbral area as well as in the in vitro human umbilical endothelial cells. Cilostazol suppressed TNF-alpha-induced decrease in viability of SK-N-SH (human neuroblastoma) cells and HCN-1A (human cortical neuron) cells in association with decrease in PTEN phosphorylation and increase in Akt/CREB phosphorylation with suppression of DNA fragmentation, all of which were antagonized by iberiotoxin, a maxi-K(+) channel blocker. Further, cilostazol prevented TNF-alpha-induced PTEN phosphorylation and apoptotic cell death via increased CK2 phosphorylation in the SK-N-SH cells. Cilostazol increased K(+) current in SK-N-SH cells by opening the maxi-K channels. Thus, it was suggested that the action of cilostazol to promote cell survival was ascribed to the maxi-K channel opening-coupled upregulation of CK2 phosphorylation and downregulation of PTEN phosphorylation with resultant increased phosphorylation of Akt and CREB. These in vitro data were confirmed in the in vivo results of rats subjected to focal transient ischemic damage.

  15. Association of CVD Candidate Gene Polymorphisms with Ischemic Stroke and Cerebral Hemorrhage in Chinese Individuals

    PubMed Central

    Shen, Yue; Li, Jiana; He, Lingbin; Yuan, Yuan; Tan, Xuerui; Liu, Lisheng; Zhao, Jingbo; Wang, Xingyu

    2014-01-01

    Background Contribution of cardiovascular disease related genetic risk factors for stroke are not clearly defined. We performed a genetic association study to assess the association of 56 previously characterized gene variants in 34 candidate genes from cardiovascular disease related biological pathways with ischemic stroke and cerebral hemorrhage in a Chinese population. Methods There were 1280 stroke patients (1101 with ischemic stroke and 179 with cerebral hemorrhage) and 1380 controls in the study. The genotypes for 56 polymorphisms of 34 candidate genes were determined by the immobilized probe approach and the associations of gene polymorphisms with ischemic stroke and cerebral hemorrhage were performed by logistic regression under an allelic model. Results After adjusting for age, sex, BMI and hypertension status by logistic regression analysis, we found that NPPA rs5063 was significantly associated with both ischemic stroke (odds ratio [OR] 0.69; 95% confidence interval [CI], 0.52 to 0.90; P = 0.006) and cerebral hemorrhage(OR = 0.39; 95%CI, 0.19 to 0.78; P = 0.007). In addition, MTHFR rs1801133 also was associated with cerebral hemorrhage (OR = 1.48; 95%CI, 1.16 to1.89; P = 0.001) but not with ischemic stroke (OR = 1.08; 95%CI, 0.96 to1.22; P = 0.210). After false discovery rate (FDR) correction, the association of NPPA rs5063 and MTHFR rs1801133 with cerebral hemorrhage remained significant. Conclusions The NPPA rs5063 is associated with reduced risk for cerebral hemorrhage and MTHFR rs1801133 is associated with increased risk of cerebral hemorrhage in a Chinese population. PMID:25144711

  16. Optimal therapeutic dose and time window of picroside II in cerebral ischemic injury

    PubMed Central

    Liu, Guangyi; Zhao, Li; Wang, Tingting; Zhang, Meizeng; Pei, Haitao

    2014-01-01

    A preliminary study from our research group showed that picroside II inhibited neuronal apoptosis in ischemic penumbra, reduced ischemic volume, and improved neurobehavioral function in rats with cerebral ischemia. The aim of the present study was to validate the neuroprotective effects of picroside II and optimize its therapeutic time window and dose in a rat model of cerebral ischemia. We found that picroside II inhibited cell apoptosis and reduced the expression of neuron-specific enolase, a marker of neuronal damage, in rats after cerebral ischemic injury. The optimal treatment time after ischemic injury and dose were determined, respectively, as follows: (1) 2.0 hours and 10 mg/kg according to the results of toluidine blue staining; (2) 1.5 hours and 10 mg/kg according to early apoptotic ratio by flow cytometry; (3) 2.0 hours and 10 mg/kg according to immunohistochemical and western blot analysis; and (4) 1.5 hours and 10 mg/kg according to reverse transcription polymerase chain reaction. The present findings suggest that an intraperitoneal injection of 10 mg/kg picroside II 1.5–2.0 hours after cerebral ischemic injury in rats is the optimal dose and time for therapeutic benefit. PMID:25317155

  17. Cerebral Hemodynamics and Vascular Reactivity in Mild and Severe Ischemic Rodent Middle Cerebral Artery Occlusion Stroke Models

    PubMed Central

    Sim, Jeongeun; Jo, Areum; Kang, Bok-Man; Lee, Sohee; Bang, Oh Young; Heo, Chaejeong; Jhon, Gil-Ja; Lee, Youngmi

    2016-01-01

    Ischemia can cause decreased cerebral neurovascular coupling, leading to a failure in the autoregulation of cerebral blood flow. This study aims to investigate the effect of varying degrees of ischemia on cerebral hemodynamic reactivity using in vivo real-time optical imaging. We utilized direct cortical stimulation to elicit hyper-excitable neuronal activation, which leads to induced hemodynamic changes in both the normal and middle cerebral artery occlusion (MCAO) ischemic stroke groups. Hemodynamic measurements from optical imaging accurately predict the severity of occlusion in mild and severe MCAO animals. There is neither an increase in cerebral blood volume nor in vessel reactivity in the ipsilateral hemisphere (I.H) of animals with severe MCAO. The pial artery in the contralateral hemisphere (C.H) of the severe MCAO group reacted more slowly than both hemispheres in the normal and mild MCAO groups. In addition, the arterial reactivity of the I.H in the mild MCAO animals was faster than the normal animals. Furthermore, artery reactivity is tightly correlated with histological and behavioral results in the MCAO ischemic group. Thus, in vivo optical imaging may offer a simple and useful tool to assess the degree of ischemia and to understand how cerebral hemodynamics and vascular reactivity are affected by ischemia. PMID:27358581

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

    PubMed

    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.

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

    PubMed

    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. PMID:26063779

  20. Protein nitration impairs the myogenic tone of rat middle cerebral arteries in both ischemic and nonischemic hemispheres after ischemic stroke.

    PubMed

    Coucha, Maha; Li, Weiguo; Johnson, Maribeth H; Fagan, Susan C; Ergul, Adviye

    2013-12-01

    The myogenic response is crucial for maintaining vascular resistance to achieve constant perfusion during pressure fluctuations. Reduced cerebral blood flow has been reported in ischemic and nonischemic hemispheres after stroke. Ischemia-reperfusion injury and the resulting oxidative stress impair myogenic responses in the ischemic hemisphere. Yet, the mechanism by which ischemia-reperfusion affects the nonischemic side is still undetermined. The goal of the present study was to determine the effect of ischemia-reperfusion injury on the myogenic reactivity of cerebral vessels from both hemispheres and whether protein nitration due to excess peroxynitrite production is the underlying mechanism of loss of tone. Male Wistar rats were subjected to sham operation or 30-min middle cerebral artery occlusion/45-min reperfusion. Rats were administered saline, the peroxynitrite decomposition catalyst 5,10,15,20-tetrakis(4-sulfonatophenyl)prophyrinato iron (III), or the nitration inhibitor epicatechin at reperfusion. Middle cerebral arteries isolated from another set of control rats were exposed to ex vivo oxygen-glucose deprivation with and without glycoprotein 91 tat (NADPH oxidase inhibitor) or N(ω)-nitro-l-arginine methyl ester. Myogenic tone and nitrotyrosine levels were determined. Ischemia-reperfusion injury impaired the myogenic tone of vessels in both hemispheres compared with the sham group (P < 0.001). Vessels exposed to ex vivo oxygen-glucose deprivation experienced a similar loss of myogenic tone. Inhibition of peroxynitrite parent radicals significantly improved the myogenic tone. Peroxynitrite scavenging or inhibition of nitration improved the myogenic tone of vessels from ischemic (P < 0.001 and P < 0.05, respectively) and nonischemic (P < 0.01 and P < 0.05, respectively) hemispheres. Nitration was significantly increased in both hemispheres versus the sham group and was normalized with epicatechin treatment. In conclusion, ischemia-reperfusion injury impairs

  1. Methyleugenol reduces cerebral ischemic injury by suppression of oxidative injury and inflammation.

    PubMed

    Choi, Yoo Keum; Cho, Geum-Sil; Hwang, Sunyoung; Kim, Byung Woo; Lim, Ji H; Lee, Jae-Chul; Kim, Hyoung Chun; Kim, Won-Ki; Kim, Yeong Sik

    2010-08-01

    The present study tested the cytoprotective effect of methyleugenol in an in vivo ischemia model (i.e. middle cerebral artery occlusion (MCAO) for 1.5 h and subsequent reperfusion for 24 h) and further investigated its mechanism of action in in vitro cerebral ischemic models. When applied shortly after reperfusion, methyleugenol largely reduced cerebral ischemic injury. Methyleugenol decreased the caspase-3 activation and death of cultured cerebral cortical neurons caused by oxygen-glucose deprivation (OGD) for 1 h and subsequent re-oxygenation for 24 h. Methyleugenol markedly reduced superoxide generation in the ischemic brain and decreased the intracellular oxidative stress caused by OGD/re-oxygenation. It was found that methyleugenol elevated the activities of superoxide dismutase and catalase. Further, methyleugenol inhibited the production of nitric oxide and decreased the protein expression of inducible nitric oxide synthase. Methyleugenol down-regulated the production of pro-inflammatory cytokines in the ischemic brain as well as in immunostimulated mixed glial cells. The results indicate that methyleugenol could be useful for the treatment of ischemia/inflammation-related diseases.

  2. A Late Case of Ischemic Cerebral Event after Resection of a Left Atrial Myxoma.

    PubMed

    Lafleur, Reginald; Watkowska, Justyna; Zhou, Guoping; Alcide, Phenix; Saint-Jacques, Henock

    2016-01-01

    Atrial myxoma is one of the most common primary cardiac tumors reported in the literature. In very rare instances, stroke has been the sequelae after a myxomatous tumor resection. We report this unique case of late ischemic cerebral event in a 46-year-old female some days after resection of a left atrial myxoma. PMID:27403129

  3. A Late Case of Ischemic Cerebral Event after Resection of a Left Atrial Myxoma

    PubMed Central

    Lafleur, Reginald; Watkowska, Justyna; Zhou, Guoping; Alcide, Phenix; Saint-Jacques, Henock

    2016-01-01

    Abstract Atrial myxoma is one of the most common primary cardiac tumors reported in the literature. In very rare instances, stroke has been the sequelae after a myxomatous tumor resection. We report this unique case of late ischemic cerebral event in a 46-year-old female some days after resection of a left atrial myxoma. PMID:27403129

  4. [Diagnosis and prognosis of cerebral ischemic disturbances course using a method of artificial neuronal networks].

    PubMed

    Ivanov, Iu S; Semin, G F

    2004-01-01

    Based on the data of examination of 224 patients with different stages of cerebral ischemic disturbances (CID) and 84 age-matched controls, an artificial neuronal network was constructed and tried in differential diagnosis of CID stages according to the data of transcranial ultrasonic dopplerography. Diagnostic efficacy of the network was 80% for sensitivity, 100% for specificity and 82.7% for reliability. A modeling of the influence of the main risk factors for cerebral ischemia and of the reserve state of cerebral hemodynamics for establishing the stage of CID was performed.

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

    PubMed Central

    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

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

    PubMed Central

    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.

  7. Electroacupuncture increased cerebral blood flow and reduced ischemic brain injury: dependence on stimulation intensity and frequency

    PubMed Central

    Zhou, Fei; Guo, Jingchun; Cheng, Jieshi; Wu, Gencheng

    2011-01-01

    Stroke causes ischemic brain injury and is a leading cause of neurological disability and death. There is, however, no promising therapy to protect the brain from ischemic stress to date. Here we show an exciting finding that optimal electroacupuncture (EA) effectively protects the brain from ischemic injury. The experiments were performed on rats subjected to middle cerebral artery occlusion (MCAO) with continuous monitoring of cerebral blood flow. EA was delivered to acupoints of “Shuigou” (Du 26) and “Baihui” (Du 20) with different intensities and frequencies to optimize the stimulation parameters. The results showed that 1) EA at 1.0–1.2 mA and 5–20 Hz remarkably reduced ischemic infarction, neurological deficit, and death rate; 2) the EA treatment increased the blood flow by >100%, which appeared immediately after the initiation of EA and disappeared after the cessation of EA; 3) the EA treatment promoted the recovery of the blood flow after MCAO; 4) “nonoptimal” parameters of EA (e.g., <0.6 mA or >40 Hz) could not improve the blood flow or reduce ischemic injury; and 5) the same EA treatment with optimal parameters could not increase the blood flow in naive brains. These novel observations suggest that appropriate EA treatment protects the brain from cerebral ischemia by increasing blood flow to the ischemic brain region via a rapid regulation. Our findings have far-reaching impacts on the prevention and treatment of ischemic encephalopathy, and the optimized EA parameters may potentially be a useful clue for the clinical application of EA. PMID:21836043

  8. Is vertebral artery hypoplasia a predisposing factor for posterior circulation cerebral ischemic events? A comprehensive review.

    PubMed

    Katsanos, Aristeidis H; Kosmidou, Maria; Kyritsis, Athanassios P; Giannopoulos, Sotirios

    2013-01-01

    Vertebral artery hypoplasia is not currently considered an independent risk factor for stroke. Emerging evidence suggest that vertebral artery hypoplasia may contribute to posterior circulation ischemic events, especially when other risk factors coexist. In the present literature review, we present published data to discuss the relationship between a hypoplastic vertebral artery and posterior circulation cerebral ischemia. Despite difficulties and controversies in the accurate definition and prevalence estimation of vertebral artery hypoplasia, ultrasound studies reveal that the reduced blood flow observed ipsilateral to the hypoplastic vertebral artery may result in local cerebral hypoperfusion and subsequent focal neurological symptomatology. That risk of cerebral ischemia is related to the severity of the hypoplasia, suggesting that the smaller of paired arteries are more vulnerable to occlusion. Existing cohort studies further support clinical observations that hypoplastic vertebral artery enhances synergistically the vascular risk for posterior circulation ischemic events and is closely associated with both atherosclerotic and prothrombotic processes.

  9. Frequency of Atrial Septal Aneurysms in Patients with Cerebral Ischemic Events

    NASA Technical Reports Server (NTRS)

    Agmon, Yoram; Khandheria, Bijoy K.; Meissner, Irene; Gentile, Federico; Whisnant, Jack P.; Sicks, JoRean D.; O'Fallon, W. Michael; Covalt, Jody L.; Wiebers, David O.; Seward, James B.

    1999-01-01

    Background-Atrial septal aneurysm (ASA) is a putative risk factor for cardioembolism. However, the frequency of ASA in the general population has not been adequately determined. Therefore, the frequency in patients with cerebral ischemic events, compared with the frequency in the general population, is poorly defined. We sought to determine the frequency of ASA in the general population and to compare the frequency of ASA in patients with cerebral ischemic events with the frequency in the general population. Methods and Results-The frequency of ASA in the population was determined in 363 subjects, a sample of the participants in the Stroke Prevention: Assessment of Risk in a Community study (control subjects), and was compared with the frequency in 355 age- and sex-matched patients undergoing transesophageal echocardiography in search of a cardiac source of embolism after a focal cerebral ischemic event. The proportion with ASA was 7.9% in patients versus 2.2% in control subjects (P=0.002; odds ratio of ASA, 3.65; 95% CI, 1.64 to 8.13, in patients versus control subjects). Patent foramen ovale (PFO) was detected with contrast injections in 56% of subjects with ASA. The presence of ASA predicted the presence of PFO (odds ratio of PFO, 4.57; 95% CI, 2.18 to 9.57, in subjects with versus those without ASA). In 86% of subjects with ASA and cerebral ischemia, transesophageal echocardiography did not detect an alternative source of cardioembolism other than an associated PFO. Conclusions-The prevalence of ASA based on this population-based study is 2.2%. The frequency of ASA is relatively higher in patients evaluated with transesophageal echocardiography after a cerebral ischemic event. ASA is frequently associated with PFO, suggesting paradoxical embolism as a mechanism of cardioembolism. In patients with cerebral ischemia and ASA, ASA (with or without PFO) commonly is the only potential cardioembolic source detected with transesophageal echocardiography.

  10. Effect of fasudil hydrochloride, a protein kinase inhibitor, on cerebral vasospasm and delayed cerebral ischemic symptoms after aneurysmal subarachnoid hemorrhage.

    PubMed

    Zhao, Jizong; Zhou, Dingbiao; Guo, Jing; Ren, Zyuan; Zhou, Liangfu; Wang, Shuo; Xu, Bainan; Wang, Renzhi

    2006-09-01

    The efficacy and safety of fasudil hydrochloride, a novel protein kinase inhibitor, were evaluated for the treatment of cerebral vasospasm and associated cerebral ischemic symptoms in patients with ruptured cerebral aneurysm. This randomized open trial with nimodipine as the control included 72 patients who underwent subarachnoid hemorrhage surgery for ruptured cerebral aneurysm of Hunt and Hess grades I to IV. For 14 days following surgery, patients were administered either 30 mg of fasudil hydrochloride by intravenous injection over a period of 30 minutes three times a day or 1 mg/hr of nimodipine by continuous intravenous infusion. Fasudil hydrochloride and nimodipine both showed inhibitory effects on cerebral vasospasm. The incidence of symptomatic vasospasm was five of 33 patients in the fasudil group and nine of 32 patients in the nimodipine group. Good recovery evaluated by the Glasgow Outcome Scale was achieved by 23 of 33 patients in the fasudil group and 19 of 34 patients in the nimodipine group. Both drugs significantly improved consciousness levels and neurological deficits such as aphasia. However, fasudil hydrochloride improved motor disturbance more than nimodipine. Adverse reactions occurred in 13 of 37 patients receiving fasudil hydrochloride and 15 of 35 patients receiving nimodipine. There were no serious adverse events in the fasudil group. The results of this clinical trial indicate that fasudil hydrochloride is a safe and efficient agent for suppressing cerebral vasospasm after subarachnoid hemorrhage surgery for ruptured cerebral aneurysm.

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

    NASA Astrophysics Data System (ADS)

    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.

  12. Epidemiology and risk factors of cerebral ischemia and ischemic heart diseases: similarities and differences.

    PubMed

    Soler, Ernest Palomeras; Ruiz, Virgina Casado

    2010-08-01

    Cerebral ischemia and ischemic heart diseases, common entities nowadays, are the main manifestation of circulatory diseases. Cardiovascular diseases, followed by stroke, represent the leading cause of mortality worldwide. Both entities share risk factors, pathophisiology and etiologic aspects by means of a main common mechanism, atherosclerosis. However, each entity has its own particularities. Ischemic stroke shows a variety of pathogenic mechanisms not present in ischemic heart disease. An ischemic stroke increases the risk of suffering a coronary heart disease, and viceversa. The aim of this chapter is to review data on epidemiology, pathophisiology and risk factors for both entities, considering the differences and similarities that could be found in between them. We discuss traditional risk factors, obtained from epidemiological data, and also some novel ones, such as hyperhomocisteinemia or sleep apnea. We separate risk factors, as clasically, in two groups: nonmodifiables, which includes age, sex, or ethnicity, and modifiables, including hypertension, dyslipidemia or diabetis, in order to discuss the role of each factor in both ischemic events, ischemic stroke and coronary heart disease.

  13. Epidemiology and Risk Factors of Cerebral Ischemia and Ischemic Heart Diseases: Similarities and Differences

    PubMed Central

    Soler, Ernest Palomeras; Ruiz, Virgina Casado

    2010-01-01

    Cerebral ischemia and ischemic heart diseases, common entities nowadays, are the main manifestation of circulatory diseases. Cardiovascular diseases, followed by stroke, represent the leading cause of mortality worldwide. Both entities share risk factors, pathophisiology and etiologic aspects by means of a main common mechanism, atherosclerosis. However, each entity has its own particularities. Ischemic stroke shows a variety of pathogenic mechanisms not present in ischemic heart disease. An ischemic stroke increases the risk of suffering a coronary heart disease, and viceversa. The aim of this chapter is to review data on epidemiology, pathophisiology and risk factors for both entities, considering the differences and similarities that could be found in between them. We discuss traditional risk factors, obtained from epidemiological data, and also some novel ones, such as hyperhomocisteinemia or sleep apnea. We separate risk factors, as clasically, in two groups: nonmodifiables, which includes age, sex, or ethnicity, and modifiables, including hypertension, dyslipidemia or diabetis, in order to discuss the role of each factor in both ischemic events, ischemic stroke and coronary heart disease. PMID:21804773

  14. Ultrasound accelerates healing of normal wounds but not of ischemic ones.

    PubMed

    Altomare, Mariane; Nascimento, Adriana P; Romana-Souza, Bruna; Amadeu, Thaís P; Monte-Alto-Costa, Andréa

    2009-01-01

    To examine the influence of therapeutic ultrasound (US) on repair of standard and ischemic cutaneous lesions, full-thickness excisional wounds were made in rats and treated with a US 3 MHz, 0.5 W/cm(2) pulsed duty cycle. We used five experimental groups: control (received US powered off on the day of surgery, and on the second and fourth day), control US (received US on the day of surgery, and on the second and fourth day), ischemic (received US powered off on the day of surgery, and on the second and fourth day), ischemic US 3X (received US on the day of surgery, and on the second and fourth day) and ischemic US 5X (received US in the day of surgery, first, second, third and fourth day). The control US group showed acceleration in wound contraction 7 days after wounding, an increase in collagen density, and only focal inflammatory areas. Neo-epidermis formation was more advanced in the control US group than in the control one. Wound contraction was delayed in the ischemic group when compared with the control group as well as the ischemic US 3X group, was but slightly accelerated in the ischemic US 5X group when compared with the ischemic group 7 days after wounding. Reepithelialization was delayed in both ischemic US groups when compared with the ischemic group. The number of inflammatory cells was higher in both US ischemic groups. We conclude that US therapy accelerates wound healing in normal wounds and delays wound healing in ischemic wounds.

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

    PubMed Central

    Wu, Zhou-Quan; Cui, Su-yang; Zhu, Liang

    2016-01-01

    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. PMID:27547233

  16. [Calcified cerebral embolism as a cause of ischemic stroke].

    PubMed

    Smeeing, Diederik P J; Kappelle, L J Jaap; Hendrikse, Jeroen

    2015-01-01

    A 60-year-old woman with a history of hypertension presented with acute onset of left-sided weakness and drowsiness. Non-contrast CT at baseline and follow-up showed a focal high density lesion in the right middle cerebral artery, consistent with a calcified embolus. CT angiography confirmed its location.

  17. Novel MRI approaches for assessing cerebral hemodynamics in ischemic cerebrovascular disease.

    PubMed

    Donahue, Manus J; Strother, Megan K; Hendrikse, Jeroen

    2012-03-01

    Changes in cerebral hemodynamics underlie a broad spectrum of ischemic cerebrovascular disorders. An ability to accurately and quantitatively measure hemodynamic (cerebral blood flow and cerebral blood volume) and related metabolic (cerebral metabolic rate of oxygen) parameters is important for understanding healthy brain function and comparative dysfunction in ischemia. Although positron emission tomography, single-photon emission tomography, and gadolinium-MRI approaches are common, more recently MRI approaches that do not require exogenous contrast have been introduced with variable sensitivity for hemodynamic parameters. The ability to obtain hemodynamic measurements with these new approaches is particularly appealing in clinical and research scenarios in which follow-up and longitudinal studies are necessary. The purpose of this review is to outline current state-of-the-art MRI methods for measuring cerebral blood flow, cerebral blood volume, and cerebral metabolic rate of oxygen and provide practical tips to avoid imaging pitfalls. MRI studies of cerebrovascular disease performed without exogenous contrast are synopsized in the context of clinical relevance and methodological strengths and limitations.

  18. Acetylbritannilactone Modulates MicroRNA-155-Mediated Inflammatory Response in Ischemic Cerebral Tissues

    PubMed Central

    Wen, Ya; Zhang, Xiangjian; Dong, Lipeng; Zhao, Jingru; Zhang, Cong; Zhu, Chunhua

    2015-01-01

    Inflammatory responses play a critical role in ischemic brain injury. MicroRNA-155 (miR-155) induces the expression of inflammatory cytokines, and acetylbritannilactone (ABL) exerts potent antiinflammatory actions by inhibiting expression of inflammation-related genes. However, the functions of miR-155 and the actual relationship between ABL and miR-155 in ischemia-induced cerebral inflammation remain unclear. In this study, cerebral ischemia of wild-type (WT) and miR-155−/− mice was induced by permanent middle cerebral artery occlusion (MCAO). pAd-miR-155 was injected into the lateral cerebral ventricle 24 h before MCAO to induce miR-155 overexpression. MCAO mice and oxygen-glucose deprivation (OGD)-treated BV2 cells were used to examine the effects of ABL and miR-155 overexpression or deletion on the expression of proinflammatory cytokines. We demonstrated that ABL treatment significantly reduced neurological deficits and cerebral infarct volume by inhibiting tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) expression in ischemic cerebral tissue and OGD-treated BV2 cells. Mechanistic studies suggested that the observed decrease in TNF-α and IL-1β expression was attributable to the ABL-induced suppression of the expression of nuclear factor-kappa B (NF-κB) and Toll-like receptor 4 (TLR4). We further found that miR-155 promoted TNF-α and IL-1β expression by upregulating TLR4 and downregulating the expression of suppressor of cytokine signaling 1 (SOCS1) and myeloid differentiation primary response gene 88 (MyD88), while ABL exerted an inhibitory effect on miR-155-mediated gene expression. In conclusion, miR-155 mediates inflammatory responses in ischemic cerebral tissue by modulating TLR4/MyD88 and SOCS1 expression, and ABL exerts its antiinflammatory action by suppressing miR-155 expression, suggesting a novel miR-155-based therapy for ischemic stroke. PMID:25811992

  19. A Combination of Remote Ischemic Perconditioning and Cerebral Ischemic Postconditioning Inhibits Autophagy to Attenuate Plasma HMGB1 and Induce Neuroprotection Against Stroke in Rat.

    PubMed

    Wang, Jue; Han, Dong; Sun, Miao; Feng, Juan

    2016-04-01

    Remote ischemic perconditioning (RIPerC) and ischemic postconditioning (IPOC) are well-acknowledged neuroprotective procedures during ischemic injury. The present study established a combined RIPerC and IPOC (RIPerC + IPOC) model in rats and studied how it would regulate the autophagy process and affect HMGB1 levels in a rat model of middle cerebral artery occlusion (MCAO). Rats with MCAO were treated with RIPerC by fastening and release of the left hind limb to achieve 4 cycles of 5 min remote ischemia reperfusion, 40 min prior to cerebral reperfusion, and then treated with IPOC by exposing the cerebral middle artery to 3 cycles of 30 s reperfusion/30 s occlusion at the onset of cerebral reperfusion. Infarction volumes, neurological deficits, and pathological changes were assessed 24 h after ischemia. The autophagy activator rapamycin (RAP) and the autophagy inhibitor 3-methyladenine (3-MA) were administrated for further mechanism. The expression and location of HMGB1 and the autophagy-related proteins like LC3, Beclin1, and P62 as well as plasma HMGB1 levels were measured. Our results suggested that RIPerC + IPOC attenuated plasma HMGB1 levels to intensify its neuroprotective effect against cerebral ischemic reperfusion injury via inhibiting the autophagy process. PMID:26852332

  20. Post-ischemic salubrinal treatment results in a neuroprotective role in global cerebral ischemia.

    PubMed

    Anuncibay-Soto, Berta; Pérez-Rodríguez, Diego; Santos-Galdiano, María; Font, Enrique; Regueiro-Purriños, Marta; Fernández-López, Arsenio

    2016-07-01

    This study describes the neuroprotective effect of treatment with salubrinal 1 and 24 h following 15 min of ischemia in a two-vessel occlusion model of global cerebral ischemia. The purpose of this study was to determine if salubrinal, an enhancer of the unfolded protein response, reduces the neural damage modulating the inflammatory response. The study was performed in CA1 and CA3 hippocampal areas as well as in the cerebral cortex whose different vulnerability to ischemic damage is widely described. Characterization of proteins was made by western blot, immunofluorescence, and ELISA, whereas mRNA levels were measured by Quantitative PCR. The salubrinal treatment decreased the cell demise in CA1 at 7 days as well as the levels of matrix metalloprotease 9 (MMP-9) in CA1 and cerebral cortex at 48 h and ICAM-1 and VCAM-1 cell adhesion molecules. However, increases in tumor necrosis factor α and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) inflammatory markers were observed at 24 h. Glial fibrillary acidic protein levels were not modified by salubrinal treatment in CA1 and cerebral cortex. We describe a neuroprotective effect of the post-ischemic treatment with salubrinal, measured as a decrease both in CA1 cell demise and in the blood-brain barrier impairment. We hypothesize that the ability of salubrinal to counteract the CA1 cell demise is because of a reduced ability of this structure to elicit unfolded protein response which would account for its greater ischemic vulnerability. Data of both treated and non-treated animals suggest that the neurovascular unit present a structure-dependent response to ischemia and a different course time for CA1/cerebral cortex compared with CA3. Finally, our study reveals a high responsiveness of endothelial cells to salubrinal in contrast to the limited responsiveness of astrocytes. The alleviation of ER stress by enhancing UPR with salubrinal treatment reduces the ischemic damage. This effect

  1. Post-ischemic salubrinal treatment results in a neuroprotective role in global cerebral ischemia.

    PubMed

    Anuncibay-Soto, Berta; Pérez-Rodríguez, Diego; Santos-Galdiano, María; Font, Enrique; Regueiro-Purriños, Marta; Fernández-López, Arsenio

    2016-07-01

    This study describes the neuroprotective effect of treatment with salubrinal 1 and 24 h following 15 min of ischemia in a two-vessel occlusion model of global cerebral ischemia. The purpose of this study was to determine if salubrinal, an enhancer of the unfolded protein response, reduces the neural damage modulating the inflammatory response. The study was performed in CA1 and CA3 hippocampal areas as well as in the cerebral cortex whose different vulnerability to ischemic damage is widely described. Characterization of proteins was made by western blot, immunofluorescence, and ELISA, whereas mRNA levels were measured by Quantitative PCR. The salubrinal treatment decreased the cell demise in CA1 at 7 days as well as the levels of matrix metalloprotease 9 (MMP-9) in CA1 and cerebral cortex at 48 h and ICAM-1 and VCAM-1 cell adhesion molecules. However, increases in tumor necrosis factor α and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) inflammatory markers were observed at 24 h. Glial fibrillary acidic protein levels were not modified by salubrinal treatment in CA1 and cerebral cortex. We describe a neuroprotective effect of the post-ischemic treatment with salubrinal, measured as a decrease both in CA1 cell demise and in the blood-brain barrier impairment. We hypothesize that the ability of salubrinal to counteract the CA1 cell demise is because of a reduced ability of this structure to elicit unfolded protein response which would account for its greater ischemic vulnerability. Data of both treated and non-treated animals suggest that the neurovascular unit present a structure-dependent response to ischemia and a different course time for CA1/cerebral cortex compared with CA3. Finally, our study reveals a high responsiveness of endothelial cells to salubrinal in contrast to the limited responsiveness of astrocytes. The alleviation of ER stress by enhancing UPR with salubrinal treatment reduces the ischemic damage. This effect

  2. Wavelet coherence analysis of dynamic cerebral autoregulation in neonatal hypoxic-ischemic encephalopathy.

    PubMed

    Tian, Fenghua; Tarumi, Takashi; Liu, Hanli; Zhang, Rong; Chalak, Lina

    2016-01-01

    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. PMID:26937380

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

    PubMed Central

    Tian, Fenghua; Tarumi, Takashi; Liu, Hanli; Zhang, Rong; Chalak, Lina

    2016-01-01

    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. PMID:26937380

  4. Association between Aortic Atheroma and Cerebral Small Vessel Disease in Patients with Ischemic Stroke

    PubMed Central

    Song, Tae-Jin; Kim, Young Dae; Yoo, Joonsang; Kim, Jinkwon; Chang, Hyuk-Jae; Hong, Geu Ru; Shim, Chi Young; Song, Dongbeom; Heo, Ji Hoe; Nam, Hyo Suk

    2016-01-01

    Background and Purpose Cerebral small vessel disease (SVDs) are related with large artery atherosclerosis. However, the association between aortic atheroma (AA) and cerebral small vessel disease has rarely been reported. This study evaluated the relationship between presence and burden of AAs and those of SVDs in patients with acute ischemic stroke. Methods We included 737 consecutive patients who underwent transesophageal echocardiography (TEE) and brain magnetic resonance imaging (MRI) for evaluation of acute stroke. AA subtypes were classified as complex aortic plaque (CAP) and simple aortic plaque (SAP). Presence and burden of SVDs including cerebral microbleeds (CMBs), white matter hyperintensities (WMHs), perivascular spaces (PVSs), asymptomatic lacunar infarctions (ALIs), and total SVD score, were investigated. Results AA was found by TEE in 360 (48.8%) patients including 11.6% with CAP and 37.2% with SAP. One or more types of SVDs was found in 269 (36.4%) patients. In multivariable analysis, presence of CMBs (odds ratio [OR] 4.68), high-grade WMHs (OR 3.13), high-grade PVSs (OR 3.35), and ALIs (OR 4.24) were frequent in patients with AA than those without AA. Each 1-point increase in total SVD score increased the odds of presence of CAP (OR 1.94, 95% confidence interval (CI) 1.44-1.85) and SAP (OR 1.54, 95% CI 1.35-1.75). Conclusions In this study, patients with AA frequently had cerebral SVDs. Larger burden of AA was associated with advanced cerebral SVDs. Our findings give an additional information for positive relationship with systemic atherosclerosis and coexisting cerebral SVDs in acute ischemic stroke patients. PMID:27488980

  5. Cerebral Hyperperfusion after Revascularization Inhibits Development of Cerebral Ischemic Lesions Due to Artery-to-Artery Emboli during Carotid Exposure in Endarterectomy for Patients with Preoperative Cerebral Hemodynamic Insufficiency: Revisiting the “Impaired Clearance of Emboli” Concept

    PubMed Central

    Fujimoto, Kentaro; Matsumoto, Yoshiyasu; Oikawa, Kohki; Nomura, Jun-ichi; Shimada, Yasuyoshi; Fujiwara, Shunrou; Terasaki, Kazunori; Kobayashi, Masakazu; Yoshida, Kenji; Ogasawara, Kuniaki

    2016-01-01

    The purpose of the present study was to determine whether cerebral hyperperfusion after revascularization inhibits development of cerebral ischemic lesions due to artery-to-artery emboli during exposure of the carotid arteries in carotid endarterectomy (CEA). In patients undergoing CEA for internal carotid artery stenosis (≥70%), cerebral blood flow (CBF) was measured using single-photon emission computed tomography (SPECT) before and immediately after CEA. Microembolic signals (MES) were identified using transcranial Doppler during carotid exposure. Diffusion-weighted magnetic resonance imaging (DWI) was performed within 24 h after surgery. Of 32 patients with a combination of reduced cerebrovascular reactivity to acetazolamide on preoperative brain perfusion SPECT and MES during carotid exposure, 14 (44%) showed cerebral hyperperfusion (defined as postoperative CBF increase ≥100% compared with preoperative values), and 16 (50%) developed DWI-characterized postoperative cerebral ischemic lesions. Postoperative cerebral hyperperfusion was significantly associated with the absence of DWI-characterized postoperative cerebral ischemic lesions (95% confidence interval, 0.001–0.179; p = 0.0009). These data suggest that cerebral hyperperfusion after revascularization inhibits development of cerebral ischemic lesions due to artery-to-artery emboli during carotid exposure in CEA, supporting the “impaired clearance of emboli” concept. Blood pressure elevation following carotid declamping would be effective when embolism not accompanied by cerebral hyperperfusion occurs during CEA. PMID:27527146

  6. Remote Ischemic Preconditioning Reduces Cerebral Oxidative Stress Following Hypothermic Circulatory Arrest in a Porcine Model.

    PubMed

    Arvola, Oiva; Haapanen, Henri; Herajärvi, Johanna; Anttila, Tuomas; Puistola, Ulla; Karihtala, Peeter; Tuominen, Hannu; Anttila, Vesa; Juvonen, Tatu

    2016-01-01

    Remote ischemic precondition has become prominent as one of the most promising methods to mitigate neurological damage following ischemic insult. The purpose of this study was to investigate whether the effects of remote ischemic preconditioning can be seen in the markers of oxidative stress or in redox-regulating enzymes in a porcine model. A total of 12 female piglets were randomly assigned to 2 groups. The study group underwent an intervention of 4 cycles of 5-minute ischemic preconditioning on the right hind leg. All piglets underwent 60-minute hypothermic circulatory arrest. Oxidative stress marker 8-hydroxydeoxyguanosine (8-OHdG) was measured from blood samples with enzyme-linked immunosorbent assay. After 7 days of follow-up, samples from the brain, heart, kidney, and ovary were harvested for histopathologic examination. The immunohistochemical stainings of hypoxia marker hypoxia-inducible factor-1-α, oxidative stress marker 8-OHdG, DNA repair enzyme 8-oxoguanine glycosylase, and antioxidant response regulators nuclear factor erythroid 2-related factor 2 and protein deglycase were analyzed. The level of 8-OHdG referred to baseline was decreased in the sagittal sinus׳ blood samples in the study group after a prolonged deep hypothermic circulatory arrest at 360 minutes after reperfusion. Total histopathologic score was 3.8 (1.8-6.0) in the study group and was 4.4 (2.5-6.5) in the control group (P = 0.72), demonstrating no statistically significant difference in cerebral injury. Our findings demonstrate that the positive effects of remote ischemic preconditioning can be seen in cellular oxidative balance regulators in an animal model after 7 days of preconditioned ischemic insult. PMID:27568144

  7. Cerebrolysin effects on neurological outcomes and cerebral blood flow in acute ischemic stroke

    PubMed Central

    Amiri-Nikpour, Mohammad Reza; Nazarbaghi, Surena; Ahmadi-Salmasi, Babak; Mokari, Tayebeh; Tahamtan, Urya; Rezaei, Yousef

    2014-01-01

    Background Cerebrolysin, a brain-derived neuropeptide, has been shown to improve the neurological outcomes of stroke, but no study has demonstrated its effect on cerebral blood flow. This study aimed to determine the cerebrolysin impact on the neurological outcomes and cerebral blood flow. Methods In a randomized, double-blinded, placebo-controlled trial, 46 patients who had acute focal ischemic stroke were randomly assigned into two groups to receive intravenously either 30 mL of cerebrolysin diluted in normal saline daily for 10 days (n=23) or normal saline alone (n=23) adjunct to 100 mg of aspirin daily. All patients were examined using the National Institutes of Health Stroke Scale and transcranial Doppler to measure the mean flow velocity and pulsatility index (PI) of their cerebral arteries at baseline as well as on days 30, 60, and 90. Results The patients’ mean age was 60±9.7 years, and 51.2% of patients were male. The National Institutes of Health Stroke Scale was significantly lower in the cerebrolysin group compared with the placebo group on day 60 (median 10, interquartile range 9–11, P=0.008) and day 90 (median 11, interquartile range 10–13.5, P=0.001). The median of PI in the right middle cerebral artery was significantly lower in the cerebrolysin group compared with the placebo group on days 30, 60, and 90 (P<0.05). One patient in the cerebrolysin group and two patients in the placebo group died before day 30 (4.3% versus 8.7%). Conclusion Cerebrolysin can be useful to improve the neurological outcomes and the PI of middle cerebral artery in patients with acute focal ischemic stroke. PMID:25516711

  8. Changes in Cerebral Oxidative Metabolism during Neonatal Seizures Following Hypoxic-Ischemic Brain Injury.

    PubMed

    Mitra, Subhabrata; Bale, Gemma; Mathieson, Sean; Uria-Avellanal, Cristina; Meek, Judith; Tachtsidis, Ilias; Robertson, Nicola J

    2016-01-01

    Seizures are common following hypoxic-ischemic brain injury in newborn infants. Prolonged or recurrent seizures have been shown to exacerbate neuronal damage in the developing brain; however, the precise mechanism is not fully understood. Cytochrome-c-oxidase is responsible for more than 90% of ATP production inside mitochondria. Using a novel broadband near-infrared spectroscopy system, we measured the concentration changes in the oxidation state of cerebral cytochrome-c-oxidase (Δ[oxCCO]) and hemodynamics during recurrent neonatal seizures following hypoxic-ischemic encephalopathy in a newborn infant. A rapid increase in Δ[oxCCO] was noted at the onset of seizures along with a rise in the baseline of amplitude-integrated electroencephalogram. Cerebral oxygenation and cerebral blood volume fell just prior to the seizure onset but recovered rapidly during seizures. Δ[oxCCO] during seizures correlated with changes in mean electroencephalogram voltage indicating an increase in neuronal activation and energy demand. The progressive decline in the Δ[oxCCO] baseline during seizures suggests a progressive decrease of mitochondrial oxidative metabolism. PMID:27559538

  9. Changes in Cerebral Oxidative Metabolism during Neonatal Seizures Following Hypoxic–Ischemic Brain Injury

    PubMed Central

    Mitra, Subhabrata; Bale, Gemma; Mathieson, Sean; Uria-Avellanal, Cristina; Meek, Judith; Tachtsidis, Ilias; Robertson, Nicola J.

    2016-01-01

    Seizures are common following hypoxic–ischemic brain injury in newborn infants. Prolonged or recurrent seizures have been shown to exacerbate neuronal damage in the developing brain; however, the precise mechanism is not fully understood. Cytochrome-c-oxidase is responsible for more than 90% of ATP production inside mitochondria. Using a novel broadband near-infrared spectroscopy system, we measured the concentration changes in the oxidation state of cerebral cytochrome-c-oxidase (Δ[oxCCO]) and hemodynamics during recurrent neonatal seizures following hypoxic–ischemic encephalopathy in a newborn infant. A rapid increase in Δ[oxCCO] was noted at the onset of seizures along with a rise in the baseline of amplitude-integrated electroencephalogram. Cerebral oxygenation and cerebral blood volume fell just prior to the seizure onset but recovered rapidly during seizures. Δ[oxCCO] during seizures correlated with changes in mean electroencephalogram voltage indicating an increase in neuronal activation and energy demand. The progressive decline in the Δ[oxCCO] baseline during seizures suggests a progressive decrease of mitochondrial oxidative metabolism. PMID:27559538

  10. Effect of glycerol on ischemic cerebral edema assessed by magnetic resonance imaging.

    PubMed

    Sakamaki, Masanori; Igarashi, Hironaka; Nishiyama, Yutaka; Hagiwara, Hiroshi; Ando, Jun; Chishiki, Tetsurou; Curran, Brian C; Katayama, Yasuo

    2003-05-15

    The aim of this study is to assess the anticerebral edema effect of glycerol on a large cerebral infarction with magnetic resonance imaging (MRI). Glycerol, which is widely used as an osmotic agent against cerebral edema, could exacerbate brain tissue shift, since it has been suggested that glycerol might shrink a noninfarcted hemisphere and worsen the mass effect after a large hemispheric cerebral infarction. To investigate these issues, changes in a large hemispheric infarction with cerebral edema were studied using MRI before and after glycerol administration. Infarct volumes, normal brain tissue volumes and lateral ventricle volumes, in addition to signal intensities of T(2)-weighted images, were measured in six patients before and after administration of 300 ml of glycerol. Ventricle volumes were significantly increased (p=0.0015) and the T(2) signal intensity of the post-treatment ischemic region decreased after glycerol administration. In contrast, no significant differences in either cerebral volume or T(2) signal intensity were seen in the noninfarcted hemisphere before and after administration. Our data suggest that glycerol does not exacerbate the mass effect on a large hemispheric infarction. PMID:12686405

  11. Cerebral oxygen metabolism in neonatal hypoxic ischemic encephalopathy during and after therapeutic hypothermia.

    PubMed

    Dehaes, Mathieu; Aggarwal, Alpna; Lin, Pei-Yi; Rosa Fortuno, C; Fenoglio, Angela; Roche-Labarbe, Nadège; Soul, Janet S; Franceschini, Maria Angela; Grant, P Ellen

    2014-01-01

    Pathophysiologic mechanisms involved in neonatal hypoxic ischemic encephalopathy (HIE) are associated with complex changes of blood flow and metabolism. Therapeutic hypothermia (TH) is effective in reducing the extent of brain injury, but it remains uncertain how TH affects cerebral blood flow (CBF) and metabolism. Ten neonates undergoing TH for HIE and seventeen healthy controls were recruited from the NICU and the well baby nursery, respectively. A combination of frequency domain near infrared spectroscopy (FDNIRS) and diffuse correlation spectroscopy (DCS) systems was used to non-invasively measure cerebral hemodynamic and metabolic variables at the bedside. Results showed that cerebral oxygen metabolism (CMRO2i) and CBF indices (CBFi) in neonates with HIE during TH were significantly lower than post-TH and age-matched control values. Also, cerebral blood volume (CBV) and hemoglobin oxygen saturation (SO2) were significantly higher in neonates with HIE during TH compared with age-matched control neonates. Post-TH CBV was significantly decreased compared with values during TH whereas SO2 remained unchanged after the therapy. Thus, FDNIRS-DCS can provide information complimentary to SO2 and can assess individual cerebral metabolic responses to TH. Combined FDNIRS-DCS parameters improve the understanding of the underlying physiology and have the potential to serve as bedside biomarkers of treatment response and optimization.

  12. Pertussis toxin reduces calcium influx to protect ischemic stroke in a middle cerebral artery occlusion model.

    PubMed

    Tang, Zhiwei; Li, Shiping; Han, Pengcheng; Yin, Junxiang; Gan, Yan; Liu, Qingwei; Wang, Jinkun; Wang, Chongqian; Li, Yu; Shi, Jiong

    2015-12-01

    Increased calcium influx secondary to glutamate induced excitotoxicity initiates and potentiates devastating pathological changes following ischemic stroke. Pertussis toxin (PTx), a G-protein blocker, is known to suppress intracellular calcium accumulation. We hypothesize that PTx can protect against stroke by blocking calcium influx. In a permanent middle cerebral artery occlusion model, PTx (1000 ng) was given intraperitoneally 30 min after inducing stroke. Magnetic Resonance Imaging of perfusion and T2-weighted brain scans were obtained to evaluate cerebral blood flow (CBF) and infarct volume. Primary neuronal culture was used to test glutamate induced excitotoxicity and calcium influx. We established a non-linear exponential curve model to minimize variations in animal cerebrovasculature. A reduction of 40-60% in relative CBF was a critical window where infarct volume started to increase as rCBF reduced. PTx showed maximal effects in reducing infarct volume at this window. In vitro studies further demonstrated PTx increased neuronal cell survival by decreasing glutamate-induced calcium influx into neurons and preventing neurons from apoptosis. PTx salvages the ischemic penumbra by blocking calcium influx. This provides us a new mechanism upon which experimental therapies can be explored to treat ischemic stroke. In ischemic stroke, excessive glutamate binds to AMPA receptor that depolarizes calcium channel and/ or NMDA receptor. Both of them allow calcium to enter the cell. The overload of calcium triggers cellular cascade that includes Caspase activation and release, leading to pre-mature cell death. We have demonstrated that PTx, a G-protein inhibitor, blocks calcium entry which in turn prevents further cellular damage.

  13. Dichotomous effects of chronic intermittent hypoxia on focal cerebral ischemic injury

    PubMed Central

    Jackman, Katherine A.; Zhou, Ping; Faraco, Giuseppe; Peixoto, Pablo M.; Coleman, Christal; Voss, Henning U.; Pickel, Virginia; Manfredi, Giovanni; Iadecola, Costantino

    2014-01-01

    Background and purpose Obstructive sleep apnea (OSA), a condition associated with chronic intermittent hypoxia (CIH), carries an increased risk of stroke. However, CIH has been reported to either increase or decrease brain injury in models of focal cerebral ischemia. The factors determining the differential effects of CIH on ischemic injury and their mechanisms remain unclear. Here, we tested the hypothesis that the intensity of the hypoxic challenge determines the protective or destructive nature of CIH by modulating mitochondrial resistance to injury. Methods Male C57Bl/6J mice were exposed to CIH with 10% or 6% O2 for up to 35 days and subjected to transient middle cerebral artery occlusion (MCAO). Motor deficits and infarct volume were assessed 3 days later. Intra-ischemic CBF was measured by laser-Doppler flowmetry and resting CBF by arterial spin labeling MRI. Ca2+-induced mitochondrial depolarization and reactive oxygen species (ROS) production were evaluated in isolated brain mitochondria. Results We found that 10% CIH is neuroprotective, while 6% CIH exacerbates tissue damage. No differences in resting or intra-ischemic CBF were observed between 6% and 10% CIH. However, 10% CIH reduced, while 6% CIH increases mitochondrial ROS production and susceptibility to Ca2+-induced depolarizations. Conclusions The influence of CIH on the ischemic brain is dichotomous and can be attributed in part to changes in the mitochondrial susceptibility to injury. The findings highlight a previously unappreciated complexity in the effect of CIH on the brain, which needs to be considered in evaluating the neurological impact of conditions associated with cyclic hypoxia. PMID:24713530

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

    SciTech Connect

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

    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.

  15. MicroRNA-378 Alleviates Cerebral Ischemic Injury by Negatively Regulating Apoptosis Executioner Caspase-3

    PubMed Central

    Zhang, Nan; Zhong, Jie; Han, Song; Li, Yun; Yin, Yanling; Li, Junfa

    2016-01-01

    miRNAs have been linked to many human diseases, including ischemic stroke, and are being pursued as clinical diagnostics and therapeutic targets. Among the aberrantly expressed miRNAs in our previous report using large-scale microarray screening, the downregulation of miR-378 in the peri-infarct region of middle cerebral artery occluded (MCAO) mice can be reversed by hypoxic preconditioning (HPC). In this study, the role of miR-378 in the ischemic injury was further explored. We found that miR-378 levels significantly decreased in N2A cells following oxygen-glucose deprivation (OGD) treatment. Overexpression of miR-378 significantly enhanced cell viability, decreased TUNEL-positive cells and the immunoreactivity of cleaved-caspase-3. Conversely, downregulation of miR-378 aggravated OGD-induced apoptosis and ischemic injury. By using bioinformatic algorithms, we discovered that miR-378 may directly bind to the predicted 3′-untranslated region (UTR) of Caspase-3 gene. The protein level of caspase-3 increased significantly upon OGD treatment, and can be downregulated by pri-miR-378 transfection. The luciferase reporter assay confirmed the binding of miR-378 to the 3′-UTR of Caspase-3 mRNA and repressed its translation. In addition, miR-378 agomir decreased cleaved-caspase-3 ratio, reduced infarct volume and neural cell death induced by MCAO. Furthermore, caspase-3 knockdown could reverse anti-miR-378 mediated neuronal injury. Taken together, our data demonstrated that miR-378 attenuated ischemic injury by negatively regulating the apoptosis executioner, caspase-3, providing a potential therapeutic target for ischemic stroke. PMID:27598143

  16. Difference in the Location and Risk Factors of Cerebral Microbleeds According to Ischemic Stroke Subtypes

    PubMed Central

    Kim, Bum Joon; Yoon, Youngshin; Sohn, Hoyon; Kang, Dong-Wha; Kim, Jong S.; Kwon, Sun U.

    2016-01-01

    Background and Purpose The location of cerebral microbleeds (CMBs) may differ according to ischemic stroke subtype, and the underlying pathomechanism may differ by their location. Here, we investigated the characteristics of CMBs according to various ischemic stroke subtypes to verify this issue. Methods Patients with acute ischemic stroke were consecutively included. The presence of CMBs was determined by gradient echo image sequence. The distribution of CMBs was classified as deep, lobar, or diffuse (both deep and lobar). The prevalence, risk factors, and distribution of CMBs were compared among patients with different stroke subtypes. Factors associated with the distribution of CMBs were investigated. Results Among the 1033 patients included in this study, ischemic stroke subtypes were classified as large artery atherosclerosis (LAA; n=432), small vessel occlusion (SVO; n=304), and cardioembolism (CE; n=297). The prevalence of CMBs was highest in patients with SVO (40.5%), followed by CE (33.0%) and LAA (24.8%; P<0.001). The locations of CMBs was different according to subtype (P=0.004). CE [odds ratio (OR)=1.85 (1.02-3.34); P=0.042] and the use of antithrombotics [OR=1.80 (1.10-2.94); P=0.019] were associated with lobar CMBs, and old age [OR=1.02 (1.00-1.04); P=0.015] and hypertension [OR=1.61 (1.08-2.40); P=0.020] were associated with deep CMBs. Conclusions CMBs were frequently located in the lobar area in patients with CE. Previous use of antithrombotic agents is associated with lobar CMBs. The pathogenic mechanism of CMB may differ according to ischemic stroke subtype and location. PMID:27733027

  17. MicroRNA-378 Alleviates Cerebral Ischemic Injury by Negatively Regulating Apoptosis Executioner Caspase-3.

    PubMed

    Zhang, Nan; Zhong, Jie; Han, Song; Li, Yun; Yin, Yanling; Li, Junfa

    2016-01-01

    miRNAs have been linked to many human diseases, including ischemic stroke, and are being pursued as clinical diagnostics and therapeutic targets. Among the aberrantly expressed miRNAs in our previous report using large-scale microarray screening, the downregulation of miR-378 in the peri-infarct region of middle cerebral artery occluded (MCAO) mice can be reversed by hypoxic preconditioning (HPC). In this study, the role of miR-378 in the ischemic injury was further explored. We found that miR-378 levels significantly decreased in N2A cells following oxygen-glucose deprivation (OGD) treatment. Overexpression of miR-378 significantly enhanced cell viability, decreased TUNEL-positive cells and the immunoreactivity of cleaved-caspase-3. Conversely, downregulation of miR-378 aggravated OGD-induced apoptosis and ischemic injury. By using bioinformatic algorithms, we discovered that miR-378 may directly bind to the predicted 3'-untranslated region (UTR) of Caspase-3 gene. The protein level of caspase-3 increased significantly upon OGD treatment, and can be downregulated by pri-miR-378 transfection. The luciferase reporter assay confirmed the binding of miR-378 to the 3'-UTR of Caspase-3 mRNA and repressed its translation. In addition, miR-378 agomir decreased cleaved-caspase-3 ratio, reduced infarct volume and neural cell death induced by MCAO. Furthermore, caspase-3 knockdown could reverse anti-miR-378 mediated neuronal injury. Taken together, our data demonstrated that miR-378 attenuated ischemic injury by negatively regulating the apoptosis executioner, caspase-3, providing a potential therapeutic target for ischemic stroke. PMID:27598143

  18. The Transcription Factor Interferon Regulatory Factor 1 Is Expressed after Cerebral Ischemia and Contributes to Ischemic Brain Injury

    PubMed Central

    Iadecola, Costantino; Salkowski, Cindy A.; Zhang, Fangyi; Aber, Tracy; Nagayama, Masao; Vogel, Stefanie N.; Elizabeth Ross, M.

    1999-01-01

    The transcription factor interferon regulatory factor 1 (IRF-1) is involved in the molecular mechanisms of inflammation and apoptosis, processes that contribute to ischemic brain injury. In this study, the induction of IRF-1 in response to cerebral ischemia and its role in ischemic brain injury were investigated. IRF-1 gene expression was markedly upregulated within 12 h of occlusion of the middle cerebral artery in C57BL/6 mice. The expression reached a peak 4 d after ischemia (6.0 ± 1.8-fold; P < 0.001) and was restricted to the ischemic regions of the brain. The volume of ischemic injury was reduced by 23 ± 3% in IRF-1+/− and by 46 ± 9% in IRF-1−/− mice (P < 0.05). The reduction in infarct volume was paralleled by a substantial attenuation in neurological deficits. Thus, IRF-1 is the first nuclear transacting factor demonstrated to contribute directly to cerebral ischemic damage and may be a novel therapeutic target in ischemic stroke. PMID:9989987

  19. Cerebral oxygen metabolism and blood flow in human cerebral ischemic infarction

    SciTech Connect

    Lenzi, G.L.; Frackowiak, R.S.; Jones, T.

    1982-09-01

    Fifteen patients with acute cerebral hemispheric infarcts have been studied with positron emission tomography and the /sup 15/O steady-state inhalation technique. Thirteen follow-up studies were also performed. The values of cerebral oxygen metabolism (CMRO/sub 2/), cerebral blood flow (CBF), and oxygen extraction ration (OER) have been calculated for the infarcted regions, their borders, the symmetrical regions in contralateral cerebral hemispheres, and the cerebellar hemispheres. This study demonstrates that in the completed stroke there are thresholds for regional CMRO/sub 2/ and regional CBF below which the general clinical outcome of the patients is usually poor. The ischaemic lesions invariably produce an uncoupling between the greatly decreased metabolic demand and the less affected blood supply, with very frequent instances of relative hyperperfusion. Remote effects of the hemispheric infarcts have been demonstrated, such as crossed cerebellar diaschisis and contralateral transhemispheric depression. The level of consciousness correlates with oxygen uptake and blood flow both in the posterior fossa and in the contralateral cerebral hemispheres. The follow-up studies of individual patients underline the high variability of metabolism-to-flow balance during the acute phase of the illness, and stress the need for more studies focused on repeated assessments of homogeneous patient populations.

  20. Arterial Spin Labeling Measurements of Cerebral Perfusion Territories in Experimental Ischemic Stroke

    PubMed Central

    Leoni, Renata F.; Paiva, Fernando F.; Kang, Byeong-Teck; Henning, Erica C.; Nascimento, George C.; Tannús, Alberto; De Araújo, Dráulio B.; Silva, Afonso C.

    2016-01-01

    Collateral circulation, defined as the supplementary vascular network that maintains cerebral blood flow (CBF) when the main vessels fail, constitutes one important defense mechanism of the brain against ischemic stroke. In the present study, continuous arterial spin labeling (CASL) was used to quantify CBF and obtain perfusion territory maps of the major cerebral arteries in spontaneously hypertensive rats (SHR) and their normotensive Wistar-Kyoto (WKY) controls. Results show that both WKY and SHR have complementary, yet significantly asymmetric perfusion territories. Right or left dominances were observed in territories of the anterior (ACA), middle and posterior cerebral arteries, and the thalamic artery. Magnetic resonance angiography showed that some of the asymmetries were correlated with variations of the ACA. The leptomeningeal circulation perfusing the outer layers of the cortex was observed as well. Significant and permanent changes in perfusion territories were obtained after temporary occlusion of the right middle cerebral artery in both SHR and WKY, regardless of their particular dominance. However, animals with right dominance presented a larger volume change of the left perfusion territory (23 ± 9%) than animals with left dominance (7 ± 5%, P < 0.002). The data suggest that animals with contralesional dominance primarily safeguard local CBF values with small changes in contralesional perfusion territory, while animals with ipsilesional dominance show a reversal of dominance and a substantial increase in contralesional perfusion territory. These findings show the usefulness of CASL to probe the collateral circulation. PMID:24323754

  1. Glutathione Suppresses Cerebral Infarct Volume and Cell Death after Ischemic Injury: Involvement of FOXO3 Inactivation and Bcl2 Expression

    PubMed Central

    Park, Joohyun; Oh, Yumi

    2015-01-01

    Ischemic stroke interrupts the flow of blood to the brain and subsequently results in cerebral infarction and neuronal cell death, leading to severe pathophysiology. Glutathione (GSH) is an antioxidant with cellular protective functions, including reactive oxygen species (ROS) scavenging in the brain. In addition, GSH is involved in various cellular survival pathways in response to oxidative stress. In the present study, we examined whether GSH reduces cerebral infarct size after middle cerebral artery occlusion in vivo and the signaling mechanisms involved in the promotion of cell survival after GSH treatment under ischemia/reperfusion conditions in vitro. To determine whether GSH reduces the extent of cerebral infarction, cell death after ischemia, and reperfusion injury, we measured infarct size in ischemic brain tissue and the expression of claudin-5 associated with brain infarct formation. We also examined activation of the PI3K/Akt pathway, inactivation of FOXO3, and expression of Bcl2 to assess the role of GSH in promoting cell survival in response to ischemic injury. Based on our results, we suggest that GSH might improve the pathogenesis of ischemic stroke by attenuating cerebral infarction and cell death. PMID:25722793

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

    PubMed

    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 (p<0.05). At those dose, the MPO content were significantly decreased in ischemic brain as compared with model group (p<0.05). LHAE at 14.4 mg/kg significantly decreased the NO level compared with the model group (p<0.05). In addition, LHAE significantly decreased the apoptosis ratio of nerve fiber compared with the model group (p<0.05). This study suggests that LHAE may be used for treatment of ischemic stroke as a neuroprotective agent. Further studies are warranted to assess the efficacy and safety of LHAE in patients.

  3. Radioactive microsphere study of cerebral blood flow under acceleration. Technical report

    SciTech Connect

    Greenlees, K.J.; Yoder, J.E.; Toth, D.M.; Oloff, C.M.; Karl, A.

    1980-11-01

    A study using radioactive microspheres for the investigation of cerebral blood flow during acceleration is described. Details of a technique for the blunt dissection of cerebral tissues are included. Results of flow studies at 3 and 5 G sub z acceleration stress indicate there is no selective regional preservation of cerebral tissue. (Author)

  4. Changes of deceleration and acceleration capacity of heart rate in patients with acute hemispheric ischemic stroke

    PubMed Central

    Xu, Yan-Hong; Wang, Xing-De; Yang, Jia-Jun; Zhou, Li; Pan, Yong-Chao

    2016-01-01

    Background and purpose Autonomic dysfunction is common after stroke, which is correlated with unfavorable outcome. Phase-rectified signal averaging is a newly developed technique for assessing cardiac autonomic function, by detecting sympathetic and vagal nerve activity separately through calculating acceleration capacity (AC) and deceleration capacity (DC) of heart rate. In this study, we used this technique for the first time to investigate the cardiac autonomic function of patients with acute hemispheric ischemic stroke. Methods A 24-hour Holter monitoring was performed in 63 patients with first-ever acute ischemic stroke in hemisphere and sinus rhythm, as well as in 50 controls with high risk of stroke. DC, AC, heart rate variability parameters, standard deviation of all normal-to-normal intervals (SDNN), and square root of the mean of the sum of the squares of differences between adjacent normal-to-normal intervals (RMSSD) were calculated. The National Institutes of Health Stroke Scale (NIHSS) was used to assess the severity of stroke. We analyzed the changes of DC, AC, SDNN, and RMSSD and also studied the correlations between these parameters and NIHSS scores. Results The R–R (R wave to R wave on electrocardiogram) intervals, DC, AC, and SDNN in the cerebral infarction group were lower than those in controls (P=0.003, P=0.002, P=0.006, and P=0.043), but the difference of RMSSD and the D-value and ratio between absolute value of AC (|AC|) and DC were not statistically significant compared with those in controls. The DC of the infarction group was significantly correlated with |AC|, SDNN, and RMSSD (r=0.857, r=0.619, and r=0.358; P=0.000, P=0.000, and P=0.004). Correlation analysis also showed that DC, |AC|, and SDNN were negatively correlated with NIHSS scores (r=−0.279, r=−0.266, and r=−0.319; P=0.027, P=0.035, and P=0.011). Conclusion Both DC and AC of heart rate decreased in patients with hemispheric infarction, reflecting a decrease in both vagal

  5. Prevalence and Characteristics of Unruptured Cerebral Aneurysms in Ischemic Stroke Patients

    PubMed Central

    Kim, Ji Hwa; Suh, Sang Hyun; Chung, Joonho; Oh, Yeo-Jin; Ahn, Sung Jun; Lee, Kyung-Yul

    2016-01-01

    Background and Purpose The prevalence of unruptured cerebral aneurysms (UCAs) in ischemic stroke patients is not clearly defined. This study aimed to measure the prevalence and characteristics of UCAs in patients with acute ischemic stroke (AIS) and to compare our findings with those of the general population. In addition, we investigated the factors associated with cerebral aneurysms in AIS patients. Methods We retrospectively reviewed the brain magnetic resonance angiography images of 955 patients with AIS and 2,118 controls who had received a brain magnetic resonance angiography as part of a health check-up. We investigated the prevalence, size, location, and risk factors of the subjects in the context of UCAs. Results UCAs were found in 74 patients with AIS (7.7%) and in 79 who received a health check-up (3.7%). The prevalence of UCAs was significantly higher in the AIS group than in the health check-up group (odds ratio 2.17, 95% confidence interval 1.56-3.01). The mean aneurysm diameter was larger in the AIS group than in the health check-up group (3.75 mm vs. 3.02 mm, P=0.009). UCAs were primarily located in the internal carotid artery in both groups, and aneurysms in the middle cerebral artery were particularly common in the AIS group. According to multivariate analysis, hypertension alone was associated with an increased prevalence of UCAs in stroke patients. Conclusions This study identified a higher prevalence and larger size of UCAs in AIS patients than in the general population. Hypertension was an independent risk factor of UCA in AIS. PMID:27488981

  6. Neuroprotection Offered by Majun Khadar, a Traditional Unani Medicine, during Cerebral Ischemic Damage in Rats

    PubMed Central

    Yousuf, Seema; Atif, Fahim; Ahmad, Muzamil; Ishrat, Tauheed; Khan, Badruzzaman; Islam, Fakhrul

    2011-01-01

    Stroke results in damages to many biochemical, molecular and behavioral deficits. Present study provides evidence of the protective efficacy of a Unani herbal medicine, Majun Khadar (MK), against cerebral ischemia-induced behavioral dysfunctions and neurochemical alterations in the hippocampus (HIP). Transient focal cerebral ischemia was induced for 2 h followed by reperfusion for 22 h in a rat model. Rats were divided into four groups: sham, middle cerebral artery occluded (MCAO), drug sham (MK; 0.816 g kg−1 orally for 15 days) and MK pre-treated ischemic group (MK + MCAO). Levels of enzymatic and non-enzymatic antioxidants were estimated in HIP along with behavioral testing. MK pre-treatment significantly (P < .05–.001) restored the activities of glutathione peroxidase (GP×), glutathione reductase (GR), glutathione S-transferase (GST) and decreased the level of lipid peroxidation (LPO) and H2O2 content in HIP in the MK + MCAO group which were severely altered in the MCAO group. The content of glutathione (GSH), total thiols (TT) and ascorbic acid (AsA) was significantly depleted in the MCAO group; pretreatment with MK was able to restore its levels. Also in the MK + MCAO group, significant (P < .5–.001) recovery in behavioral testing by rota rod and open-field activities was seen as compared with the MCAO group. MK alone did not show any change neither in the status of various antioxidants nor behavioral functions over sham values. Although detailed studies are required for the evaluation of exact neuroprotective mechanism of MK against cerebral ischemia these preliminary experimental findings conclude that MK exhibits neuroprotective effect in cerebral ischemia by potentiating the antioxidant defense system of the brain. PMID:20047892

  7. p90RSK activation contributes to cerebral ischemic damage via phosphorylation of Na+/H+ exchanger isoform 1

    PubMed Central

    Manhas, Namratta; Shi, Yejie; Taunton, Jack; Sun, Dandan

    2010-01-01

    Excessive activation of Na+/H+ exchanger isoform 1 (NHE-1) plays a role in cerebral ischemic injury. The current study investigated whether NHE-1 protein in ischemic brains is regulated by extracellular signal-regulated kinase (ERK)/90-kDa ribosomal S6 kinase (p90RSK) signaling pathways. A transient focal ischemia in mice was induced by a 60 min-occlusion of the middle cerebral artery followed by reperfusion for 3, 10, or 60 min (Rp). Expression of phosphorylated ERK 1/2 was significantly elevated in the ipsilateral hemispheres at 3 – 10 min Rp and reduced by 60 min Rp. An increase in phosphorylation of p90RSK, a known NHE-1 kinase, was also detected at 3 – 10 min Rp, which was accompanied with a transient elevation of NHE-1 phosphorylation (p-NHE-1). Stimulation of p90RSK in ischemic neurons was downstream of ERK activation because inhibition of MEK1 (MAP kinase/ERK kinase) with its inhibitor U0126 blocked phosphorylation of p90RSK. Moreover, direct inhibition of p90RSK by its selective inhibitor FMK not only reduced p-NHE-1 expression but also ischemic infarct volume. Taken together, our study revealed that reperfusion triggers a transient stimulation of the ERK/p90RSK pathway. p90RSK activation contributes to cerebral ischemic damage in part via activation of NHE-1 protein. PMID:20557427

  8. Effects of hyperbaric oxygenation on oxidative stress in acute transient focal cerebral ischemic rats.

    PubMed

    Wang, Ray-Yau; Chang, Heng-Chih; Chen, Chun-Hao; Tsai, Yi-Wei; Yang, Yea-Ru

    2012-01-01

    The aim of this study was to investigate the effects of hyperbaric oxygenation (HBO) after brain ischemia. Middle cerebral artery occlusion (MCAO) procedure was used to induce the brain ischemia. Rats were assigned to control or HBO group after brain ischemia. In order to examine the role of glutathione after HBO treatment, another group of brain ischemic rats were included to receive the glutathione synthesis inhibitor and HBO treatment. HBO was administered at a pressure of 3 atmospheres absolute for 1 h with 100% oxygen, starting at 3 h post brain ischemia in HBO groups. Animals in control group were placed in their home cage and exposed to normobaric room air. The infarct volume (IV), activation of astrocyte, and level of total glutathione and lipid peroxidation (LP) were assessed 24 h post-reperfusion. Significant reduction in IV was noted in HBO group when compared with control group. The activation of astrocyte was significantly increased in the right cerebral cortex and right striatum in the HBO group when compared with those of the control group. The glutathione level was higher with lower LP level in right cortex and right striatum after HBO as compared with those of the control. However, such effects of HBO treatment were markedly reduced by glutathione synthesis inhibitor administration. These results show that inhibiting glutathione synthesis dramatically reduces the effectiveness of HBO in acute transient focal cerebral ischemia.

  9. Down-regulated Na+/K+-ATPase activity in ischemic penumbra after focal cerebral ischemia/reperfusion in rats

    PubMed Central

    Huang, Hao; Chen, Yang-Mei; Zhu, Fei; Tang, Shi-Ting; Xiao, Ji-Dong; Li, Lv-Li; Lin, Xin-Jing

    2015-01-01

    This study was aimed to examine whether the Na+/K+ adenosine triphosphatase (Na+/K+-ATPase) activity in ischemic penumbra is associated with the pathogenesis of ischemia/reperfusion-induced brain injury. An experimental model of cerebral ischemia/reperfusion was made by transient middle cerebral artery occlusion (tMCAO) in rats and the changes of Na+/K+-ATPase activity in the ischemic penumbra was examined by Enzyme Assay Kit. Extensive infarction was observed in the frontal and parietal cortical and subcortical areas at 6 h, 24 h, 48 h, 3 d and 7 d after tMCAO. Enzyme Assay analyses revealed the activity of Na+/K+-ATPase was decreased in the ischemic penumbra of model rats after focal cerebral ischemia/reperfusion compared with sham-operated rats, and reduced to its minimum at 48 h, while the infarct volume was enlarged gradually. In addition, accompanied by increased brain water content, apoptosis-related bcl-2 and Bax proteins, apoptotic index and neurologic deficits Longa scores, but fluctuated the ratio of bcl-2/Bax. Correlation analysis showed that the infarct volume, apoptotic index, neurologic deficits Longa scores and brain water content were negatively related with Na+/K+-ATPase activity, while the ratio of bcl-2/Bax was positively related with Na+/K+-ATPase activity. Our results suggest that down-regulated Na+/K+-ATPase activity in ischemic penumbra might be involved in the pathogenesis of cerebral ischemia/reperfusion injury presumably through the imbalance ratio of bcl-2/Bax and neuronal apoptosis, and identify novel target for neuroprotective therapeutic intervention in cerebral ischemic disease. PMID:26722460

  10. A Simple Geometric Assessment of Perfusion Lesion Volume at Hyperacute Stage of Ischemic Stroke in Patients with Symptomatic Steno-Occlusion of Major Cerebral Arteries and Risk of Subsequent Cerebral Ischemic Events.

    PubMed

    Kang, Jihoon; Jung, Cheolkyu; Kim, Nayoung; Son, Yoo Ri; Choi, Byungse; Kim, Jae-Hyoung; Lee, Ji Sung; Lee, Juneyoung; Lee, Jun; Jang, Myung Suk; Yang, Mi Hwa; Han, Moon-Ku; Bae, Hee-Joon

    2015-12-01

    Our objective is to elucidate the association of baseline perfusion lesion volume on perfusion-weighted magnetic resonance imaging (PWI) obtained at hyperacute stage of ischemic stroke with subsequent cerebral ischemic events (SIEs) in patients with symptomatic steno-occlusion of major cerebral arteries. Using a prospective stroke registry database, patients arriving within 24 hours of onset with symptomatic steno-occlusion of major supratentorial cerebral arteries were identified. On baseline PWI, time-to-peak lesion volume (TTP-LV) was determined by a simple geometric method and dichotomized into the highest tertile (large) and the other tertiles (small to medium) according to the vascular territory of occluded arteries. Primary outcome was a time to SIE up to 1 year after stroke onset. A total of 385 patients (a median time delay from onset to arrival, 2.2 hours) were enrolled. During the first year of stroke, the SIE rate of the large TTP-LV group was twice that of the small-to-medium TTP-LV group (35.7% versus 17.4%; P < .001). Large TTP-LV independently raised the hazard of SIE (hazard ratio, 2.24; 95% confidence interval, 1.45-3.44). This study demonstrates that TTP-LV on PWI measured through a simple geometric method at an emergency setting can be used to predict progression or recurrence of ischemic stroke in patients with symptomatic steno-occlusion of major cerebral arteries.

  11. Multi-parametric imaging of cerebral hemodynamic and metabolic response followed by ischemic injury

    NASA Astrophysics Data System (ADS)

    Qin, Jia; Shi, Lei; Dziennis, Suzan; Wang, Ruikang K.

    2014-02-01

    We use rodent parietal cortex as a model system and utilize a synchronized dual wavelength laser speckle imaging (SDW-LSCI) technique to explore the hemodynamic response of infarct and penumbra to a brain injury (middle cerebral artery occlusion (MCAO) model). The SDW-LSCI system is able to take snapshots rapidly (maximum 500 Hz) over the entire brain surface, providing key information about the hemodynamic response, in terms of which it may be used to elucidate evolution of penumbra region from onsite to 90 min of MCAO. Changes in flow are quantified as to the flow experiencing physical occlusions of the MCA normalized to that of baseline. Furthermore, the system is capable of providing information as to the changes of the concentration of oxygenated, (HbO) deoxygenated (Hb), and total hemoglobin (HbT) in the cortex based on the spectral characteristics of HbO and Hb. We observe that the oxygenation variations in the four regions are detectable and distinct. Combining the useful information, four regions of interest (ROI), infarct, penumbra, reduced flow and contralateral portions in the brain upon ischemic injury may be differentiated. Implications of our results are discussed with respect to current understanding of the mechanisms underlying MCAO. We anticipate that SDW-LSCI holds promise for rapid and large field of view localization of ischemic injury.

  12. Acceleration of cerebral ventricular expansion in the Cardiovascular Health Study.

    PubMed

    Carmichael, Owen T; Kuller, L H; Lopez, O L; Thompson, P M; Dutton, R A; Lu, A; Lee, S E; Lee, J Y; Aizenstein, H J; Meltzer, C C; Liu, Y; Toga, A W; Becker, J T

    2007-09-01

    Interactions between prevalent late-life medical conditions and expansion of the cerebral ventricles are not well understood. Thirty elderly subjects received three magnetic resonance (MR) scans each, in 1997-1999, 2002-2004, and 2003-2005. A linear expansion model of MR-measured lateral ventricle volume was estimated for each subject by fitting a line to a plot of their 1997-1999 and 2002-2004 volumes as a function of time. Acceleration in ventricular expansion was defined as the deviation between the 2003-2005 volumes measured from MR and the 2003-2005 volumes predicted by the linear expansion model. Ventricular acceleration was analyzed in a multivariate model with age, race, history of heart disease, diabetes, and hypertension as fixed effects. Ventricular acceleration was significantly higher in non-whites, diabetics, and those without heart disease (p<0.05). Ventricular acceleration was higher in subjects with a history of hypertension, but the difference was not statistically significant (p=0.08). Acceleration of ventricular expansion in the elderly may be related to demographic and cardiovascular factors.

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

    PubMed Central

    2016-01-01

    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. PMID:27703487

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

    PubMed Central

    Liu, Yin; Liu, Jun; Liu, Huanghui; Liao, Yunjie; Cao, Lu; Ye, Bin; Wang, Wei

    2016-01-01

    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. PMID:27574434

  15. Early retinal inflammatory biomarkers in the middle cerebral artery occlusion model of ischemic stroke

    PubMed Central

    Ritzel, Rodney M.; Pan, Sarah J.; Verma, Rajkumar; Wizeman, John; Crapser, Joshua; Patel, Anita R.; Lieberman, Richard; Mohan, Royce

    2016-01-01

    Purpose The transient middle cerebral artery occlusion (MCAO) model of stroke is one of the most commonly used models to study focal cerebral ischemia. This procedure also results in the simultaneous occlusion of the ophthalmic artery that supplies the retina. Retinal cell death is seen days after reperfusion and leads to functional deficits; however, the mechanism responsible for this injury has not been investigated. Given that the eye may have a unique ocular immune response to an ischemic challenge, this study examined the inflammatory response to retinal ischemia in the MCAO model. Methods Young male C57B/6 mice were subjected to 90-min transient MCAO and were euthanized at several time points up to 7 days. Transcription of inflammatory cytokines was measured with quantitative real-time PCR, and immune cell activation (e.g., phagocytosis) and migration were assessed with ophthalmoscopy and flow cytometry. Results Observation of the affected eye revealed symptoms consistent with Horner’s syndrome. Light ophthalmoscopy confirmed the reduced blood flow of the retinal arteries during occlusion. CX3CR1-GFP reporter mice were then employed to evaluate the extent of the ocular microglia and monocyte activation. A significant increase in green fluorescent protein (GFP)-positive macrophages was seen throughout the ischemic area compared to the sham and contralateral control eyes. RT–PCR revealed enhanced expression of the monocyte chemotactic molecule CCL2 early after reperfusion followed by a delayed increase in the proinflammatory cytokine TNF-α. Further analysis of peripheral leukocyte recruitment by flow cytometry determined that monocytes and neutrophils were the predominant immune cells to infiltrate at 72 h. A transient reduction in retinal microglia numbers was also observed, demonstrating the ischemic sensitivity of these cells. Blood–eye barrier permeability to small and large tracer molecules was increased by 72 h. Retinal microglia exhibited enhanced

  16. Predictors of quality of life in pediatric survivors of arterial ischemic stroke and cerebral sinovenous thrombosis.

    PubMed

    Friefeld, Sharon J; Westmacott, Robyn; Macgregor, Daune; Deveber, Gabrielle A

    2011-09-01

    Predictors of quality of life can define potentially modifiable factors to increase favorable outcomes after pediatric stroke. Quality of life was measured using the Centre for Health Promotion's Quality of Life Profile (CHP-QOL) in 112 children surviving arterial ischemic stroke or cerebral sinovenous thrombosis at mean 3 years after stroke. Overall quality of life was poor in 17.8% children despite mean scores (3.52) in the "adequate" range. Quality of life related to school and play was most problematic and that related to physical and home environment was least problematic. Female gender, cerebral sinovenous thrombosis stroke, and older age at testing predicted reduced overall and domain-specific quality of life (P < .05), whereas neurological outcome and family socioeconomic status did not. Cognitive/behavioral deficit and low Verbal IQ adversely affected socialization and quality of life, especially among older children and females. Altered cognition/behavior has a major impact on quality of life after pediatric stroke. Implementation of ameliorative strategies warrants further study.

  17. Matrine attenuates focal cerebral ischemic injury by improving antioxidant activity and inhibiting apoptosis in mice

    PubMed Central

    ZHAO, PENG; ZHOU, RU; ZHU, XIAO-YUN; HAO, YIN-JU; LI, NAN; WANG, JIE; NIU, YANG; SUN, TAO; LI, YU-XIANG; YU, JIAN-QIANG

    2015-01-01

    cerebral ischemic injury and that these effects are associated with its antioxidant and anti-apoptotic properties. PMID:26135032

  18. Matrine attenuates focal cerebral ischemic injury by improving antioxidant activity and inhibiting apoptosis in mice.

    PubMed

    Zhao, Peng; Zhou, Ru; Zhu, Xiao-Yun; Hao, Yin-Ju; Li, Nan; Wang, Jie; Niu, Yang; Sun, Tao; Li, Yu-Xiang; Yu, Jian-Qiang

    2015-09-01

    cerebral ischemic injury and that these effects are associated with its antioxidant and anti-apoptotic properties.

  19. Matrine attenuates focal cerebral ischemic injury by improving antioxidant activity and inhibiting apoptosis in mice.

    PubMed

    Zhao, Peng; Zhou, Ru; Zhu, Xiao-Yun; Hao, Yin-Ju; Li, Nan; Wang, Jie; Niu, Yang; Sun, Tao; Li, Yu-Xiang; Yu, Jian-Qiang

    2015-09-01

    cerebral ischemic injury and that these effects are associated with its antioxidant and anti-apoptotic properties. PMID:26135032

  20. Lysine and Arginine Reduce the Effects of Cerebral Ischemic Insults and Inhibit Glutamate-Induced Neuronal Activity in Rats

    PubMed Central

    Kondoh, Takashi; Kameishi, Makiko; Mallick, Hruda Nanda; Ono, Taketoshi; Torii, Kunio

    2010-01-01

    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 2 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. PMID:20589237

  1. The emerging role of signal transducer and activator of transcription 3 in cerebral ischemic and hemorrhagic stroke.

    PubMed

    Liang, Zhenxing; Wu, Guiling; Fan, Chongxi; Xu, Jing; Jiang, Shuai; Yan, Xiaolong; Di, Shouyin; Ma, Zhiqiang; Hu, Wei; Yang, Yang

    2016-02-01

    Signal transducers and activators of transcription (STATs) comprise a family of cytoplasmic transcription factors that mediate intracellular signaling. This signaling is typically generated at cell surface receptors, the activation of which results in the translocation of STATs to the nucleus. STATs are involved in biological events as diverse as embryonic development, programmed cell death, organogenesis, innate immunity, adaptive immunity and cell growth regulation in organisms ranging from slime molds to insects to humans. Numerous studies have demonstrated the activation of STAT3 in neurological diseases, particularly in cerebral ischemic and hemorrhagic stroke. Additionally, STAT3 has also been reported to play a critical role in neuroprotective therapies. In light of the pleiotropic effects of STAT3 on the nervous system, we present the elaborate network of roles that STAT3 plays in cerebral ischemia and hemorrhage in this review. First, we introduce basic knowledge regarding STAT3 and briefly summarize the activation, inactivation, and regulation of the STAT3 pathway. Next, we describe the activation of STAT3 following cerebral ischemia and hemorrhage. Subsequently, we discuss the physiopathological roles of STAT3 in cerebral ischemia and hemorrhage. Moreover, we summarize several significant cerebral ischemic and hemorrhagic stroke treatments that target the STAT3 signaling pathway, including pharmacological and physical therapies. Finally, we highlight research progress on STAT3 in stroke. This review presents the important roles of STAT3 in the nervous system and may contribute to the promotion of STAT3 as a new therapeutic target. PMID:26738445

  2. TIGAR contributes to ischemic tolerance induced by cerebral preconditioning through scavenging of reactive oxygen species and inhibition of apoptosis.

    PubMed

    Zhou, Jun-Hao; Zhang, Tong-Tong; Song, Dan-Dan; Xia, Yun-Fei; Qin, Zheng-Hong; Sheng, Rui

    2016-01-01

    Previous study showed that TIGAR (TP53-induced glycolysis and apoptosis regulator) protected ischemic brain injury via enhancing pentose phosphate pathway (PPP) flux and preserving mitochondria function. This study was aimed to study the role of TIGAR in cerebral preconditioning. The ischemic preconditioning (IPC) and isoflurane preconditioning (ISO) models were established in primary cultured cortical neurons and in mice. Both IPC and ISO increased TIGAR expression in cortical neurons. Preconditioning might upregulate TIGAR through SP1 transcription factor. Lentivirus mediated knockdown of TIGAR significantly abolished the ischemic tolerance induced by IPC and ISO. ISO also increased TIGAR in mouse cortex and hippocampus and alleviated subsequent brain ischemia-reperfusion injury, while the ischemic tolerance induced by ISO was eliminated with TIGAR knockdown in mouse brain. ISO increased the production of NADPH and glutathione (GSH), and scavenged reactive oxygen species (ROS), while TIGAR knockdown decreased GSH and NADPH production and increased the level of ROS. Supplementation of ROS scavenger NAC and PPP product NADPH effectively rescue the neuronal injury caused by TIGAR deficiency. Notably, TIGAR knockdown inhibited ISO-induced anti-apoptotic effects in cortical neurons. These results suggest that TIGAR participates in the cerebral preconditioning through reduction of ROS and subsequent cell apoptosis. PMID:27256465

  3. Neuroprotection of a novel synthetic caffeic acid-syringic acid hybrid compound against experimentally induced transient cerebral ischemic damage.

    PubMed

    Kim, In Hye; Yan, Bing Chun; Park, Joon Ha; Yeun, Go Heum; Yim, Yongbae; Ahn, Ji Hyeon; Lee, Jae-Chul; Hwang, In Koo; Cho, Jun Hwi; Kim, Young-Myeong; Lee, Yun Lyul; Park, Jeong Ho; Won, Moo-Ho

    2013-03-01

    We investigated effects of caffeic acid, syringic acid, and their synthesis on transient cerebral ischemic damage in the gerbil hippocampal CA1 region. In the 10 mg/kg caffeic acid-, syringic acid-, and 20 mg/kg syringic-treated ischemia groups, we did not find any significant neuroprotection in the ischemic hippocampal CA region. In the 20 mg/kg caffeic acid- and 10 mg/kg caffeic acid-syringic acid-treated ischemia groups, moderate neuroprotection was found in the hippocampal CA1 region. In the 20 mg/kg caffeic acid-syringic acid-treated ischemia group, a strong neuroprotective effect was found in the ischemic hippocampal CA1 region: about 89 % of hippocampal CA1 region pyramidal neurons survived. We also observed changes in glial cells (astrocytes and microglia) in the ischemic hippocampal CA1 region in all the groups. Among them, the distribution pattern of the glial cells was only in the 20 mg/kg caffeic acid-syringic acid-treated ischemia group similar to that in the sham group (control). In brief, 20 mg/kg caffeic acid-syringic acid showed a strong neuroprotective effect with an inhibition of glia activation in the hippocampal CA1 region induced by transient cerebral ischemia.

  4. TIGAR contributes to ischemic tolerance induced by cerebral preconditioning through scavenging of reactive oxygen species and inhibition of apoptosis

    PubMed Central

    Zhou, Jun-Hao; Zhang, Tong-Tong; Song, Dan-Dan; Xia, Yun-Fei; Qin, Zheng-Hong; Sheng, Rui

    2016-01-01

    Previous study showed that TIGAR (TP53-induced glycolysis and apoptosis regulator) protected ischemic brain injury via enhancing pentose phosphate pathway (PPP) flux and preserving mitochondria function. This study was aimed to study the role of TIGAR in cerebral preconditioning. The ischemic preconditioning (IPC) and isoflurane preconditioning (ISO) models were established in primary cultured cortical neurons and in mice. Both IPC and ISO increased TIGAR expression in cortical neurons. Preconditioning might upregulate TIGAR through SP1 transcription factor. Lentivirus mediated knockdown of TIGAR significantly abolished the ischemic tolerance induced by IPC and ISO. ISO also increased TIGAR in mouse cortex and hippocampus and alleviated subsequent brain ischemia-reperfusion injury, while the ischemic tolerance induced by ISO was eliminated with TIGAR knockdown in mouse brain. ISO increased the production of NADPH and glutathione (GSH), and scavenged reactive oxygen species (ROS), while TIGAR knockdown decreased GSH and NADPH production and increased the level of ROS. Supplementation of ROS scavenger NAC and PPP product NADPH effectively rescue the neuronal injury caused by TIGAR deficiency. Notably, TIGAR knockdown inhibited ISO-induced anti-apoptotic effects in cortical neurons. These results suggest that TIGAR participates in the cerebral preconditioning through reduction of ROS and subsequent cell apoptosis. PMID:27256465

  5. Value of ABCD2-F in Predicting Cerebral Ischemic Attacks: Three Months Follow-Up after the Primary Attack.

    PubMed

    Chardoli, Mojtaba; Firoozabadi, Nader H; Nouri, Mohsen; Rahimi-Movaghar, Vafa

    2016-06-01

    Cerebrovascular attack (CVA) and transient ischemic attack (TIA) are major causes of emergency department visits around the globe. A significant number of these patients may experience repeat attacks if left untreated. Several risk stratifying scoring systems have been developed in recent years to point out the high risk patients. ABCD2 is based on age, blood pressure, clinical status, diabetes mellitus, and duration of symptoms and is used commonly for this purpose. In this study, we were to enhance its sensitivity and specificity with the addition of another criterion namely atrial fibrillation and making ABCD2-F. A prospective study in two hospitals was performed and 138 patients diagnosed with TIA/CVA were enrolled. Demographic, clinical, and paraclinical data of all patients were registered. All patients were followed for three months for any sign or symptom of a recurrent ischemic attack. Recurrent ischemic attacks happened in 9.4% of the patients. None of the criteria of ABCD2-F was associated with higher chance of ischemic attacks. Similarly, ABCD2-F was not different between patients with or without repeat cerebral ischemia. The addition of atrial fibrillation to ABCD2 did not enhance the accuracy of this scoring system to detect patients high risk for repeat cerebral ischemia. More studies in the future to improve sensitivity and specificity of this test are warranted. PMID:27306346

  6. Somatosensory evoked potentials in carotid artery stenting: Effectiveness in ascertaining cerebral ischemic events.

    PubMed

    Adhikari, Rupendra Bahadur; Takeda, Masaaki; Kolakshyapati, Manish; Sakamoto, Shigeyuki; Morishige, Mizuki; Kiura, Yoshihiro; Okazaki, Takahito; Shinagawa, Katsuhiro; Ichinose, Nobuhiko; Yamaguchi, Satoshi; Kurisu, Kaoru

    2016-08-01

    Somatosensory evoked potentials (SSEP) have been used in various endovascular procedures and carotid endarterectomy, but to our knowledge no literature deals exclusively with the utility of SSEP in carotid artery stenting (CAS). The purpose of this study was to evaluate the efficacy of SSEP in detecting cerebral ischemic events during CAS. We conducted a prospective study in 35 CAS procedures in 31 patients during an 18month period. Thirty-three patients without near occlusion underwent stenting using dual protection (simultaneous flow reversal and distal filter) combined with blood aspiration, while two patients with near occlusion underwent stenting without dual protection. All 35 patients underwent SSEP monitoring. SSEP were generated by stimulating median and/or tibial nerves and recorded by scalp electrodes. During the aspiration phase post-dilation, seven patients (20%) exhibited SSEP changes with a mean duration of 11.3±8.5minutes (range: 3-25minutes), three of whom later developed minor stroke/transient ischemic attack. Diffusion-weighted imaging showed new lesions in 10 patients (28.6%). Change in SSEP exhibited mean sensitivity of 100% (95% confidence interval, 0.29-1.0) and specificity of 88% (95% confidence interval, 0.71-0.96) in predicting clinical stroke post-CAS. Intra-procedural SSEP change was predictive of post-procedural complications (p=0.005, Fisher's exact test). Longer span of SSEP change was positively correlated with complications (p=0.032, Mann-Whitney test). Intra-procedural SSEP changes are highly sensitive in predicting neurological outcome following CAS. Chances of complications are increased with prolongation of such changes. SSEP allows for prompt intra-procedural ischemia prevention measures and stratification to pursue an aggressive peri-procedural protocol for high risk patients to mitigate neurological deficits. PMID:27291465

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

    PubMed Central

    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. PMID:21960958

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

    PubMed Central

    Wattanathorn, Jintanaporn; Tong-Un, Terdthai; Muchimapura, Supaporn; Wannanon, Panakaporn; Jittiwat, Jinatta

    2013-01-01

    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. PMID:24367723

  9. Cerebroprotective effect of Moringa oleifera against focal ischemic stroke induced by middle cerebral artery occlusion.

    PubMed

    Kirisattayakul, Woranan; Wattanathorn, Jintanaporn; Tong-Un, Terdthai; Muchimapura, Supaporn; Wannanon, Panakaporn; Jittiwat, Jinatta

    2013-01-01

    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. PMID:24367723

  10. Protein Kinase C Epsilon Promotes Cerebral Ischemic Tolerance Via Modulation of Mitochondrial Sirt5

    PubMed Central

    Morris-Blanco, Kahlilia C.; Dave, Kunjan R.; Saul, Isabel; Koronowski, Kevin B.; Stradecki, Holly M.; Perez-Pinzon, Miguel A.

    2016-01-01

    Sirtuin 5 (SIRT5) is a mitochondrial-localized NAD+-dependent lysine desuccinylase and a major regulator of the mitochondrial succinylome. We wanted to determine whether SIRT5 is activated by protein kinase C epsilon (PKCε)-mediated increases in mitochondrial Nampt and whether SIRT5 regulates mitochondrial bioenergetics and neuroprotection against cerebral ischemia. In isolated mitochondria from rat cortical cultures, PKCε activation increased SIRT5 levels and desuccinylation activity in a Nampt-dependent manner. PKCε activation did not lead to significant modifications in SIRT3 activity, the major mitochondrial lysine deacetylase. Assessments of mitochondrial bioenergetics in the cortex of wild type (WT) and SIRT5−/− mice revealed that SIRT5 regulates oxygen consumption in the presence of complex I, complex II, and complex IV substrates. To explore the potential role of SIRT5 in PKCε-mediated protection, we compared WT and SIRT5−/− mice by employing both in vitro and in vivo ischemia paradigms. PKCε-mediated decreases in cell death following oxygen-glucose deprivation were abolished in cortical cultures harvested from SIRT5−/− mice. Furthermore, PKCε failed to prevent cortical degeneration following MCAO in SIRT5−/− mice. Collectively this demonstrates that SIRT5 is an important mitochondrial enzyme for protection against metabolic and ischemic stress following PKCε activation in the brain. PMID:27435822

  11. PET Demonstrates Functional Recovery after Treatment by Danhong Injection in a Rat Model of Cerebral Ischemic-Reperfusion Injury.

    PubMed

    Wang, Zefeng; Song, Fahuan; Li, Jinhui; Zhang, Yuyan; He, Yu; Yang, Jiehong; Zhou, Huifen; Zhao, Tao; Fu, Wei; Xing, Panke; Wan, Haitong; Tian, Mei; Zhang, Hong

    2014-01-01

    This study aimed to investigate neuroprotection of Danhong injection (DHI) in a rat model of cerebral ischemia using (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET). Method. Rats were divided into 5 groups: sham group, ischemia-reperfusion untreated (IRU) group, DHI-1 group (DHI 1 mL/kg/d), DHI-2 group (DHI 2 mL/kg/d), and DHI-4 group (DHI 4 mL/kg/d). AII the treated groups were intraperitoneally injected with DHI daily for 14 days. The therapeutic effects in terms of cerebral infarct volume, neurological function, and cerebral glucose metabolism were evaluated. Expression of TNF-α and IL-1β was detected with enzyme-linked immunosorbent assay (ELISA). Levels of mature neuronal marker (NeuN), glial marker (GFAP), vascular density factor (vWF), and glucose transporter 1 (GLUT1) were assessed by immunohistochemistry. Results. Compared with the IRU group, rats treated with DHI showed dose dependent reductions in cerebral infarct volume and levels of proinflammatory cytokines, improvement of neurological function, and recovery of cerebral glucose metabolism. Meanwhile, the significantly increased numbers of neurons, gliocytes, and vessels and the recovery of glucose utilization were found in the peri-infarct region after DHI treatment using immunohistochemical analysis. Conclusion. This study demonstrated the metabolic recovery after DHI treatment by micro-PET imaging with (18)F-FDG and the neuroprotective effects of DHI in a rat model of cerebral ischemic-reperfusion injury.

  12. Progression of stenosis into occlusion of the distal posterior cerebral artery supplying an occipital arteriovenous malformation manifesting as multiple ischemic attacks: case report.

    PubMed

    Goto, Hisaharu; Suzuki, Michiyasu; Akimura, Tatsuo; Fujisawa, Hirosuke; Yoneda, Hiroshi; Oka, Fumiaki; Nomura, Sadahiro; Kajiwara, Koji; Kato, Shoichi; Fujii, Masami

    2012-01-01

    A 31-year-old healthy male presented with a rare case of cerebral arteriovenous malformation (AVM) manifesting as repeated ischemic attacks and cerebral infarction causing left sensori-motor disturbance. Neuroimaging revealed cerebral infarction in the right thalamus as well as right occipital AVM without bleeding. The AVM was mainly fed by the right angular artery, and the right posterior cerebral artery (PCA) showed mild stenosis and segmental dilation at the P(2)-P(3) portion. After referral to our hospital, transient ischemic attacks causing left homonymous hemianopsia, and left arm and leg numbness were frequently recognized. Additional imaging revealed a new ischemic lesion in the occipital lobe, and repeated cerebral angiography showed right PCA occlusion at the P(2)-P(3) segment. Cerebral AVM presenting with cerebral infarction due to occlusion of feeding arteries is rare. In our case, intimal injury due to increased blood flow or spontaneous dissection of the artery were possible causes. We should monitor any changes in the architecture and rheology of the feeding vessels during the clinical course to prevent ischemic complications.

  13. Fullerenols and glucosamine fullerenes reduce infarct volume and cerebral inflammation after ischemic stroke in normotensive and hypertensive rats.

    PubMed

    Fluri, Felix; Grünstein, Dan; Cam, Ertugrul; Ungethuem, Udo; Hatz, Florian; Schäfer, Juliane; Samnick, Samuel; Israel, Ina; Kleinschnitz, Christoph; Orts-Gil, Guillermo; Moch, Holger; Zeis, Thomas; Schaeren-Wiemers, Nicole; Seeberger, Peter

    2015-03-01

    Cerebral inflammation plays a crucial role in the pathophysiology of ischemic stroke and is involved in all stages of the ischemic cascade. Fullerene derivatives, such as fullerenol (OH-F) are radical scavengers acting as neuroprotective agents while glucosamine (GlcN) attenuates cerebral inflammation after stroke. We created novel glucosamine-fullerene conjugates (GlcN-F) to combine their protective effects and compared them to OH-F regarding stroke-induced cerebral inflammation and cellular damage. Fullerene derivatives or vehicle was administered intravenously in normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) immediately after transient middle cerebral artery occlusion (tMCAO). Infarct size was determined at day 5 and neurological outcome at days 1 and 5 after tMCAO. CD68- and NeuN-staining were performed to determine immunoreactivity and neuronal survival respectively. Cytokine and toll like receptor 4 (TLR-4) expression was assessed using quantitative real-time PCR. Magnetic resonance imaging revealed a significant reduction of infarct volume in both, WKY and SHR that were treated with fullerene derivatives. Treated rats showed an amelioration of neurological symptoms as both OH-F and GlcN-F prevented neuronal loss in the perilesional area. Cerebral immunoreactivity was reduced in treated WKY and SHR. Expression of IL-1β and TLR-4 was attenuated in OH-F-treated WKY rats. In conclusion, OH-F and GlcN-F lead to a reduction of cellular damage and inflammation after stroke, rendering these compounds attractive therapeutics for stroke.

  14. Failure in neuroprotection of remote limb ischemic postconditioning in the hippocampus of a gerbil model of transient cerebral ischemia.

    PubMed

    Lee, Jae-Chul; Tae, Hyun-Jin; Chen, Bai Hui; Cho, Jeong Hwi; Kim, In Hye; Ahn, Ji Hyeon; Park, Joon Ha; Shin, Bich-Na; Lee, Hui Young; Cho, Young Shin; Cho, Jun Hwi; Hong, Seongkweon; Choi, Soo Young; Won, Moo-Ho; Park, Chan Woo

    2015-11-15

    Remote ischemic postconditioning (RIPoC) has been proven to provide potent protection of the heart and brain against ischemia-reperfusion injury. However, despite the evidence of cerebral protection with RIPoC is compelling, RIPoC-mediated neuroprotection against transient cerebral ischemic insult is still mired in controversy. In this study, we examined the effect of RIPoC induced by sublathal transient hind limb ischemia on neuronal death in the hippocampus following 5 min of transient cerebral ischemia in gerbils. Animals were randomly assigned to sham-, ischemia-, sham plus (+) RIPoC- and ischemia+RIPoC-groups. RIPoC was induced by three cycles of 5-min and 10-min occlusion-reperfusion of both femoral arteries at predetermined points in time (0, 1, 3, 6, 12 and 24h after transient cerebral ischemia). CV staining, F-J B histofluorescence staining and NeuN immunohistochemistry were carried out to examine neuroprotection in the RIPoC-mediated hippocampus 5 days after ischemia-reperfusion. In the ischemia-group, we found a significant loss of pyramidal cells in the stratum pyramidale (SP) of the hippocampal CA1 region at 5 days post-ischemia compared with the sham-group. In all of the ischemia+RIPoC-groups, the loss of pyramidal cells in the CA1 region at 5 days post-ischemia was not different from that in the ischemia-group. Our present findings indicate that RIPoC does not prevent hippocampal CA1 pyramidal cells from neuronal death induced by transient cerebral ischemia.

  15. An Evaluation of Cerebral and Systemic Predictors of 18-Month Outcomes for Neonates With Hypoxic Ischemic Encephalopathy.

    PubMed

    Shellhaas, Renée A; Kushwaha, Juhi S; Plegue, Melissa A; Selewski, David T; Barks, John D E

    2015-10-01

    Amplitude-integrated EEG (aEEG) is a commonly used predictor of outcome after hypoxic ischemic encephalopathy. Cerebral and systemic near-infrared spectroscopy and acute kidney injury might also have prognostic value. The authors monitored neonates with aEEG, cerebral and systemic near-infrared spectroscopy during therapeutic hypothermia, assigned an acute kidney injury stage, and measured neurodevelopmental outcome. For 18 infants, cerebral near-infrared spectroscopy variables did not differentiate between those with favorable (n = 13) versus adverse (death or moderate-severe disability; n = 5) 18-month outcomes. However, systemic rSO2 variability was higher during hours 48-72 of cooling among those with favorable outcomes (.02 < P < .03). Mean aEEG amplitude during hours 24 to 48 of cooling was higher among those with good outcomes (.027 < P < .032). The aEEG lower margin was also higher during hours 12 to 48 for those with good outcomes (.014 < P < .035). Acute kidney injury did not predict outcome (P > .05). aEEG is a useful prognostic tool for outcomes after neonatal hypoxic ischemic encephalopathy, but the role of near-infrared spectroscopy in the hypothermia-treated population remains uncertain.

  16. An Evaluation of Cerebral and Systemic Predictors of 18-Month Outcomes for Neonates With Hypoxic Ischemic Encephalopathy.

    PubMed

    Shellhaas, Renée A; Kushwaha, Juhi S; Plegue, Melissa A; Selewski, David T; Barks, John D E

    2015-10-01

    Amplitude-integrated EEG (aEEG) is a commonly used predictor of outcome after hypoxic ischemic encephalopathy. Cerebral and systemic near-infrared spectroscopy and acute kidney injury might also have prognostic value. The authors monitored neonates with aEEG, cerebral and systemic near-infrared spectroscopy during therapeutic hypothermia, assigned an acute kidney injury stage, and measured neurodevelopmental outcome. For 18 infants, cerebral near-infrared spectroscopy variables did not differentiate between those with favorable (n = 13) versus adverse (death or moderate-severe disability; n = 5) 18-month outcomes. However, systemic rSO2 variability was higher during hours 48-72 of cooling among those with favorable outcomes (.02 < P < .03). Mean aEEG amplitude during hours 24 to 48 of cooling was higher among those with good outcomes (.027 < P < .032). The aEEG lower margin was also higher during hours 12 to 48 for those with good outcomes (.014 < P < .035). Acute kidney injury did not predict outcome (P > .05). aEEG is a useful prognostic tool for outcomes after neonatal hypoxic ischemic encephalopathy, but the role of near-infrared spectroscopy in the hypothermia-treated population remains uncertain. PMID:25724376

  17. A global transcriptomic view of the multifaceted role of glutathione peroxidase-1 in cerebral ischemic-reperfusion injury.

    PubMed

    Chen, Minghui Jessica; Wong, Connie H Y; Peng, Zhao Feng; Manikandan, Jayapal; Melendez, Alirio J; Tan, Theresa M; Crack, Peter J; Cheung, Nam Sang

    2011-03-15

    Transient cerebral ischemia often results in secondary ischemic/reperfusion injury, the pathogenesis of which remains unclear. This study provides a comprehensive, temporal description of the molecular events contributing to neuronal injury after transient cerebral ischemia. Intraluminal middle cerebral artery occlusion (MCAO) was performed to induce a 2-h ischemia with reperfusion. Microarray analysis was then performed on the infarct cortex of wild-type (WT) and glutathione peroxidase-1 (a major antioxidant enzyme) knockout (Gpx1(-/-)) mice at 8 and 24h postreperfusion to identify differential gene expression profile patterns and potential alternative injury cascades in the absence of Gpx1, a crucial antioxidant enzyme, in cerebral ischemia. Genes with at least ±1.5-fold change in expression at either time point were considered significant. Global transcriptomic analyses demonstrated that 70% of the WT-MCAO profile overlapped with that of Gpx1(-/-)-MCAO, and 28% vice versa. Critical analysis of the 1034 gene probes specific to the Gpx1(-/-)-MCAO profile revealed regulation of additional novel pathways, including the p53-mediated proapoptotic pathway and Fas ligand (CD95/Apo1)-mediated pathways; downplay of the Nrf2 antioxidative cascade; and ubiquitin-proteasome system dysfunction. Therefore, this comparative study forms the foundation for the establishment of screening platforms for target definition in acute cerebral ischemia intervention.

  18. Accelerated development of cerebral small vessel disease in young stroke patients

    PubMed Central

    Arntz, Renate M.; van den Broek, Steffen M.A.; van Uden, Inge W.M.; Ghafoorian, Mohsen; Platel, Bram; Rutten-Jacobs, Loes C.A.; Maaijwee, Noortje A.M.; Schaapsmeerders, Pauline; Schoonderwaldt, Hennie C.; van Dijk, Ewoud J.

    2016-01-01

    Objective: To study the long-term prevalence of small vessel disease after young stroke and to compare this to healthy controls. Methods: This prospective cohort study comprises 337 patients with an ischemic stroke or TIA, aged 18–50 years, without a history of TIA or stroke. In addition, 90 age- and sex-matched controls were included. At follow-up, lacunes, microbleeds, and white matter hyperintensity (WMH) volume were assessed using MRI. To investigate the relation between risk factors and small vessel disease, logistic and linear regression were used. Results: After mean follow-up of 9.9 (SD 8.1) years, 337 patients were included (227 with an ischemic stroke and 110 with a TIA). Mean age of patients was 49.8 years (SD 10.3) and 45.4% were men; for controls, mean age was 49.4 years (SD 11.9) and 45.6% were men. Compared with controls, patients more often had at least 1 lacune (24.0% vs 4.5%, p < 0.0001). In addition, they had a higher WMH volume (median 1.5 mL [interquartile range (IQR) 0.5–3.7] vs 0.4 mL [IQR 0.0–1.0], p < 0.001). Compared with controls, patients had the same volume WMHs on average 10–20 years earlier. In the patient group, age at stroke (β = 0.03, 95% confidence interval [CI] 0.02–0.04) hypertension (β = 0.22, 95% CI 0.04–0.39), and smoking (β = 0.18, 95% CI 0.01–0.34) at baseline were associated with WMH volume. Conclusions: Patients with a young stroke have a higher burden of small vessel disease than controls adjusted for confounders. Cerebral aging seems accelerated by 10–20 years in these patients, which may suggest an increased vulnerability to vascular risk factors. PMID:27521431

  19. Recurrent stroke risk and cerebral microbleed burden in ischemic stroke and TIA

    PubMed Central

    Wilson, Duncan; Charidimou, Andreas; Ambler, Gareth; Fox, Zoe V.; Gregoire, Simone; Rayson, Phillip; Imaizumi, Toshio; Fluri, Felix; Naka, Hiromitsu; Horstmann, Solveig; Veltkamp, Roland; Rothwell, Peter M.; Kwa, Vincent I.H.; Thijs, Vincent; Lee, Yong-Seok; Kim, Young Dae; Huang, Yining; Wong, Ka Sing; Jäger, Hans Rolf

    2016-01-01

    Objective: To determine associations between cerebral microbleed (CMB) burden with recurrent ischemic stroke (IS) and intracerebral hemorrhage (ICH) risk after IS or TIA. Methods: We identified prospective studies of patients with IS or TIA that investigated CMBs and stroke (ICH and IS) risk during ≥3 months follow-up. Authors provided aggregate summary-level data on stroke outcomes, with CMBs categorized according to burden (single, 2–4, and ≥5 CMBs) and distribution. We calculated absolute event rates and pooled risk ratios (RR) using random-effects meta-analysis. Results: We included 5,068 patients from 15 studies. There were 115/1,284 (9.6%) recurrent IS events in patients with CMBs vs 212/3,781 (5.6%) in patients without CMBs (pooled RR 1.8 for CMBs vs no CMBs; 95% confidence interval [CI] 1.4–2.5). There were 49/1,142 (4.3%) ICH events in those with CMBs vs 17/2,912 (0.58%) in those without CMBs (pooled RR 6.3 for CMBs vs no CMBs; 95% CI 3.5–11.4). Increasing CMB burden increased the risk of IS (pooled RR [95% CI] 1.8 [1.0–3.1], 2.4 [1.3–4.4], and 2.7 [1.5–4.9] for 1 CMB, 2–4 CMBs, and ≥5 CMBs, respectively) and ICH (pooled RR [95% CI] 4.6 [1.9–10.7], 5.6 [2.4–13.3], and 14.1 [6.9–29.0] for 1 CMB, 2–4 CMBs, and ≥5 CMBs, respectively). Conclusions: CMBs are associated with increased stroke risk after IS or TIA. With increasing CMB burden (compared to no CMBs), the risk of ICH increases more steeply than that of IS. However, IS absolute event rates remain higher than ICH absolute event rates in all CMB burden categories. PMID:27590288

  20. Intravenous Administration of Cilostazol Nanoparticles Ameliorates Acute Ischemic Stroke in a Cerebral Ischemia/Reperfusion-Induced Injury Model.

    PubMed

    Nagai, Noriaki; Yoshioka, Chiaki; Ito, Yoshimasa; Funakami, Yoshinori; Nishikawa, Hiroyuki; Kawabata, Atsufumi

    2015-01-01

    It was reported that cilostazol (CLZ) suppressed disruption of the microvasculature in ischemic areas. In this study, we have designed novel injection formulations containing CLZ nanoparticles using 0.5% methylcellulose, 0.2% docusate sodium salt, and mill methods (CLZnano dispersion; particle size 81 ± 59 nm, mean ± S.D.), and investigated their toxicity and usefulness in a cerebral ischemia/reperfusion-induced injury model (MCAO/reperfusion mice). The pharmacokinetics of injections of CLZnano dispersions is similar to that of CLZ solutions prepared with 2-hydroxypropyl-β-cyclodextrin, and no changes in the rate of hemolysis of rabbit red blood cells, a model of cell injury, were observed with CLZnano dispersions. In addition, the intravenous injection of 0.6 mg/kg CLZnano dispersions does not affect the blood pressure and blood flow, and the 0.6 mg/kg CLZnano dispersions ameliorate neurological deficits and ischemic stroke in MCAO/reperfusion mice. It is possible that the CLZnano dispersions will provide effective therapy for ischemic stroke patients, and that injection preparations of lipophilic drugs containing drug nanoparticles expand their therapeutic usage. PMID:26690139

  1. Intravenous Administration of Cilostazol Nanoparticles Ameliorates Acute Ischemic Stroke in a Cerebral Ischemia/Reperfusion-Induced Injury Model

    PubMed Central

    Nagai, Noriaki; Yoshioka, Chiaki; Ito, Yoshimasa; Funakami, Yoshinori; Nishikawa, Hiroyuki; Kawabata, Atsufumi

    2015-01-01

    It was reported that cilostazol (CLZ) suppressed disruption of the microvasculature in ischemic areas. In this study, we have designed novel injection formulations containing CLZ nanoparticles using 0.5% methylcellulose, 0.2% docusate sodium salt, and mill methods (CLZnano dispersion; particle size 81 ± 59 nm, mean ± S.D.), and investigated their toxicity and usefulness in a cerebral ischemia/reperfusion-induced injury model (MCAO/reperfusion mice). The pharmacokinetics of injections of CLZnano dispersions is similar to that of CLZ solutions prepared with 2-hydroxypropyl-β-cyclodextrin, and no changes in the rate of hemolysis of rabbit red blood cells, a model of cell injury, were observed with CLZnano dispersions. In addition, the intravenous injection of 0.6 mg/kg CLZnano dispersions does not affect the blood pressure and blood flow, and the 0.6 mg/kg CLZnano dispersions ameliorate neurological deficits and ischemic stroke in MCAO/reperfusion mice. It is possible that the CLZnano dispersions will provide effective therapy for ischemic stroke patients, and that injection preparations of lipophilic drugs containing drug nanoparticles expand their therapeutic usage. PMID:26690139

  2. Baicalin attenuates focal cerebral ischemic reperfusion injury through inhibition of nuclear factor {kappa}B p65 activation

    SciTech Connect

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

    2010-12-17

    Research highlights: {yields} Permanent NF-{kappa}B p65 activation contributes to the infarction after ischemia-reperfusion injury in rats. {yields} Baicalin can markedly inhibit the nuclear NF-{kappa}B p65 expression and m RNA levels after ischemia-reperfusion injury in rats. {yields} Baicalin decreased the cerebral infarction area via inhibiting the activation of nuclear NF-{kappa}B 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-{kappa}B 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-{kappa}B p65 in cortex was increased after ischemia reperfusion injury, indicating the molecular mechanism of ischemia reperfusion injury. The level of NF-{kappa}B 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-{kappa}B p65.

  3. Reduction of zinc accumulation in mitochondria contributes to decreased cerebral ischemic injury by normobaric hyperoxia treatment in an experimental stroke model.

    PubMed

    Dong, Wen; Qi, Zhifeng; Liang, Jia; Shi, Wenjuan; Zhao, Yongmei; Luo, Yumin; Ji, Xunming; Liu, Ke Jian

    2015-10-01

    Cerebral ischemia interrupts oxygen supply to the affected tissues. Our previous studies have reported that normobaric hyperoxia (NBO) can maintain interstitial partial pressure of oxygen (pO2) in the penumbra of ischemic stroke rats at the physiological level, thus affording significant neuroprotection. However, the mechanisms that are responsible for the penumbra rescue by NBO treatment are not fully understood. Recent studies have shown that zinc, an important mediator of intracellular and intercellular neuronal signaling, accumulates in neurons and leads to ischemic neuronal injury. In this study, we investigate whether NBO could regulate zinc accumulation in the penumbra and prevent mitochondrial damage in penumbral tissue using a transient cerebral ischemic rat model. Our results showed that NBO significantly reduced zinc-staining positive cells and zinc-staining intensity in penumbral tissues, but not in the ischemic core. Moreover, ischemia-induced zinc accumulation in mitochondria, isolated from penumbral tissues, was greatly attenuated by NBO or a zinc-specific chelator, N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN). NBO or TPEN administration stabilized the mitochondrial membrane potential in the penumbra after cerebral ischemia. Finally, ischemia-induced cytochrome c release from mitochondria in penumbral tissues was significantly reduced by NBO or TPEN treatment. These findings demonstrate a novel mechanism for NBO's neuroprotection, especially to penumbral tissues, providing further evidence for the potential clinical benefit of NBO for acute ischemic stroke.

  4. Deterioration of baroreflex by transient global cerebral ischemia: its correlation with the degree of ischemia or post-ischemic hypoperfusion in the medulla oblongata.

    PubMed

    Kurihara, J; Sahara, T; Kato, H

    1989-12-01

    In a canine model of transient global cerebral ischemia, the correlation between the decrease in baroreflex sensitivity (BRS) following 5-min ischemia and the degree of ischemia or post-ischemic hypoperfusion was investigated. Although the medulla oblongata and the cerebral cortex suffered a similar degree of ischemia, the extent of post-ischemic decrease in BRS was inversely correlated with the residual blood flow during ischemia in the medulla, but not with that in the cerebral cortex. A similar degree of post-ischemic hypoperfusion occurred in the medulla and the cerebral cortex. However, the extent of decrease in BRS was not correlated with the degree of hypoperfusion, and the cortical EEG was not significantly affected. These results suggest that the decrease in BRS may be due to the functional damage in the medulla and that the selective decrease in BRS without concomitant impairment of the EEG cannot be ascribed to the regional difference in the degree of ischemia or post-ischemic hypoperfusion. PMID:2615041

  5. Differential expression of the calcium-sensing receptor in the ischemic and border zones after transient focal cerebral ischemia in rats.

    PubMed

    Noh, Jeong Sook; Pak, Ha-Jin; Shin, Yoo-Jin; Riew, Tae-Ryong; Park, Joo-Hee; Moon, Young Wha; Lee, Mun-Yong

    2015-01-01

    G-protein-coupled calcium-sensing receptor (CaSR) has been recently recognized as an important modulator of diverse cellular functions, beyond the regulation of systemic calcium homeostasis. To identify whether CaSR is involved in the pathophysiology of stroke, we studied the spatiotemporal regulation of CaSR protein expression in rats undergoing transient focal cerebral ischemia, which was induced by middle cerebral artery occlusion. We observed very weak or negligible immunoreactivity for CaSR in the striatum of sham-operated rats, as well as in the contralateral striatum of ischemic rats after reperfusion. However, CaSR expression was induced in the ischemic and border zones of the lesion in ischemic rats. Six hours post-reperfusion there was an upregulation of CaSR in the ischemic zone, which seemed to decrease after seven days. This upregulation preferentially affected some neurons and cells associated with blood vessels, particularly endothelial cells and pericytes. In contrast, CaSR expression in the peri-infarct region was prominent three days after reperfusion, and with the exception of some neurons, it was mostly located in reactive astrocytes, up to day 14 after ischemia. On the other hand, activated microglia/macrophages in both the ischemic and border zones were devoid of specific labeling for CaSR at any time point after reperfusion, despite their massive infiltration in both regions. Our results show heterogeneity in CaSR-positive cells within the ischemic and border zones, suggesting that CaSR expression is regulated in response to the altered extracellular ionic environment caused by ischemic injury. Thus, CaSR may have a multifunctional role in the pathophysiology of ischemic stroke, possibly in vascular remodeling and astrogliosis. PMID:26013410

  6. Differential expression of the calcium-sensing receptor in the ischemic and border zones after transient focal cerebral ischemia in rats.

    PubMed

    Noh, Jeong Sook; Pak, Ha-Jin; Shin, Yoo-Jin; Riew, Tae-Ryong; Park, Joo-Hee; Moon, Young Wha; Lee, Mun-Yong

    2015-01-01

    G-protein-coupled calcium-sensing receptor (CaSR) has been recently recognized as an important modulator of diverse cellular functions, beyond the regulation of systemic calcium homeostasis. To identify whether CaSR is involved in the pathophysiology of stroke, we studied the spatiotemporal regulation of CaSR protein expression in rats undergoing transient focal cerebral ischemia, which was induced by middle cerebral artery occlusion. We observed very weak or negligible immunoreactivity for CaSR in the striatum of sham-operated rats, as well as in the contralateral striatum of ischemic rats after reperfusion. However, CaSR expression was induced in the ischemic and border zones of the lesion in ischemic rats. Six hours post-reperfusion there was an upregulation of CaSR in the ischemic zone, which seemed to decrease after seven days. This upregulation preferentially affected some neurons and cells associated with blood vessels, particularly endothelial cells and pericytes. In contrast, CaSR expression in the peri-infarct region was prominent three days after reperfusion, and with the exception of some neurons, it was mostly located in reactive astrocytes, up to day 14 after ischemia. On the other hand, activated microglia/macrophages in both the ischemic and border zones were devoid of specific labeling for CaSR at any time point after reperfusion, despite their massive infiltration in both regions. Our results show heterogeneity in CaSR-positive cells within the ischemic and border zones, suggesting that CaSR expression is regulated in response to the altered extracellular ionic environment caused by ischemic injury. Thus, CaSR may have a multifunctional role in the pathophysiology of ischemic stroke, possibly in vascular remodeling and astrogliosis.

  7. Heat shock protein 90 inhibition by 17-Dimethylaminoethylamino-17-demethoxygeldanamycin protects blood-brain barrier integrity in cerebral ischemic stroke.

    PubMed

    Qi, Jia; Liu, Yan; Yang, Ping; Chen, Ting; Liu, Xin Zhu; Yin, You; Zhang, Jian; Wang, Feng

    2015-01-01

    Metalloproteinase (MMP)9 plays a pivotal role in ischemic stroke induced blood brain barrier (BBB) disruption. Correlation between HSP90 and MMP9 in several diseases prompted us to evaluate the efficacy of HSP90 inhibition as a novel approach to protect BBB integrity in ischemic stroke. ELISA was used to detect HSP90α and MMP9 in serum samples of stroke patients, which showed that HSP90α significantly correlated with MMP9 among 63 serum samples of stroke patients. Male C57/BL6 mice were pretreated with 17-Dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) or vehicle before being subjected to transient occlusion of middle cerebral artery and reperfusion (MCAO). Infarction, neurological scores, Evans blue (EB) extravasation, inflammatory responses and tight junction protein expression were examined 24 h after MCAO. We also investigated if 17-DMAG protected BBB integrity by suppressing inflammation and MMP9 activation. Oxygen glucose deprivation (OGD) was performed on bEnd.3 cells to explore the mechanisms of HSP90 inhibition in inhibiting MMP9. The results demonstrated that infarct volume was reduced in 17-DMAG-treated mice compared to control group following MCAO. Neurological outcomes were greatly improved in 17-DMAG-treated mice. Inflammatory responses, MMP9 activity and EB extravasation were decreased by 17-DMAG. In addition, 17-DMAG inhibited nuclear factor kappa B (NF-κB) activation following MCAO. Furthermore, HSP90 inhibition decreased NF-κB dependent MMP9 expression in bEnd.3 after OGD /reoxygenation. These findings suggested that HSP90 could be a novel therapeutic target in BBB breakdown during ischemic stroke. As several HSP90 inhibitors are in clinical trials for cancer, these findings have translational implications. PMID:26692927

  8. Heat shock protein 90 inhibition by 17-Dimethylaminoethylamino-17-demethoxygeldanamycin protects blood-brain barrier integrity in cerebral ischemic stroke

    PubMed Central

    Qi, Jia; Liu, Yan; Yang, Ping; Chen, Ting; Liu, Xin Zhu; Yin, You; Zhang, Jian; Wang, Feng

    2015-01-01

    Metalloproteinase (MMP)9 plays a pivotal role in ischemic stroke induced blood brain barrier (BBB) disruption. Correlation between HSP90 and MMP9 in several diseases prompted us to evaluate the efficacy of HSP90 inhibition as a novel approach to protect BBB integrity in ischemic stroke. ELISA was used to detect HSP90α and MMP9 in serum samples of stroke patients, which showed that HSP90α significantly correlated with MMP9 among 63 serum samples of stroke patients. Male C57/BL6 mice were pretreated with 17-Dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) or vehicle before being subjected to transient occlusion of middle cerebral artery and reperfusion (MCAO). Infarction, neurological scores, Evans blue (EB) extravasation, inflammatory responses and tight junction protein expression were examined 24 h after MCAO. We also investigated if 17-DMAG protected BBB integrity by suppressing inflammation and MMP9 activation. Oxygen glucose deprivation (OGD) was performed on bEnd.3 cells to explore the mechanisms of HSP90 inhibition in inhibiting MMP9. The results demonstrated that infarct volume was reduced in 17-DMAG-treated mice compared to control group following MCAO. Neurological outcomes were greatly improved in 17-DMAG-treated mice. Inflammatory responses, MMP9 activity and EB extravasation were decreased by 17-DMAG. In addition, 17-DMAG inhibited nuclear factor kappa B (NF-κB) activation following MCAO. Furthermore, HSP90 inhibition decreased NF-κB dependent MMP9 expression in bEnd.3 after OGD /reoxygenation. These findings suggested that HSP90 could be a novel therapeutic target in BBB breakdown during ischemic stroke. As several HSP90 inhibitors are in clinical trials for cancer, these findings have translational implications. PMID:26692927

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

    PubMed Central

    Shiao, Young-Ji; Liou, Kuo-Tong; Hsu, Wei-Hsiang; Hsieh, Pei-Hsuan; Lee, Chi-Ying; Chen, Yet-Ran; Lin, Yun-Lian

    2015-01-01

    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. PMID:26492191

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

    PubMed

    Chen, Hong-Jhang; Shen, Yuh-Chiang; Shiao, Young-Ji; Liou, Kuo-Tong; Hsu, Wei-Hsiang; Hsieh, Pei-Hsuan; Lee, Chi-Ying; Chen, Yet-Ran; Lin, Yun-Lian

    2015-01-01

    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. PMID:26492191

  11. Effects of hypnosis on regional cerebral blood flow during ischemic pain with and without suggested hypnotic analgesia.

    PubMed

    Crawford, H J; Gur, R C; Skolnick, B; Gur, R E; Benson, D M

    1993-11-01

    Using 133Xe regional cerebral blood flow (CBF) imaging, two male groups having high and low hypnotic susceptibility were compared in waking and after hypnotic induction, while at rest and while experiencing ischemic pain to both arms under two conditions: attend to pain and suggested analgesia. Differences between low and highly-hypnotizable persons were observed during all hypnosis conditions: only highly-hypnotizable persons showed a significant increase in overall CBF, suggesting that hypnosis requires cognitive effort. As anticipated, ischemic pain produced CBF increases in the somatosensory region. Of major theoretical interest is a highly-significant bilateral CBF activation of the orbito-frontal cortex in the highly-hypnotizable group only during hypnotic analgesia. During hypnotic analgesia, highly-hypnotizable persons showed CBF increase over the somatosensory cortex, while low-hypnotizable persons showed decreases. Research is supportive of a neuropsychophysiological model of hypnosis (Crawford, 1991; Crawford and Gruzelier, 1992) and suggests that hypnotic analgesia involves the supervisory, attentional control system of the far-frontal cortex in a topographically specific inhibitory feedback circuit that cooperates in the regulation of thalamocortical activities. PMID:8166843

  12. [A Case of Aplastic or Twig-Like Middle Cerebral Artery Presenting with an Intracranial Hemorrhage Two Years after a Transient Ischemic Attack].

    PubMed

    Uchiyama, Taku; Okamoto, Hiroaki; Koguchi, Motofumi; Tajima, Yutaka; Suzuyama, Kenji

    2016-02-01

    Aplastic or twig-like middle cerebral artery (Ap/T-MCA) is a rare anatomical anomaly, which can be associated with intracranial hemorrhage and cerebral ischemia. A 52-year-old woman who presented with sudden headache was admitted to our hospital. Computed tomography (CT) and magnetic resonance imaging showed no abnormality; however, magnetic resonance angiogram revealed an occlusion or severe stenosis in the left middle cerebral artery. Three-dimensional CT angiography demonstrated severe stenosis in the left middle cerebral artery. The patient was discharged without any neurological deficit; however, she subsequently complained of temporary weakness in the right hand. It was possibly due to a transient ischemic attack; therefore, cilostazol 200 mg/day was administered for prevention of cerebral ischemia. Single photon emission computed tomography(with or without administration of acetazolamide)showed neither significant decrease in the cerebral blood flow nor cerebrovascular reactivity; hence, surgical revascularization was not performed. However, two years after the initial admission, she was urgently admitted to our hospital with sudden headache and nausea followed by aphasia and weakness of the right extremities. CT images showed diffuse subarachnoid hemorrhage and intracerebral hemorrhage in the left temporo-parietal lobe. Cerebral angiography revealed that the left middle cerebral artery was Ap/T-MCA without cerebral aneurysms. The patient was treated conservatively, and she eventually recovered without any neurological deficit except mild aphasia. Since Ap/T-MCA is associated with both hemorrhagic and ischemic stroke, antiplatelet therapy should be administered carefully. Moreover, it is necessary to consider extracranial-intracranial bypass to reduce hemodynamic stress on the abnormal vessels.

  13. Optical bedside monitoring of cerebral perfusion: technological and methodological advances applied in a study on acute ischemic stroke

    NASA Astrophysics Data System (ADS)

    Steinkellner, Oliver; Gruber, Clemens; Wabnitz, Heidrun; Jelzow, Alexander; Steinbrink, Jens; Fiebach, Jochen B.; MacDonald, Rainer; Obrig, Hellmuth

    2010-11-01

    We present results of a clinical study on bedside perfusion monitoring of the human brain by optical bolus tracking. We measure the kinetics of the contrast agent indocyanine green using time-domain near-IR spectroscopy (tdNIRS) in 10 patients suffering from acute unilateral ischemic stroke. In all patients, a delay of the bolus over the affected when compared to the unaffected hemisphere is found (mean: 1.5 s, range: 0.2 s to 5.2 s). A portable time-domain near-IR reflectometer is optimized and approved for clinical studies. Data analysis based on statistical moments of time-of-flight distributions of diffusely reflected photons enables high sensitivity to intracerebral changes in bolus kinetics. Since the second centralized moment, variance, is preferentially sensitive to deep absorption changes, it provides a suitable representation of the cerebral signals relevant for perfusion monitoring in stroke. We show that variance-based bolus tracking is also less susceptible to motion artifacts, which often occur in severely affected patients. We present data that clearly manifest the applicability of the tdNIRS approach to assess cerebral perfusion in acute stroke patients at the bedside. This may be of high relevance to its introduction as a monitoring tool on stroke units.

  14. Effects of ischemic preconditioning on VEGF and pFlk-1 immunoreactivities in the gerbil ischemic hippocampus after transient cerebral ischemia.

    PubMed

    Park, Yoo Seok; Cho, Jun Hwi; Kim, In Hye; Cho, Geum-Sil; Cho, Jeong-Hwi; Park, Joon Ha; Ahn, Ji Hyeon; Chen, Bai Hui; Shin, Bich-Na; Shin, Myoung Cheol; Tae, Hyun-Jin; Cho, Young Shin; Lee, Yun Lyul; Kim, Young-Myeong; Won, Moo-Ho; Lee, Jae-Chul

    2014-12-15

    Ischemia preconditioning (IPC) displays an important adaptation of the CNS to sub-lethal ischemia. In the present study, we examined the effect of IPC on immunoreactivities of VEGF-, and phospho-Flk-1 (pFlk-1) following transient cerebral ischemia in gerbils. The animals were randomly assigned to four groups (sham-operated-group, ischemia-operated-group, IPC plus (+) sham-operated-group, and IPC+ischemia-operated-group). IPC was induced by subjecting gerbils to 2 min of ischemia followed by 1 day of recovery. In the ischemia-operated-group, a significant loss of neurons was observed in the stratum pyramidale (SP) of the hippocampal CA1 region (CA1) alone 5 days after ischemia-reperfusion, however, in all the IPC+ischemia-operated-groups, pyramidal neurons in the SP were well protected. In immunohistochemical study, VEGF immunoreactivity in the ischemia-operated-group was increased in the SP at 1 day post-ischemia and decreased with time. Five days after ischemia-reperfusion, strong VEGF immunoreactivity was found in non-pyramidal cells, which were identified as pericytes, in the stratum oriens (SO) and radiatum (SR). In the IPC+sham-operated- and IPC+ischemia-operated-groups, VEGF immunoreactivity was significantly increased in the SP. pFlk-1 immunoreactivity in the sham-operated- and ischemia-operated-groups was hardly found in the SP, and, from 2 days post-ischemia, pFlk-1 immunoreactivity was strongly increased in non-pyramidal cells, which were identified as pericytes. In the IPC+sham-operated-group, pFlk-1 immunoreactivity was significantly increased in both pyramidal and non-pyramidal cells; in the IPC+ischemia-operated-groups, the similar pattern of VEGF immunoreactivity was found in the ischemic CA1, although the VEGF immunoreactivity was strong in non-pyramidal cells at 5 days post-ischemia. In brief, our findings show that IPC dramatically augmented the induction of VEGF and pFlk-1 immunoreactivity in the pyramidal cells of the CA1 after ischemia

  15. Effects of ischemic preconditioning on VEGF and pFlk-1 immunoreactivities in the gerbil ischemic hippocampus after transient cerebral ischemia.

    PubMed

    Park, Yoo Seok; Cho, Jun Hwi; Kim, In Hye; Cho, Geum-Sil; Cho, Jeong-Hwi; Park, Joon Ha; Ahn, Ji Hyeon; Chen, Bai Hui; Shin, Bich-Na; Shin, Myoung Cheol; Tae, Hyun-Jin; Cho, Young Shin; Lee, Yun Lyul; Kim, Young-Myeong; Won, Moo-Ho; Lee, Jae-Chul

    2014-12-15

    Ischemia preconditioning (IPC) displays an important adaptation of the CNS to sub-lethal ischemia. In the present study, we examined the effect of IPC on immunoreactivities of VEGF-, and phospho-Flk-1 (pFlk-1) following transient cerebral ischemia in gerbils. The animals were randomly assigned to four groups (sham-operated-group, ischemia-operated-group, IPC plus (+) sham-operated-group, and IPC+ischemia-operated-group). IPC was induced by subjecting gerbils to 2 min of ischemia followed by 1 day of recovery. In the ischemia-operated-group, a significant loss of neurons was observed in the stratum pyramidale (SP) of the hippocampal CA1 region (CA1) alone 5 days after ischemia-reperfusion, however, in all the IPC+ischemia-operated-groups, pyramidal neurons in the SP were well protected. In immunohistochemical study, VEGF immunoreactivity in the ischemia-operated-group was increased in the SP at 1 day post-ischemia and decreased with time. Five days after ischemia-reperfusion, strong VEGF immunoreactivity was found in non-pyramidal cells, which were identified as pericytes, in the stratum oriens (SO) and radiatum (SR). In the IPC+sham-operated- and IPC+ischemia-operated-groups, VEGF immunoreactivity was significantly increased in the SP. pFlk-1 immunoreactivity in the sham-operated- and ischemia-operated-groups was hardly found in the SP, and, from 2 days post-ischemia, pFlk-1 immunoreactivity was strongly increased in non-pyramidal cells, which were identified as pericytes. In the IPC+sham-operated-group, pFlk-1 immunoreactivity was significantly increased in both pyramidal and non-pyramidal cells; in the IPC+ischemia-operated-groups, the similar pattern of VEGF immunoreactivity was found in the ischemic CA1, although the VEGF immunoreactivity was strong in non-pyramidal cells at 5 days post-ischemia. In brief, our findings show that IPC dramatically augmented the induction of VEGF and pFlk-1 immunoreactivity in the pyramidal cells of the CA1 after ischemia

  16. Urgent endarterectomy using pretreatment with free radical scavenger, edaravone, and early clamping of the parent arteries for cervical carotid artery stenosis with crescendo transient ischemic attacks caused by mobile thrombus and hemodynamic cerebral ischemia. Case report.

    PubMed

    Kobayashi, Masakazu; Ogasawara, Kuniaki; Inoue, Takashi; Saito, Hideo; Komoribayashi, Nobukazu; Suga, Yasunori; Ogawa, Akira

    2007-03-01

    A 68-year-old man with left cervical internal carotid artery stenosis suffered crescendo transient ischemic attacks caused by mobile thrombus detected by carotid echography and secondary impairment of cerebral hemodynamic reserve demonstrated by positron emission tomography. Urgent carotid endarterectomy (CEA) was performed following pretreatment with edaravone and early clamping of the carotid arteries without intraluminal shunting. The postoperative course was uneventful, and postoperative magnetic resonance imaging and single-photon emission computed tomography revealed no new cerebral ischemic lesions and no findings of cerebral hyperperfusion, respectively. The risks associated with CEA are higher for patients with evolving stroke or crescendo transient ischemic attacks than that for patients with stable disease. This case demonstrates that urgent endarterectomy for cervical carotid artery stenosis with crescendo transient ischemic attacks caused by mobile thrombi and hemodynamic cerebral ischemia can be successfully performed following pretreatment with edaravone and early clamping of the carotid arteries.

  17. Angiogenesis and Improved Cerebral Blood Flow in the Ischemic Boundary Area Detected by MRI after Administration of Sildenafil to Rats with Embolic Stroke

    PubMed Central

    Li, Lian; Jiang, Quan; Zhang, Li; Ding, Guangliang; Zhang, Zheng Gang; Li, Qingjiang; Ewing, James R.; Lu, Mei; Panda, Swayamprava; Ledbetter, Karyn A.; Whitton, Polly A.; Chopp, Michael

    2007-01-01

    To dynamically investigate the long-term response of an ischemic lesion in rat brain to the administration of sildenafil, male Wistar rats subjected to embolic stroke were treated with sildenafil (n=11) or saline (n=10) at a dose of 10mg/Kg administered subcutaneously 24-hours after stroke and daily for an additional 6-days. Magnetic resonance images were acquired and functional performance was measured in all animals at 1-day, 2-days and weekly for 6-weeks post-stroke. All rats were sacrificed 6-weeks after stroke and endothelial barrier antigen immunostaining was employed for morphological analysis and quantification of cerebral vessels. Map-ISODATA was computed from T1, T2 and T1sat maps. ISODATA derived tissue signatures characterize the degree of ischemic injury. Based on the map-ISODATA calculated at 6-weeks, the ischemic lesion for each animal was divided into two specific regions, the ischemic boundary and ischemic core. The temporal profiles of cerebral blood flow (CBF) and tissue signature were retrospectively tracked in these two regions and were compared with histological evaluation and functional outcome. After 1-week of sildenafil treatment, the ischemic lesion exhibited two significantly different regions, with higher CBF level and correspondingly, lower tissue signature value in the boundary region than in the core region. Sildenafil treatment did not significantly reduce the lesion size, but did enhance angiogenesis. Functional performance was significantly increased after sildenafil treatment compared with the control group. Administration of sildenafil to rats with embolic stroke enhances angiogenesis and selectively increases the CBF level in the ischemic boundary, and improves neurological functional recovery compared to saline-treated rats. PMID:17188664

  18. Neuroprotective effect of curcumin on focal cerebral ischemic rats by preventing blood-brain barrier damage.

    PubMed

    Jiang, Jun; Wang, Wei; Sun, Yong Jun; Hu, Mei; Li, Fei; Zhu, Dong Ya

    2007-04-30

    Curcumin, a member of the curcuminoid family of compounds, is a yellow colored phenolic pigment obtained from 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. Disruption of the blood-brain barrier occurs after stroke. Protection of the blood-brain barrier has become an important target of stroke interventions in experimental therapeutic. The objective of the present study was to determine whether curcumin prevents cerebral ischemia/reperfusion injury by protecting blood-brain barrier integrity. We report that a single injection of curcumin (1 and 2 mg/kg, i.v.) 30 min after focal cerebral ischemia/reperfusion in rats significantly diminished infarct volume, improved neurological deficit, decreased mortality, reduced the water content of the brain and the extravasation of Evans blue dye in ipsilateral hemisphere in a dose-dependent manner. In cultured astrocytes, curcumin significantly inhibited inducible nitric oxide synthase (iNOS) expression and NO(x) (Nitrites/nitrates contents) production induced by lipopolysaccharide (LPS)/tumor necrosis factor alpha (TNF(alpha)). Furthermore, curcumin prevented ONOO(-) donor SIN-1-induced cerebral capillaries endothelial cells damage. We concluded that curcumin ameliorates cerebral ischemia/reperfusion injury by preventing ONOO(-) mediated blood-brain barrier damage. PMID:17303117

  19. Protective effects of allicin against ischemic stroke in a rat model of middle cerebral artery occlusion.

    PubMed

    Zhang, Benping; Li, Feng; Zhao, Weijiang; Li, Jiebing; Li, Qingsong; Wang, Weizhi

    2015-09-01

    Allicin, a molecule predominantly responsible for the pungent odor and the antibiotic function of garlic, exhibits various pharmacological activities and has been suggested to be beneficial in the treatment of various disorders. The present study aimed to elucidate the effect of allicin in cerebral ischemia/reperfusion (I/R) injury in rats. Rats were subjected to 1.5 h of transient middle cerebral artery occlusion (MCAO), followed by 24 h of reperfusion. Rats were randomly assigned to the sham surgery group, the MCAO group and the MCAO + allicin group. Neurological score, cerebral infarct size, brain water content, neuronal apoptosis, serum tumor necrosis factor (TNF)‑α and myeloperoxidase (MPO) activity were measured. The results suggested that allicin reduced cerebral infarction area, brain water content, neuronal apoptosis, TNF‑α levels and MPO activity in the serum. The results of the present study indicated that allicin protects the brain from cerebral I/R injury, which may be ascribed to its anti‑apoptotic and anti‑inflammatory effects.

  20. Protective effects of allicin against ischemic stroke in a rat model of middle cerebral artery occlusion.

    PubMed

    Zhang, Benping; Li, Feng; Zhao, Weijiang; Li, Jiebing; Li, Qingsong; Wang, Weizhi

    2015-09-01

    Allicin, a molecule predominantly responsible for the pungent odor and the antibiotic function of garlic, exhibits various pharmacological activities and has been suggested to be beneficial in the treatment of various disorders. The present study aimed to elucidate the effect of allicin in cerebral ischemia/reperfusion (I/R) injury in rats. Rats were subjected to 1.5 h of transient middle cerebral artery occlusion (MCAO), followed by 24 h of reperfusion. Rats were randomly assigned to the sham surgery group, the MCAO group and the MCAO + allicin group. Neurological score, cerebral infarct size, brain water content, neuronal apoptosis, serum tumor necrosis factor (TNF)‑α and myeloperoxidase (MPO) activity were measured. The results suggested that allicin reduced cerebral infarction area, brain water content, neuronal apoptosis, TNF‑α levels and MPO activity in the serum. The results of the present study indicated that allicin protects the brain from cerebral I/R injury, which may be ascribed to its anti‑apoptotic and anti‑inflammatory effects. PMID:26045182

  1. Hydrogen sulfide protects the brain against ischemic reperfusion injury in a transient model of focal cerebral ischemia.

    PubMed

    Gheibi, Sevda; Aboutaleb, Nahid; Khaksari, Mehdi; Kalalian-Moghaddam, Hamid; Vakili, Abedin; Asadi, Yasin; Mehrjerdi, Fatemeh Zare; Gheibi, Azam

    2014-01-01

    Hydrogen sulfide (H(2)S), a well-known toxic gas, is regarded as endogenous neuromodulator and plays multiple roles in the central nervous system under physiological and pathological states, especially in secondary neuronal injury. Recent studies have shown relatively high concentrations of hydrogen sulfide (H(2)S) in the brain and also cytoprotective effects of endogenous and exogenous H(2)S in models of in vitro and in vivo ischemic injury. H(2)S protects neurons by functioning as an anti-oxidant, anti-inflammatory, and anti-apoptotic mediator and by improving neurological function. Moreover, it protects neurons from glutamate toxicity. Therefore, the present study aimed to determine whether H(2)S provides protection in transient focal cerebral ischemia. Focal ischemia was induced by 60-min middle cerebral artery occlusion (MCAO), followed by 23-h reperfusion. Saline as a vehicle and NaHS (H(2)S donor; 1 and 5 mg) were intraperitoneally injected (IP) at the beginning of ischemia. Infarct volume, brain edema, and apoptosis were assessed 24 h after MCAO.Treatment with NaHS at doses of 1 and 5 mg markedly reduced total infarct volumes by 29 and 51 %, respectively (P < 0.001). In addition, NaHS at doses of 1 and 5 mg reduced brain edema (P < 0.05) and inhibited apoptosis by decreasing positive TUNEL cells (P < 0.001).The present study shows that treatment with H(2)S reduces brain injuries and postischemic cerebral edema in a dose-dependent manner likely through the blocking programmed cell death.We propose that H(2)S might be a promising therapeutic target for stroke, although more researches are necessary to take into account the potential therapeutic effects of H(2)S in stroke patients.

  2. Vulnerability of the developing brain to hypoxic-ischemic damage: contribution of the cerebral vasculature to injury and repair?

    PubMed Central

    Baburamani, Ana A.; Ek, C. Joakim; Walker, David W.; Castillo-Melendez, Margie

    2012-01-01

    As clinicians attempt to understand the underlying reasons for the vulnerability of different regions of the developing brain to injury, it is apparent that little is known as to how hypoxia-ischemia may affect the cerebrovasculature in the developing infant. Most of the research investigating the pathogenesis of perinatal brain injury following hypoxia-ischemia has focused on excitotoxicity, oxidative stress and an inflammatory response, with the response of the developing cerebrovasculature receiving less attention. This is surprising as the presentation of devastating and permanent injury such as germinal matrix-intraventricular haemorrhage (GM-IVH) and perinatal stroke are of vascular origin, and the origin of periventricular leukomalacia (PVL) may also arise from poor perfusion of the white matter. This highlights that cerebrovasculature injury following hypoxia could primarily be responsible for the injury seen in the brain of many infants diagnosed with hypoxic-ischemic encephalopathy (HIE). Interestingly the highly dynamic nature of the cerebral blood vessels in the fetus, and the fluctuations of cerebral blood flow and metabolic demand that occur following hypoxia suggest that the response of blood vessels could explain both regional protection and vulnerability in the developing brain. However, research into how blood vessels respond following hypoxia-ischemia have mostly been conducted in adult models of ischemia or stroke, further highlighting the need to investigate how the developing cerebrovasculature responds and the possible contribution to perinatal brain injury following hypoxia. This review discusses the current concepts on the pathogenesis of perinatal brain injury, the development of the fetal cerebrovasculature and the blood brain barrier (BBB), and key mediators involved with the response of cerebral blood vessels to hypoxia. PMID:23162470

  3. Visualization of in vivo metabolic flows reveals accelerated utilization of glucose and lactate in penumbra of ischemic heart

    PubMed Central

    Sugiura, Yuki; Katsumata, Yoshinori; Sano, Motoaki; Honda, Kurara; Kajimura, Mayumi; Fukuda, Keiichi; Suematsu, Makoto

    2016-01-01

    Acute ischemia produces dynamic changes in labile metabolites. To capture snapshots of such acute metabolic changes, we utilized focused microwave treatment to fix metabolic flow in vivo in hearts of mice 10 min after ligation of the left anterior descending artery. The left ventricle was subdivided into short-axis serial slices and the metabolites were analyzed by capillary electrophoresis mass spectrometry and matrix-assisted laser desorption/ionization imaging mass spectrometry. These techniques allowed us to determine the fate of exogenously administered 13C6-glucose and 13C3-lactate. The penumbra regions, which are adjacent to the ischemic core, exhibited the greatest adenine nucleotide energy charge and an adenosine overflow extending from the ischemic core, which can cause ischemic hyperemia. Imaging analysis of metabolic pathway flows revealed that the penumbra executes accelerated glucose oxidation, with remaining lactate utilization for tricarboxylic acid cycle for energy compensation, suggesting unexpected metabolic interplays of the penumbra with the ischemic core and normoxic regions. PMID:27581923

  4. Visualization of in vivo metabolic flows reveals accelerated utilization of glucose and lactate in penumbra of ischemic heart.

    PubMed

    Sugiura, Yuki; Katsumata, Yoshinori; Sano, Motoaki; Honda, Kurara; Kajimura, Mayumi; Fukuda, Keiichi; Suematsu, Makoto

    2016-01-01

    Acute ischemia produces dynamic changes in labile metabolites. To capture snapshots of such acute metabolic changes, we utilized focused microwave treatment to fix metabolic flow in vivo in hearts of mice 10 min after ligation of the left anterior descending artery. The left ventricle was subdivided into short-axis serial slices and the metabolites were analyzed by capillary electrophoresis mass spectrometry and matrix-assisted laser desorption/ionization imaging mass spectrometry. These techniques allowed us to determine the fate of exogenously administered (13)C6-glucose and (13)C3-lactate. The penumbra regions, which are adjacent to the ischemic core, exhibited the greatest adenine nucleotide energy charge and an adenosine overflow extending from the ischemic core, which can cause ischemic hyperemia. Imaging analysis of metabolic pathway flows revealed that the penumbra executes accelerated glucose oxidation, with remaining lactate utilization for tricarboxylic acid cycle for energy compensation, suggesting unexpected metabolic interplays of the penumbra with the ischemic core and normoxic regions. PMID:27581923

  5. Immediate remote ischemic postconditioning after hypoxia ischemia in piglets protects cerebral white matter but not grey matter

    PubMed Central

    Ezzati, Mojgan; Bainbridge, Alan; Broad, Kevin D; Kawano, Go; Oliver-Taylor, Aaron; Rocha-Ferreira, Eridan; Alonso-Alconada, Daniel; Fierens, Igor; Rostami, Jamshid; Jane Hassell, K; Tachtsidis, Ilias; Gressens, Pierre; Hristova, Mariya; Bennett, Kate; Lebon, Sophie; Fleiss, Bobbi; Yellon, Derek; Hausenloy, Derek J; Golay, Xavier

    2015-01-01

    Remote ischemic postconditioning (RIPostC) is a promising therapeutic intervention whereby brief episodes of ischemia/reperfusion of one organ (limb) mitigate damage in another organ (brain) that has experienced severe hypoxia-ischemia. Our aim was to assess whether RIPostC is protective following cerebral hypoxia-ischemia in a piglet model of neonatal encephalopathy (NE) using magnetic resonance spectroscopy (MRS) biomarkers and immunohistochemistry. After hypoxia-ischemia (HI), 16 Large White female newborn piglets were randomized to: (i) no intervention (n = 8); (ii) RIPostC – with four, 10-min cycles of bilateral lower limb ischemia/reperfusion immediately after HI (n = 8). RIPostC reduced the hypoxic-ischemic-induced increase in white matter proton MRS lactate/N acetyl aspartate (p = 0.005) and increased whole brain phosphorus-31 MRS ATP (p = 0.039) over the 48 h after HI. Cell death was reduced with RIPostC in the periventricular white matter (p = 0.03), internal capsule (p = 0.002) and corpus callosum (p = 0.021); there was reduced microglial activation in corpus callosum (p = 0.001) and more surviving oligodendrocytes in corpus callosum (p = 0.029) and periventricular white matter (p = 0.001). Changes in gene expression were detected in the white matter at 48 h, including KATP channel and endothelin A receptor. Immediate RIPostC is a potentially safe and promising brain protective therapy for babies with NE with protection in white but not grey matter. PMID:26661194

  6. Tongxinluo Enhances Neurogenesis and Angiogenesis in Peri-Infarct Area and Subventricular Zone and Promotes Functional Recovery after Focal Cerebral Ischemic Infarction in Hypertensive Rats

    PubMed Central

    Chen, Li; Wang, Xiaoting; Zhang, Jian; Dang, Chao; Liu, Gang; Liang, Zhijian; Huang, Gelun; Zhao, Weijia; Zeng, Jinsheng

    2016-01-01

    Background. Tongxinluo is a traditional Chinese medicine compound with the potential to promote the neuronal functional recovery in cerebral ischemic infarction. Objective. This study aimed to disclose whether tongxinluo promotes neurological functional recovery and neurogenesis and angiogenesis in the infarcted area and SVZ after cerebral ischemic infarction in hypertensive rats. Methods. The ischemic model was prepared by distal middle cerebral artery occlusion (MCAO) in hypertensive rats. Tongxinluo was administrated 24 h after MCAO and lasted for 3, 7, or 14 days. Behavioral tests were performed to evaluate the protection of tongxinluo. Immunochemical staining was applied on brain tissue to evaluate the effects of tongxinluo on neurogenesis and vascularization in the MCAO model rats. Results. Postinjury administration of tongxinluo ameliorated the neuronal function deficit in the MCAO model rats. As evidenced by the immunochemical staining, BrdU+/DCX+, BrdU+/nestin+, and BrdU+ vascular endothelial cells were promoted to proliferate in SVZ after tongxinluo administration. The matured neurons stained by NeuN and vascularization by laminin staining were observed after tongxinluo administration in the peri-infarct area. Conclusion. Tongxinluo postischemia administration could ameliorate the neurological function deficit in the model rats. Possible mechanisms are related to neurogenesis and angiogenesis in the peri-infarct area and SVZ. PMID:27069496

  7. Effect of Urinary Kallidinogenase on Transforming Growth Factor-β1 and High-Sensitivity C-Reactive Protein Expression in Rat Focal Cerebral Ischemic Injury

    PubMed Central

    Dong, Ting-Fang; Lv, Hai-Xia; Niu, Xiao-Lu; Gui, Yong-Kun; Zhang, Ping; Yan, Hai-Qing; Li, Tong

    2016-01-01

    Background In this study we investigated the effect of urinary kallidinogenase (UK) on transforming growth factor beta 1 (TGF-β1) expression in brain tissue. We also explored the neuroprotective mechanism of UK against ischemic injury by measuring serum high-sensitivity C-reactive protein (hs-CRP) level changes after rat cerebral ischemic injury. Material/Methods The rat middle cerebral artery ischemia/reperfusion model was established using the suture method. Sprague-Dawley rats were randomly divided into 3 groups: treatment, Gegen control, and blank control. Each group was subsequently divided into 5 subgroups according to time (6, 12, 24, 48, and 72 h). Rats in the treatment group were administered UK as treatment. TGF-β1 expression was observed at each time point using SABC and immunohistochemical staining methods to estimate cerebral infarct volume percentage. Serum hs-CRP levels were also measured. Results TGF-β1 protein expression in ischemic brain tissues of the treatment group significantly increased at each time point (P<0.01) compared with both control groups. Treatment group serum hs-CRP levels significantly decreased at each time point (P<0.05) compared with both control groups. Conclusions UK exerts a neuroprotective effect by upregulating TGF-β1 expression and inhibiting excessive inflammatory responses. PMID:27521289

  8. Limb Ischemic Perconditioning Attenuates Blood-Brain Barrier Disruption by Inhibiting Activity of MMP-9 and Occludin Degradation after Focal Cerebral Ischemia

    PubMed Central

    Ren, Changhong; Li, Ning; Wang, Brian; Yang, Yong; Gao, Jinhuan; Li, Sijie; Ding, Yuchuan; Jin, Kunlin; Ji, Xunming

    2015-01-01

    Remote ischemic perconditioning (PerC) has been proved to have neuroprotective effects on cerebral ischemia, however, the effect of PerC on the BBB disruption and underlying mechanisms remains largely unknown. To address these issues, total 90 adult male Sprague Dawley (SD) rats were used. The rats underwent 90-min middle cerebral artery occlusion (MCAO), and the limb remote ischemic PerC was immediately applied after the onset of MCAO. We found that limb remote PerC protected BBB breakdown and brain edema, in parallel with reduced infarct volume and improved neurological deficits, after MCAO. Immunofluorescence studies revealed that MCAO resulted in disrupted continuity of claudin-5 staining in the cerebral endothelial cells with significant gap formation, which was significantly improved after PerC. Western blot analysis demonstrated that expression of tight junction (TJ) protein occludin was significantly increased, but other elements of TJ proteins, claudin-5 and ZO-1, in the BBB endothelial cells were not altered at 48 h after PerC, compared to MCAO group. The expression of matrix metalloproteinase (MMP-9), which was involved in TJ protein degradation, was decreased after PerC. Interestingly, phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2), an upstream of MMP-9 signaling, was significantly reduced in the PerC group. Our data suggest that PerC inhibits MMP-9-mediated occludin degradation, which could lead to decreased BBB disruption and brain edema after ischemic stroke. PMID:26618042

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

    PubMed

    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 < 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

  10. Experimental animal models and inflammatory cellular changes in cerebral ischemic and hemorrhagic stroke

    PubMed Central

    Yan, Tao; Chopp, Michael; Chen, Jieli

    2015-01-01

    Stroke, including cerebral ischemia, intracerebral hemorrhage, and subarachnoid hemorrhage, is the leading cause of long-term disability and death worldwide. Animal models have greatly contributed to our understanding of the risk factors and the pathophysiology of stroke, as well as the development of therapeutic strategies for its treatment. Further development and investigation of experimental models, however, are needed to elucidate the pathogenesis of stroke and to enhance and expand novel therapeutic targets. In this article, we provide an overview of the characteristics of commonly-used animal models of stroke and focus on the inflammatory responses to cerebral stroke, which may provide insights into a framework for developing effective therapies for stroke in humans. PMID:26625873

  11. Progression from ischemic injury to infarct following middle cerebral artery occlusion in the rat.

    PubMed Central

    Garcia, J. H.; Yoshida, Y.; Chen, H.; Li, Y.; Zhang, Z. G.; Lian, J.; Chen, S.; Chopp, M.

    1993-01-01

    Focal brain ischemia induced in rats by occlusion of an intracranial artery is a widely used paradigm of human brain infarct. Details of the structural changes that develop in either the human or the rat brain at various times after occlusion of an intracranial artery are incompletely characterized. We studied, in 48 adult Wistar rats, structural alterations involving the cerebral hemisphere ipsilateral to an arterial occlusion, at intervals ranging from 30 min to 7 days. Microscopic changes developed over time in separate areas of the corresponding cerebral hemisphere in a predictable pattern, appearing as small lesions in the preoptic area (30 minutes), enlarging to involve the striatum, and finally involving the cerebral cortex. Two types of neuronal responses were noted according to the time elapsed; acute changes (up to 6 hours) included scalloping, shrinkage, and swelling, whereas delayed changes (eosinophilia and karyolysis) appeared later (> or = 12 hours). Three types of astrocytic responses were noted. 1) Cytoplasmic disintegration occurred in the preoptic area at a time and in a place where neurons appeared minimally injured. 2) Nuclear and cytoplasmic swelling were prominent responses in the caudoputamen and cerebral cortex at a time when neurons showed minimal alterations. 3) Increased astrocytic glial fibrillary acidic protein reactivity was noted at the interface between the lesion and the surrounding brain tissue after 4 to 6 hours. The gross pattern of the brain lesion and the maturation of neuronal changes typical of a brain infarct have a predictable progression. Focal brain ischemia of up to 6-hour duration does not induce coagulation necrosis. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:8434652

  12. An integrated pathway interaction network for the combination of four effective compounds from ShengMai preparations in the treatment of cardio-cerebral ischemic diseases

    PubMed Central

    Li, Fang; Lv, Yan-ni; Tan, Yi-sha; Shen, Kai; Zhai, Ke-feng; Chen, Hong-lin; Kou, Jun-ping; Yu, Bo-yang

    2015-01-01

    Aim: SMXZF (a combination of ginsenoside Rb1, ginsenoside Rg1, schizandrin and DT-13) derived from Chinese traditional medicine formula ShengMai preparations) is capable of alleviating cerebral ischemia-reperfusion injury in mice. In this study we used network pharmacology approach to explore the mechanisms of SMXZF in the treatment of cardio-cerebral ischemic diseases. Methods: Based upon the chemical predictors, such as chemical structure, pharmacological information and systems biology functional data analysis, a target-pathway interaction network was constructed to identify potential pathways and targets of SMXZF in the treatment of cardio-cerebral ischemia. Furthermore, the most related pathways were verified in TNF-α-treated human vascular endothelial EA.hy926 cells and H2O2-treated rat PC12 cells. Results: Three signaling pathways including the NF-κB pathway, oxidative stress pathway and cytokine network pathway were demonstrated to be the main signaling pathways. The results from the gene ontology analysis were in accordance with these signaling pathways. The target proteins were found to be associated with other diseases such as vision, renal and metabolic diseases, although they exerted therapeutic actions on cardio-cerebral ischemic diseases. Furthermore, SMXZF not only dose-dependently inhibited the phosphorylation of NF-κB, p50, p65 and IKKα/β in TNF-α-treated EA.hy926 cells, but also regulated the Nrf2/HO-1 pathway in H2O2-treated PC12 cells. Conclusion: NF-κB signaling pathway, oxidative stress pathway and cytokine network pathway are mainly responsible for the therapeutic actions of SMXZF against cardio-cerebral ischemic diseases. PMID:26456587

  13. Methylene Blue Reduces Acute Cerebral Ischemic Injury via the Induction of Mitophagy.

    PubMed

    Di, Yao; He, Yun-Ling; Zhao, Tong; Huang, Xin; Wu, Kui-Wu; Liu, Shu-Hong; Zhao, Yong-Qi; Fan, Ming; Wu, Li-Ying; Zhu, Ling-Ling

    2015-05-19

    The treatment of stroke is limited by a short therapeutic window and a lack of effective clinical drugs. Methylene blue (MB) has been used in laboratories and clinics since the 1890s. Few studies have reported the neuroprotective role of MB in cerebral ischemia-reperfusion injury. However, whether and how MB protects against acute cerebral ischemia (ACI) injury was unclear. In this study, we investigated the effect of MB on this injury and revealed that MB protected against ACI injury by augmenting mitophagy. Using a rat middle cerebral artery occlusion (MCAO) model, we demonstrated that MB improved neurological function and reduced the infarct volume and necrosis after ACI injury. These improvements depended on the effect of MB on mitochondrial structure and function. ACI caused the disorder and disintegration of mitochondrial structure, while MB ameliorated the destruction of mitochondria. In addition, mitophagy was inhibited at 24 h after stroke and MB augmented mitophagy. In an oxygen-glucose deprivation (OGD) model in vitro, we further revealed that the elevation of mitochondrial membrane potential (MMP) by MB under OGD conditions mediated the augmented mitophagy. In contrast, exacerbating the decline of MMP during OGD abolished the MB-induced activation of mitophagy. Taken together, MB promotes mitophagy by maintaining the MMP at a relatively high level, which contributes to a decrease in necrosis and an improvement in neurological function, thereby protecting against ACI injury.

  14. In vivo imaging of hemodynamics and oxygen metabolism in acute focal cerebral ischemic rats with laser speckle imaging and functional photoacoustic microscopy

    NASA Astrophysics Data System (ADS)

    Deng, Zilin; Wang, Zhen; Yang, Xiaoquan; Luo, Qingming; Gong, Hui

    2012-08-01

    Stroke is a devastating disease. The changes in cerebral hemodynamics and oxygen metabolism associated with stroke play an important role in pathophysiology study. But the changes were difficult to describe with a single imaging modality. Here the changes in cerebral blood flow (CBF), cerebral blood volume (CBV), and oxygen saturation (SO2) were yielded with laser speckle imaging (LSI) and photoacoustic microscopy (PAM) during and after 3-h acute focal ischemic rats. These hemodynamic measures were further synthesized to deduce the changes in oxygen extraction fraction (OEF). The results indicate that all the hemodynamics except CBV had rapid declines within 40-min occlusion of middle cerebral artery (MCAO). CBV in arteries and veins first increased to the maximum value of 112.42±36.69% and 130.58±31.01% by 15 min MCAO; then all the hemodynamics had a persistent reduction with small fluctuations during the ischemic. When ischemia lasted for 3 h, CBF in arteries, veins decreased to 17±14.65%, 24.52±20.66%, respectively, CBV dropped to 62±18.56% and 59±18.48%. And the absolute SO2 decreased by 40.52±22.42% and 54.24±11.77%. After 180-min MCAO, the changes in hemodynamics and oxygen metabolism were also quantified. The study suggested that combining LSI and PAM provides an attractive approach for stroke detection in small animal studies.

  15. Relationship Between Cerebral Oxygenation and Metabolism During Rewarming in Newborn Infants After Therapeutic Hypothermia Following Hypoxic-Ischemic Brain Injury.

    PubMed

    Mitra, Subhabrata; Bale, Gemma; Meek, Judith; Uria-Avellanal, Cristina; Robertson, Nicola J; Tachtsidis, Ilias

    2016-01-01

    Therapeutic hypothermia (TH) has become a standard of care following hypoxic ischemic encephalopathy (HIE). After TH, body temperature is brought back to 37 °C over 14 h. Lactate/N-acetylasperatate (Lac/NAA) peak area ratio on proton magnetic resonance spectroscopy ((1)H MRS) is the best available outcome biomarker following HIE. We hypothesized that broadband near infrared spectroscopy (NIRS) measured changes in the oxidation state of cytochrome-c-oxidase concentration (Δ[oxCCO]) and cerebral hemodynamics during rewarming would relate to Lac/NAA. Broadband NIRS and systemic data were collected during rewarming from 14 infants following HIE over a mean period of 12.5 h. (1)H MRS was performed on day 5-9. Heart rate increased by 20/min during rewarming while blood pressure and peripheral oxygen saturation (SpO2) remained stable. The relationship between mitochondrial metabolism and oxygenation (measured as Δ[oxCCO] and Δ[HbD], respectively) was calculated by linear regression analysis. This was reviewed in three groups: Lac/NAA values <0.5, 0.5-1, >1. Mean regression coefficient (r (2)) values in these groups were 0.41 (±0.27), 0.22 (±0.21) and 0.01, respectively. The relationship between mitochondrial metabolism and oxygenation became impaired with rising Lac/NAA. Cardiovascular parameters remained stable during rewarming.

  16. Endovascular treatment of asymptomatic cerebral aneurysms: anatomic and technical factors related to ischemic events and coil stabilization.

    PubMed

    Soeda, Akio; Sakai, Nobuyuki; Sakai, Hideki; Iihara, Koji; Nagata, Izumi

    2004-09-01

    The present study assessed the safety and efficacy of embolization using Guglielmi detachable coils (GDCs) in 100 asymptomatic cerebral aneurysms classified as sidewall (70) or terminal (30) aneurysms according to the parent artery (68 small aneurysms with a small neck, 21 small aneurysms with a wide neck, and 11 large aneurysms). A balloon-assisted technique was used in 49 aneurysms. Immediate angiography revealed that 71 aneurysms were completely obliterated. Transient deficits occurred in 19 patients, permanent deficits in four patients, and one patient died. Most complications occurred during or immediately after treatment and resolved within a few minutes to a few weeks. None of the surviving patients manifested significant morbidity at 1-year follow up. Follow-up angiographic study was performed in 79 aneurysms. Rates of recanalization and progressive thrombosis (total occlusion of the residual aneurysm at follow up) were 11% and 38%, respectively, in sidewall aneurysms, and 26% and 0%, respectively, in terminal aneurysms. Treatment with GDCs was effective for patients with small aneurysms with small necks, the morbidity was acceptable, and progressive thrombosis occurred during the follow-up period. GDC treatment achieved unsatisfactory results in patients with small terminal aneurysms with wide necks and in large aneurysms, because the obliteration rate was low, and the recanalization and complication rates were high. Multivariate analysis showed that complete occlusion was associated with small-necked aneurysms, and ischemic events tended to occur in terminal aneurysms and in aneurysms treated by the balloon-assisted technique.

  17. Transient ischemic cerebral lesions during induction chemotherapy for acute lymphoblastic leukemia.

    PubMed

    Pihko, H; Tyni, T; Virkola, K; Valanne, L; Sainio, K; Hovi, L; Saarinen, U M

    1993-11-01

    Ninety children were treated for acute lymphoblastic leukemia or non-Hodgkin lymphoma during 1986 through 1992 in the Children's Hospital, University of Helsinki, in Finland. During induction chemotherapy, nine of the children had visual hallucinations progressing to confusion and seizure. The symptoms were often preceded by severe constipation and significantly elevated blood pressure. Neuroradiologic examinations showed bilateral cortical or subcortical white matter lesions. Despite the stroke like manifestations, the lesions were reversible. The triangular shape and location of the lesions in the watershed areas between the major cerebral arteries suggest vascular ischemia as the cause.

  18. Bone marrow derived mesenchymal stem cells alleviated brain injury via down-regulation of interleukin-1β in focal cerebral ischemic rats

    PubMed Central

    Zhao, Yansong; Wang, Xiaoli; Dong, Peng; Xu, Qinyan; Ma, Ze; Mu, Qingjie; Sun, Xihe; Jiang, Zhengchen; Wang, Xin

    2016-01-01

    Interleukin-1β (IL-1β) plays an important role in brain injury after focal ischemia, and bone marrow-derived mesenchymal stem cells (BMSCs) are capable of reducing the expression of IL-1β, we investigated the effects of BMSCs transplantation on brain edema and cerebral infarction as well as the underlying mechanisms via IL-1β. Male Sprague-Dawley rats were randomly divided into five groups: Normal + phosphate-buffered saline (PBS), middle cerebral artery occlusion (MCAO) + PBS, Normal + BMSCs, MCAO + BMSCs and MCAO + IL-1ra (an antagonist of IL-1β). BMSCs were transplanted 24 hours after MCAO, and brain edema was evaluated by Magnetic Resonance Imaging (MRI) and brain water content method after BMSCs transplantation. The expression of NeuN and AQP4 was analyzed by immunofluorescence staining. Protein level of AQP4 and IL-1β was detected by western blot analysis 48 hours after transplantation. The results showed that BMSCs transplantation reduced brain edema by measurement of brain water content and ADC Value of MRI, as well as the expression of AQP4 and IL-1β. It was also found that BMSCs transplantation could alleviate the cerebral infarction volume and neuronal damage. Both the brain edema and the cerebral infarction were associated with IL-1β expression. In conclusion, BMSCs transplantation was capable of alleviating brain edema as well as reducing cerebral infarction via down-regulation of IL-1β expression, thus repair the injured brain in focal cerebral ischemic rats. PMID:27186280

  19. Protective effects of ginsenoside Rg1 on astrocytes and cerebral ischemic-reperfusion mice.

    PubMed

    Sun, Chenghong; Lai, Xinqiang; Huang, Xiuyan; Zeng, Yaoying

    2014-01-01

    Ginsenoside Rg1 (Rg1), one of the active ingredients in Panax ginseng, has been known to regulate many cellular processes. The purpose of this study was to investigate the protective effects of Rg1 on apoptosis in mouse cultured astrocytes in vitro and a mouse model of cerebral ischemia and reperfusion in vivo. The cell apoptosis was measured by fluorescence microplate reader and xCELLigence system and the Ca(2+) overload was recorded by confocal microscopy. The mitochondrial membrane potential and reactive oxygen species (ROS) were determined by flow cytometry. BALB/c mice were subjected to transient middle cerebral artery occlusion (MCAO) and randomly divided into four groups: Sham (sham-operated +0.9% saline), MCAO (MCAO+0.9% saline), Rg1-L (MCAO+Rg1 20 mg/kg) and Rg1-H (MCAO+Rg1 40 mg/kg). Neurological deficit scores, brain water content and infarct volume were evaluated at 24 h after reperfusion. The results showed that Rg1 significantly attenuated H2O2-induced apoptosis in astrocytes. Rg1 efficiently inhibited intracellular Ca(2+) overload, loss of mitochondrial membrane potential, and ROS production in astrocytes. In vivo study, it was also observed that Rg1 markedly reduced the neurological deficit scores, brain edema, and infarct volume in the model mice. These results suggest that Rg1 possesses significant neuroprotective effects, which might be related to the prevention of astrocytes from apoptosis. PMID:25451838

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

    PubMed

    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. PMID:27362436

  1. Outcome of cerebral arteriovenous malformations after linear accelerator reirradiation

    PubMed Central

    Moraes, Paulo L.; Dias, Rodrigo S.; Weltman, Eduardo; Giordani, Adelmo J.; Benabou, Salomon; Segreto, Helena R. C.; Segreto, Roberto A.

    2015-01-01

    Background: The aim of this study was to evaluate the clinical outcome of patients undergoing single-dose reirradiation using the Linear Accelerator (LINAC) for brain arteriovenous malformations (AVM). Methods: A retrospective study of 37 patients with brain AVM undergoing LINAC reirradiation between April 2003 and November 2011 was carried out. Patient characteristics, for example, gender, age, use of medications, and comorbidities; disease characteristics, for example, Spetzler–Martin grading system, location, volume, modified Pollock–Flickinger score; and treatment characteristics, for example, embolization, prescription dose, radiation dose–volume curves, and conformity index were analyzed. During the follow-up period, imaging studies were performed to evaluate changes after treatment and AVM cure. Complications, such as edema, rupture of the blood–brain barrier, and radionecrosis were classified as symptomatic and asymptomatic. Results: Twenty-seven patients underwent angiogram after reirradiation and the percentage of angiographic occlusion was 55.5%. In three patients without obliteration, AVM shrinkage made it possible to perform surgical resection with a 2/3 cure rate. A reduction in AVM nidus volume greater than 50% after the first procedure was shown to be the most important predictor of obliteration. Another factor associated with AVM cure was a prescription dose higher than 15.5 Gy in the first radiosurgery. Two patients had permanent neurologic deficits. Factors correlated with complications were the prescription dose and maximum dose in the first procedure. Conclusion: This study suggests that single-dose reirradiation is safe and feasible in partially occluded AVM. Reirradiation may not benefit candidates whose prescribed dose was lower than 15.5 Gy in the first procedure and initial AVM nidus volume did not decrease by more than 50% before reirradiation. PMID:26110078

  2. The study of cerebral ischemic reversibility: Part II. Preliminary preoperative results of fluoromethane positron emission tomographic determination of perfusion reserve in patients with carotid TIA and stroke.

    PubMed

    Levine, R L; Sunderland, J J; Rowe, B R; Nickles, R J

    1986-01-01

    Symmetries and asymmetries in regional cerebral blood flow (rCBF) determinations are reported in eleven patients with symptomatic carotid artery occlusive disease. Flourine-18-fluoromethane rCBF values are obtained by means of a noninvasive positron emission tomographic (PET) technique during room air (RA) and following induced hypercapnia (CO2). Areas of abnormal CO2 reactivity predict both the hemodynamic significance of the vascular lesion in question and the areas most vulnerable for ischemic infarction. This data is intended to be preliminary in nature; future expansions of this data base will be made to include rCBF/CO2 estimations, rCBF/glucose metabolism determinations, and rCBF/"reserve" evaluations over time and following brain-specific therapies. Once established, the potential viability and reversibility of these ischemic, uninfarcted or minimally infarcted areas can then be reestablished over time, thus providing a quantitative measure of the natural history of flow/metabolic coupling or uncoupling. PMID:3502524

  3. Cerebral Arteriosclerosis

    MedlinePlus

    ... Cerebral arteriosclerosis is the result of thickening and hardening of the walls of the arteries in the ... cause an ischemic stroke. When the thickening and hardening is uneven, arterial walls can develop bulges (called ...

  4. Non-hypotensive dose of telmisartan and nimodipine produced synergistic neuroprotective effect in cerebral ischemic model by attenuating brain cytokine levels.

    PubMed

    Justin, A; Sathishkumar, M; Sudheer, A; Shanthakumari, S; Ramanathan, M

    2014-07-01

    The hypothesis of the present study is that the anti-inflammatory property of telmisartan (TM), an AT1 blocker that may exert neuroprotection through attenuation of excitatory amino acids by controlling cytokines and reactive oxygen species, release during ischemia. The neuroprotective effect of TM and its combination with nimodipine (NM) were studied in rats by using middle cerebral artery occlusion method followed by ischemic reperfusion (IR) after 2 h of occlusion. The drugs were administered 30 min prior to the surgery and continued throughout the study period. After 24 h of IR the neurological deficit was assessed, and the locomotor activity and open field behaviour were assessed on the seventh day. On the ninth day, the brains were isolated for neurochemical and cytokine measurements and histopathological studies. The results have shown that treatment of TM (5 & 10 mg/kg) gradually reduced the glutamate, aspartate and glutamine synthetase levels. It also restored the ATP, Na(+)K(+)ATPase, glutathione and synapse integrity in the different regions of the brain in comparison to ischemic brain. TM ameliorated the pro-inflammatory cytokine (IL-1β, IL-6, TNF-α), lipid peroxide and nitric oxide levels. Anti-inflammatory cytokine IL-10 level was found to be concurrently increased. Combination therapy of TM with NM (5 mg/kg) has shown additive effects in the above said parameters. Further a positive correlation between glutamate and cytokine release was observed, and it indicated that synaptic clearance of glutamate can be regulated by cytokines. It can be concluded that TM induces neuroprotective activity through amelioration of pro-inflammatory cytokine release during cerebral ischemia. The additive effect of NM on TM neuroprotective effect would be through controlling cytokine release, ATP restoration by cerebrovasodilation, and along with prevention of Ca(2+) dependent glutamate toxicity in neurons. The advantage of TM therapy in ischemic state can be explored

  5. Cerebral blood flow velocity and cranial fluid volume decrease during +Gz acceleration

    NASA Technical Reports Server (NTRS)

    Kawai, Y.; Puma, S. C.; Hargens, A. R.; Murthy, G.; Warkander, D.; Lundgren, C. E.

    1997-01-01

    Cerebral blood flow (CBF) velocity and cranial fluid volume, which is defined as the total volume of intra- and extracranial fluid, were measured using transcranial Doppler ultrasonography and rheoencephalography, respectively, in humans during graded increase of +Gz acceleration (onset rate: 0.1 G/s) without straining maneuvers. Gz acceleration was terminated when subjects' vision decreased to an angle of less than or equal to 60 degrees, which was defined as the physiological end point. In five subjects, mean CBF velocity decreased 48% from a baseline value of 59.4 +/- 11.2 cm/s to 31.0 +/- 5.6 cm/s (p<0.01) with initial loss of peripheral vision at 5.7 +/- 0.9 Gz. On the other hand, systolic CBF velocity did not change significantly during increasing +Gz acceleration. Cranial impedance, which is proportional to loss of cranial fluid volume, increased by 2.0 +/- 0.8% above the baseline value at the physiological end point (p<0.05). Both the decrease of CBF velocity and the increase of cranial impedance correlated significantly with Gz. These results suggest that +Gz acceleration without straining maneuvers decreases CBF velocity to half normal and probably causes a caudal fluid shift from both intra- and extracranial tissues.

  6. Neuroprotective Effect of Scutellarin on Ischemic Cerebral Injury by Down-Regulating the Expression of Angiotensin-Converting Enzyme and AT1 Receptor

    PubMed Central

    Han, Jichun; Zhou, Mingjie; Ren, Huanhuan; Pan, Qunwen; Zheng, Chunli; Zheng, Qiusheng

    2016-01-01

    Background and Purpose Previous studies have demonstrated that angiotensin-converting enzyme (ACE) is involved in brain ischemic injury. In the present study, we investigated whether Scutellarin (Scu) exerts neuroprotective effects by down-regulating the Expression of Angiotensin-Converting Enzyme and AT1 receptor in a rat model of permanent focal cerebral ischemia. Methods Adult Sprague–Dawley rats were administrated with different dosages of Scu by oral gavage for 7 days and underwent permanent middle cerebral artery occlusion (pMCAO). Blood pressure was measured 7 days after Scu administration and 24 h after pMCAO surgery by using a noninvasive tail cuff method. Cerebral blood flow (CBF) was determined by Laser Doppler perfusion monitor and the neuronal dysfunction was evaluated by analysis of neurological deficits before being sacrificed at 24 h after pMCAO. Histopathological change, cell apoptosis and infarct area were respectively determined by hematoxylin–eosin staining, terminal deoxynucleotidyl transfer-mediated dUTP nick end labeling (TUNEL) analysis and 2,3,5-triphenyltetrazolium chloride staining. Tissue angiotensin II (Ang II) and ACE activity were detected by enzyme-linked immunosorbent assays. The expression levels of ACE, Ang II type 1 receptor (AT1R), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) were measured by Western blot and real-time PCR. ACE inhibitory activity of Scu in vitro was detected by the photometric determination. Results Scu treatment dose-dependently decreased neurological deficit score, infarct area, cell apoptosis and morphological changes induced by pMCAO, which were associated with reductions of ACE and AT1R expression and the levels of Ang II, TNF-α, IL-6, and IL-1β in ischemic brains. Scu has a potent ACE inhibiting activity. Conclusion Scu protects brain from acute ischemic injury probably through its inhibitory effect on the ACE/Ang II/AT1 axis, CBF preservation and

  7. Melatonin Counteracts at a Transcriptional Level the Inflammatory and Apoptotic Response Secondary to Ischemic Brain Injury Induced by Middle Cerebral Artery Blockade in Aging Rats

    PubMed Central

    Paredes, Sergio D.; Rancan, Lisa; Kireev, Roman; González, Alberto; Louzao, Pedro; González, Pablo; Rodríguez-Bobada, Cruz; García, Cruz; Vara, Elena; Tresguerres, Jesús A.F.

    2015-01-01

    Abstract Aging increases oxidative stress and inflammation. Melatonin counteracts inflammation and apoptosis. This study investigated the possible protective effect of melatonin on the inflammatory and apoptotic response secondary to ischemia induced by blockade of the right middle cerebral artery (MCA) in aging male Wistar rats. Animals were subjected to MCA obstruction. After 24 h or 7 days of procedure, 14-month-old nontreated and treated rats with a daily dose of 10 mg/kg melatonin were sacrificed and right and left hippocampus and cortex were collected. Rats aged 2 and 6 months, respectively, were subjected to the same brain injury protocol, but they were not treated with melatonin. mRNA expression of interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), Bcl-2-associated death promoter (BAD), Bcl-2-associated X protein (BAX), glial fibrillary acidic protein (GFAP), B-cell lymphoma 2 (Bcl-2), and sirtuin 1 was measured by reverse transcription–polymerase chain reaction. In nontreated animals, a significant time-dependent increase in IL-1β, TNF-α, BAD, and BAX was observed in the ischemic area of both hippocampus and cortex, and to a lesser extent in the contralateral hemisphere. Hippocampal GFAP was also significantly elevated, while Bcl-2 and sirtuin 1 decreased significantly in response to ischemia. Aging aggravated these changes. Melatonin administration was able to reverse significantly these alterations. In conclusion, melatonin may ameliorate the age-dependent inflammatory and apoptotic response secondary to ischemic cerebral injury. PMID:26594596

  8. The Antiepileptic Drug Levetiracetam Suppresses Non-Convulsive Seizure Activity and Reduces Ischemic Brain Damage in Rats Subjected to Permanent Middle Cerebral Artery Occlusion

    PubMed Central

    Cuomo, Ornella; Rispoli, Vincenzo; Leo, Antonio; Politi, Giovanni Bosco; Vinciguerra, Antonio; di Renzo, Gianfranco; Cataldi, Mauro

    2013-01-01

    The antiepileptic drug Levetiracetam (Lev) has neuroprotective properties in experimental stroke, cerebral hemorrhage and neurotrauma. In these conditions, non-convulsive seizures (NCSs) propagate from the core of the focal lesion into perilesional tissue, enlarging the damaged area and promoting epileptogenesis. Here, we explore whether Lev neuroprotective effect is accompanied by changes in NCS generation or propagation. In particular, we performed continuous EEG recordings before and after the permanent occlusion of the middle cerebral artery (pMCAO) in rats that received Lev (100 mg/kg) or its vehicle immediately before surgery. Both in Lev-treated and in control rats, EEG activity was suppressed after pMCAO. In control but not in Lev-treated rats, EEG activity reappeared approximately 30-45 min after pMCAO. It initially consisted in single spikes and, then, evolved into spike-and-wave and polyspike-and-wave discharges. In Lev-treated rats, only rare spike events were observed and the EEG power was significantly smaller than in controls. Approximately 24 hours after pMCAO, EEG activity increased in Lev-treated rats because of the appearance of polyspike events whose power was, however, significantly smaller than in controls. In rats sacrificed 24 hours after pMCAO, the ischemic lesion was approximately 50% smaller in Lev-treated than in control rats. A similar neuroprotection was observed in rats sacrificed 72 hours after pMCAO. In conclusion, in rats subjected to pMCAO, a single Lev injection suppresses NCS occurrence for at least 24 hours. This electrophysiological effect could explain the long lasting reduction of ischemic brain damage caused by this drug. PMID:24236205

  9. Delayed hippocampal neuronal death in young gerbil following transient global cerebral ischemia is related to higher and longer-term expression of p63 in the ischemic hippocampus.

    PubMed

    Bae, Eun Joo; Chen, Bai Hui; Yan, Bing Chun; Shin, Bich Na; Cho, Jeong Hwi; Kim, In Hye; Ahn, Ji Hyeon; Lee, Jae Chul; Tae, Hyun-Jin; Hong, Seongkweon; Kim, Dong Won; Cho, Jun Hwi; Lee, Yun Lyul; Won, Moo-Ho; Park, Joon Ha

    2015-06-01

    The tumor suppressor p63 is one of p53 family members and plays a vital role as a regulator of neuronal apoptosis in the development of the nervous system. However, the role of p63 in mature neuronal death has not been addressed yet. In this study, we first compared ischemia-induced effects on p63 expression in the hippocampal regions (CA1-3) between the young and adult gerbils subjected to 5 minutes of transient global cerebral ischemia. Neuronal death in the hippocampal CA1 region of young gerbils was significantly slow compared with that in the adult gerbils after transient global cerebral ischemia. p63 immunoreactivity in the hippocampal CA1 pyramidal neurons in the sham-operated young group was significantly low compared with that in the sham-operated adult group. p63 immunoreactivity was apparently changed in ischemic hippocampal CA1 pyramidal neurons in both ischemia-operated young and adult groups. In the ischemia-operated adult groups, p63 immunoreactivity in the hippocampal CA1 pyramidal neurons was significantly decreased at 4 days post-ischemia; however, p63 immunoreactivity in the ischemia-operated young group was significantly higher than that in the ischemia-operated adult group. At 7 days post-ischemia, p63 immunoreactivity was decreased in the hippocampal CA1 pyramidal neurons in both ischemia-operated young and adult groups. Change patterns of p63 level in the hippocampal CA1 region of adult and young gerbils after ischemic damage were similar to those observed in the immunohistochemical results. These findings indicate that higher and longer-term expression of p63 in the hippocampal CA1 region of the young gerbils after ischemia/reperfusion may be related to more delayed neuronal death compared to that in the adults. PMID:26199612

  10. Delayed hippocampal neuronal death in young gerbil following transient global cerebral ischemia is related to higher and longer-term expression of p63 in the ischemic hippocampus

    PubMed Central

    Bae, Eun Joo; Chen, Bai Hui; Yan, Bing Chun; Shin, Bich Na; Cho, Jeong Hwi; Kim, In Hye; Ahn, Ji Hyeon; Lee, Jae Chul; Tae, Hyun-Jin; Hong, Seongkweon; Kim, Dong Won; Cho, Jun Hwi; Lee, Yun Lyul; Won, Moo-Ho; Park, Joon Ha

    2015-01-01

    The tumor suppressor p63 is one of p53 family members and plays a vital role as a regulator of neuronal apoptosis in the development of the nervous system. However, the role of p63 in mature neuronal death has not been addressed yet. In this study, we first compared ischemia-induced effects on p63 expression in the hippocampal regions (CA1–3) between the young and adult gerbils subjected to 5 minutes of transient global cerebral ischemia. Neuronal death in the hippocampal CA1 region of young gerbils was significantly slow compared with that in the adult gerbils after transient global cerebral ischemia. p63 immunoreactivity in the hippocampal CA1 pyramidal neurons in the sham-operated young group was significantly low compared with that in the sham-operated adult group. p63 immunoreactivity was apparently changed in ischemic hippocampal CA1 pyramidal neurons in both ischemia-operated young and adult groups. In the ischemia-operated adult groups, p63 immunoreactivity in the hippocampal CA1 pyramidal neurons was significantly decreased at 4 days post-ischemia; however, p63 immunoreactivity in the ischemia-operated young group was significantly higher than that in the ischemia-operated adult group. At 7 days post-ischemia, p63 immunoreactivity was decreased in the hippocampal CA1 pyramidal neurons in both ischemia-operated young and adult groups. Change patterns of p63 level in the hippocampal CA1 region of adult and young gerbils after ischemic damage were similar to those observed in the immunohistochemical results. These findings indicate that higher and longer-term expression of p63 in the hippocampal CA1 region of the young gerbils after ischemia/reperfusion may be related to more delayed neuronal death compared to that in the adults. PMID:26199612

  11. A cohort study of relationship between serum calcium levels and cerebral microbleeds (CMBs) in ischemic stroke patients with AF and/or RHD

    PubMed Central

    Liu, Junfeng; Wang, Deren; Xiong, Yao; Liu, Bian; Wei, Chenchen; Ma, Zhenxing; Wu, Bo; Yuan, Ruozhen; Tang, Hehan; Liu, Ming

    2016-01-01

    Abstract Calcium is an essential element for life and has cerebroprotective property in stroke patients. Low serum calcium levels were found to be related to large hematoma volumes in intracerebral hemorrhagic patients and hemorrhagic transformation in ischemic stroke patients after thrombolysis. However, their impact on hemorrhage-prone small vessel disease represented by cerebral microbleeds (CMBs) is uncertain. We aim to investigate whether low serum calcium levels are associated with presence and location of CMBs. Ischemic stroke patients with atrial fibrillation (AF) and/or rheumatic heart disease admitted to our hospital were consecutively and prospectively enrolled. Demographic and clinical information were collected and analyzed according to the occurrence and location of CMBs, and levels of serum calcium. We used logistic regression analysis to estimate the multivariable adjusted relationship between serum calcium levels and the presence or location of CMBs. Among the 67 patients (28 males; mean age, 67.3 years) in the final analysis, 39 (58.2%) were found to have CMBs. After adjustment for age, sex, smoking habits, drinking habits, and renal impairment, the presence of CMBs and deep CMBs was, respectively, 4.96- and 4.83-fold higher in patients with lower serum calcium levels (≤2.15 mmol/L) than in patients with higher serum calcium levels. Lower serum calcium levels (≤2.15 mmol/L) are independently associated with the presence of CMBs and deep CMBs in ischemic stroke patients with AF and/or rheumatic heart disease, which should be verified and extended in large cohorts, with other types of stroke patients and the general population. PMID:27368027

  12. Study of cerebral ischemic reversibility: Part II. Preliminary preoperative results of fluoromethane positron emission tomographic determination of perfusion reserve in patients with carotid TIA and stroke

    SciTech Connect

    Levine, R.L.; Sunderland, J.J.; Rowe, B.R.; Nickles, R.J.

    1986-01-01

    Symmetries and asymmetries in regional cerebral blood flow (rCBF) determinations are reported in eleven patients with symptomatic carotid artery occlusive disease. Flourine-18-fluoromethane rCBF values are obtained by means of a noninvasive positron emission tomographic (PET) technique during room air (RA) and following induced hypercapnia (CO/sub 2/). Areas of abnormal CO/sub 2/ reactivity predict both the hemodynamic significance of the vascular lesion in question and the areas most vulnerable for ischemic infarction. This data is intended to be preliminary in nature; future expansions of this data base will be made to include rCBF/CO/sub 2/ estimations, rCBF/glucose metabolism determinations, and rCBF/reserve evaluations over time and following brain-specific therapies. Once established, the potential viability and reversibility of these ischemic, uninfarcted or minimally infarcted areas can then be reestablished over time, thus providing a quantitative measure of the natural history of flow/metabolic coupling or uncoupling.

  13. Epac2-deficiency leads to more severe retinal swelling, glial reactivity and oxidative stress in transient middle cerebral artery occlusion induced ischemic retinopathy.

    PubMed

    Liu, Jin; Yeung, Patrick Ka Kit; Cheng, Lu; Lo, Amy Cheuk Yin; Chung, Stephen Sum Man; Chung, Sookja Kim

    2015-06-01

    Ischemia occurs in diabetic retinopathy with neuronal loss, edema, glial cell reactivity and oxidative stress. Epacs, consisting of Epac1 and Epac2, are cAMP mediators playing important roles in maintenance of endothelial barrier and neuronal functions. To investigate the roles of Epacs in the pathogenesis of ischemic retinopathy, transient middle cerebral artery occlusion (tMCAO) was performed on Epac1-deficient (Epac1 (-/-)) mice, Epac2-deficient (Epac2 (-/-)) mice, and their wild type counterparts (Epac1 (+/+) and Epac2 (+/+)). Two-hour occlusion and 22-hour reperfusion were conducted to induce ischemia/reperfusion injury to the retina. After tMCAO, the contralateral retinae displayed similar morphology between different genotypes. Neuronal loss, retinal edema and increase in immunoreactivity for aquaporin 4 (AQP4), glial fibrillary acidic protein (GFAP), peroxiredoxin 6 (Prx6) were observed in ipsilateral retinae. Epac2 (-/-) ipsilateral retinae showed more neuronal loss in retinal ganglion cell layer, increased retinal thickness and stronger immunostaining of AQP4, GFAP, and Prx6 than those of Epac2 (+/+). However, Epac1 (-/-) ipsilateral retinae displayed similar pathology as those in Epac1 (+/+) mice. Our observations suggest that Epac2-deficiency led to more severe ischemic retinopathy after retinal ischemia/reperfusion injury.

  14. Dehydration accelerates reductions in cerebral blood flow during prolonged exercise in the heat without compromising brain metabolism

    PubMed Central

    Trangmar, Steven J.; Chiesa, Scott T.; Llodio, Iñaki; Garcia, Benjamin; Kalsi, Kameljit K.; Secher, Niels H.

    2015-01-01

    Dehydration hastens the decline in cerebral blood flow (CBF) during incremental exercise, whereas the cerebral metabolic rate for O2 (CMRO2) is preserved. It remains unknown whether CMRO2 is also maintained during prolonged exercise in the heat and whether an eventual decline in CBF is coupled to fatigue. Two studies were undertaken. In study 1, 10 male cyclists cycled in the heat for ∼2 h with (control) and without fluid replacement (dehydration) while internal and external carotid artery blood flow and core and blood temperature were obtained. Arterial and internal jugular venous blood samples were assessed with dehydration to evaluate CMRO2. In study 2, in 8 male subjects, middle cerebral artery blood velocity was measured during prolonged exercise to exhaustion in both dehydrated and euhydrated states. After a rise at the onset of exercise, internal carotid artery flow declined to baseline with progressive dehydration (P < 0.05). However, cerebral metabolism remained stable through enhanced O2 and glucose extraction (P < 0.05). External carotid artery flow increased for 1 h but declined before exhaustion. Fluid ingestion maintained cerebral and extracranial perfusion throughout nonfatiguing exercise. During exhaustive exercise, however, euhydration delayed but did not prevent the decline in cerebral perfusion. In conclusion, during prolonged exercise in the heat, dehydration accelerates the decline in CBF without affecting CMRO2 and also restricts extracranial perfusion. Thus, fatigue is related to a reduction in CBF and extracranial perfusion rather than CMRO2. PMID:26371170

  15. Dehydration accelerates reductions in cerebral blood flow during prolonged exercise in the heat without compromising brain metabolism.

    PubMed

    Trangmar, Steven J; Chiesa, Scott T; Llodio, Iñaki; Garcia, Benjamin; Kalsi, Kameljit K; Secher, Niels H; González-Alonso, José

    2015-11-01

    Dehydration hastens the decline in cerebral blood flow (CBF) during incremental exercise, whereas the cerebral metabolic rate for O2 (CMRO2 ) is preserved. It remains unknown whether CMRO2 is also maintained during prolonged exercise in the heat and whether an eventual decline in CBF is coupled to fatigue. Two studies were undertaken. In study 1, 10 male cyclists cycled in the heat for ∼2 h with (control) and without fluid replacement (dehydration) while internal and external carotid artery blood flow and core and blood temperature were obtained. Arterial and internal jugular venous blood samples were assessed with dehydration to evaluate CMRO2 . In study 2, in 8 male subjects, middle cerebral artery blood velocity was measured during prolonged exercise to exhaustion in both dehydrated and euhydrated states. After a rise at the onset of exercise, internal carotid artery flow declined to baseline with progressive dehydration (P < 0.05). However, cerebral metabolism remained stable through enhanced O2 and glucose extraction (P < 0.05). External carotid artery flow increased for 1 h but declined before exhaustion. Fluid ingestion maintained cerebral and extracranial perfusion throughout nonfatiguing exercise. During exhaustive exercise, however, euhydration delayed but did not prevent the decline in cerebral perfusion. In conclusion, during prolonged exercise in the heat, dehydration accelerates the decline in CBF without affecting CMRO2 and also restricts extracranial perfusion. Thus, fatigue is related to a reduction in CBF and extracranial perfusion rather than CMRO2 .

  16. Dehydration accelerates reductions in cerebral blood flow during prolonged exercise in the heat without compromising brain metabolism.

    PubMed

    Trangmar, Steven J; Chiesa, Scott T; Llodio, Iñaki; Garcia, Benjamin; Kalsi, Kameljit K; Secher, Niels H; González-Alonso, José

    2015-11-01

    Dehydration hastens the decline in cerebral blood flow (CBF) during incremental exercise, whereas the cerebral metabolic rate for O2 (CMRO2 ) is preserved. It remains unknown whether CMRO2 is also maintained during prolonged exercise in the heat and whether an eventual decline in CBF is coupled to fatigue. Two studies were undertaken. In study 1, 10 male cyclists cycled in the heat for ∼2 h with (control) and without fluid replacement (dehydration) while internal and external carotid artery blood flow and core and blood temperature were obtained. Arterial and internal jugular venous blood samples were assessed with dehydration to evaluate CMRO2 . In study 2, in 8 male subjects, middle cerebral artery blood velocity was measured during prolonged exercise to exhaustion in both dehydrated and euhydrated states. After a rise at the onset of exercise, internal carotid artery flow declined to baseline with progressive dehydration (P < 0.05). However, cerebral metabolism remained stable through enhanced O2 and glucose extraction (P < 0.05). External carotid artery flow increased for 1 h but declined before exhaustion. Fluid ingestion maintained cerebral and extracranial perfusion throughout nonfatiguing exercise. During exhaustive exercise, however, euhydration delayed but did not prevent the decline in cerebral perfusion. In conclusion, during prolonged exercise in the heat, dehydration accelerates the decline in CBF without affecting CMRO2 and also restricts extracranial perfusion. Thus, fatigue is related to a reduction in CBF and extracranial perfusion rather than CMRO2 . PMID:26371170

  17. First Autologous Cord Blood Therapy for Pediatric Ischemic Stroke and Cerebral Palsy Caused by Cephalic Molding during Birth: Individual Treatment with Mononuclear Cells

    PubMed Central

    Hamelmann, E.

    2016-01-01

    Intracranial laceration due to traumatic birth injury is an extremely rare event affecting approximately one newborn per a population of 4.5 million. However, depending on the mode of injury, the resulting brain damage may lead to lifelong sequelae, for example, cerebral palsy for which there is no cure at present. Here we report a rare case of neonatal arterial ischemic stroke and cerebral palsy caused by fetal traumatic molding and parietal depression of the head during delivery caused by functional cephalopelvic disproportion due to a “long pelvis.” This patient was treated by autologous cord blood mononuclear cells (45.8 mL, cryopreserved, TNC 2.53 × 10e8) with a remarkable recovery. Active rehabilitation was provided weekly. Follow-up examinations were at 3, 18, 34, and 57 months. Generous use of neonatal head MRI in case of molding, craniofacial deformity, and a sentinel event during parturition is advocated to enhance diagnosis of neonatal brain damage as a basis for fast and potentially causative treatment modalities including autologous cord blood transplantation in a timely manner. PMID:27239361

  18. [A case of cerebral cardioembolism successfully treated by Merci retriever despite a large ischemic change on diffusion-weighted MR imaging].

    PubMed

    Kouge, Junpei; Torii, Takako; Nakagaki, Hideaki; Matsumoto, Shoji; Kawajiri, Masakazu; Yamada, Takeshi

    2013-01-01

    A 63-year-old man with paroxysmal atrial fibrillation presented with aphasia (16:30) followed by right hemiplegia. The last known time that he was clinically well was 14:30. On admission (17:43), his baseline NIHSS score was 34. Head diffusion-weighted MR imaging (DWI) demonstrated large hyperintense signals throughout the left middle cerebral artery (MCA) territory. The left carotid angiogram (CAG) demonstrated occlusion of the left ICA 2 cm distal from the bifurcation. The right CAG showed a small branch laterally extending from the left anterior cerebral artery (ACA). Mechanical thrombectomy with a Merci retriever removed a large amount of thrombi after the first trial. The left ICA and MCA were recanalized to grade TICI 2b. The left hemiplegia was markedly improved, and he could walk independently. His NIHSS score was 11 at discharge. Revascularization therapy may improve a motor deficit in patients with possible penumbra of the precentral gyrus by collateral circulation from the ACA even if the ischemic lesion in the MCA territory is large on DWI.

  19. Remote ischemic preconditioning for cerebral and cardiac protection during carotid endarterectomy: results from a pilot randomized clinical trial.

    PubMed

    Walsh, Stewart R; Nouraei, S A; Tang, Tjun Y; Sadat, Umar; Carpenter, Roger H; Gaunt, Michael E

    2010-08-01

    Remote ischemic preconditioning (RIPC) is a physiological mechanism whereby brief ischemia-reperfusion episodes attenuate damage by subsequent prolonged ischemic insults. It reduces myocardial injury following cardiac and aortic aneurysm surgery. We aimed to determine whether RIPC affects neurological or cardiac injury following carotid endarterectomy (CEA). Patients were preconditioned using 10 minutes of lower limb ischemia-reperfusion. The primary neurological outcome was saccadic latency deterioration. The primary cardiac outcome measure was increased in serum troponin I >0.15 mg/dL. In all, 70 patients were randomized, of whom 55 completed the neurological surveillance protocol. Although there were fewer saccadic latency deteriorations in the RIPC arm, this did not reach statistical significance (32% versus 53%; P = .11). The primary cardiac outcome occurred in 1 patient in each arm (P = .97). There were no adverse events related to the preconditioning protocol. Remote ischemic preconditioning appears safe in patients with CEA. Large-scale trials are required to determine whether RIPC confers clinical benefits.

  20. Neuroimmunomodulatory effects of transcranial laser therapy combined with intravenous tPA administration for acute cerebral ischemic injury

    PubMed Central

    Peplow, Philip V.

    2015-01-01

    At present, the only FDA approved treatment for ischemic strokes is intravenous administration of tissue plasminogen activator within 4.5 hours of stroke onset. Owing to this brief window only a small percentage of patients receive tissue plasminogen activator. Transcranial laser therapy has been shown to be effective in animal models of acute ischemic stroke, resulting in significant improvement in neurological score and function. NEST-1 and NEST-2 clinical trials in human patients have demonstrated the safety and positive trends in efficacy of transcranial laser therapy for the treatment of ischemic stroke when initiated close to the time of stroke onset. Combining intravenous tissue plasminogen activator treatment with transcranial laser therapy may provide better functional outcomes. Statins given within 4 weeks of stroke onset improve stroke outcomes at 90 days compared to patients not given statins, and giving statins following transcranial laser therapy may provide an effective treatment for patients not able to be given tissue plasminogen activator due to time constraints. PMID:26487831

  1. Migraine prophylaxis, ischemic depolarizations and stroke outcomes in mice

    PubMed Central

    Eikermann-Haerter, Katharina; Lee, Jeong Hyun; Yalcin, Nilufer; Yu, Esther Sori; Daneshmand, Ali; Wei, Ying; Zheng, Yi; Can, Anil; Sengul, Buse; Ferrari, Michel D.; van den Maagdenberg, Arn M. J. M.; Ayata, Cenk

    2014-01-01

    Background and Purpose Migraine with aura is an established stroke risk factor, and excitatory mechanisms such as spreading depression are implicated in the pathogenesis of both migraine and stroke. Spontaneous spreading depression waves originate within the peri-infarct tissue and exacerbate the metabolic mismatch during focal cerebral ischemia. Genetically enhanced spreading depression susceptibility facilitates anoxic depolarizations and peri-infarct spreading depressions and accelerates infarct growth, suggesting that susceptibility to spreading depression is a critical determinant of vulnerability to ischemic injury. Because chronic treatment with migraine prophylactic drugs suppresses spreading depression susceptibility, we tested whether migraine prophylaxis can also suppress ischemic depolarizations and improve stroke outcome. Methods We measured the cortical susceptibility to spreading depression and ischemic depolarizations, and determined tissue and neurological outcome after middle cerebral artery occlusion in wild type and familial hemiplegic migraine type 1 knock-in mice treated with vehicle, topiramate or lamotrigine daily for 7 weeks or as a single dose shortly before testing. Results Chronic treatment with topiramate or lamotrigine reduces the susceptibility to KCl- or electrical stimulation-induced spreading depressions as well as ischemic depolarizations in both wild-type and familial hemiplegic migraine type 1 mutant mice. Consequently, both tissue and neurological outcomes are improved. Notably, treatment with a single dose of either drug is ineffective. Conclusions These data underscore the importance of hyperexcitability as a mechanism for increased stroke risk in migraineurs, and suggest that migraine prophylaxis may not only prevent migraine attacks but also protect migraineurs against ischemic injury. PMID:25424478

  2. Interhemispheric Cerebral Blood Flow Balance during Recovery of Motor Hand Function after Ischemic Stroke—A Longitudinal MRI Study Using Arterial Spin Labeling Perfusion

    PubMed Central

    Missimer, John; Schroth, Gerhard; Hess, Christian W.; Sturzenegger, Matthias; Wang, Danny J. J.; Weder, Bruno; Federspiel, Andrea

    2014-01-01

    Background Unilateral ischemic stroke disrupts the well balanced interactions within bilateral cortical networks. Restitution of interhemispheric balance is thought to contribute to post-stroke recovery. Longitudinal measurements of cerebral blood flow (CBF) changes might act as surrogate marker for this process. Objective To quantify longitudinal CBF changes using arterial spin labeling MRI (ASL) and interhemispheric balance within the cortical sensorimotor network and to assess their relationship with motor hand function recovery. Methods Longitudinal CBF data were acquired in 23 patients at 3 and 9 months after cortical sensorimotor stroke and in 20 healthy controls using pulsed ASL. Recovery of grip force and manual dexterity was assessed with tasks requiring power and precision grips. Voxel-based analysis was performed to identify areas of significant CBF change. Region-of-interest analyses were used to quantify the interhemispheric balance across nodes of the cortical sensorimotor network. Results Dexterity was more affected, and recovered at a slower pace than grip force. In patients with successful recovery of dexterous hand function, CBF decreased over time in the contralesional supplementary motor area, paralimbic anterior cingulate cortex and superior precuneus, and interhemispheric balance returned to healthy control levels. In contrast, patients with poor recovery presented with sustained hypoperfusion in the sensorimotor cortices encompassing the ischemic tissue, and CBF remained lateralized to the contralesional hemisphere. Conclusions Sustained perfusion imbalance within the cortical sensorimotor network, as measured with task-unrelated ASL, is associated with poor recovery of dexterous hand function after stroke. CBF at rest might be used to monitor recovery and gain prognostic information. PMID:25191858

  3. Unraveling the Specific Ischemic Core and Penumbra Transcriptome in the Permanent Middle Cerebral Artery Occlusion Mouse Model Brain Treated with the Neuropeptide PACAP38

    PubMed Central

    Hori, Motohide; Nakamachi, Tomoya; Shibato, Junko; Rakwal, Randeep; Shioda, Seiji; Numazawa, Satoshi

    2015-01-01

    Our group has been systematically investigating the effects of the neuropeptide pituitary adenylate-cyclase activating polypeptide (PACAP) on the ischemic brain. To do so, we have established and utilized the permanent middle cerebral artery occlusion (PMCAO) mouse model, in which PACAP38 (1 pmol) injection is given intracerebroventrically and compared to a control saline (0.9% sodium chloride, NaCl) injection, to unravel genome-wide gene expression changes using a high-throughput DNA microarray analysis approach. In our previous studies, we have accumulated a large volume of data (gene inventory) from the whole brain (ipsilateral and contralateral hemispheres) after both PMCAO and post-PACAP38 injection. In our latest research, we have targeted specifically infarct or ischemic core (hereafter abbreviated IC) and penumbra (hereafter abbreviated P) post-PACAP38 injections in order to re-examine the transcriptome at 6 and 24 h post injection. The current study aims to delineate the specificity of expression and localization of differentially expressed molecular factors influenced by PACAP38 in the IC and P regions. Utilizing the mouse 4 × 44 K whole genome DNA chip we show numerous changes (≧/≦ 1.5/0.75-fold) at both 6 h (654 and 456, and 522 and 449 up- and down-regulated genes for IC and P, respectively) and 24 h (2568 and 2684, and 1947 and 1592 up- and down-regulated genes for IC and P, respectively) after PACAP38 treatment. Among the gene inventories obtained here, two genes, brain-derived neurotrophic factor (Bdnf) and transthyretin (Ttr) were found to be induced by PACAP38 treatment, which we had not been able to identify previously using the whole hemisphere transcriptome analysis. Using bioinformatics analysis by pathway- or specific-disease-state focused gene classifications and Ingenuity Pathway Analysis (IPA) the differentially expressed genes are functionally classified and discussed. Among these, we specifically discuss some novel and previously

  4. The window of opportunity for treatment of focal cerebral ischemic damage with noninvasive intranasal insulin-like growth factor-I in rats.

    PubMed

    Liu, Xin-Feng; Fawcett, John R; Hanson, Leah R; Frey, William H

    2004-01-01

    Intracerebroventricular injection of insulin-like growth factor (IGF)-I has been shown to protect against stroke in rats. This method of delivery is not practical in human beings, as it requires an operation with risk of infection and other complications. Intranasal (i.n.) delivery offers a noninvasive method of bypassing the blood-brain barrier to deliver IGF-I to the brain. This study delineates the window of opportunity for treatment of focal cerebral ischemic damage using i.n. IGF-I after middle cerebral artery occlusion (MCAO). Rats were allowed to survive 7 days after 2 hours of MCAO. Infarct volume, apoptosis after 7 days, and neurologic deficit scores from the postural reflex and adhesive tape tests assessing motor-sensory and somatosensory functions, respectively, at 1 to 7 days were used to evaluate the efficacy of i.n. IGF-I (150 microg) administered at different times after MCAO. I.n. IGF-I significantly reduced infarct volume by 54%; and 39%; versus control when administered at 2 or 4 hours, respectively, after the onset of MCAO (P < .05) and improved motor-sensory and somatosensory functions (P < .05) when administered 2 hours after the onset of MCAO. In addition, treatment with i.n. IGF-I at 2, 4, or 6 hours after MCAO decreased apoptotic cell counts by more than 90%; in the hemisphere ipsilateral to the occlusion. I.n. IGF-I is a promising treatment for stroke with a therapeutic window of opportunity for up to 6 hours after the onset of ischemia. This noninvasive method provides a simpler, safer, and potentially more cost-effective method of delivery than other methods currently in use.

  5. A Comparative Study of Variables Influencing Ischemic Injury in the Longa and Koizumi Methods of Intraluminal Filament Middle Cerebral Artery Occlusion in Mice

    PubMed Central

    Morris, Gary P.; Gladbach, Amadeus; Ittner, Lars M.; Vissel, Bryce

    2016-01-01

    The intraluminal filament model of middle cerebral artery occlusion (MCAO) in mice and rats has been plagued by inconsistency, owing in part to the multitude of variables requiring control. In this study we investigated the impact of several major variables on survival rate, lesion volume, neurological scores, cerebral blood flow (CBF) and body weight including filament width, time after reperfusion, occlusion time and the choice of surgical method. Using the Koizumi method, we found ischemic injury can be detected as early as 30 min after reperfusion, to a degree that is not statistically different from 24 h post-perfusion, using 2,3,5-Triphenyltetrazolium chloride (TTC) staining. We also found a distinct increase in total lesion volume with increasing occlusion time, with 30–45 min a critical time for the development of large, reproducible lesions. Furthermore, although we found no significant difference in total lesion volume generated by the Koizumi and Longa methods of MCAO, nor were survival rates appreciably different between the two at 4 h after reperfusion, the Longa method produces significantly greater reperfusion. Finally, we found no statistical evidence to support the exclusion of data from animals experiencing a CBF reduction of <70% in the MCA territory following MCAO, using laser-Doppler flowmetry. Instead we suggest the main usefulness of laser-Doppler flowmetry is for guiding filament placement and the identification of subarachnoid haemorrhages and premature reperfusion. In summary, this study provides detailed evaluation of the Koizumi method of intraluminal filament MCAO in mice and a direct comparison to the Longa method. PMID:26870954

  6. Computational Pipeline for NIRS-EEG Joint Imaging of tDCS-Evoked Cerebral Responses—An Application in Ischemic Stroke

    PubMed Central

    Guhathakurta, Debarpan; Dutta, Anirban

    2016-01-01

    Transcranial direct current stimulation (tDCS) modulates cortical neural activity and hemodynamics. Electrophysiological methods (electroencephalography-EEG) measure neural activity while optical methods (near-infrared spectroscopy-NIRS) measure hemodynamics coupled through neurovascular coupling (NVC). Assessment of NVC requires development of NIRS-EEG joint-imaging sensor montages that are sensitive to the tDCS affected brain areas. In this methods paper, we present a software pipeline incorporating freely available software tools that can be used to target vascular territories with tDCS and develop a NIRS-EEG probe for joint imaging of tDCS-evoked responses. We apply this software pipeline to target primarily the outer convexity of the brain territory (superficial divisions) of the middle cerebral artery (MCA). We then present a computational method based on Empirical Mode Decomposition of NIRS and EEG time series into a set of intrinsic mode functions (IMFs), and then perform a cross-correlation analysis on those IMFs from NIRS and EEG signals to model NVC at the lesional and contralesional hemispheres of an ischemic stroke patient. For the contralesional hemisphere, a strong positive correlation between IMFs of regional cerebral hemoglobin oxygen saturation and the log-transformed mean-power time-series of IMFs for EEG with a lag of about −15 s was found after a cumulative 550 s stimulation of anodal tDCS. It is postulated that system identification, for example using a continuous-time autoregressive model, of this coupling relation under tDCS perturbation may provide spatiotemporal discriminatory features for the identification of ischemia. Furthermore, portable NIRS-EEG joint imaging can be incorporated into brain computer interfaces to monitor tDCS-facilitated neurointervention as well as cortical reorganization. PMID:27378836

  7. Computational Pipeline for NIRS-EEG Joint Imaging of tDCS-Evoked Cerebral Responses-An Application in Ischemic Stroke.

    PubMed

    Guhathakurta, Debarpan; Dutta, Anirban

    2016-01-01

    Transcranial direct current stimulation (tDCS) modulates cortical neural activity and hemodynamics. Electrophysiological methods (electroencephalography-EEG) measure neural activity while optical methods (near-infrared spectroscopy-NIRS) measure hemodynamics coupled through neurovascular coupling (NVC). Assessment of NVC requires development of NIRS-EEG joint-imaging sensor montages that are sensitive to the tDCS affected brain areas. In this methods paper, we present a software pipeline incorporating freely available software tools that can be used to target vascular territories with tDCS and develop a NIRS-EEG probe for joint imaging of tDCS-evoked responses. We apply this software pipeline to target primarily the outer convexity of the brain territory (superficial divisions) of the middle cerebral artery (MCA). We then present a computational method based on Empirical Mode Decomposition of NIRS and EEG time series into a set of intrinsic mode functions (IMFs), and then perform a cross-correlation analysis on those IMFs from NIRS and EEG signals to model NVC at the lesional and contralesional hemispheres of an ischemic stroke patient. For the contralesional hemisphere, a strong positive correlation between IMFs of regional cerebral hemoglobin oxygen saturation and the log-transformed mean-power time-series of IMFs for EEG with a lag of about -15 s was found after a cumulative 550 s stimulation of anodal tDCS. It is postulated that system identification, for example using a continuous-time autoregressive model, of this coupling relation under tDCS perturbation may provide spatiotemporal discriminatory features for the identification of ischemia. Furthermore, portable NIRS-EEG joint imaging can be incorporated into brain computer interfaces to monitor tDCS-facilitated neurointervention as well as cortical reorganization. PMID:27378836

  8. A Comparative Study of Variables Influencing Ischemic Injury in the Longa and Koizumi Methods of Intraluminal Filament Middle Cerebral Artery Occlusion in Mice.

    PubMed

    Morris, Gary P; Wright, Amanda L; Tan, Richard P; Gladbach, Amadeus; Ittner, Lars M; Vissel, Bryce

    2016-01-01

    The intraluminal filament model of middle cerebral artery occlusion (MCAO) in mice and rats has been plagued by inconsistency, owing in part to the multitude of variables requiring control. In this study we investigated the impact of several major variables on survival rate, lesion volume, neurological scores, cerebral blood flow (CBF) and body weight including filament width, time after reperfusion, occlusion time and the choice of surgical method. Using the Koizumi method, we found ischemic injury can be detected as early as 30 min after reperfusion, to a degree that is not statistically different from 24 h post-perfusion, using 2,3,5-Triphenyltetrazolium chloride (TTC) staining. We also found a distinct increase in total lesion volume with increasing occlusion time, with 30-45 min a critical time for the development of large, reproducible lesions. Furthermore, although we found no significant difference in total lesion volume generated by the Koizumi and Longa methods of MCAO, nor were survival rates appreciably different between the two at 4 h after reperfusion, the Longa method produces significantly greater reperfusion. Finally, we found no statistical evidence to support the exclusion of data from animals experiencing a CBF reduction of <70% in the MCA territory following MCAO, using laser-Doppler flowmetry. Instead we suggest the main usefulness of laser-Doppler flowmetry is for guiding filament placement and the identification of subarachnoid haemorrhages and premature reperfusion. In summary, this study provides detailed evaluation of the Koizumi method of intraluminal filament MCAO in mice and a direct comparison to the Longa method. PMID:26870954

  9. Transfusion of CXCR4-primed endothelial progenitor cells reduces cerebral ischemic damage and promotes repair in db/db diabetic mice.

    PubMed

    Chen, Ji; Chen, Jianying; Chen, Shuzhen; Zhang, Cheng; Zhang, Liangqing; Xiao, Xiang; Das, Avik; Zhao, Yuhui; Yuan, Bin; Morris, Mariana; Zhao, Bin; Chen, Yanfang

    2012-01-01

    This study investigated the role of stromal cell-derived factor-1α (SDF-1α)/CXC chemokine receptor 4 (CXCR4) axis in brain and endothelial progenitor cells (EPCs), and explored the efficacy of CXCR4 primed EPCs in treating ischemic stroke in diabetes. The db/db diabetic and db/+ mice were used in this study. Levels of plasma SDF-1α and circulating CD34+CXCR4+ cells were measured. Brain SDF-1α and CXCR4 expression were quantified at basal and after middle cerebral artery occlusion (MCAO). In in vitro study, EPCs were transfected with adenovirus carrying null (Ad-null) or CXCR4 (Ad-CXCR4) followed with high glucose (HG) treatment for 4 days. For pathway block experiments, cells were pre-incubated with PI3K inhibitor or nitric oxide synthase (NOS) inhibitor for two hours. The CXCR4 expression, function and apoptosis of EPCs were determined. The p-Akt/Akt and p-eNOS/eNOS expression in EPCs were also measured. In in vivo study, EPCs transfected with Ad-null or Ad-CXCR4 were infused into mice via tail vein. On day 2 and 7, the cerebral blood flow, neurologic deficit score, infarct volume, cerebral microvascular density, angiogenesis and neurogenesis were determined. We found: 1) The levels of plasma SDF-1α and circulating CD34+CXCR4+ cells were decreased in db/db mice; 2) The basal level of SDF-1α and MCAO-induced up-regulation of SDF-1α/CXCR4 axis were reduced in the brain of db/db mice; 3) Ad-CXCR4 transfection increased CXCR4 expression in EPCs and enhanced EPC colonic forming capacity; 4) Ad-CXCR4 transfection prevented EPCs from HG-induced dysfunction (migration and tube formation) and apoptosis via activation of PI3K/Akt/eNOS signal pathway; 4) Ad-CXCR4 transfection enhanced the efficacy of EPC infusion in attenuating infarct volume and promoting angiogenesis and neurogenesis. Our data suggest that Ad-CXCR4 primed EPCs have better therapeutic effects for ischemia stroke in diabetes than unmodified EPCs do. PMID:23185548

  10. [Middle and anterior cerebral arteries dissection as a cause of ischemic stroke in a 7-year-old boy].

    PubMed

    Kalashnikova, L A; Dreval', M V; Dobrynina, L A; Krotenkova, M V

    2016-01-01

    Authors describe a 7-year-old boy, who developed a severe right-sided hemiparesis, aphasia, seizure, and confusion state during sport games. There was no headache. Allergic dermatitis in the past medical history and influenza vaccination 2 weeks before stroke were recorded. On the 12th day of disease, MRI of the brain revealed an acute infarction in the territory of left anterior and middle cerebral arteries with hemorrhagic transformation. MPA (15 day) showed occlusion of the left ACA and MCA. HR-MRI T1_db_fs weighted imaging (36 day) found intramural hematoma (IMH) in ACA and MCA with marked stenosis of the lumen. After 3 months, HR-MRI/MRA showed the complete regression of IMH, recanalization of the arterial lumen, prolonged irregular MCA stenosis. Neurological deficit regressed significantly.

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

    PubMed Central

    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

  12. Joint moment contributions to swing knee extension acceleration during gait in children with spastic hemiplegic cerebral palsy.

    PubMed

    Goldberg, Evan J; Requejo, Philip S; Fowler, Eileen G

    2010-03-22

    Inadequate peak knee extension during the swing phase of gait is a major deficit in individuals with spastic cerebral palsy (CP). The biomechanical mechanisms responsible for knee extension have not been thoroughly examined in CP. The purpose of this study was to assess the contributions of joint moments and gravity to knee extension acceleration during swing in children with spastic hemiplegic CP. Six children with spastic hemiplegic CP were recruited (age=13.4+/-4.8 years). Gait data were collected using an eight-camera system. Induced acceleration analysis was performed for each limb during swing. Average joint moment and gravity contributions to swing knee extension acceleration were calculated. Total swing and stance joint moment contributions were compared between the hemiplegic and non-hemiplegic limbs using paired t-tests (p<0.05). Swing limb joint moment contributions from the hemiplegic limb decelerated swing knee extension significantly more than those of the non-hemiplegic limb and resulted in significantly reduced knee extension acceleration. Total stance limb joint moment contributions were not statistically different. Swing limb joint moment contributions that decelerated knee extension appeared to be the primary cause of inadequate knee extension acceleration during swing. Stance limb muscle strength did not appear to be the limiting factor in achieving adequate knee extension in children with CP. Recent research has shown that the ability to extend the knee during swing is dependent on the selective voluntary motor control of the limb. Data from individual participants support this concept.

  13. The effects of therapeutic hypothermia on cerebral metabolism in neonates with hypoxic-ischemic encephalopathy: An in vivo 1H-MR spectroscopy study.

    PubMed

    Wisnowski, Jessica L; Wu, Tai-Wei; Reitman, Aaron J; McLean, Claire; Friedlich, Philippe; Vanderbilt, Douglas; Ho, Eugenia; Nelson, Marvin D; Panigrahy, Ashok; Blüml, Stefan

    2016-06-01

    Therapeutic hypothermia has emerged as the first empirically supported therapy for neuroprotection in neonates with hypoxic-ischemic encephalopathy (HIE). We used magnetic resonance spectroscopy ((1)H-MRS) to characterize the effects of hypothermia on energy metabolites, neurotransmitters, and antioxidants. Thirty-one neonates with HIE were studied during hypothermia and after rewarming. Metabolite concentrations (mmol/kg) were determined from the thalamus, basal ganglia, cortical grey matter, and cerebral white matter. In the thalamus, phosphocreatine concentrations were increased by 20% during hypothermia when compared to after rewarming (3.49 ± 0.88 vs. 2.90 ± 0.65, p < 0.001) while free creatine concentrations were reduced to a similar degree (3.00 ± 0.50 vs. 3.74 ± 0.85, p < 0.001). Glutamate (5.33 ± 0.82 vs. 6.32 ± 1.12, p < 0.001), aspartate (3.39 ± 0.66 vs. 3.87 ± 1.19, p < 0.05), and GABA (0.92 ± 0.36 vs. 1.19 ± 0.41, p < 0.05) were also reduced, while taurine (1.39 ± 0.52 vs. 0.79 ± 0.61, p < 0.001) and glutathione (2.23 ± 0.41 vs. 2.09 ± 0.33, p < 0.05) were increased. Similar patterns were observed in other brain regions. These findings support that hypothermia improves energy homeostasis by decreasing the availability of excitatory neurotransmitters, and thereby, cellular energy demand.

  14. The effects of therapeutic hypothermia on cerebral metabolism in neonates with hypoxic-ischemic encephalopathy: An in vivo 1H-MR spectroscopy study.

    PubMed

    Wisnowski, Jessica L; Wu, Tai-Wei; Reitman, Aaron J; McLean, Claire; Friedlich, Philippe; Vanderbilt, Douglas; Ho, Eugenia; Nelson, Marvin D; Panigrahy, Ashok; Blüml, Stefan

    2016-06-01

    Therapeutic hypothermia has emerged as the first empirically supported therapy for neuroprotection in neonates with hypoxic-ischemic encephalopathy (HIE). We used magnetic resonance spectroscopy ((1)H-MRS) to characterize the effects of hypothermia on energy metabolites, neurotransmitters, and antioxidants. Thirty-one neonates with HIE were studied during hypothermia and after rewarming. Metabolite concentrations (mmol/kg) were determined from the thalamus, basal ganglia, cortical grey matter, and cerebral white matter. In the thalamus, phosphocreatine concentrations were increased by 20% during hypothermia when compared to after rewarming (3.49 ± 0.88 vs. 2.90 ± 0.65, p < 0.001) while free creatine concentrations were reduced to a similar degree (3.00 ± 0.50 vs. 3.74 ± 0.85, p < 0.001). Glutamate (5.33 ± 0.82 vs. 6.32 ± 1.12, p < 0.001), aspartate (3.39 ± 0.66 vs. 3.87 ± 1.19, p < 0.05), and GABA (0.92 ± 0.36 vs. 1.19 ± 0.41, p < 0.05) were also reduced, while taurine (1.39 ± 0.52 vs. 0.79 ± 0.61, p < 0.001) and glutathione (2.23 ± 0.41 vs. 2.09 ± 0.33, p < 0.05) were increased. Similar patterns were observed in other brain regions. These findings support that hypothermia improves energy homeostasis by decreasing the availability of excitatory neurotransmitters, and thereby, cellular energy demand. PMID:26661180

  15. Cerebral blood flow and CO/sub 2/ reactivity in transient ischemic attacks: comparison between TIAs due to the ICA occlusion and ICA mild stenosis

    SciTech Connect

    Tsuda, Y.; Kimura, K.; Yoneda, S.; Etani, H.; Asai, T.; Nakamura, M.; Abe, H.

    1983-01-01

    Hemispheric mean cerebral blood flow (CBF), together with its CO2 reactivity in response to hyperventilation, was investigated in 18 patients with transient ischemic attacks (TIAs) by intraarterial 133Xe injection method in a subacute-chronic stage of the clinical course. In 8 patients, the lesion responsible for symptoms was regarded as unilateral internal carotid artery (ICA) occlusion, and in 10 patients, it was regarded as unilateral ICA mild stenosis (less than 50% stenosis in diameter). Resting flow values were significantly decreased in the affected hemisphere of TIA due to the ICA occlusion as compared with the unaffected hemisphere of the same patient, regarded as the relative control. It was not decreased in the affected hemisphere of TIA due to the ICA mild stenosis as compared with the control. With respect to the responsiveness of CBF to changes in PaCO2, it was preserved in both TIAs, due to the ICA occlusion and ICA mild stenosis. Vasoparalysis was not observed in either types of TIAs in the subacute-chronic stage. However, in the relationship of blood pressure and CO2 reactivity, expressed as delta CBF(%)/delta PaCO2, pressure-dependent CO2 reactivity as a group was observed with significance in 8 cases of TIA due to the ICA occlusion, while no such relationship was noted in 10 cases of TIA due to the ICA mild stenosis. Moreover, clinical features were different between TIAs due to the ICA occlusion and ICA mild stenosis, i.e., more typical, repeatable TIA (6.3 +/- 3.7 times) with shorter duration (less than 30 minutes) was observed in TIAs due to the ICA mild stenosis, while more prolonged, less repeatable TIA (2.4 +/- 1.4 times) was observed in TIAs due to fixed obstruction of the ICA. From these observations, two different possible mechanisms as to the pathogenesis of TIA might be expected.

  16. Protective effect of naringin against ischemic reperfusion cerebral injury: possible neurobehavioral, biochemical and cellular alterations in rat brain.

    PubMed

    Gaur, Vaibhav; Aggarwal, Aditi; Kumar, Anil

    2009-08-15

    The present study was conducted with an aim to explore the possible role of naringin against ischemia reperfusion induced-neurobehavioral alterations, oxidative damage, cellular and histopathological alterations in cortex, striatum, hippocampus areas of brain. Male Wistar rats (200-220 g) were subjected to bilateral carotid artery occlusion for 30 min followed by reperfusion for 24 h to induce reperfusion (I/R) cerebral injury. Naringin (50, 100 mg/kg, i.p.) was administered for 7 days continuously before animals were subjected to ischemia reperfusion injury. Various behavioral tests [locomotor activity, neurological score (inclined beam test), transfer latency, resistance to lateral push] and biochemical parameters (lipid peroxidation, nitrite level, reduced glutathione, superoxide dismutase and catalase activity), mitochondrial enzyme dysfunctions (Complex I, II, III and IV) in cortex, striatum, hippocampus of brain and histopathological alterations were assessed subsequently. Seven days naringin (50 and 100 mg/kg) treatment significantly improved neurobehavioral alterations (improved locomotor activity, inclined beam walking and reduced resistance to lateral push, transfer latency) as compared to control ischemia reperfusion. Naringin (50 mg/kg and 100 mg/kg) treatment significantly attenuated oxidative damage as indicated by reduced lipid peroxidation, nitrite concentration, restored reduced glutathione and catalase activity and mitochondrial enzyme activities in cortex, striatum, cerebellum as compared to control (ischemia reperfusion) animals. In addition, naringin treatment significantly reversed histopathological alterations in cortex, striatum, hippocampus areas as compared to control (ischemia reperfusion). Present study suggests the protective effect of naringin and its therapeutic potential against ischemia reperfusion induced and related behavioral alterations in rats. PMID:19577560

  17. [The relationship between placental lesions and early hemorrhagic-ischemic cerebral injury in very low birth weight infants].

    PubMed

    Vaihinger, Mara; Mazzitelli, Nancy; Balanian, Nora; Grandi, Carlos

    2013-01-01

    Introducción: El examen histopatológico de la placenta es trascendente para evidenciar desordenes relacionados con el embarazo que se asocian a lesiones isquémico hemorrágicas cerebrales (LIHC) en recién nacidos prematuros (RNPT). Objetivo: Estudiar la asociación entre lesiones placentarias y LIHC precoces detectadas con ecografía en RNPT ≤ 1500 g y 32 semanas. Material y Métodos: diseño caso – control. Criterios de inclusión: RNPT ≥ 24 y ≤ 32 semanas, ≥ 500 y ≤ 1500 g, nacidos en la Maternidad Sardá entre años 2006 y 2012. Criterios de exclusión: RNPT gemelares, con malformaciones o infecciones intrauterinas específicas y los fallecidos antes de las 24 horas de vida. Resultados: fueron incluidos 198 RNPT, 49 con LIHC (casos) y 149 sin LIHC (controles). No se encontraron diferencias en las lesiones histopatológicas placentarias entre los dos grupos, aunque se apreció una clara tendencia de lesiones inflamatorias en los casos (67.3%) en comparación con los controles (48 %, p = 0.018). La ruptura prematura de las membranas (p = 0.027) y la corioamnionitis clínica fueron más frecuentes en los casos. Complicaciones fuertemente asociadas a prematurez fueron estadísticamente más evidentes entre los casos. La hemorragia intraventricular fue la lesión cerebral más hallada. El 50% de los casos persistieron con LIHC a las 36-40 semanas, mientras que a mayor edad gestacional el riesgo de LIHC fue menor . Conclusiones: las lesiones histopatológicas placentarias no estuvieron asociadas independientemente a mayor riesgo de LIHC, aunque se observó un predominio de lesiones inflamatorias en los casos.

  18. pH-Responsive biodegradable polymeric micelles with anchors to interface magnetic nanoparticles for MR imaging in detection of cerebral ischemic area

    NASA Astrophysics Data System (ADS)

    Yang, Hong Yu; Jang, Moon-Sun; Gao, Guang Hui; Lee, Jung Hee; Lee, Doo Sung

    2016-06-01

    A novel type of pH-responsive biodegradable copolymer was developed based on methyloxy-poly(ethylene glycol)-block-poly[dopamine-2-(dibutylamino) ethylamine-l-glutamate] (mPEG-b-P(DPA-DE)LG) and applied to act as an intelligent nanocarrier system for magnetic resonance imaging (MRI). The mPEG-b-P(DPA-DE)LG copolymer was synthesized by a typical ring opening polymerization of N-carboxyanhydrides (NCAs-ROP) using mPEG-NH2 as a macroinitiator, and two types of amine-terminated dopamine groups and pH-sensitive ligands were grafted onto a side chain by a sequential aminolysis reaction. This design greatly benefits from the addition of the dopamine groups to facilitate self-assembly, as these groups can act as high-affinity anchors for iron oxide nanoparticles, thereby increasing long-term stability at physiological pH. The mPEG moiety in the copolymers helped the nanoparticles to remain well-dispersed in an aqueous solution, and pH-responsive groups could control the release of hydrophobic Fe3O4 nanoparticles in an acidic environment. The particle size of the Fe3O4-loaded mPEG-b-P(DPA-DE)LG micelles was measured by dynamic light scattering (DLS) and cryo-TEM. The superparamagnetic properties of the Fe3O4-loaded mPEG-b-P(DPA-DE)LG micelles were confirmed by a superconducting quantum interference device (SQUID). T2-weighted magnetic resonance imaging (MRI) of Fe3O4-loaded mPEG-b-P(DPA-DE)LG phantoms exhibited enhanced negative contrast with an r2 relaxivity of approximately 106.7 mM-1 s-1. To assess the ability of the Fe3O4-loaded mPEG-P(DE-DPA)LG micelles to act as MRI probes, we utilized a cerebral ischemia disease rat model with acidic tissue. We found that a gradual change in contrast in the cerebral ischemic area could be visualized by MRI after 1 h, and maximal signal loss was detected after 24 h post-injection. These results demonstrated that the Fe3O4-loaded mPEG-b-P(DPA-DE)LG micelles can act as pH-triggered MRI probes for diagnostic imaging of acidic

  19. pH-Responsive biodegradable polymeric micelles with anchors to interface magnetic nanoparticles for MR imaging in detection of cerebral ischemic area

    NASA Astrophysics Data System (ADS)

    Yang, Hong Yu; Jang, Moon-Sun; Gao, Guang Hui; Lee, Jung Hee; Lee, Doo Sung

    2016-06-01

    A novel type of pH-responsive biodegradable copolymer was developed based on methyloxy-poly(ethylene glycol)-block-poly[dopamine-2-(dibutylamino) ethylamine-l-glutamate] (mPEG-b-P(DPA-DE)LG) and applied to act as an intelligent nanocarrier system for magnetic resonance imaging (MRI). The mPEG-b-P(DPA-DE)LG copolymer was synthesized by a typical ring opening polymerization of N-carboxyanhydrides (NCAs-ROP) using mPEG-NH2 as a macroinitiator, and two types of amine-terminated dopamine groups and pH-sensitive ligands were grafted onto a side chain by a sequential aminolysis reaction. This design greatly benefits from the addition of the dopamine groups to facilitate self-assembly, as these groups can act as high-affinity anchors for iron oxide nanoparticles, thereby increasing long-term stability at physiological pH. The mPEG moiety in the copolymers helped the nanoparticles to remain well-dispersed in an aqueous solution, and pH-responsive groups could control the release of hydrophobic Fe3O4 nanoparticles in an acidic environment. The particle size of the Fe3O4-loaded mPEG-b-P(DPA-DE)LG micelles was measured by dynamic light scattering (DLS) and cryo-TEM. The superparamagnetic properties of the Fe3O4-loaded mPEG-b-P(DPA-DE)LG micelles were confirmed by a superconducting quantum interference device (SQUID). T2-weighted magnetic resonance imaging (MRI) of Fe3O4-loaded mPEG-b-P(DPA-DE)LG phantoms exhibited enhanced negative contrast with an r2 relaxivity of approximately 106.7 mM-1 s-1. To assess the ability of the Fe3O4-loaded mPEG-P(DE-DPA)LG micelles to act as MRI probes, we utilized a cerebral ischemia disease rat model with acidic tissue. We found that a gradual change in contrast in the cerebral ischemic area could be visualized by MRI after 1 h, and maximal signal loss was detected after 24 h post-injection. These results demonstrated that the Fe3O4-loaded mPEG-b-P(DPA-DE)LG micelles can act as pH-triggered MRI probes for diagnostic imaging of acidic

  20. Chronic Cerebral Hypoperfusion Accelerates Alzheimer's Disease Pathology with Cerebrovascular Remodeling in a Novel Mouse Model.

    PubMed

    Zhai, Yun; Yamashita, Toru; Nakano, Yumiko; Sun, Zhuoran; Shang, Jingwei; Feng, Tian; Morihara, Ryuta; Fukui, Yusuke; Ohta, Yasuyuki; Hishikawa, Nozomi; Abe, Koji

    2016-06-13

    Recently, aging societies have been showing an increasingly strong relationship between Alzheimer's disease (AD) and chronic cerebral hypoperfusion (HP). In the present study, we created a new mouse model for AD with HP, and investigated its clinical and pathological characteristics. Alzheimer's disease transgenic mice (APP23) were subjected to bilateral common carotid arteries stenosis with ameroid constrictors for slowly progressive cerebral HP. In contrast to simple APP23 mice, cerebral HP exacerbated motor and cognitive dysfunctions with white matter lesions and meningo-parenchymal amyloid-β (Aβ) burdens. Strong cerebrovascular inflammation and severe amyloid angiopathy with cerebrovascular remodeling were also observed in APP23 + HP mouse brains. An acetylcholinesterase inhibitor galantamine improved such clinical dysfunctions, retrieved above neuropathological characteristics, and enhanced nicotinic acetylcholine receptor (nAChR)-binding activity. The present study demonstrates that chronic cerebral HP enhanced cognitive/motor dysfunctions with parenchymal/cerebrovascular Aβ accumulation and cerebrovascular remodeling. These neuropathological abnormalities were greatly ameliorated by galantamine treatment associated with nAChR-mediated neuroprotection by allosterically potentiating ligand action. PMID:27314529

  1. Astrocyte-mediated ischemic tolerance.

    PubMed

    Hirayama, Yuri; Ikeda-Matsuo, Yuri; Notomi, Shoji; Enaida, Hiroshi; Kinouchi, Hiroyuki; Koizumi, Schuichi

    2015-03-01

    Preconditioning (PC) using a preceding sublethal ischemic insult is an attractive strategy for protecting neurons by inducing ischemic tolerance in the brain. Although the underlying molecular mechanisms have been extensively studied, almost all studies have focused on neurons. Here, using a middle cerebral artery occlusion model in mice, we show that astrocytes play an essential role in the induction of brain ischemic tolerance. PC caused activation of glial cells without producing any noticeable brain damage. The spatiotemporal pattern of astrocytic, but not microglial, activation correlated well with that of ischemic tolerance. Interestingly, such activation in astrocytes lasted at least 8 weeks. Importantly, inhibiting astrocytes with fluorocitrate abolished the induction of ischemic tolerance. To investigate the underlying mechanisms, we focused on the P2X7 receptor as a key molecule in astrocyte-mediated ischemic tolerance. P2X7 receptors were dramatically upregulated in activated astrocytes. PC-induced ischemic tolerance was abolished in P2X7 receptor knock-out mice. Moreover, our results suggest that hypoxia-inducible factor-1α, a well known mediator of ischemic tolerance, is involved in P2X7 receptor-mediated ischemic tolerance. Unlike previous reports focusing on neuron-based mechanisms, our results show that astrocytes play indispensable roles in inducing ischemic tolerance, and that upregulation of P2X7 receptors in astrocytes is essential. PMID:25740510

  2. Ischemic Stroke

    MedlinePlus

    A stroke is a medical emergency. There are two types - ischemic and hemorrhagic. Ischemic stroke is the most common type. It is usually ... are at risk for having a more serious stroke. Symptoms of stroke are Sudden numbness or weakness ...

  3. Cellular Basis of Anoxic-Ischemic Brain Injury

    PubMed Central

    Bronshvag, Michael M.

    1978-01-01

    Anoxic-ischemic cerebral disease is an important primary cause of morbidity and mortality, and also complicates a number of systemic diseases. Its clinical manifestations, such as hemiparesis and coma, represent cellular injury sustained by the complex, inhomogeneous brain. An understanding of the nature and pattern of anoxic-ischemic cerebral injury, and of the logical basis for avenues of therapy, is necessary to the management of patients with the various anoxic-ischemic disorders. PMID:685270

  4. Ischemic perinatal stroke: challenge and opportunities.

    PubMed

    Raju, Tonse N K

    2008-08-01

    The second highest risk group for developing a cerebral stroke is the perinatal period, generally defined as 20 weeks of gestation through 28th postnatal day of age. In this commentary, a brief overview of ischemic perinatal strokes is presented. Ischemic perinatal stroke (IPS) occurs at a rate of 1 : 2300 to 1 : 5000 births, accounting for 30% of children with hemiplegic cerebral palsy (CP). Thus, IPS is the most common known cause for CP [1-3]. Although they occur frequently, much remains to be studied about perinatal strokes in general and the ischemic variety in particular. PMID:18705894

  5. Neuroprotective effects of systemic cerebral endothelial cell transplantation in a rat model of cerebral ischemia.

    PubMed

    Moon, Jong-Hyun; Na, Joo-Young; Lee, Min-Cheol; Choi, Kang-Ho; Lee, Jeong-Kil; Min, Jung-Joon; Kim, Kyung-Tae; Park, Jong-Tae; Park, Man-Seok; Kim, Hyung-Seok

    2016-01-01

    Human cerebral microvascular endothelial cell line (hCMEC)/D3 cells, which are from a stable clonal cell line of human immortalized cerebral endothelial cells, were intra-arterially transplanted through the common carotid artery in a rat model of photochemical-induced cerebral ischemia. Their therapeutic effects on infarct size, blood-brain barrier (BBB) breakdown, and outcome were examined. The hCMEC/D3 cells were genetically modified with the firefly luciferase gene for in vivo imaging post-transplantation. Transplanted hCMEC/D3 cells were identified in the infarcted brain by bioluminescence imaging at 1 day after transplantation. Compared with the control group, the hCMEC/D3-transplanted group showed reduced infarct size on day 3, reduced Evans blue dye leakage on day 1 indicating decreased BBB breakdown, and early recovery from Rotarod test neurological deficits. The hCMEC/D3-transplanted group also showed decreased levels of matrix metalloproteinase (MMP)-9, which were inversely correlated with TIMP-1 levels on post-transplantation days 1 and 3. The expression of tumor necrosis factor-α and interleukin-1β were markedly diminished in the hCMEC/D3-transplanted group compared with controls. The systemically transplanted cells selectively migrated and integrated into the ischemically lesioned area, which accelerated neurological recovery. This new cerebral endothelial cell-based therapy may hold promise for clinical trials in patients with ischemic stroke. PMID:27347342

  6. Neuroprotective effects of systemic cerebral endothelial cell transplantation in a rat model of cerebral ischemia.

    PubMed

    Moon, Jong-Hyun; Na, Joo-Young; Lee, Min-Cheol; Choi, Kang-Ho; Lee, Jeong-Kil; Min, Jung-Joon; Kim, Kyung-Tae; Park, Jong-Tae; Park, Man-Seok; Kim, Hyung-Seok

    2016-01-01

    Human cerebral microvascular endothelial cell line (hCMEC)/D3 cells, which are from a stable clonal cell line of human immortalized cerebral endothelial cells, were intra-arterially transplanted through the common carotid artery in a rat model of photochemical-induced cerebral ischemia. Their therapeutic effects on infarct size, blood-brain barrier (BBB) breakdown, and outcome were examined. The hCMEC/D3 cells were genetically modified with the firefly luciferase gene for in vivo imaging post-transplantation. Transplanted hCMEC/D3 cells were identified in the infarcted brain by bioluminescence imaging at 1 day after transplantation. Compared with the control group, the hCMEC/D3-transplanted group showed reduced infarct size on day 3, reduced Evans blue dye leakage on day 1 indicating decreased BBB breakdown, and early recovery from Rotarod test neurological deficits. The hCMEC/D3-transplanted group also showed decreased levels of matrix metalloproteinase (MMP)-9, which were inversely correlated with TIMP-1 levels on post-transplantation days 1 and 3. The expression of tumor necrosis factor-α and interleukin-1β were markedly diminished in the hCMEC/D3-transplanted group compared with controls. The systemically transplanted cells selectively migrated and integrated into the ischemically lesioned area, which accelerated neurological recovery. This new cerebral endothelial cell-based therapy may hold promise for clinical trials in patients with ischemic stroke.

  7. Linear accelerator and Greitz-Bergstrom's head fixation system in radiosurgery of single cerebral metastases. A report of 86 cases.

    PubMed

    Valentino, V; Mirri, M A; Schinaia, G; Dalle Ore, G

    1993-01-01

    Between 1984 and 1991 86 patients with single cerebral metastases underwent linear accelerator radiosurgery using the atraumatic and reproducible Greitz-Bergström head-fixation device. Routine one-month follow-up documented disappearance of the tumour in 16 patients, with resolution of the oedema and ventricular shift. Shrinkage of the metastasis occurred in 51 patients. In 9 patients the tumour remained stable, in 7 there was progression of tumour size. Among the patients showing shrinkage of the tumour or unchanged tumour volume, repeated radiosurgery resulted in disappearance of the metastasis in 5 and further shrinkage in 28. In 14 patients routine stereotactic CT follow-up study led to the detection of a new metastasis, again treated with excellent results. Local recurrence occurred in 2 patients and radiation necrosis in the target area in 5 patients. Radiosurgery thus proves to be an appropriate alternative to surgery. The versatility of our non-invasive and painless method permits CT staging (which we consider essential) without hospitalization of the patient.

  8. Statins and cerebral hemodynamics

    PubMed Central

    Giannopoulos, Sotirios; Katsanos, Aristeidis H; Tsivgoulis, Georgios; Marshall, Randolph S

    2012-01-01

    HMG-CoA reductase inhibitors (statins) are associated with improved stroke outcome. This observation has been attributed in part to the palliative effect of statins on cerebral hemodynamics and cerebral autoregulation (CA), which are mediated mainly through the upregulation of endothelium nitric oxide synthase (eNOS). Several animal studies indicate that statin pretreatment enhances cerebral blood flow after ischemic stroke, although this finding is not further supported in clinical settings. Cerebral vasomotor reactivity, however, is significantly improved after long-term statin administration in most patients with severe small vessel disease, aneurysmal subarachnoid hemorrhage, or impaired baseline CA. PMID:22929438

  9. Complications Following Linear Accelerator Based Stereotactic Radiation for Cerebral Arteriovenous Malformations

    SciTech Connect

    Skjoth-Rasmussen, Jane; Roed, Henrik; Ohlhues, Lars; Jespersen, Bo; Juhler, Marianne

    2010-06-01

    Purpose: Primarily, gamma knife centers are predominant in publishing results on arteriovenous malformations (AVM) treatments including reports on risk profile. However, many patients are treated using a linear accelerator-most of these at smaller centers. Because this setting is different from a large gamma knife center, the risk profile at Linac departments could be different from the reported experience. Prescribed radiation doses are dependent on AVM volume. This study details results from a medium sized Linac department center focusing on risk profiles. Method and Materials: A database was searched for all patients with AVMs. We included 50 consecutive patients with a minimum of 24 months follow-up (24-51 months). Results: AVM occlusion was verified in 78% of patients (39/50). AVM occlusion without new deficits (excellent outcome) was obtained in 44%. Good or fair outcome (AVM occlusion with mild or moderate new deficits) was seen in 30%. Severe complications after AVM occlusion occurred in 4% with a median interval of 15 months after treatment (range, 1-26 months). Conclusions: We applied an AVM grading score developed at the Mayo Clinic to predict probable outcome after radiosurgery in a large patient population treated with Gamma knife. A cutoff above and below a score of 1.5 could not discriminate between the likelihood of having an excellent outcome (approximately 45%). The chance of having an excellent or good outcome was slightly higher in patients with an AVM score below 1.5 (64% vs. 57%).

  10. Characterization of the interaction between local cerebral metabolic rate for glucose and acid-base index in ischemic rat brain employing a double-isotope methodology

    SciTech Connect

    Peek, K.E.H.

    1988-01-01

    The association between increases in cerebral glucose metabolism and the development of acidosis is largely inferential, based on reports linking hyperglycemia with poor neurological outcome, lactate accumulation, and the severity of acidosis. We measured local cerebral metabolic rate for glucose (lCMRglc) and an index of brain pH-the acid-base index (ABI)-concurrently and characterized their interaction in a model of focal cerebral ischemia in rats in a double-label autoradiographic study, using ({sup 14}C)2-deoxyglucose and ({sup 14}C)dimethyloxazolidinedione. Computer-assisted digitization and analysis permitted the simultaneous quantification of the two variables on a pixel-by-pixel basis in the same brain slices.

  11. Drug Delivery to the Ischemic Brain

    PubMed Central

    Thompson, Brandon J.; Ronaldson, Patrick T.

    2014-01-01

    Cerebral ischemia occurs when blood flow to the brain is insufficient to meet metabolic demand. This can result from cerebral artery occlusion that interrupts blood flow, limits CNS supply of oxygen and glucose, and causes an infarction/ischemic stroke. Ischemia initiates a cascade of molecular events inneurons and cerebrovascular endothelial cells including energy depletion, dissipation of ion gradients, calcium overload, excitotoxicity, oxidative stress, and accumulation of ions and fluid. Blood-brain barrier (BBB) disruption is associated with cerebral ischemia and leads to vasogenic edema, a primary cause of stroke-associated mortality. To date, only a single drug has received US Food and Drug Administration (FDA) approval for acute ischemic stroke treatment, recombinant tissue plasminogen activator (rt-PA). While rt-PA therapy restores perfusion to ischemic brain, considerable tissue damage occurs when cerebral blood flow is re-established. Therefore, there is a critical need for novel therapeutic approaches that can “rescue” salvageable brain tissue and/or protect BBB integrity during ischemic stroke. One class of drugs that may enable neural cell rescue following cerebral ischemia/reperfusion injury is the HMG-CoA reductase inhibitors (i.e., statins). Understanding potential CNS drug delivery pathways for statins is critical to their utility in ischemic stroke. Here, we review molecular pathways associated with cerebral ischemia and novel approaches for delivering drugs to treat ischemic disease. Specifically, we discuss utility of endogenous BBB drug uptake transporters such as organic anion transporting polypeptides (OATPs/Oatps) and nanotechnology-based carriers for optimization of CNS drug delivery. Overall, this chapter highlights state-of-the-art technologies that may improve pharmacotherapy of cerebral ischemia. PMID:25307217

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

    PubMed Central

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

    2015-01-01

    Rationale Collaterals lessen tissue injury in occlusive disease. However, aging causes progressive decline in their number and smaller diameters in those that remain (collateral rarefaction), beginning at 16 months-age in mice (ie, middle age), and worse ischemic injury—effects that are accelerated in even 3 months-old eNOS−/− mice. These findings have found indirect support in recent human studies. Objective We sought to determine if other cardiovascular risk factors (CVRFs) associated with endothelial dysfunction cause collateral rarefaction, investigate possible mechanisms, and test strategies for prevention. Methods and Results Mice with nine different models of CVRFs of 4–12 months-age were assessed for number and diameter of native collaterals in skeletal muscle and brain, and for collateral-dependent perfusion and ischemic injury after arterial occlusion. Hypertension caused collateral rarefaction whose severity increased with duration and level of hypertension, accompanied by greater hindlimb ischemia and cerebral infarct volume. Chronic treatment of wildtype mice with L-NG-nitro-arginine methylester caused similar rarefaction and worse ischemic injury that were not prevented by lowering arterial pressure with hydralazine. Metabolic syndrome, hypercholesterolemia, diabetes mellitus, and obesity also caused collateral rarefaction. Neither chronic statin treatment nor exercise training lessened hypertension-induced rarefaction. Conclusion Chronic CVRF presence caused collateral rarefaction and worse ischemic injury, even at relatively young ages. Rarefaction was associated with increased proliferation rate of collateral endothelial cells, effects that may promote accelerated endothelial cell senescence. PMID:25862671

  13. Neurovascular Regulation in the Ischemic Brain

    PubMed Central

    Jackman, Katherine

    2015-01-01

    Abstract Significance: The brain has high energetic requirements and is therefore highly dependent on adequate cerebral blood supply. To compensate for dangerous fluctuations in cerebral perfusion, the circulation of the brain has evolved intrinsic safeguarding measures. Recent Advances and Critical Issues: The vascular network of the brain incorporates a high degree of redundancy, allowing the redirection and redistribution of blood flow in the event of vascular occlusion. Furthermore, active responses such as cerebral autoregulation, which acts to maintain constant cerebral blood flow in response to changing blood pressure, and functional hyperemia, which couples blood supply with synaptic activity, allow the brain to maintain adequate cerebral perfusion in the face of varying supply or demand. In the presence of stroke risk factors, such as hypertension and diabetes, these protective processes are impaired and the susceptibility of the brain to ischemic injury is increased. One potential mechanism for the increased injury is that collateral flow arising from the normally perfused brain and supplying blood flow to the ischemic region is suppressed, resulting in more severe ischemia. Future Directions: Approaches to support collateral flow may ameliorate the outcome of focal cerebral ischemia by rescuing cerebral perfusion in potentially viable regions of the ischemic territory. Antioxid. Redox Signal. 22, 149–160. PMID:24328757

  14. Genetic susceptibility to ischemic stroke

    PubMed Central

    Meschia, James F.; Worrall, Bradford B.; Rich, Stephen S.

    2014-01-01

    Clinicians who treat patients with stroke need to be aware of several single-gene disorders that have ischemic stroke as a major feature, including sickle cell disease, Fabry disease, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, and retinal vasculopathy with cerebral leukodystrophy. The reported genome-wide association studies of ischemic stroke and several related phenotypes (for example, ischemic white matter disease) have shown that no single common genetic variant imparts major risk. Larger studies with samples numbering in the thousands are ongoing to identify common variants with smaller effects on risk. Pharmacogenomic studies have uncovered genetic determinants of response to warfarin, statins and clopidogrel. Despite increasing knowledge of stroke genetics, incorporating this new knowledge into clinical practice remains a challenge. The goals of this article are to review common single-gene disorders relevant to ischemic stroke, summarize the status of candidate gene and genome-wide studies aimed at discovering genetic stroke risk factors, and to briefly discuss pharmacogenomics related to stroke treatment. PMID:21629240

  15. Middle Cerebral Artery Calcification

    PubMed Central

    Kao, Hung-Wen; Liou, Michelle; Chung, Hsiao-Wen; Liu, Hua-Shan; Tsai, Ping-Huei; Chiang, Shih-Wei; Chou, Ming-Chung; Peng, Giia-Sheun; Huang, Guo-Shu; Hsu, Hsian-He; Chen, Cheng-Yu

    2015-01-01

    Abstract Calcification of the middle cerebral artery (MCA) is uncommon in the healthy elderly. Whether calcification of the MCA is associated with cerebral ischemic stroke remains undetermined. We intended to investigate the association using Agatston calcium scoring of the MCA. This study retrospectively included 354 subjects with ischemic stroke in the MCA territory and 1518 control subjects who underwent computed tomography (CT) of the brain. We recorded major known risk factors for ischemic stroke, including age, gender, hypertension, diabetes mellitus, smoking, hyperlipidemia, and obesity, along with the MCA calcium burden, measured with the Agatston calcium scoring method. Univariate and modified logistic regression analyses were performed to examine the association between the MCA calcification and ischemic stroke. The univariate analyses showed significant associations of ischemic stroke with age, hypertension, diabetes mellitus, smoking, total MCA Agatston score, and the presence of calcification on both or either side of the MCA. Subjects with the presence of MCA calcification on both or either side of the MCA were 8.46 times (95% confidence interval, 4.93–14.53; P < 0.001) more likely to have a cerebral infarct than subjects without MCA calcification after adjustment for the major known risk factors, including age, hypertension, diabetes mellitus, and smoking. However, a higher degree of MCA calcification reflected by the Agatston score was not associated with higher risk of MCA ischemic stroke after adjustment for the confounding factors and presence of MCA calcification. These results suggest that MCA calcification is associated with ischemic stroke in the MCA territory. Further prospective studies are required to verify the clinical implications of the MCA calcification. PMID:26683969

  16. Tissue plasminogen activator for acute ischemic stroke: calculation of dose based on estimated patient weight can increase the risk of cerebral bleeding.

    PubMed

    García-Pastor, Andrés; Díaz-Otero, Fernando; Funes-Molina, Carmen; Benito-Conde, Beatriz; Grandes-Velasco, Sandra; Sobrino-García, Pilar; Vázquez-Alén, Pilar; Fernández-Bullido, Yolanda; Villanueva-Osorio, Jose Antonio; Gil-Núñez, Antonio

    2015-10-01

    A dose of 0.9 mg/kg of intravenous tissue plasminogen activator (t-PA) has proven to be beneficial in the treatment of acute ischemic stroke (AIS). Dosing of t-PA based on estimated patient weight (PW) increases the likelihood of errors. Our objectives were to evaluate the accuracy of estimated PW and assess the effectiveness and safety of the actual applied dose (AAD) of t-PA. We performed a prospective single-center study of AIS patients treated with t-PA from May 2010 to December 2011. Dose was calculated according to estimated PW. Patients were weighed during the 24 h following treatment with t-PA. Estimation errors and AAD were calculated. Actual PW was measured in 97 of the 108 included patients. PW estimation errors were recorded in 22.7 % and were more frequent when weight was estimated by stroke unit staff (44 %). Only 11 % of patients misreported their own weight. Mean AAD was significantly higher in patients who had intracerebral hemorrhage (ICH) after t-PA than in patients who did not (0.96 vs. 0.92 mg/kg; p = 0.02). Multivariate analysis showed an increased risk of ICH for each 10 % increase in t-PA dose above the optimal dose of 0.90 mg/kg (OR 3.10; 95 % CI 1.14-8.39; p = 0.026). No effects of t-PA misdosing were observed on symptomatic ICH, functional outcome or mortality. Estimated PW is frequently inaccurate and leads to t-PA dosing errors. Increasing doses of t-PA above 0.90 mg/kg may increase the risk of ICH. Standardized weighing methods before t-PA is administered should be considered.

  17. [Vascular brain lesions and ischemic heart disease].

    PubMed

    Levin, G Z

    1979-01-01

    The role of essential hypertension in the pathogenesis of cerebral vessel disorders (not only hemorrhagic, but also ischemic) is greater than in the pathogenesis of the heart ischemic disease. An analysis of the evidences left by ancient doctors, when compared with statistical data of our time, gives one grounds to believe that cerebral hemorrhages have been a rather common disease, at least, since the time of the antique civilization of Greece and Rome, whereas ischemic heart disease has become a widespread disease among the population of the developed countries only in our time. This makes it possible to assume that the role of essential hypertension and that of atherosclerosis are not equal in the "diseases of civilization", if the diseases of today's developed society are meant.

  18. Ischemic Colitis

    PubMed Central

    FitzGerald, James F.; Hernandez III, Luis O.

    2015-01-01

    Most clinicians associate ischemic colitis with elderly patients who have underlying cardiovascular comorbidities. While the majority of cases probably occur in this population, the disease can present in younger patients as a result of different risk factors, making the diagnosis challenging. While a majority of patients respond to medical management, surgery is required in approximately 20% of the cases and is associated with high morbidity and mortality. PMID:26034405

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

    PubMed Central

    Geuskens, Ralph R. E. G.; Borst, Jordi; Lucas, Marit; Boers, A. M. Merel; Berkhemer, Olvert A.; Roos, Yvo B. W. E. M.; van Walderveen, Marianne A. A.; Jenniskens, Sjoerd F. M.; van Zwam, Wim H.; Dippel, Diederik W. J.; Majoie, Charles B. L. M.; Marquering, Henk A.

    2015-01-01

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

  20. Relationship between cerebral sodium-glucose transporter and hyperglycemia in cerebral ischemia.

    PubMed

    Yamazaki, Yui; Harada, Shinichi; Tokuyama, Shogo

    2015-09-14

    Post-ischemic hyperglycemia exacerbates the development of cerebral ischemia. To elucidate this exacerbation mechanism, we focused on sodium-glucose transporter (SGLT) as a mediator that lead hyperglycemia to cerebral ischemia. SGLT transport glucose into the cell, together with sodium ion, using the sodium concentration gradient. We have previously reported that suppression of cerebral SGLT ameliorates cerebral ischemic neuronal damage. However, detail relationship cerebral between SGLT and post-ischemic hyperglycemia remain incompletely defined. Therefore, we examined the involvement of cerebral SGLT on cerebral ischemic neuronal damage with or without hyperglycemic condition. Cell survival rate of primary cultured neurons was assessed by biochemical assay. A mouse model of focal ischemia was generated using a middle cerebral artery occlusion (MCAO). Neuronal damage was assessed with histological and behavioral analyses. Concomitant hydrogen peroxide/glucose treatment exacerbated hydrogen peroxide alone-induced cell death. Although a SGLT family-specific inhibitor, phlorizin had no effect on developed hydrogen peroxide alone-induced cell death, it suppressed cell death induced by concomitant hydrogen peroxide/glucose treatment. α-MG induced a concentration-dependent and significant decrease in neuronal survival. PHZ administered on immediately after reperfusion had no effect, but PHZ given at 6h after reperfusion had an effect. Our in vitro study indicates that SGLT is not involved in neuronal cell death in non-hyperglycemic condition. We have already reported that post-ischemic hyperglycemia begins to develop at 6h after MCAO. Therefore, current our in vivo study show post-ischemic hyperglycemic condition may be necessary for the SGLT-mediated exacerbation of cerebral ischemic neuronal damage.

  1. Neural Stem Cells and Ischemic Brain

    PubMed Central

    Zhang, Zhenggang; Chopp, Michael

    2016-01-01

    Stroke activates neural stem cells in the ventricular-subventricular zone (V/SVZ) of the lateral ventricle, which increases neuroblasts and oligodendrocyte progenitor cells (OPCs). Within the ischemic brain, neural stem cells, neuroblasts and OPCs appear to actively communicate with cerebral endothelial cells and other brain parenchymal cells to mediate ischemic brain repair; however, stroke-induced neurogenesis unlikely plays any significant roles in neuronal replacement. In this mini-review, we will discuss recent findings how intercellular communications between stroke-induced neurogenesis and oligodendrogenesis and brain parenchymal cells could potentially facilitate brain repair processes. PMID:27488979

  2. A Report of Accelerated Coronary Artery Disease Associated with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy

    PubMed Central

    Rubin, Courtney B.; Hahn, Virginia; Kobayashi, Taisei; Litwack, Andrew

    2015-01-01

    Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common heritable form of vascular dementia and it is caused by mutations in the NOTCH3 gene. The neurologic manifestations of CADASIL syndrome have been well characterized; however, here we report one of the first de novo cases of CADASIL-associated coronary artery disease. A 45-year-old woman with a history of CADASIL and remote tobacco use presented with unstable angina. She was found to have diffuse and irregular narrowing of the left anterior descending artery and a drug eluting stent was deployed. Months later, she developed two subsequent episodes of unstable angina, requiring stent placement in the distal left anterior descending artery and the right coronary artery. Though the neurologic manifestations of CADASIL have been well described, these patients may also be predisposed to developing premature coronary artery disease. Patients with CADASIL and their physicians should be aware of this possible association because these patients may not be identified as high risk by traditional cardiovascular risk estimators. These patients may benefit from more aggressive interventions to reduce cardiac risk. PMID:26435852

  3. Cerebral Palsy

    MedlinePlus

    ... How Can I Help a Friend Who Cuts? Cerebral Palsy KidsHealth > For Teens > Cerebral Palsy Print A A ... do just what everyone else does. What Is Cerebral Palsy? Cerebral palsy (CP) is a disorder of the ...

  4. [Ocular ischemic syndrome--a case report].

    PubMed

    Zemba, M; Avram, Corina Ioana; Ochinciuc, Uliana; Stamate, Alina Cristina; Camburu, Raluca Lăcrămioara

    2013-01-01

    Ocular ischemic syndrome, also known as hypoperfusion/ hypotensive retinopathy or as ischemic oculopathy is a rare ocular disease determined by chronic arterial hypoperfusion through central retinal artery, posterior and anterior ciliary arteries. It is bilateral in 20% of the cases. Most often it appears due to severe occlusion of the carotid arteries (ICA, MCA>ECA), described in 1963 by Kearns and Hollenhorst. Occasionally it can be determined by the obstruction of ophtalmic artery or some arterities (Takayasu, giant cell arteritis). The risk factors are: age between 50-80 years, males (M:F = 2:1), arterial hypertension, diabetes, coronary diseases (5% of the cases develop ocular ischemic syndrome), vascular stroke, hemodialysis. The case we present is of an 63 years old man known with primary arterial hypertension, hypercholesterolemia, diabetes type 2 non insulin dependent and diagnosticated with ischemic cerebral stroke and bilateral obstruction of internal carotid arteries in march 2010, who is presenting for visual impairment in both eyes. The imaging investigations show important carotid occlusion and at the ophthalmologic evaluation there are ocular hypertension and rubeosis iridis at the right eye, optic atrophy at both eyes (complete in the right eye and partial in the left eye), with superior altitudinal visual field defect in left eye. The following diagnosis was established: Chronic ocular ischemic syndrome in both eyes with Neovascular glaucoma at the right eye, Anterior ischemic optic neuropathy at the left eye and laser panphotocoagulation at the right eye was started. PMID:24386788

  5. [Ocular ischemic syndrome--a case report].

    PubMed

    Zemba, M; Avram, Corina Ioana; Ochinciuc, Uliana; Stamate, Alina Cristina; Camburu, Raluca Lăcrămioara

    2013-01-01

    Ocular ischemic syndrome, also known as hypoperfusion/ hypotensive retinopathy or as ischemic oculopathy is a rare ocular disease determined by chronic arterial hypoperfusion through central retinal artery, posterior and anterior ciliary arteries. It is bilateral in 20% of the cases. Most often it appears due to severe occlusion of the carotid arteries (ICA, MCA>ECA), described in 1963 by Kearns and Hollenhorst. Occasionally it can be determined by the obstruction of ophtalmic artery or some arterities (Takayasu, giant cell arteritis). The risk factors are: age between 50-80 years, males (M:F = 2:1), arterial hypertension, diabetes, coronary diseases (5% of the cases develop ocular ischemic syndrome), vascular stroke, hemodialysis. The case we present is of an 63 years old man known with primary arterial hypertension, hypercholesterolemia, diabetes type 2 non insulin dependent and diagnosticated with ischemic cerebral stroke and bilateral obstruction of internal carotid arteries in march 2010, who is presenting for visual impairment in both eyes. The imaging investigations show important carotid occlusion and at the ophthalmologic evaluation there are ocular hypertension and rubeosis iridis at the right eye, optic atrophy at both eyes (complete in the right eye and partial in the left eye), with superior altitudinal visual field defect in left eye. The following diagnosis was established: Chronic ocular ischemic syndrome in both eyes with Neovascular glaucoma at the right eye, Anterior ischemic optic neuropathy at the left eye and laser panphotocoagulation at the right eye was started.

  6. Ischemic preconditioning protects against ischemic brain injury

    PubMed Central

    Ma, Xiao-meng; Liu, Mei; Liu, Ying-ying; Ma, Li-li; Jiang, Ying; Chen, Xiao-hong

    2016-01-01

    In this study, we hypothesized that an increase in integrin αvβ3 and its co-activator vascular endothelial growth factor play important neuroprotective roles in ischemic injury. We performed ischemic preconditioning with bilateral common carotid artery occlusion for 5 minutes in C57BL/6J mice. This was followed by ischemic injury with bilateral common carotid artery occlusion for 30 minutes. The time interval between ischemic preconditioning and lethal ischemia was 48 hours. Histopathological analysis showed that ischemic preconditioning substantially diminished damage to neurons in the hippocampus 7 days after ischemia. Evans Blue dye assay showed that ischemic preconditioning reduced damage to the blood-brain barrier 24 hours after ischemia. This demonstrates the neuroprotective effect of ischemic preconditioning. Western blot assay revealed a significant reduction in protein levels of integrin αvβ3, vascular endothelial growth factor and its receptor in mice given ischemic preconditioning compared with mice not given ischemic preconditioning 24 hours after ischemia. These findings suggest that the neuroprotective effect of ischemic preconditioning is associated with lower integrin αvβ3 and vascular endothelial growth factor levels in the brain following ischemia. PMID:27335560

  7. Persimmon leaf flavonoid induces brain ischemic tolerance in mice.

    PubMed

    Miao, Mingsan; Zhang, Xuexia; Wang, Linan

    2013-05-25

    The persimmon leaf has been shown to improve cerebral ischemic outcomes; however, its mechanism of action remains unclear. In this study, mice were subjected to 10 minutes of ischemic preconditioning, and persimmon leaf flavonoid was orally administered for 5 days. Results showed that the persimmon leaf flavonoid significantly improved the content of tissue type plasminogen activator and 6-keto prostaglandin-F1 α in the cerebral cortex, decreased the content of thromboxane B2, and reduced the content of plasminogen activator inhibitor-1 in mice. Following optical microscopy, persimmon leaf flavonoid was also shown to reduce cell swelling and nuclear hyperchromatism in the cerebral cortex and hippocampus of mice. These results suggested that persimmon leaf flavonoid can effectively inhibit brain thrombosis, improve blood supply to the brain, and relieve ischemia-induced pathological damage, resulting in brain ischemic tolerance.

  8. Intermittent fasting attenuates inflammasome activity in ischemic stroke.

    PubMed

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

    2014-07-01

    Recent findings have revealed a novel inflammatory mechanism that contributes to tissue injury in cerebral ischemia mediated by multi-protein complexes termed inflammasomes. Intermittent fasting (IF) can decrease the levels of pro-inflammatory cytokines in the periphery and brain. Here we investigated the impact of IF (16h of food deprivation daily) for 4months on NLRP1 and NLRP3 inflammasome activities following cerebral ischemia. Ischemic stroke was induced in C57BL/6J mice by middle cerebral artery occlusion, followed by reperfusion (I/R). IF decreased the activation of NF-κB and MAPK signaling pathways, the expression of NLRP1 and NLRP3 inflammasome proteins, and both IL-1β and IL-18 in the ischemic brain tissue. These findings demonstrate that IF can attenuate the inflammatory response and tissue damage following ischemic stroke by a mechanism involving suppression of NLRP1 and NLRP3 inflammasome activity. PMID:24805069

  9. Peroxisomal Biogenesis in Ischemic Brain

    PubMed Central

    Young, Jennifer M.; Nelson, Jonathan W.; Cheng, Jian; Zhang, Wenri; Mader, Sarah; Davis, Catherine M.; Morrison, Richard S.

    2015-01-01

    Abstract Aims: Peroxisomes are highly adaptable and dynamic organelles, adjusting their size, number, and enzyme composition to changing environmental and metabolic demands. We determined whether peroxisomes respond to ischemia, and whether peroxisomal biogenesis is an adaptive response to cerebral ischemia. Results: Focal cerebral ischemia induced peroxisomal biogenesis in peri-infarct neurons, which was associated with a corresponding increase in peroxisomal antioxidant enzyme catalase. Peroxisomal biogenesis was also observed in primary cultured cortical neurons subjected to ischemic insult induced by oxygen-glucose deprivation (OGD). A catalase inhibitor increased OGD-induced neuronal death. Moreover, preventing peroxisomal proliferation by knocking down dynamin-related protein 1 (Drp1) exacerbated neuronal death induced by OGD, whereas enhancing peroxisomal biogenesis pharmacologically using a peroxisome proliferator-activated receptor-alpha agonist protected against neuronal death induced by OGD. Innovation: This is the first documentation of ischemia-induced peroxisomal biogenesis in mammalian brain using a combined in vivo and in vitro approach, electron microscopy, high-resolution laser-scanning confocal microscopy, and super-resolution structured illumination microscopy. Conclusion: Our findings suggest that neurons respond to ischemic injury by increasing peroxisome biogenesis, which serves a protective function, likely mediated by enhanced antioxidant capacity of neurons. Antioxid. Redox Signal. 22, 109–120. PMID:25226217

  10. Anticoagulation for the Acute Management of Ischemic Stroke

    PubMed Central

    Robinson, Austin A.; Ikuta, Kevin; Soverow, Jonathan

    2014-01-01

    Few prospective studies support the use of anticoagulation during the acute phase of ischemic stroke, though observational data suggest a role in certain populations. Depending on the mechanism of stroke, systemic anticoagulation may prevent recurrent cerebral infarction, but concomitantly carries a risk of hemorrhagic transformation. In this article, we describe a case where anticoagulation shows promise for ischemic stroke and review the evidence that has discredited its use in some circumstances while showing its potential in others. PMID:24910565

  11. Cerebrovascular arteriopathy (arteriosclerosis) and ischemic childhood stroke.

    PubMed

    Daniels, S R; Bates, S; Lukin, R R; Benton, C; Third, J; Glueck, C J

    1982-01-01

    The aim of this report is to describe the intracranial cerebrovascular abnormalities and clinical status of 8 children who had familial lipoprotein disorders and evidence of thromboembolic cerebrovascular disease. Six of the 8 children had low levels of plasma high density lipoprotein cholesterol, two had high triglyceride levels, and all came from kindreds characterized by familial lipoprotein abnormalities and premature cardio- and/or cerebrovascular atherosclerosis. Vascular occlusion, irregularities of the arterial lumen, beading, tortuosity, and evidence of collateralization were consistently noted. We speculate that cerebrovascular arteriosclerosis in pediatric ischemic stroke victims who have familial lipoprotein abnormalities may be related to lipoprotein-mediated endothelial damage and thrombosis formation, or to the failure to restore endothelial cells' integrity following damage. The apparent association of lipoproteins and strokes in children and their families merits further exploration, particularly when assessing cerebral angiograms in pediatric ischemic stroke victims. In children with unexplained ischemic cerebrovascular accidents, the diagnostic possibility of occlusive arteriosclerosis with thrombosis must be entertained.

  12. [The developing profile of cerebral ischemia].

    PubMed

    Martí-Vilalta, J L; Martí-Fábregas, J

    1999-01-01

    Cerebral ischemia, which may be silently manifested as transitory ischemia attacks or cerebral infarction, is not a stable, but rather, a moving process. In cerebral infarctions the initial ischemic area may change or move in a high percentage of patients and may involve a significant volume (mean of 32%) of neuronal tissue. The negative changes of initial cerebral ischemia which produce a worsening of the same may be due to the progression of the thrombus, appearance of new embolisms, cerebral edema, hemorrhage, blood reperfusion and systemias causes. These changes may determine the conversion of the shaded ischemic area into a definitive, irreversible infarction. The negative changes may also be produced some distance from the initial ischemic area, either because of microthromboembolisms or diaschisis. The positive changes of initial cerebral ischemia which produce as improvement of the same, may be due to collateral circulation, lysis or fragmentation of the embolism and a decrease in cerebral edema. Clinical changes with no evident clinical manifestations may also be produced and may be diagnosed with the use of clinical scales, imaging techniques, ultrasound and hematological and biochemical markers. Acknowledgement of these cerebral ischemia changes in the acute phase may determine the salvation of a part of the brain, and thereby modify the future clinical situation of the patient.

  13. Tocilizumab inhibits neuronal cell apoptosis and activates STAT3 in cerebral infarction rat model

    PubMed Central

    Wang, Shaojun; Zhou, Jun; Kang, Weijie; Dong, Zhaoni; Wang, Hezuo

    2016-01-01

    Cerebral infarction is a severe hypoxic ischemic necrosis with accelerated neuronal cell apoptosis in the brain. As a monoclonal antibody against interleukin 6, tocilizumab (TCZ) is widely used in immune diseases, whose function in cerebral infarction has not been studied. This study aims to reveal the role of TCZ in regulating neuronal cell apoptosis in cerebral infarction. The cerebral infarction rat model was constructed by middle cerebral artery occlusion and treated with TCZ. Cell apoptosis in hippocampus and cortex of the brain was examined with TUNEL method. Rat neuronal cells cultured in oxygen-glucose deprivation (OGD) conditions and treated with TCZ were used to compare cell viability and apoptosis. Apoptosis-related factors including B-cell lymphoma extra large (Bcl-xL) and Caspase 3, as well as the phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in brain cortex were analyzed from the protein level. Results indicated that TCZ treatment could significantly prevent the promoted cell apoptosis caused by cerebral infarction or OGD (P < 0.05 or P < 0.01). In brain cortex of the rat model, TCZ up-regulated Bcl-xL and down-regulated Caspase 3, consistent with the inhibited cell apoptosis. It also promoted tyrosine 705 phosphorylation of STAT3, which might be the potential regulatory mechanism of TCZ in neuronal cells. This study provided evidence for the protective role of TCZ against neuronal cell apoptosis in cerebral infarction. Based on these fundamental data, TCZ is a promising option for treating cerebral infarction, but further investigations on related mechanisms are still necessary. PMID:26773188

  14. [Experimental model of ocular ischemic diseases].

    PubMed

    Kiseleva, T N; Chudin, A V

    2014-01-01

    The review presents the most common methods of modeling of retinal ischemia in vitro (chemical ischemia with iodoacetic acid, incubation of the retinal pigment epithelium cells with oligomycin, deprivation of oxygen and glucose) and in vivo (a model with increased intraocular pressure, cerebral artery occlusion, chronic ligation of the carotid arteries, photocoagulation of the retinal vessels, occlusion of the central retinal artery, endothelin-1 administration). Modeling ischemic injury in rats is the most frequently used method in studies, because the blood supply of their eyes is similar to blood flow in the human eyes. Each method has its own advantages and disadvantages. Application of methods depends on the purpose of the experimental study. Currently model of ocular ischemic disease can be obtained easily by injecting vasoconstrictive drug endothelin-1. It is the most widely used method of high intraocular pressure induced ocular ischemic damage similar to glaucoma, occlusion of central retinal artery or ophthalmic artery in human. The development of experimental models of ocular ischemic diseases and detailed investigation of mechanisms of impairment of microcirculation are useful for improve the efficiency of diagnostic and treatment of ischemic diseases of retina and optic nerve. PMID:25971134

  15. [Neuroimaging of the penumbra in ischemic stroke].

    PubMed

    Maksimova, M Iu; Korobkova, D Z; Krotenkova, M V

    2013-01-01

    Brain ischemia has been recently a central problem in basic and applied studies in angioneurology. The latest investigations that give an insight into a relationship between metabolic changes and cerebral blood flow and make it possible to study ischemia at the molecular level and its changes over time have promoted the accumulation of fundamentally new facts and some reappraisal of existing ideas. Ischemic semishadow or penumbra is one of the most important presently studied phenomena. Detection of penumbra signs suggests that it is expedient to evaluate cerebral blood flow and metabolism when planning treatment (thrombolysis or neuroprotective therapy) and that it is important to predict the severity of ischemic stroke. Positron emission tomography (PET) is the reference method for detecting the penumbra; however, its application is limited in clinical practice. Computed tomography (CT) perfusion and perfusion MRI, a combination of diffusion-weighted and perfusion MRI, single-photon emission CT, and xenon-enhanced CT are most frequently used to evaluate a cerebral ischemia area and its blood flow. However, there are no standardized approaches to quantifying the thresholds for cerebral blood flow or unified algorithms for penumbra verification, which calls for further investigations. PMID:25702445

  16. Cerebral Hypoxia

    MedlinePlus

    ... Enhancing Diversity Find People About NINDS NINDS Cerebral Hypoxia Information Page Synonym(s): Hypoxia, Anoxia Table of Contents ( ... Trials Organizations Publicaciones en Español What is Cerebral Hypoxia? Cerebral hypoxia refers to a condition in which ...

  17. Inflammatory mechanisms in ischemic stroke: role of inflammatory cells

    PubMed Central

    Jin, Rong; Yang, Guojun; Li, Guohong

    2010-01-01

    Inflammation plays an important role in the pathogenesis of ischemic stroke and other forms of ischemic brain injury. Experimentally and clinically, the brain responds to ischemic injury with an acute and prolonged inflammatory process, characterized by rapid activation of resident cells (mainly microglia), production of proinflammatory mediators, and infiltration of various types of inflammatory cells (including neutrophils, different subtypes of T cells, monocyte/macrophages, and other cells) into the ischemic brain tissue. These cellular events collaboratively contribute to ischemic brain injury. Despite intense investigation, there are still numerous controversies concerning the time course of the recruitment of inflammatory cells in the brain and their pathogenic roles in ischemic brain injury. In this review, we provide an overview of the time-dependent recruitment of different inflammatory cells following focal cerebral I/R. We discuss how these cells contribute to ischemic brain injury and highlight certain recent findings and currently unanswered questions about inflammatory cells in the pathophysiology of ischemic stroke. PMID:20130219

  18. Reduction of oxidative stress during recovery accelerates normalization of primary cilia length that is altered after ischemic injury in murine kidneys.

    PubMed

    Kim, Jee In; Kim, Jinu; Jang, Hee-Seong; Noh, Mi Ra; Lipschutz, Joshua H; Park, Kwon Moo

    2013-05-15

    The primary cilium is a microtubule-based nonmotile organelle that extends from the surface of cells, including renal tubular cells. Here, we investigated the alteration of primary cilium length during epithelial cell injury and repair, following ischemia/reperfusion (I/R) insult, and the role of reactive oxygen species in this alteration. Thirty minutes of bilateral renal ischemia induced severe renal tubular cell damage and an increase of plasma creatinine (PCr) concentration. Between 8 and 16 days following the ischemia, the increased PCr returned to normal range, although without complete histological restoration. Compared with the primary cilium length in normal kidney tubule cells, the length was shortened 4 h and 1 day following ischemia, increased over normal 8 days after ischemia, and then returned to near normal 16 days following ischemia. In the urine of I/R-subjected mice, acetylated tubulin was detected. The cilium length of proliferating cells was shorter than that in nonproliferating cells. Mature cells had shorter cilia than differentiating cells. Treatment with Mn(III) tetrakis(1-methyl-4-pyridyl) porphyrin (MnTMPyP), an antioxidant, during the recovery of damaged kidneys accelerated normalization of cilia length concomitant with a decrease of oxidative stress and morphological recovery in the kidney. In the Madin-Darby canine kidney (MDCK) cells, H(2)O(2) treatment caused released ciliary fragment into medium, and MnTMPyP inhibited the deciliation. The ERK inhibitor U0126 inhibited elongation of cilia in normal and MDCK cells recovering from H(2)O(2) stress. Taken together, our results suggest that primary cilia length reflects cell proliferation and the length of primary cilium is regulated, at least, in part, by reactive oxygen species through ERK.

  19. [Two cases of cryptococcal meningitis revealed by an ischemic stroke].

    PubMed

    Kouame-Assouan, A E; Cowppli-Bony, P; Aka-Anghui Diarra, E; Assi, B; Doumbia, M; Diallo, L; Adjien, K C; Akani, E; Sonan, T; Diagana, M; Boa, Y E; Kouassi, B

    2007-02-01

    The usual clinical expression of neuromeningeal cryptococcosis is a meningoencephalitis. We report two cases of neurocryptococcosis which have been revealed by an unusual clinical aspect: an ischemic stroke with a vasculitis mechanism. The two patients had a positive reaction for the HIV and we discussed the responsibility of the HIV or the Cryptococcus in the occurrence of the cerebral infarct.

  20. Ischemic preconditioning and clinical scenarios

    PubMed Central

    Narayanan, Srinivasan V.; Dave, Kunjan R.; Perez-Pinzon, Miguel A.

    2013-01-01

    Purpose of review Ischemic preconditioning (IPC) is gaining attention as a novel neuroprotective therapy and could provide an improved mechanistic understanding of tolerance to cerebral ischemia. The purpose of this article is to review the recent work in the field of IPC and its applications to clinical scenarios. Recent findings The cellular signaling pathways that are activated following IPC are now better understood and have enabled investigators to identify several IPC mimetics. Most of these studies were performed in rodents, and efficacy of these mimetics remains to be evaluated in human patients. Additionally, remote ischemic preconditioning (RIPC) may have higher translational value than IPC. Repeated cycles of temporary ischemia in a remote organ can activate protective pathways in the target organ, including the heart and brain. Clinical trials are underway to test the efficacy of RIPC in protecting brain against subarachnoid hemorrhage. Summary IPC, RIPC, and IPC mimetics have the potential to be therapeutic in various clinical scenarios. Further understanding of IPC-induced neuroprotection pathways and utilization of clinically relevant animal models are necessary to increase the translational potential of IPC in the near future. PMID:23197083

  1. Vascular endothelial growth factor: an attractive target in the treatment of hypoxic/ischemic brain injury.

    PubMed

    Guo, Hui; Zhou, Hui; Lu, Jie; Qu, Yi; Yu, Dan; Tong, Yu

    2016-01-01

    Cerebral hypoxia or ischemia results in cell death and cerebral edema, as well as other cellular reactions such as angiogenesis and the reestablishment of functional microvasculature to promote recovery from brain injury. Vascular endothelial growth factor is expressed in the central nervous system after hypoxic/ischemic brain injury, and is involved in the process of brain repair via the regulation of angiogenesis, neurogenesis, neurite outgrowth, and cerebral edema, which all require vascular endothelial growth factor signaling. In this review, we focus on the role of the vascular endothelial growth factor signaling pathway in the response to hypoxic/ischemic brain injury, and discuss potential therapeutic interventions. PMID:26981109

  2. Vascular endothelial growth factor: an attractive target in the treatment of hypoxic/ischemic brain injury

    PubMed Central

    Guo, Hui; Zhou, Hui; Lu, Jie; Qu, Yi; Yu, Dan; Tong, Yu

    2016-01-01

    Cerebral hypoxia or ischemia results in cell death and cerebral edema, as well as other cellular reactions such as angiogenesis and the reestablishment of functional microvasculature to promote recovery from brain injury. Vascular endothelial growth factor is expressed in the central nervous system after hypoxic/ischemic brain injury, and is involved in the process of brain repair via the regulation of angiogenesis, neurogenesis, neurite outgrowth, and cerebral edema, which all require vascular endothelial growth factor signaling. In this review, we focus on the role of the vascular endothelial growth factor signaling pathway in the response to hypoxic/ischemic brain injury, and discuss potential therapeutic interventions. PMID:26981109

  3. Ischemic optic neuropathy.

    PubMed

    Athappilly, Geetha; Pelak, Victoria S; Mandava, Naresh; Bennett, Jeffrey L

    2008-10-01

    Ischemic optic neuropathy is the most frequent cause of vision loss in middle age. Clinical and laboratory research studies have begun to clarify the natural history, clinical presentation, diagnostic criteria and pathogenesis of various ischemic nerve injuries. As a result, physicians are acquiring new tools to aid in the diagnosis and potential treatment of ischemic nerve injury. The aim of this review is to examine recent data on anterior and posterior ischemic optic neuropathy and to provide a framework for physicians to manage and counsel affected individuals. PMID:18826805

  4. [Cerebral artery thrombosis in pregnancy].

    PubMed

    Charco Roca, L M; Ortiz Sanchez, V E; Hernandez Gutierrez-Manchon, O; Quesada Villar, J; Bonmatí García, L; Rubio Postigo, G

    2015-11-01

    A 28 year old woman, ASA I, who, in the final stages of her pregnancy presented with signs of neural deficit that consisted of distortion of the oral commissure, dysphagia, dysarthria, and weakness on the left side of the body. She was diagnosed with thrombosis in a segment of the right middle cerebral artery which led to an ischemic area in the right frontal lobe. Termination of pregnancy and conservative treatment was decided, with good resolution of the symptoms. PMID:25698610

  5. [Cerebral artery thrombosis in pregnancy].

    PubMed

    Charco Roca, L M; Ortiz Sanchez, V E; Hernandez Gutierrez-Manchon, O; Quesada Villar, J; Bonmatí García, L; Rubio Postigo, G

    2015-11-01

    A 28 year old woman, ASA I, who, in the final stages of her pregnancy presented with signs of neural deficit that consisted of distortion of the oral commissure, dysphagia, dysarthria, and weakness on the left side of the body. She was diagnosed with thrombosis in a segment of the right middle cerebral artery which led to an ischemic area in the right frontal lobe. Termination of pregnancy and conservative treatment was decided, with good resolution of the symptoms.

  6. Acute headache at emergency department: reversible cerebral vasoconstriction syndrome complicated by subarachnoid haemorrhage and cerebral infarction.

    PubMed

    Yger, M; Zavanone, C; Abdennour, L; Koubaa, W; Clarençon, F; Dupont, S; Samson, Y

    2015-01-01

    Introduction. Reversible cerebral vasoconstriction syndrome is becoming widely accepted as a rare cause of both ischemic and haemorrhagic stroke and should be evocated in case of thunderclap headaches associated with stroke. We present the case of a patient with ischemic stroke associated with cortical subarachnoid haemorrhage (cSAH) and reversible diffuse arteries narrowing, leading to the diagnosis of reversible vasoconstriction syndrome. Case Report. A 48-year-old woman came to the emergency department because of an unusual thunderclap headache. The computed tomography of the brain completed by CT-angiography was unremarkable. Eleven days later, she was readmitted because of a left hemianopsia. One day after her admission, she developed a sudden left hemiparesis. The brain MRI showed ischemic lesions in the right frontal and occipital lobe and diffuse cSAH. The angiography showed vasoconstriction of the right anterior cerebral artery and stenosis of both middle cerebral arteries. Nimodipine treatment was initiated and vasoconstriction completely regressed on day 16 after the first headache. Conclusion. Our case shows a severe reversible cerebral vasoconstriction syndrome where both haemorrhagic and ischemic complications were present at the same time. The history we reported shows that reversible cerebral vasoconstriction syndrome is still underrecognized, in particular in general emergency departments.

  7. Transient Ischemic Attack

    MedlinePlus

    Transient Ischemic Attack TIA , or transient ischemic attack, is a "mini stroke" that occurs when a blood clot blocks an artery for a short time. The only ... TIA is that with TIA the blockage is transient (temporary). TIA symptoms occur rapidly and last a ...

  8. Astaxanthin reduces ischemic brain injury in adult rats.

    PubMed

    Shen, Hui; Kuo, Chi-Chung; Chou, Jenny; Delvolve, Alice; Jackson, Shelley N; Post, Jeremy; Woods, Amina S; Hoffer, Barry J; Wang, Yun; Harvey, Brandon K

    2009-06-01

    Astaxanthin (ATX) is a dietary carotenoid of crustaceans and fish that contributes to their coloration. Dietary ATX is important for development and survival of salmonids and crustaceans and has been shown to reduce cardiac ischemic injury in rodents. The purpose of this study was to examine whether ATX can protect against ischemic injury in the mammalian brain. Adult rats were injected intracerebroventricularly with ATX or vehicle prior to a 60-min middle cerebral artery occlusion (MCAo). ATX was present in the infarction area at 70-75 min after onset of MCAo. Treatment with ATX, compared to vehicle, increased locomotor activity in stroke rats and reduced cerebral infarction at 2 d after MCAo. To evaluate the protective mechanisms of ATX against stroke, brain tissues were assayed for free radical damage, apoptosis, and excitoxicity. ATX antagonized ischemia-mediated loss of aconitase activity and reduced glutamate release, lipid peroxidation, translocation of cytochrome c, and TUNEL labeling in the ischemic cortex. ATX did not alter physiological parameters, such as body temperature, brain temperature, cerebral blood flow, blood gases, blood pressure, and pH. Collectively, our data suggest that ATX can reduce ischemia-related injury in brain tissue through the inhibition of oxidative stress, reduction of glutamate release, and antiapoptosis. ATX may be clinically useful for patients vulnerable or prone to ischemic events. PMID:19218497

  9. Astaxanthin reduces ischemic brain injury in adult rats.

    PubMed

    Shen, Hui; Kuo, Chi-Chung; Chou, Jenny; Delvolve, Alice; Jackson, Shelley N; Post, Jeremy; Woods, Amina S; Hoffer, Barry J; Wang, Yun; Harvey, Brandon K

    2009-06-01

    Astaxanthin (ATX) is a dietary carotenoid of crustaceans and fish that contributes to their coloration. Dietary ATX is important for development and survival of salmonids and crustaceans and has been shown to reduce cardiac ischemic injury in rodents. The purpose of this study was to examine whether ATX can protect against ischemic injury in the mammalian brain. Adult rats were injected intracerebroventricularly with ATX or vehicle prior to a 60-min middle cerebral artery occlusion (MCAo). ATX was present in the infarction area at 70-75 min after onset of MCAo. Treatment with ATX, compared to vehicle, increased locomotor activity in stroke rats and reduced cerebral infarction at 2 d after MCAo. To evaluate the protective mechanisms of ATX against stroke, brain tissues were assayed for free radical damage, apoptosis, and excitoxicity. ATX antagonized ischemia-mediated loss of aconitase activity and reduced glutamate release, lipid peroxidation, translocation of cytochrome c, and TUNEL labeling in the ischemic cortex. ATX did not alter physiological parameters, such as body temperature, brain temperature, cerebral blood flow, blood gases, blood pressure, and pH. Collectively, our data suggest that ATX can reduce ischemia-related injury in brain tissue through the inhibition of oxidative stress, reduction of glutamate release, and antiapoptosis. ATX may be clinically useful for patients vulnerable or prone to ischemic events.

  10. Protective effect of extract of Cordyceps sinensis in middle cerebral artery occlusion-induced focal cerebral ischemia in rats

    PubMed Central

    2010-01-01

    Background Ischemic hypoxic brain injury often causes irreversible brain damage. The lack of effective and widely applicable pharmacological treatments for ischemic stroke patients may explain a growing interest in traditional medicines. From the point of view of "self-medication" or "preventive medicine," Cordyceps sinensis was used in the prevention of cerebral ischemia in this paper. Methods The right middle cerebral artery occlusion model was used in the study. The effects of Cordyceps sinensis (Caterpillar fungus) extract on mortality rate, neurobehavior, grip strength, lactate dehydrogenase, glutathione content, Lipid Peroxidation, glutathione peroxidase activity, glutathione reductase activity, catalase activity, Na+K+ATPase activity and glutathione S transferase activity in a rat model were studied respectively. Results Cordyceps sinensis extract significantly improved the outcome in rats after cerebral ischemia and reperfusion in terms of neurobehavioral function. At the same time, supplementation of Cordyceps sinensis extract significantly boosted the defense mechanism against cerebral ischemia by increasing antioxidants activity related to lesion pathogenesis. Restoration of the antioxidant homeostasis in the brain after reperfusion may have helped the brain recover from ischemic injury. Conclusions These experimental results suggest that complement Cordyceps sinensis extract is protective after cerebral ischemia in specific way. The administration of Cordyceps sinensis extract significantly reduced focal cerebral ischemic/reperfusion injury. The defense mechanism against cerebral ischemia was by increasing antioxidants activity related to lesion pathogenesis. PMID:20955613

  11. Cardiogenic embolism producing crescendo transient ischemic attacks.

    PubMed

    Geraghty, Patrick J; Oak, Jack; Choi, Eric T

    2005-09-01

    Lateralizing, repetitive transient ischemic attacks are characteristic of symptomatic carotid bifurcation atherosclerotic plaques. We report a case in which a cardiogenic embolus, after lodging at the left carotid bifurcation, produced crescendo episodes of expressive aphasia and mild right upper extremity weakness. Complete neurological recovery was achieved following emergent carotid embolectomy and endarterectomy. This case demonstrates that the laminar nature of internal carotid blood flow may result in the localization of embolic events to a single region of the cerebral vasculature, regardless of the source lesion in the carotid artery. The role of endoluminal techniques in the diagnosis and management of such lesions is discussed.

  12. Normobaric hyperoxia-based neuroprotective therapies in ischemic stroke

    PubMed Central

    2013-01-01

    Stroke is a leading cause of death and disability due to disturbance of blood supply to the brain. As brain is highly sensitive to hypoxia, insufficient oxygen supply is a critical event contributing to ischemic brain injury. Normobaric hyperoxia (NBO) that aims to enhance oxygen delivery to hypoxic tissues has long been considered as a logical neuroprotective therapy for ischemic stroke. To date, many possible mechanisms have been reported to elucidate NBO’s neuroprotection, such as improving tissue oxygenation, increasing cerebral blood flow, reducing oxidative stress and protecting the blood brain barrier. As ischemic stroke triggers a battery of damaging events, combining NBO with other agents or treatments that target multiple mechanisms of injury may achieve better outcome than individual treatment alone. More importantly, time loss is brain loss in acute cerebral ischemia. NBO can be a rapid therapy to attenuate or slow down the evolution of ischemic tissues towards necrosis and therefore “buy time” for reperfusion therapies. This article summarizes the current literatures on NBO as a simple, widely accessible, and potentially cost-effective therapeutic strategy for treatment of acute ischemic stroke. PMID:23298701

  13. The Time of Maximum Post-Ischemic Hyperperfusion Indicates Infarct Growth Following Transient Experimental Ischemia

    PubMed Central

    Wegener, Susanne; Artmann, Judith; Luft, Andreas R.; Buxton, Richard B.; Weller, Michael; Wong, Eric C.

    2013-01-01

    After recanalization, cerebral blood flow (CBF) can increase above baseline in cerebral ischemia. However, the significance of post-ischemic hyperperfusion for tissue recovery remains unclear. To analyze the course of post-ischemic hyperperfusion and its impact on vascular function, we used magnetic resonance imaging (MRI) with pulsed arterial spin labeling (pASL) and measured CBF quantitatively during and after a 60 minute transient middle cerebral artery occlusion (MCAO) in adult rats. We added a 5% CO2 - challenge to analyze vasoreactivity in the same animals. Results from MRI were compared to histological correlates of angiogenesis. We found that CBF in the ischemic area recovered within one day and reached values significantly above contralateral thereafter. The extent of hyperperfusion changed over time, which was related to final infarct size: early (day 1) maximal hyperperfusion was associated with smaller lesions, whereas a later (day 4) maximum indicated large lesions. Furthermore, after initial vasoparalysis within the ischemic area, vasoreactivity on day 14 was above baseline in a fraction of animals, along with a higher density of blood vessels in the ischemic border zone. These data provide further evidence that late post-ischemic hyperperfusion is a sequel of ischemic damage in regions that are likely to undergo infarction. However, it is transient and its resolution coincides with re-gaining of vascular structure and function. PMID:23741488

  14. Cerebral Palsy

    MedlinePlus

    ... Got Homework? Here's Help White House Lunch Recipes Cerebral Palsy KidsHealth > For Kids > Cerebral Palsy Print A A ... the things that kids do every day. What's CP? Some kids with CP use wheelchairs and others ...

  15. Cerebral Palsy

    MedlinePlus

    ... Loss > Birth defects & other health conditions > Cerebral palsy Cerebral palsy E-mail to a friend Please fill in ... movement problems a child has. What is spastic CP? Spastic means tight or stiff muscles, or muscles ...

  16. Cerebral Palsy

    MedlinePlus

    Cerebral palsy is a group of disorders that affect a person's ability to move and to maintain balance ... do not get worse over time. People with cerebral palsy may have difficulty walking. They may also have ...

  17. Morinda citrifolia fruit juice prevents ischemic neuronal damage through suppression of the development of post-ischemic glucose intolerance.

    PubMed

    Harada, Shinichi; Fujita-Hamabe, Wakako; Kamiya, Kohei; Mizushina, Yoshiyuki; Satake, Toshiko; Tokuyama, Shogo

    2010-10-01

    Fruit juice of Morinda citrifolia (Noni juice) is a well-known health drink and has various pharmacological properties including antioxidant and anti-inflammatory effects. We have hitherto found the protective effect of Noni juice on brain damage caused by ischemic stress in mice. In addition, we also recently reported that regulation of post-ischemic glucose intolerance might be important for good prognosis. Here, we focused on the effect of Noni juice on the development of the post-ischemic glucose intolerance as a cerebral protective mechanism. Noni juice was obtained from the mature fruit grown in Okinawa (about 1.5 L/4 kg of fruit; 100% ONJ). Male ddY mice were given 10% ONJ in drinking water for 7 days. Then, mice were subjected to 2 h of middle cerebral artery occlusion (MCAO). Ingestion of 10% ONJ suppressed the development of neuronal damage after MCAO. Interestingly, glucose intolerance observed on the 1st day after MCAO completely disappeared after 10% ONJ administration. Furthermore, ONJ treatment significantly increased serum insulin levels much further than the control group on the 1st day, while serum adiponectin levels were not affected at all. These results suggest that ONJ could facilitate insulin secretion after ischemic stress and may attenuate the development of glucose intolerance. These mechanisms may contribute to the neuronal protective effect of ONJ against ischemic stress.

  18. Myogenic tone as a therapeutic target for ischemic stroke.

    PubMed

    Palomares, Sara M; Cipolla, Marilyn J

    2014-01-01

    Ischemic stroke causes vascular paralysis and impaired autoregulation in the brain, the degree of which is dependent on the depth and duration of ischemia and reperfusion (I/R). Ischemic stroke also impairs the myogenic response of middle cerebral arteries (MCA) that may be an underlying mechanism by which autoregulation is impaired. Myogenic responses are affected by I/R through several mechanisms, including production of peroxynitrite, depolymerization of F-actin in vascular smooth muscle, and circulating vasoactive factors. The vascular endothelium is also significantly affected during focal ischemia that has a particularly large influence on vascular tone in the cerebral circulation. Endothelial nitric oxide (NO) and endothelin-1 (ET-1) are important endothelium-dependent vasoactive substances that can influence the level of myogenic tone in cerebral arteries and arterioles that are significantly affected during ischemic stroke. Unlike MCA, brain penetrating arterioles have considerable myogenic tone that appears less affected by focal ischemia. The persistent tone of brain parenchymal arterioles during focal ischemia could contribute to perfusion deficit and infarct expansion. These arterioles within the cerebral cortex are also unique from MCA in that they constrict to small- and intermediate- conductance calcium-activated potassium channel (SKCa and IKCa, respectively) inhibition, suggesting basal endothelium-derived hyperpolarizing factor (EDHF) is preserved during focal ischemia. This review will highlight our current understanding of the effects of I/R on myogenic response in both MCA and parenchymal arterioles and discuss underlying mechanisms by which focal ischemia affects myogenic tone in these different vascular segments.

  19. Neonatal brain injury as a consequence of insufficient cerebral oxygenation.

    PubMed

    Placha, Katerina; Luptakova, Dominika; Baciak, Ladislav; Ujhazy, Eduard; Juranek, Ivo

    2016-01-01

    Neonatal brain hypoxic-ischemic injury represents a serious health care and socio-economical problem since it is one of the most common causes of mortality and morbidity of newborns. Neonatal hypoxic-ischemic encephalopathy is often associated with signs of perinatal asphyxia, with an incidence of about 2-4 per 1,000 live births and mortality rate up to 20%. In about one half of survivors, cerebral hypoxic-ischemic insult may result in more or less pronounced neuro-psychological sequelae of immediate or delayed nature, such as seizures, cerebral palsy or behavioural and learning disabilities, including attention-deficit hyperactivity disorder. Hypoxic-ischemic injury develops as a consequence of transient or permanent restriction of blood supply to the brain. Severity of hypoxic-ischemic encephalopathy varies depending on the intensity and duration of hypoxia-ischemia, on the type and size of the brain region affected, and on the maturity of the foetal/neonatal brain. Though a primary cause of hypoxic-ischemic injury is lack of oxygen in the neonatal brain, underlying mechanisms of subsequent events that are critical for developing hypoxic-ischemic encephalopathy are less understood. Their understanding is however necessary for elaborating effective management for newborns that underwent cerebral hypoxic-ischemic insult and thus are at risk of a negative outcome. The present paper summarizes current knowledge on cerebral hypoxic-ischemic injury of the neonate, fundamental processes involved in etiopathogenesis, with a special focus on cellular and molecular mechanisms and particular attention on certain controversial aspects of oxidative stress involvement. PMID:27179569

  20. Cerebral Palsy

    MedlinePlus

    ... Awards Enhancing Diversity Find People About NINDS NINDS Cerebral Palsy Information Page Clinical Trials Trial of Erythropoietin Neuroprotection ... en Español Additional resources from MedlinePlus What is Cerebral Palsy? The term cerebral palsy refers to a group ...

  1. Cerebral Aneurysms

    MedlinePlus

    ... Enhancing Diversity Find People About NINDS NINDS Cerebral Aneurysms Information Page Synonym(s): Aneurysm, Brain Aneurysm Condensed from ... Español Additional resources from MedlinePlus What is Cerebral Aneurysms? A cerebral aneurysm is a weak or thin ...

  2. Leukocyte Recruitment and Ischemic Brain Injury

    PubMed Central

    Yilmaz, Gokhan

    2010-01-01

    Leukocytes are recruited into the cerebral microcirculation following an ischemic insult. The leukocyte–endothelial cell adhesion manifested within a few hours after ischemia (followed by reperfusion, I/R) largely reflects an infiltration of neutrophils, while other leukocyte populations appear to dominate the adhesive interactions with the vessel wall at 24 h of reperfusion. The influx of rolling and adherent leukocytes is accompanied by the recruitment of adherent platelets, which likely enhances the cytotoxic potential of the leukocytes to which they are attached. The recruitment of leukocytes and platelets in the postischemic brain is mediated by specific adhesion glycoproteins expressed by the activated blood cells and on cerebral microvascular endothelial cells. This process is also modulated by different signaling pathways (e.g., CD40/CD40L, Notch) and cytokines (e.g., RANTES) that are activated/released following I/R. Some of the known risk factors for cardiovascular disease, including hypercholesterolemia and obesity appear to exacerbate the leukocyte and platelet recruitment elicited by brain I/R. Although lymphocyte–endothelial cell and –platelet interactions in the postischemic cerebral microcirculation have not been evaluated to date, recent evidence in experimental animals implicate both CD4+ and CD8+ T-lymphocytes in the cerebral microvascular dysfunction, inflammation, and tissue injury associated with brain I/R. Evidence implicating regulatory T-cells as cerebroprotective modulators of the inflammatory and tissue injury responses to brain I/R support a continued focus on leukocytes as a target for therapeutic intervention in ischemic stroke. PMID:19579016

  3. The Many Roles of Statins in Ischemic Stroke

    PubMed Central

    Zhao, Jingru; Zhang, Xiangjian; Dong, Lipeng; Wen, Ya; Cui, Lili

    2014-01-01

    Stroke is the third leading cause of human death. Endothelial dysfunction, thrombogenesis, inflammatory and oxidative stress damage, and angiogenesis play an important role in cerebral ischemic pathogenesis and represent a target for prevention and treatment. Statins have been found to improve endothelial function, modulate thrombogenesis, attenuate inflammatory and oxidative stress damage, and facilitate angiogenesis far beyond lowering cholesterol levels. Statins have also been proved to significantly decrease cardiovascular risk and to improve clinical outcome. Could statins be the new candidate agent for the prevention and therapy in ischemic stroke? In recent years, a vast expansion in the understanding of the pathophysiology of ischemic stroke and the pleiotropic effects of statins has occurred and clinical trials involving statins for the prevention and treatment of ischemic stroke have begun. These facts force us to revisit ischemic stroke and consider new strategies for prevention and treatment. Here, we survey the important developments in the non-lipid dependent pleiotropic effects and clinical effects of statins in ischemic stroke. PMID:25977681

  4. Two children with both arm ischemia and arterial ischemic stroke during the perinatal period.

    PubMed

    McKasson, Marilyn J; Golomb, Meredith R

    2011-12-01

    It is rare for both limb ischemia and arterial ischemic stroke to occur in the same child during the perinatal period. Two children who appear to have had perinatal emboli to both an arm and a middle cerebral artery territory are presented here. One child required amputation of the ischemic limb below the shoulder, and the other required skin grafts to the distal ischemic fingers. Each of these children later received cerebral magnetic resonance imaging for evaluation of developmental delay and was found to have what appeared to be old perinatal arterial ischemic stroke. Both children were homozygous for the methylenetetrahydrofolate reductase C677T gene variant. Eight other children with perinatal limb ischemia and stroke were found on literature review; several also had delayed diagnosis of perinatal stroke. This report examines the approach to diagnosis and treatment in each of these and makes suggestions for the similar cases in the future. PMID:21862833

  5. Reduction of the prenatal hypoxic-ischemic brain edema with noscapine.

    PubMed

    Mahmoudian, M; Siadatpour, Zahra; Ziai, S A; Mehrpour, M; Benaissa, Faouzya; Nobakht, M

    2003-01-01

    Cytotoxic free radicals and release of several neurotransmitters such as bradykinin contribute to the pathogenesis of hypoxic-ischemic brain damage. We have studied the efficacy of noscapine, an opium alkaloid and a bradykinin antagonist, in reducing post-hypoxic-ischemic damage in developing brain of 7-d-old rat pups. Hypoxic-ischemic injury to the right cerebral hemisphere was produced by legation of the right common carotid artery followed by 3 h of hypoxia with 8% oxygen. Thirty to 45 min before hypoxia the rat pups received noscapine (dose = 0.5-2 mg/kg) or saline. Pups were scarified at 24 h post recovery for the assessment of cerebral damage by histological methods. Our results showed that noscapine was an effective agent in reducing the extent of brain injury after hypoxic-ischemic insult to neonatal rats. Therefore, it is concluded that noscapine may be a useful drug in the managements of patients after stroke.

  6. Medullary Hemorrhage after Ischemic Wallenberg's Syndrome in a Patient with Cavernous Angioma

    PubMed Central

    Lee, Kyung Hoe

    2010-01-01

    Background The main complication of cerebral cavernous angioma is hemorrhage. Ischemic stroke as a complication of cerebral cavernous angioma has rarely been described, and hemorrhage after ischemic Wallenberg's syndrome has not been reported before. Case Report A 45-year-old woman presented with perioral numbness, hoarseness, dysphagia, and worsening of her previous sensory symptoms. The patient had been taking aspirin for 3 years after suffering from ischemic Wallenberg's syndrome with left paresthesia as a residual symptom. Brain computed tomography revealed an acute medullary hematoma in the previously infarcted area. Follow-up magnetic resonance imaging revealed a cavernous angioma in the right medulla. Conclusions We presume that cerebral cavernous angioma was responsible for both the ischemia and the hemorrhage, and we also cautiously speculate that the aspirin contributed to the development of hemorrhage in the previously infarcted area. PMID:21264204

  7. Complement in the Homeostatic and Ischemic Brain

    PubMed Central

    Alawieh, Ali; Elvington, Andrew; Tomlinson, Stephen

    2015-01-01

    The complement system is a component of the immune system involved in both recognition and response to pathogens, and it is implicated in an increasing number of homeostatic and disease processes. It is well documented that reperfusion of ischemic tissue results in complement activation and an inflammatory response that causes post-reperfusion injury. This occurs following cerebral ischemia and reperfusion and triggers secondary damage that extends beyond the initial infarcted area, an outcome that has rationalized the use of complement inhibitors as candidate therapeutics after stroke. In the central nervous system, however, recent studies have revealed that complement also has essential roles in synaptic pruning, neurogenesis, and neuronal migration. In the context of recovery after stroke, these apparent divergent functions of complement may account for findings that the protective effect of complement inhibition in the acute phase after stroke is not always maintained in the subacute and chronic phases. The development of effective stroke therapies based on modulation of the complement system will require a detailed understanding of complement-dependent processes in both early neurodegenerative events and delayed neuro-reparatory processes. Here, we review the role of complement in normal brain physiology, the events initiating complement activation after cerebral ischemia-reperfusion injury, and the contribution of complement to both injury and recovery. We also discuss how the design of future experiments may better characterize the dual role of complement in recovery after ischemic stroke. PMID:26322048

  8. Long-term window of ischemic tolerance: An evolutionarily conserved form of metabolic plasticity regulated by epigenetic modifications?

    PubMed Central

    Khoury, Nathalie; Koronowski, Kevin B.; Perez-Pinzon, Miguel A.

    2016-01-01

    In the absence of effective neuroprotective agents in the clinic, ischemic and pharmacological preconditioning are gaining increased interest in the field of cerebral ischemia. Our lab recently reported that resveratrol preconditioning affords tolerance against a focal cerebral ischemic insult in mice that can last for at least 14 days in vivo making it the longest window of ischemic tolerance discovered to date by a single administration of a pharmacological agent. The mechanism behind this novel extended window of ischemic tolerance remains elusive. In the below commentary we discuss potential mechanisms that could explain this novel extended window of ischemic tolerance in the context of previously identified windows and the known mechanisms behind them. We also draw parallels from the fields of hibernation and hypoxia-tolerance, which are chronic adaptations to severe conditions of hypoxia and ischemia known to be mediated by a form of metabolic depression. We also briefly discuss the importance of epigenetic modifications in maintaining this depressed state of metabolism.

  9. The Chinese traditional medicine 'Bushen Yinao Pian' increased the level of ageing-related gene LRPAP-1 expression in the cerebral tissue of accelerated senescence-prone mouse 8/Ta.

    PubMed

    Zhang, Chong; Yang, Ting; Wang, Jingang; Liu, Guisheng; Chen, Qingxuan

    2005-04-01

    The molecular mechanism of the Chinese traditional medicine 'Bushen Yinao Pian' (a complex prescription used for clinical anti-ageing in China for over 20 years) is elusive. In this study, the cDNA of low-density lipoprotein related-receptor associated protein-1 (LRPAP-1), an ageing-related gene, which functions as a chaperon or escort protein in the intracellular transport of low-density lipoprotein related-receptor, a transporter of amyloid beta protein (AbetaP), had been cloned by screening cDNA library based on analyzing the gene expression in cerebral tissue between the test and the control accelerated senescence-prone mouse 8/Ta (SAMP8/Ta). The result shows that this complex prescription increased the expression level of LRPAP-1. It indicated that the Chinese traditional medicine 'Bushen Yinao Pian' plays an important role in anti-ageing by increasing LRPAP-1 expression level. PMID:15763364

  10. Optical-resolution photoacoustic microscopy of ischemic stroke

    NASA Astrophysics Data System (ADS)

    Hu, Song; Gonzales, Ernie; Soetikno, Brian; Gong, Enhao; Yan, Ping; Maslov, Konstantin; Lee, Jin-Moo; Wang, Lihong V.

    2011-03-01

    A major obstacle in understanding the mechanism of ischemic stroke is the lack of a tool to noninvasively or minimally invasively monitor cerebral hemodynamics longitudinally. Here, we applied optical-resolution photoacoustic microscopy (OR-PAM) to longitudinally study ischemic stroke induced brain injury in a mouse model with transient middle cerebral artery occlusion (MCAO). OR-PAM showed that, during MCAO, the average hemoglobin oxygen saturation (sO2) values of feeder arteries and draining veins within the stroke core region dropped ~10% and ~34%, respectively. After reperfusion, arterial sO2 recovered back to the baseline; however, the venous sO2 increased above the baseline value by ~7%. Thereafter, venous sO2 values were close to the arterial sO2 values, suggesting eventual brain tissue infarction.

  11. Angiogenesis-regulating microRNAs and Ischemic Stroke.

    PubMed

    Yin, Ke-Jie; Hamblin, Milton; Chen, Y Eugene

    2015-01-01

    Stroke is a leading cause of death and disability worldwide. Ischemic stroke is the dominant subtype of stroke and results from focal cerebral ischemia due to occlusion of major cerebral arteries. Thus, the restoration or improvement of reduced regional cerebral blood supply in a timely manner is very critical for improving stroke outcomes and poststroke functional recovery. The recovery from ischemic stroke largely relies on appropriate restoration of blood flow via angiogenesis. Newly formed vessels would allow increased cerebral blood flow, thus increasing the amount of oxygen and nutrients delivered to affected brain tissue. Angiogenesis is strictly controlled by many key angiogenic factors in the central nervous system, and these molecules have been well-documented to play an important role in the development of angiogenesis in response to various pathological conditions. Promoting angiogenesis via various approaches that target angiogenic factors appears to be a useful treatment for experimental ischemic stroke. Most recently, microRNAs (miRs) have been identified as negative regulators of gene expression in a post-transcriptional manner. Accumulating studies have demonstrated that miRs are essential determinants of vascular endothelial cell biology/angiogenesis as well as contributors to stroke pathogenesis. In this review, we summarize the knowledge of stroke-associated angiogenic modulators, as well as the role and molecular mechanisms of stroke-associated miRs with a focus on angiogenesis-regulating miRs. Moreover, we further discuss their potential impact on miR-based therapeutics in stroke through targeting and enhancing post-ischemic angiogenesis.

  12. [NDT-Bobath method used in the rehabilitation of patients with a history of ischemic stroke].

    PubMed

    Klimkiewicz, Paulina; Kubsik, Anna; Woldańska-Okońska, Marta

    2012-01-01

    Ischemic stroke is the third leading cause of death and disability in human. The vitally important problem after ischemic stroke is hemiparesis of the body. The most common methods used in improving the mobility of patients after ischemic stroke is a Bobath-NDT (Neuro-Developmental Treatment - Bobath), which initiated the Berta and Karel Bobath for children with cerebral palsy. It is a method designed to neurophysiological recovery of these vital functions that the patient was lost due to illness, and wants it back. PMID:23289255

  13. Alpha 1-Antitrypsin Therapy Mitigated Ischemic Stroke Damage in Rats

    PubMed Central

    Moldthan, Huong L.; Hirko, Aaron C.; Thinschmidt, Jeffrey S.; Grant, Maria; Li, Zhimin; Peris, Joanna; Lu, Yuanqing; Elshikha, Ahmed; King, Michael A.; Hughes, Jeffrey A.; Song, Sihong

    2014-01-01

    Currently, the only effective therapy for acute ischemic stroke is the thrombolytic agent recombinant tissue plasminogen activator. α1-Antitrypsin, an endogenous inhibitor of serine proteinases and a primary acute phase protein with potent anti-inflammatory, anti-apoptotic, antimicrobial and cytoprotective activities, could be beneficial in stroke.. The goal of this study was to test whether α1-antitrypsin could improve ischemic stroke outcome in an established rat model. Middle cerebral artery occlusion was induced in male rats via intracranial microinjection of endothelin-1. Five to ten minutes following stroke induction rats received either intracranial or intravenous delivery of human α1-antitrypsin. Cylinder and vibrissae tests were used to evaluate sensorimotor function before and 72 hours after middle cerebral artery occlusion. Infarct volumes were examined via either 2,3,5-triphenyltetrazolium chloride assay or magnetic resonance imaging 72 hours after middle cerebral artery occlusion. Despite equivalent initial strokes, at 72 hours the infarct volumes of the human α1-antitrypsin treatment groups (local and systemic injection) were statistically significantly reduced by 83% and 63% (p<0.0001 and p < 0.05 respectively) compared with control rats. Human α1-antitrypsin significantly limited sensory motor systems deficits. Human α1-antitrypsin could be a potential novel therapeutic drug for the protection against neurodegeneration following ischemic stroke, but more studies are needed to investigate the protective mechanisms and efficacy in other animal models. PMID:24582784

  14. Limb remote ischemic per-conditioning in combination with post-conditioning reduces brain damage and promotes neuroglobin expression in the rat brain after ischemic stroke

    PubMed Central

    Ren, Changhong; Wang, Pengcheng; Wang, Brian; Li, Ning; Li, Weiguang; Zhang, Chenggang; Jin, Kunlin; Ji, Xunming

    2015-01-01

    Abstract Purpose: Limb remote ischemic per-conditioning or post-conditioning has been shown to be neuroprotective after cerebral ischemic stroke. However, the effect of combining remote per-conditioning with post-conditioning on ischemic/reperfusion injury as well as the underlying mechanisms are largely unexplored. Methods: Here, adult male Sprague Dawley rats were subjected to middle cerebral artery occlusion (MCAO). The limb ischemic stimulus was immediately applied after onset of focal ischemia (per-conditioning), followed by repeated short episodes of remote ischemia 24 hr after reperfusion (post-conditioning). The infarct volume, motor function, and the expression of neuroglobin (Ngb) were measured at different durations after reperfusion. Results: We found that a single episode of limb remote per-conditioning afforded short-term protection, but combining repeated remote post-conditioning during the 14 days after reperfusion significantly ameliorated cerebral ischemia/reperfusion injury. Interestingly, we also found that ischemic per- and post-conditioning significantly increased expression of Ngb, an oxygen-binding globin protein that has been demonstrated to be neuroprotective against stroke, at peri-infarct regions from day 1 to day 14 following ischemia/reperfusion. Conclusion: Our results suggest that the conventional per-conditioning combined with post-conditioning may be used as a novel neuroprotective strategy against ischemia-reperfusion injury, and Ngb seems to be one of the important players in limb remote ischemia-mediated neuroprotection. PMID:25868435

  15. Current knowledge on the neuroprotective and neuroregenerative properties of citicoline in acute ischemic stroke

    PubMed Central

    Martynov, Mikhail Yu; Gusev, Eugeny I

    2015-01-01

    Ischemic stroke is one of the leading causes of long-lasting disability and death. Two main strategies have been proposed for the treatment of ischemic stroke: restoration of blood flow by thrombolysis or mechanical thrombus extraction during the first few hours of ischemic stroke, which is one of the most effective treatments and leads to a better functional and clinical outcome. The other direction of treatment, which is potentially applicable to most of the patients with ischemic stroke, is neuroprotection. Initially, neuroprotection was mainly targeted at protecting gray matter, but during the past few years there has been a transition from a neuron-oriented approach toward salvaging the whole neurovascular unit using multimodal drugs. Citicoline is a multimodal drug that exhibits neuroprotective and neuroregenerative effects in a variety of experimental and clinical disorders of the central nervous system, including acute and chronic cerebral ischemia, intracerebral hemorrhage, and global cerebral hypoxia. Citicoline has a prolonged therapeutic window and is active at various temporal and biochemical stages of the ischemic cascade. In acute ischemic stroke, citicoline provides neuroprotection by attenuating glutamate exitotoxicity, oxidative stress, apoptosis, and blood–brain barrier dysfunction. In the subacute and chronic phases of ischemic stroke, citicoline exhibits neuroregenerative effects and activates neurogenesis, synaptogenesis, and angiogenesis and enhances neurotransmitter metabolism. Acute and long-term treatment with citicoline is safe and in most clinical studies is effective and improves functional outcome. PMID:27186142

  16. Developmental regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor subunit expression in forebrain and relationship to regional susceptibility to hypoxic/ischemic injury. I. Rodent cerebral white matter and cortex.

    PubMed

    Talos, Delia M; Fishman, Rachel E; Park, Hyunkyung; Folkerth, Rebecca D; Follett, Pamela L; Volpe, Joseph J; Jensen, Frances E

    2006-07-01

    This is the first part of a two-part study to investigate the cellular distribution and temporal regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR) subunits in the developing white matter and cortex in rat (part I) and human (part II). Western blot and immunocytochemistry were used to evaluate the differential expression of AMPAR subunits on glial and neuronal subtypes during the first 3 postnatal weeks in the Long Evans and Sprague Dawley rat strains. In Long Evans rats during the first postnatal week, GluR2-lacking AMPARs were expressed predominantly on white matter cells, including radial glia, premyelinating oligodendrocytes, and subplate neurons, whereas, during the second postnatal week, these AMPARs were highly expressed on cortical neurons, coincident with decreased expression on white matter cells. Immunocytochemical analysis revealed that cell-specific developmental changes in AMPAR expression occurred 2-3 days earlier by chronological age in Sprague Dawley rats compared with Long Evans rats, despite overall similar temporal sequencing. In both white and gray matter, the periods of high GluR2 deficiency correspond to those of regional susceptibility to hypoxic/ischemic injury in each of the two rat strains, supporting prior studies suggesting a critical role for Ca2+-permeable AMPARs in excitotoxic cellular injury and epileptogenesis. The developmental regulation of these receptor subunits strongly suggests that Ca2+ influx through GluR2-lacking AMPARs may play an important role in neuronal and glial development and injury in the immature brain. Moreover, as demonstrated in part II, there are striking similarities between rat and human in the regional and temporal maturational regulation of neuronal and glial AMPAR expression.

  17. Neuroprotective effect of nobiletin on cerebral ischemia-reperfusion injury in transient middle cerebral artery-occluded rats.

    PubMed

    Yasuda, Nodoka; Ishii, Takayuki; Oyama, Dai; Fukuta, Tatsuya; Agato, Yurika; Sato, Akihiko; Shimizu, Kosuke; Asai, Tomohiro; Asakawa, Tomohiro; Kan, Toshiyuki; Yamada, Shizuo; Ohizumi, Yasushi; Oku, Naoto

    2014-04-22

    Nobiletin, a citrus polymethoxylated flavone, is reported to possess various pharmacological activities such as anticancer, anti-inflammation, and antioxidant effects. Recently, nobiletin was shown to provide therapeutic benefit for the treatment of Alzheimer׳s disease by activating cAMP-response element-binding protein (CREB). In the present study, we investigated whether nobiletin could protect the brain against ischemia-reperfusion (I/R) injury and improve functional outcome in cerebral I/R model rats, since CREB activation is known to protect neuronal cells in cerebral ischemia. Nobiletin was injected twice at 0 and 1h after the start of reperfusion in transient middle cerebral artery occlusion (t-MCAO) rats. Cerebral I/R induced prominent brain damage in the ischemic hemisphere of t-MCAO rat brains; however, nobiletin treatment significantly reduced the infarct volume and suppressed the brain edema. Immunohistochemical and TUNEL staining indicated that nobiletin treatment significantly suppressed neutrophil invasion into the ischemic region and significantly decreased apoptotic brain cell death in ischemic hemisphere, suggesting that the anti-inflammatory effect and anti-apoptotic effect should be regarded as the neuroprotective mechanism of nobiletin. Moreover, nobiletin treatment ameliorated motor functional deficits in the ischemic rats compared with those deficits of the vehicle-treated group. These results indicate that nobiletin is a potential neuroprotectant for the treatment of cerebral I/R injury.

  18. Cerebral palsy.

    PubMed

    Wimalasundera, Neil; Stevenson, Valerie L

    2016-06-01

    Cerebral palsy has always been known as a disorder of movement and posture resulting from a non-progressive injury to the developing brain; however, more recent definitions allow clinicians to appreciate more than just the movement disorder. Accurate classification of cerebral palsy into distribution, motor type and functional level has advanced research. It also facilitates appropriate targeting of interventions to functional level and more accurate prognosis prediction. The prevalence of cerebral palsy remains fairly static at 2-3 per 1000 live births but there have been some changes in trends for specific causal groups. Interventions for cerebral palsy have historically been medical and physically focused, often with limited evidence to support their efficacy. The use of more appropriate outcome measures encompassing quality of life and participation is helping to deliver treatments which are more meaningful for people with cerebral palsy and their carers.

  19. Effects of cerebral ischemia on neuronal hemoglobin

    PubMed Central

    He, Yangdong; Hua, Ya; Liu, Wenquan; Hu, Haitao; Keep, Richard F.; Xi, Guohua

    2009-01-01

    Summary The present study examined whether or not neuronal hemoglobin (Hb) is present in rats. It then examined whether cerebral ischemia or ischemic preconditioning (IPC) affects neuronal Hb levels in vivo and in vitro. In vivo, male Sprague-Dawley rats were subjected to either 15 minutes of transient middle cerebral artery occlusion with 24 hours of reperfusion, an IPC stimulus, or 24 hours of permanent middle cerebral artery occlusion (pMCAO), or IPC followed three days later by 24 hours of pMCAO. In vitro, primary cultured neurons were exposed to 2 hours of oxygen-glucose deprivation with 22 hours of reoxygenation. Results showed that Hb is widely expressed in rat cerebral neurons but not astrocytes. Hb expression was significantly upregulated in the ipsilateral caudate and the cortical core of the middle cerebral artery territory after IPC. Hb levels also increased in more penumbral cortex and the contralateral hemisphere 24 hours after pMCAO, but expression in the ipsilateral caudate and cortical core area were decreased. Ischemic preconditioning modified pMCAO-induced brain Hb changes. Neuronal Hb levels in vitro were increased by 2 hours of oxygen-glucose deprivation and 22 hours of reoxygenation. These results indicate that Hb is synthesized in neurons and can be upregulated by ischemia. PMID:19066615

  20. The Effects of Methylene Blue on Autophagy and Apoptosis in MRI-Defined Normal Tissue, Ischemic Penumbra and Ischemic Core

    PubMed Central

    Jiang, Zhao; Watts, Lora Talley; Huang, Shiliang; Shen, Qiang; Rodriguez, Pavel; Chen, Chunhua; Zhou, Changman; Duong, Timothy Q.

    2015-01-01

    Methylene blue (MB) USP, which has energy-enhancing and antioxidant properties, is currently used to treat methemoglobinemia and cyanide poisoning in humans. We recently showed that MB administration reduces infarct volume and behavioral deficits in rat models of ischemic stroke and traumatic brain injury. This study reports the underlying molecular mechanisms of MB neuroprotection following transient ischemic stroke in rats. Rats were subjected to transient (60-mins) ischemic stroke. Multimodal MRI during the acute phase and at 24hrs were used to define three regions of interest (ROIs): i) the perfusion-diffusion mismatch salvaged by reperfusion, ii) the perfusion-diffusion mismatch not salvaged by reperfusion, and iii) the ischemic core. The tissues from these ROIs were extracted for western blot analyses of autophagic and apoptotic markers. The major findings were: 1) MB treatment reduced infarct volume and behavioral deficits, 2) MB improved cerebral blood flow to the perfusion-diffusion mismatch tissue after reperfusion and minimized harmful hyperperfusion 24hrs after stroke, 3) MB inhibited apoptosis and enhanced autophagy in the perfusion-diffusion mismatch, 4) MB inhibited apoptotic signaling cascades (p53-Bax-Bcl2-Caspase3), and 5) MB enhanced autophagic signaling cascades (p53-AMPK-TSC2-mTOR). MB induced neuroprotection, at least in part, by enhancing autophagy and reducing apoptosis in the perfusion-diffusion mismatch tissue following ischemic stroke. PMID:26121129

  1. Ischemic Nerve Block.

    ERIC Educational Resources Information Center

    Williams, Ian D.

    This experiment investigated the capability for movement and muscle spindle function at successive stages during the development of ischemic nerve block (INB) by pressure cuff. Two male subjects were observed under six randomly ordered conditions. The duration of index finger oscillation to exhaustion, paced at 1.2Hz., was observed on separate…

  2. Cerebral palsy.

    PubMed

    Graham, H Kerr; Rosenbaum, Peter; Paneth, Nigel; Dan, Bernard; Lin, Jean-Pierre; Damiano, Diane L; Becher, Jules G; Gaebler-Spira, Deborah; Colver, Allan; Reddihough, Dinah S; Crompton, Kylie E; Lieber, Richard L

    2016-01-07

    Cerebral palsy is the most common cause of childhood-onset, lifelong physical disability in most countries, affecting about 1 in 500 neonates with an estimated prevalence of 17 million people worldwide. Cerebral palsy is not a disease entity in the traditional sense but a clinical description of children who share features of a non-progressive brain injury or lesion acquired during the antenatal, perinatal or early postnatal period. The clinical manifestations of cerebral palsy vary greatly in the type of movement disorder, the degree of functional ability and limitation and the affected parts of the body. There is currently no cure, but progress is being made in both the prevention and the amelioration of the brain injury. For example, administration of magnesium sulfate during premature labour and cooling of high-risk infants can reduce the rate and severity of cerebral palsy. Although the disorder affects individuals throughout their lifetime, most cerebral palsy research efforts and management strategies currently focus on the needs of children. Clinical management of children with cerebral palsy is directed towards maximizing function and participation in activities and minimizing the effects of the factors that can make the condition worse, such as epilepsy, feeding challenges, hip dislocation and scoliosis. These management strategies include enhancing neurological function during early development; managing medical co-morbidities, weakness and hypertonia; using rehabilitation technologies to enhance motor function; and preventing secondary musculoskeletal problems. Meeting the needs of people with cerebral palsy in resource-poor settings is particularly challenging.

  3. Cerebral palsy.

    PubMed

    Graham, H Kerr; Rosenbaum, Peter; Paneth, Nigel; Dan, Bernard; Lin, Jean-Pierre; Damiano, Diane L; Becher, Jules G; Gaebler-Spira, Deborah; Colver, Allan; Reddihough, Dinah S; Crompton, Kylie E; Lieber, Richard L

    2016-01-01

    Cerebral palsy is the most common cause of childhood-onset, lifelong physical disability in most countries, affecting about 1 in 500 neonates with an estimated prevalence of 17 million people worldwide. Cerebral palsy is not a disease entity in the traditional sense but a clinical description of children who share features of a non-progressive brain injury or lesion acquired during the antenatal, perinatal or early postnatal period. The clinical manifestations of cerebral palsy vary greatly in the type of movement disorder, the degree of functional ability and limitation and the affected parts of the body. There is currently no cure, but progress is being made in both the prevention and the amelioration of the brain injury. For example, administration of magnesium sulfate during premature labour and cooling of high-risk infants can reduce the rate and severity of cerebral palsy. Although the disorder affects individuals throughout their lifetime, most cerebral palsy research efforts and management strategies currently focus on the needs of children. Clinical management of children with cerebral palsy is directed towards maximizing function and participation in activities and minimizing the effects of the factors that can make the condition worse, such as epilepsy, feeding challenges, hip dislocation and scoliosis. These management strategies include enhancing neurological function during early development; managing medical co-morbidities, weakness and hypertonia; using rehabilitation technologies to enhance motor function; and preventing secondary musculoskeletal problems. Meeting the needs of people with cerebral palsy in resource-poor settings is particularly challenging. PMID:27188686

  4. Dynamic changes in neuronal autophagy and apoptosis in the ischemic penumbra following permanent ischemic stroke.

    PubMed

    Deng, Yi-Hao; He, Hong-Yun; Yang, Li-Qiang; Zhang, Peng-Yue

    2016-07-01

    The temporal dynamics of neuronal autophagy and apoptosis in the ischemic penumbra following stroke remains unclear. Therefore, in this study, we investigated the dynamic changes in autophagy and apoptosis in the penumbra to provide insight into potential therapeutic targets for stroke. An adult Sprague-Dawley rat model of permanent ischemic stroke was prepared by middle cerebral artery occlusion. Neuronal autophagy and apoptosis in the penumbra post-ischemia were evaluated by western blot assay and immunofluorescence staining with antibodies against LC3-II and cleaved caspase-3, respectively. Levels of both LC3-II and cleaved caspase-3 in the penumbra gradually increased within 5 hours post-ischemia. Thereafter, levels of both proteins declined, especially LC3-II. The cerebral infarct volume increased slowly 1-4 hours after ischemia, but subsequently increased rapidly until 5 hours after ischemia. The severity of the neurological deficit was positively correlated with infarct volume. LC3-II and cleaved caspase-3 levels were high in the penumbra within 5 hours after ischemia, and after that, levels of these proteins decreased at different rates. LC3-II levels were reduced to a very low level, but cleaved caspase-3 levels remained high 72 hours after ischemia. These results indicate that there are temporal differences in the activation status of the autophagic and apoptotic pathways. This suggests that therapeutic targeting of these pathways should take into consideration their unique temporal dynamics. PMID:27630694

  5. Dynamic changes in neuronal autophagy and apoptosis in the ischemic penumbra following permanent ischemic stroke

    PubMed Central

    Deng, Yi-hao; He, Hong-yun; Yang, Li-qiang; Zhang, Peng-yue

    2016-01-01

    The temporal dynamics of neuronal autophagy and apoptosis in the ischemic penumbra following stroke remains unclear. Therefore, in this study, we investigated the dynamic changes in autophagy and apoptosis in the penumbra to provide insight into potential therapeutic targets for stroke. An adult Sprague-Dawley rat model of permanent ischemic stroke was prepared by middle cerebral artery occlusion. Neuronal autophagy and apoptosis in the penumbra post-ischemia were evaluated by western blot assay and immunofluorescence staining with antibodies against LC3-II and cleaved caspase-3, respectively. Levels of both LC3-II and cleaved caspase-3 in the penumbra gradually increased within 5 hours post-ischemia. Thereafter, levels of both proteins declined, especially LC3-II. The cerebral infarct volume increased slowly 1–4 hours after ischemia, but subsequently increased rapidly until 5 hours after ischemia. The severity of the neurological deficit was positively correlated with infarct volume. LC3-II and cleaved caspase-3 levels were high in the penumbra within 5 hours after ischemia, and after that, levels of these proteins decreased at different rates. LC3-II levels were reduced to a very low level, but cleaved caspase-3 levels remained high 72 hours after ischemia. These results indicate that there are temporal differences in the activation status of the autophagic and apoptotic pathways. This suggests that therapeutic targeting of these pathways should take into consideration their unique temporal dynamics. PMID:27630694

  6. Emergency EEG and continuous EEG monitoring in acute ischemic stroke.

    PubMed

    Jordan, Kenneth G

    2004-01-01

    There is physiologic coupling of EEG morphology, frequencies, and amplitudes with cerebral blood flow. Intraoperative continuous electroencephalographic monitoring (CEEG) is an established modality that has been used for 30 years to detect cerebral ischemia during carotid surgery. These facts have generated interest in applying EEG/CEEG in the intensive care unit to monitor cerebral ischemia. However, its use in acute ischemic stroke (AIS) has been limited, and its value has been questioned in comparison with modern MRI imaging techniques and the clinical neurologic examination. This review presents evidence that EEG/CEEG adds value to early diagnosis, outcome prediction, patient selection for treatment, clinical management, and seizure detection in AIS. Research studies correlating EEG/CEEG and advanced imaging techniques in AIS are encouraged. Improvements in real-time ischemia detection systems are needed for EEG/CEEG to have wider application in AIS. PMID:15592008

  7. [Effects of total saponins of semen ziziphi Spinosae on brain damages and brain biochemical parameters under cerebral ischemia of rats].

    PubMed

    Bai, X; Huang, Z; Mo, Z; Pan, H; Ding, H

    1996-02-01

    Total saponins of Semen Ziziphi Spinosae (ZS) can reduce the contents of water and MDA in ischemic rat's brain tissues, elevate the activity of SOD, CK and LDH, cut down the content of lactate and alleviate the damages of nerve cells in brain. The study shows that ZS possesses protective effects on cerebral ischemic injuries. PMID:8758767

  8. Cerebral palsy

    MedlinePlus

    ... with pain and spasticity Place feeding tubes Release joint contractures ... the hip joint Injuries from falls Pressure sores Joint ... of the people who are affected by cerebral palsy) Social stigma

  9. Cerebral Palsy

    MedlinePlus

    ... Español (Spanish) Recommend on Facebook Tweet Share Compartir Cerebral palsy (CP) is a group of disorders that affect a ... ability to move and maintain balance and posture. CP is the most common motor disability in childhood. ...

  10. Cerebral hypoxia

    MedlinePlus

    ... death. Treatment depends on the cause of the hypoxia. Basic life support is most important. Treatment involves: Breathing ... Complications of cerebral hypoxia include a prolonged vegetative ... sleep-wake cycle, and eye opening, but the person is not alert ...

  11. [Current registry studies of acute ischemic stroke].

    PubMed

    Veltkamp, R; Jüttler, E; Pfefferkorn, T; Purrucker, J; Ringleb, P

    2012-10-01

    Study registries offer the opportunity to evaluate the effects of new therapies or to observe the consequences of new treatments in clinical practice. The SITS-MOST registry confirmed the validity of findings from randomized trials on intravenous thrombolysis concerning safety and efficacy in the clinical routine. Current study registries concerning new interventional thrombectomy techniques suggest a high recanalization rate; however, the clinical benefit can only be evaluated in randomized, controlled trials. Similarly, the experiences of the BASICS registry on basilar artery occlusion have led to the initiation of a controlled trial. The benefit of hemicraniectomy in malignant middle cerebral artery infarction has been demonstrated by the pooled analysis of three randomized trials. Numerous relevant aspects are currently documented in the DESTINY-R registry. Finally, the recently started RASUNOA registry examines diagnostic and therapeutic aspects of ischemic and hemorrhagic stroke occurring during therapy with new oral anticoagulants.

  12. Recent Progress in Therapeutic Strategies for Ischemic Stroke.

    PubMed

    Yamashita, Toru; Abe, Koji

    2016-01-01

    Possible strategies for treating stroke include neuroprotection in the acute phase of cerebral ischemia and stem cell therapy in the chronic phase of cerebral ischemia. Previously, we have studied the temporal and spatial expression patterns of c-fos, hypoxia inducible factor-1α (HIF-1α), heat shock protein 70 (HSP70), and annexin V after 90 min of transient middle cerebral occlusion in rats and concluded that there is a time window for neuroprotection from 12 to 48 h after ischemia. In addition, we have estimated the neuroprotective effect of glial cell line-derived neurotrophic factor (GDNF) by injecting Sendai viral vector containing the GDNF gene into the postischemic brain. This Sendai virus-mediated gene transfer of GDNF showed a significant neuroprotective effect in the ischemic brain. Additionally, we have administered GDNF and hepatocyte growth factor (HGF) protein into the postischemic rat brain and estimated the infarct size and antiapoptotic and antiautophagic effects. GDNF and HGF significantly reduced infarct size, the number of microtubule-associated protein 1 light chain 3 (LC3)-positive cells, and the number of terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick-end labeling (TUNEL)-positive cells, indicating that GDNF and HGF were greatly associated with not only the antiapoptotic effect but also the antiautophagic effects. Finally, we have previously transplanted undifferentiated iPSCs into the ipsilateral striatum and cortex at 24 h after cerebral ischemia. Histological analysis was performed at 14 and 28 days after cell transplantation, and we found that iPSCs could supply a great number of doublecortin-positive neuroblasts but also formed tridermal teratoma in the ischemic brain. Our results suggest that iPSCs have a potential to provide neural cells after ischemic brain injury if tumorigenesis is properly controlled. In the future, we will combine these strategies to develop more effective therapies for the treatment of

  13. Cerebral Paragonimiasis.

    PubMed

    Miyazaki, I

    1975-01-01

    The first case of cerebral paragonimiasis was reported by Otani in Japan in 1887. This was nine years after Kerbert's discovery of the fluke in the lungs of Bengal tigers and seven years after a human pulmonary infection by the fluke was demonstrated by Baelz and Manson. The first case was a 26-year-old man who had been suffering from cough and hemosputum for one year. The patient developed convulsive seizures with subsequent coma and died. The postmortem examination showed cystic lesions in the right frontal and occipital lobes. An adult fluke was found in the occipital lesion and another was seen in a gross specimen of normal brain tissue around the affected occipital lobe. Two years after Otani's discovery, at autopsy a 29-year-old man with a history of Jacksonian seizure was reported as having cerebral paragonimiasis. Some time later, however, it was confirmed that the case was actually cerebral schistosomiasis japonica. Subsequently, cases of cerebral paragonimiasis were reported. However, the majority of these cases were not confirmed histologically. It was pointed out that some of these early cases were probably not Paragonimus infection. After World War II, reviews as well as case reports were published. Recently, investigations have been reported from Korea, with a clinicla study on 62 cases of cerebral paragonimiasis seen at the Neurology Department of the National Medical Center, Seoul, between 1958 and 1964. In 1971 Higashi described a statistical study on 105 cases of cerebral paragonimiasis that had been treated surgically in Japan.

  14. Cerebral Paragonimiasis.

    PubMed

    Miyazaki, I

    1975-01-01

    The first case of cerebral paragonimiasis was reported by Otani in Japan in 1887. This was nine years after Kerbert's discovery of the fluke in the lungs of Bengal tigers and seven years after a human pulmonary infection by the fluke was demonstrated by Baelz and Manson. The first case was a 26-year-old man who had been suffering from cough and hemosputum for one year. The patient developed convulsive seizures with subsequent coma and died. The postmortem examination showed cystic lesions in the right frontal and occipital lobes. An adult fluke was found in the occipital lesion and another was seen in a gross specimen of normal brain tissue around the affected occipital lobe. Two years after Otani's discovery, at autopsy a 29-year-old man with a history of Jacksonian seizure was reported as having cerebral paragonimiasis. Some time later, however, it was confirmed that the case was actually cerebral schistosomiasis japonica. Subsequently, cases of cerebral paragonimiasis were reported. However, the majority of these cases were not confirmed histologically. It was pointed out that some of these early cases were probably not Paragonimus infection. After World War II, reviews as well as case reports were published. Recently, investigations have been reported from Korea, with a clinicla study on 62 cases of cerebral paragonimiasis seen at the Neurology Department of the National Medical Center, Seoul, between 1958 and 1964. In 1971 Higashi described a statistical study on 105 cases of cerebral paragonimiasis that had been treated surgically in Japan. PMID:1095292

  15. Transient ischemic attack as a medical emergency.

    PubMed

    Okada, Yasushi

    2014-01-01

    Since transient ischemic attack (TIA) is regarded as a medical emergency with high risk for early stroke recurrence, the underlying mechanisms should be immediately clarified to conclude a definitive diagnosis and provide early treatment. Early risk stratification using ABCD(2) scores can predict the risk of ischemic stroke occurring after TIA. Carotid ultrasonography (US) can evaluate the degree of stenosis, plaque properties and flow velocity of ICA lesions. High-risk mobile plaques can be classified by carotid US, and aortogenic sources of emboli can be detected by transesophageal echocardiography. Cardiac monitoring and blood findings are thought to play a key role in a diagnosis of cardioembolic TIA. Diffusion-weighted imaging (DWI)-MRI and MR angiography are also indispensable to understand the mechanism of TIA and cerebral circulation. To prevent subsequent stroke arising from TIA, antiplatelet and anticoagulant therapies should be started immediately along with comprehensive management of life-style, hypertension, diabetes mellitus, dyslipidemia and other atherosclerotic diseases. Carotid endarterectomy and endovascular intervention are critical for treating symptomatic patients with significant stenosis of ICA. A novel concept of acute cerebrovascular syndrome (ACVS) has recently been advocated to increase awareness of TIA among citizens, patients and medical professionals. TIA should be recognized as the last opportunity to avoid irreversible ischemic stroke and its sequelae. The clinical relevance of the new concept of ACVS is advocated by early recurrence after TIA, analysis of high-risk TIA, treatment strategies and the optimal management of TIA. Raising TIA awareness should also proceed across many population sectors. PMID:24157554

  16. Blood biomarkers in the early stage of cerebral ischemia.

    PubMed

    Maestrini, I; Ducroquet, A; Moulin, S; Leys, D; Cordonnier, C; Bordet, R

    2016-03-01

    In ischemic stroke patients, blood-based biomarkers may be applied for the diagnosis of ischemic origin and subtype, prediction of outcomes and targeted treatment in selected patients. Knowledge of the pathophysiology of cerebral ischemia has led to the evaluation of proteins, neurotransmitters, nucleic acids and lipids as potential biomarkers. The present report focuses on the role of blood-based biomarkers in the early stage of ischemic stroke-within 72h of its onset-as gleaned from studies published in English in such patients. Despite growing interest in their potential role in clinical practice, the application of biomarkers for the management of cerebral ischemia is not currently recommended by guidelines. However, there are some promising clinical biomarkers, as well as the N-methyl-d-aspartate (NMDA) peptide and NMDA-receptor (R) autoantibodies that appear to identify the ischemic nature of stroke, and the glial fibrillary acidic protein (GFAP) that might be able to discriminate between acute ischemic and hemorrhagic strokes. Moreover, genomics and proteomics allow the characterization of differences in gene expression, and protein and metabolite production, in ischemic stroke patients compared with controls and, thus, may help to identify novel markers with sufficient sensitivity and specificity. Additional studies to validate promising biomarkers and to identify novel biomarkers are needed. PMID:26988891

  17. Cerebral Palsy (For Parents)

    MedlinePlus

    ... Story" 5 Things to Know About Zika & Pregnancy Cerebral Palsy KidsHealth > For Parents > Cerebral Palsy Print A A ... kids who are living with the condition. About Cerebral Palsy Cerebral palsy is one of the most common ...

  18. Cerebral palsy - resources

    MedlinePlus

    Resources - cerebral palsy ... The following organizations are good resources for information on cerebral palsy : National Institute of Neurological Disorders and Stroke -- www.ninds.nih.gov/disorders/cerebral_palsy/cerebral_palsy. ...

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

    PubMed Central

    Lin, Chi-Hsin; Wang, Chen-Hsuan; Hsu, Shih-Lan; Liao, Li-Ya; Lin, Ting-An; Hsueh, Chi-Mei

    2016-01-01

    The protective value of neuron-derived conditioned medium (NCM) in cerebral ischemia and the underlying mechanism(s) responsible for NCM-mediated brain protection against cerebral ischemia were investigated in the study. NCM was first collected from the neuronal culture growing under the in vitro ischemic condition (glucose-, oxygen- and serum-deprivation or GOSD) for 2, 4 or 6 h. Through the focal cerebral ischemia (bilateral CCAO/unilateral MCAO) animal model, we discovered that ischemia/reperfusion (I/R)-induced brain infarction was significantly reduced by NCM, given directly into the cistern magna at the end of 90 min of CCAO/MCAO. Immunoblocking and chemical blocking strategies were applied in the in vitro ischemic studies to show that NCM supplement could protect microglia, astrocytes and neurons from GOSD-induced cell death, in a growth factor (TGFβ1, NT-3 and GDNF) and p-ERK dependent manner. Brain injection with TGFβ1, NT3, GDNF and ERK agonist (DADS) alone or in combination, therefore also significantly decreased the infarct volume of ischemic brain. Moreover, NCM could inhibit ROS but stimulate IL-1β release from GOSD-treated microglia and limit the infiltration of IL-β-positive microglia into the core area of ischemic brain, revealing the anti-oxidant and anti-inflammatory activities of NCM. In overall, NCM-mediated brain protection against cerebral ischemia has been demonstrated for the first time in S.D. rats, due to its anti-apoptotic, anti-oxidant and potentially anti-glutamate activities (NCM-induced IL-1β can inhibit the glutamate-mediated neurotoxicity) and restriction upon the infiltration of inflammatory microglia into the core area of ischemic brain. The therapeutic potentials of NCM, TGFβ1, GDNF, NT-3 and DADS in the control of cerebral ischemia in human therefore have been suggested and require further investigation. PMID:26745377

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

    PubMed

    Lin, Chi-Hsin; Wang, Chen-Hsuan; Hsu, Shih-Lan; Liao, Li-Ya; Lin, Ting-An; Hsueh, Chi-Mei

    2016-01-01

    The protective value of neuron-derived conditioned medium (NCM) in cerebral ischemia and the underlying mechanism(s) responsible for NCM-mediated brain protection against cerebral ischemia were investigated in the study. NCM was first collected from the neuronal culture growing under the in vitro ischemic condition (glucose-, oxygen- and serum-deprivation or GOSD) for 2, 4 or 6 h. Through the focal cerebral ischemia (bilateral CCAO/unilateral MCAO) animal model, we discovered that ischemia/reperfusion (I/R)-induced brain infarction was significantly reduced by NCM, given directly into the cistern magna at the end of 90 min of CCAO/MCAO. Immunoblocking and chemical blocking strategies were applied in the in vitro ischemic studies to show that NCM supplement could protect microglia, astrocytes and neurons from GOSD-induced cell death, in a growth factor (TGFβ1, NT-3 and GDNF) and p-ERK dependent manner. Brain injection with TGFβ1, NT3, GDNF and ERK agonist (DADS) alone or in combination, therefore also significantly decreased the infarct volume of ischemic brain. Moreover, NCM could inhibit ROS but stimulate IL-1β release from GOSD-treated microglia and limit the infiltration of IL-β-positive microglia into the core area of ischemic brain, revealing the anti-oxidant and anti-inflammatory activities of NCM. In overall, NCM-mediated brain protection against cerebral ischemia has been demonstrated for the first time in S.D. rats, due to its anti-apoptotic, anti-oxidant and potentially anti-glutamate activities (NCM-induced IL-1β can inhibit the glutamate-mediated neurotoxicity) and restriction upon the infiltration of inflammatory microglia into the core area of ischemic brain. The therapeutic potentials of NCM, TGFβ1, GDNF, NT-3 and DADS in the control of cerebral ischemia in human therefore have been suggested and require further investigation. PMID:26745377

  1. Acute ischemic stroke update.

    PubMed

    Baldwin, Kathleen; Orr, Sean; Briand, Mary; Piazza, Carolyn; Veydt, Annita; McCoy, Stacey

    2010-05-01

    Stroke is the third most common cause of death in the United States and is the number one cause of long-term disability. Legislative mandates, largely the result of the American Heart Association, American Stroke Association, and Brain Attack Coalition working cooperatively, have resulted in nationwide standardization of care for patients who experience a stroke. Transport to a skilled facility that can provide optimal care, including immediate treatment to halt or reverse the damage caused by stroke, must occur swiftly. Admission to a certified stroke center is recommended for improving outcomes. Most strokes are ischemic in nature. Acute ischemic stroke is a heterogeneous group of vascular diseases, which makes targeted treatment challenging. To provide a thorough review of the literature since the 2007 acute ischemic stroke guidelines were developed, we performed a search of the MEDLINE database (January 1, 2004-July 1, 2009) for relevant English-language studies. Results (through July 1, 2009) from clinical trials included in the Internet Stroke Center registry were also accessed. Results from several pivotal studies have contributed to our knowledge of stroke. Additional data support the efficacy and safety of intravenous alteplase, the standard of care for acute ischemic stroke since 1995. Due to these study results, the American Stroke Association changed its recommendation to extend the time window for administration of intravenous alteplase from within 3 hours to 4.5 hours of symptom onset; this recommendation enables many more patients to receive the drug. Other findings included clinically useful biomarkers, the role of inflammation and infection, an expanded role for placement of intracranial stents, a reduced role for urgent carotid endarterectomy, alternative treatments for large-vessel disease, identification of nontraditional risk factors, including risk factors for women, and newly published pediatric stroke guidelines. In addition, new devices for

  2. Cerebral palsy.

    PubMed

    Colver, Allan; Fairhurst, Charles; Pharoah, Peter O D

    2014-04-01

    The syndrome of cerebral palsy encompasses a large group of childhood movement and posture disorders. Severity, patterns of motor involvement, and associated impairments such as those of communication, intellectual ability, and epilepsy vary widely. Overall prevalence has remained stable in the past 40 years at 2-3·5 cases per 1000 livebirths, despite changes in antenatal and perinatal care. The few studies available from developing countries suggest prevalence of comparable magnitude. Cerebral palsy is a lifelong disorder; approaches to intervention, whether at an individual or environmental level, should recognise that quality of life and social participation throughout life are what individuals with cerebral palsy seek, not improved physical function for its own sake. In the past few years, the cerebral palsy community has learned that the evidence of benefit for the numerous drugs, surgery, and therapies used over previous decades is weak. Improved understanding of the role of multiple gestation in pathogenesis, of gene environment interaction, and how to influence brain plasticity could yield significant advances in treatment of the disorder. Reduction in the prevalence of post-neonatal cerebral palsy, especially in developing countries, should be possible through improved nutrition, infection control, and accident prevention.

  3. Progress in AQP Research and New Developments in Therapeutic Approaches to Ischemic and Hemorrhagic Stroke

    PubMed Central

    Previch, Lauren E.; Ma, Linlin; Wright, Joshua C.; Singh, Sunpreet; Geng, Xiaokun; Ding, Yuchuan

    2016-01-01

    Cerebral edema often manifests after the development of cerebrovascular disease, particularly in the case of stroke, both ischemic and hemorrhagic. Without clinical intervention, the influx of water into brain tissues leads to increased intracranial pressure, cerebral herniation, and ultimately death. Strategies to manage the development of edema constitute a major unmet therapeutic need. However, despite its major clinical significance, the mechanisms underlying cerebral water transport and edema formation remain elusive. Aquaporins (AQPs) are a class of water channel proteins which have been implicated in the regulation of water homeostasis and cerebral edema formation, and thus represent a promising target for alleviating stroke-induced cerebral edema. This review examines the significance of relevant AQPs in stroke injury and subsequently explores neuroprotective strategies aimed at modulating AQP expression, with a particular focus on AQP4, the most abundant AQP in the central nervous system. PMID:27438832

  4. [Cerebral venous thrombosis during tuberculous meningoencephalitis].

    PubMed

    Guenifi, W; Boukhrissa, H; Gasmi, A; Rais, M; Ouyahia, A; Hachani, A; Diab, N; Mechakra, S; Lacheheb, A

    2016-05-01

    Cerebral venous thrombosis is a rare disease characterized by its clinical polymorphism and multiplicity of risk factors. Infections represent less than 10% of etiologies. Tuberculosis is not a common etiology, only a few observations are published in the literature. Between January 2005 and March 2015, 61 patients were hospitalized for neuro-meningeal tuberculosis. Among them, three young women had presented one or more cerebral venous sinus thromboses. No clinical feature was observed in these patients; vascular localizations were varied: sagittal sinus (2 cases), lateral sinus (2 cases) and transverse sinus (1 case). With anticoagulant and antituberculosis drugs, the outcome was favorable in all cases. During neuro-meningeal tuberculosis, the existence of consciousness disorders or neurological focal signs is not always the translation of encephalitis, hydrocephalus, tuberculoma or ischemic stroke; cerebral venous sinus thrombosis may be the cause and therefore should be sought. PMID:27090100

  5. [Gene-stem Cell therapy for ischemic stroke].

    PubMed

    Abe, Koji

    2009-09-01

    Besides blood flow restoration, neuroprotection is essential for treating strokes at an acute stage. Both neurotrophic factors (NTFs) and free radical scavengers can act as neuroprotective agents with abilities to inhibit cell death and facilitate cell survival under cerebral ischemia. For example, topical application of glial cell line-derived neurotrophic factor (GDNF) remarkably reduced infarct size and brain edema after middle cerebral artery (MCA) occlusion in rats. Reduction in the infarct size was not found to be related to a change in the cerebral blood flow (CBF), but was accompanied by marked reduction in BrdU-positive cells in the affected area after TdT-mediated dUTP-biotin nick end labeling (TUNEL) for caspses. Thus, GDNF elicited a direct protective effect against ischemic brain damage, but without improving CBF. Sendai virus vectors harboring the GDNF gene led to a remarkable reduction in infract volume without affecting regional CBF but reduced the translocation of apoptosis inducible factor (AIF) from the mitochondria to cytoplasm. Regenerative therapy involving neural stem cells which are intrinsically activated or exogenously transplanted, is an important treatment strategy. To facilitate stem cell migration, an artificial scaffold can be implanted into the injured brain for promoting ischemic brain repair. Addition of NTFs greatly enhanced an intrinsic migration or invasion of stem cells into the scaffold: this strategy could be used in the future for enhancing regenerative potential of brain cells after chronic ischemia-induced brain damage. PMID:19803403

  6. Perfusion Angiography in Acute Ischemic Stroke

    PubMed Central

    Liebeskind, David S.

    2016-01-01

    Visualization and quantification of blood flow are essential for the diagnosis and treatment evaluation of cerebrovascular diseases. For rapid imaging of the cerebrovasculature, digital subtraction angiography (DSA) remains the gold standard as it offers high spatial resolution. This paper lays out a methodological framework, named perfusion angiography, for the quantitative analysis and visualization of blood flow parameters from DSA images. The parameters, including cerebral blood flow (CBF) and cerebral blood volume (CBV), mean transit time (MTT), time-to-peak (TTP), and Tmax, are computed using a bolus tracking method based on the deconvolution of the time-density curve on a pixel-by-pixel basis. The method is tested on 66 acute ischemic stroke patients treated with thrombectomy and/or tissue plasminogen activator (tPA) and also evaluated on an estimation task with known ground truth. This novel imaging tool provides unique insights into flow mechanisms that cannot be observed directly in DSA sequences and might be used to evaluate the impact of endovascular interventions more precisely. PMID:27446232

  7. Delayed treatment with NSC23766 in streptozotocin-induced diabetic rats ameliorates post-ischemic neuronal apoptosis through suppression of mitochondrial p53 translocation.

    PubMed

    Liao, Juan; Ye, Zhi; Huang, Guoqing; Xu, Chang; Guo, Qulian; Wang, E

    2014-10-01

    NSC23766, a specific inhibitor of Rac1, has recently been shown to protect against cerebral ischemic injury, although the effects of NSC23766 in a diabetic model have not been examined. Therefore, the aim of our study was to investigate if NSC23766 provided neuroprotection in streptozotocin-induced diabetic rats and to determine the potential mechanism through which NSC23766 works. Diabetic Sprague-Dawley rats were subjected to right middle cerebral artery occlusion (MCAO) for 90 min. NSC23766 (10 or 30 mg kg(-1)) or isotonic saline were administered intraperitoneally twice daily starting 24 h after cerebral ischemia, for three consecutive days. Cerebral infarct volume, neurological deficit scores, neuronal apoptosis, and the release of cytochrome c, as well as the generation of ROS and mitochondrial integrity, were evaluated 96 h after reperfusion. In addition, the mitochondrial translocation of p53 and the expression of p53-upregulated modulator of apoptosis (PUMA) in the mitochondria of the cerebral ischemic cortex were determined by western blotting. NSC23766 not only ameliorated post-ischemic neuronal apoptosis but also decreased cerebral ischemia-induced mitochondrial p53 translocation and the expression of PUMA in mitochondria in diabetic rats. Thus, our data indicate that NSC23766 has therapeutic potential against cerebral ischemic reperfusion injury and that NSC23766 significantly ameliorates neuronal apoptosis by suppressing mitochondrial p53 translocation in streptozotocin-induced diabetic rats.

  8. A schizophrenic patient with cerebral infarctions after hemorrhagic shock

    PubMed Central

    Yanagawa, Youichi; Ohara, Keiichiro; Tanaka, Yasutaka; Tanaka, Ryota

    2013-01-01

    We herein report the fourth case of cerebral infarction, concomitant with hemorrhagic shock, in English literature. A 33-year-old male, who had been diagnosed with schizophrenia and given a prescription for Olanzapine, was discovered with multiple self-inflicted bleeding cuts on his wrist. On arrival, he was in hemorrhagic shock without verbal responsiveness, but his vital signs were normalized following infusion of Lactate Ringer's solution. The neuroradiological studies revealed multiple cerebral ischemic lesions without any vascular abnormality. He was diagnosed with speech apraxia, motor aphasia, and dysgraphia, due to multiple cerebral infarctions. As there was no obvious causative factor with regard to the occurrence of cerebral infarction in the patient, the hypoperfusion due to hemorrhagic shock, and the thromboembolic tendency due to Olanzapine, might have acted together to lead to the patient's cerebral ischemia. PMID:23493336

  9. Looks like a stroke, acts like a stroke, but it's more than a stroke: a case of cerebral mucormycosis.

    PubMed

    Ermak, David; Kanekar, Sangam; Specht, Charles S; Wojnar, Margaret; Lowden, Max

    2014-09-01

    Mucormycosis is a fungus that exhibits angiocentric growth and can cause a thrombotic arteritis. Infection with this organism is uncommon and cerebral involvement is most often secondary to direct invasion through the paranasal sinuses. Here, we present a case of mucormycosis with cerebral involvement without sinus disease, which resulted in ischemic stroke with rapid progression resulting in death.

  10. Trypanosomiasis, cardiomyopathy and the risk of ischemic stroke.

    PubMed

    Carod-Artal, Francisco Javier

    2010-05-01

    American (Chagas disease) and African (sleeping sickness) trypanosomiasis are neglected tropical diseases and are a heavy burden in Latin America and Africa, respectively. Chagas disease is an independent risk factor for stroke. Apical aneurysm, heart failure and cardiac arrhythmias are associated with ischemic stroke in chagasic cardiomyopathy. Not all chagasic patients who suffer an ischemic stroke have a severe cardiomyopathy, and stroke may be the first manifestation of Chagas disease. Cardioembolism affecting the middle cerebral artery is the most common stroke subtype. Risk of recurrence is high and careful evaluation of recurrence risk should be addressed. Repolarization changes, low voltage and prolonged QT interval are common electrocardiography alterations in human African trypanosomiasis, and can be found in more than 70% of patients. Epidemiological studies are needed to asses the risk of stroke in African trypanosomiasis perimyocarditis.

  11. Ischemic infarction in 25 children with tuberculous meningitis.

    PubMed

    Leiguarda, R; Berthier, M; Starkstein, S; Nogués, M; Lylyk, P

    1988-02-01

    Twenty-five cases (38%) of ischemic infarction occurred among 65 cases of tuberculous meningitis in patients less than 14 years of age. The male:female ratio was 1.3:1. The most frequent clinical findings were meningeal signs, fever, alteration of consciousness, cranial nerve involvement, seizures, and focal neurologic deficit. Twenty-three patients had anterior circulation infarcts, and two more had infarcts in the vertebrobasilar territories. Distribution of infarcts in the anterior circulation was shown by computed tomography in the territories of the following arteries: lenticulostriate, 10 cases unilateral and 6 bilateral; middle cerebral, 3 cases; internal carotid, 1 case; multiple areas, 3 cases. Of the 25 ischemic infarction cases, 23 (92%) had hydrocephalus, 19 (76%) basal exudates, and 2 (8%) tuberculomas. Outcome was poor since no patient with infarction recovered completely. Six died and bilateral subcortical infarcts led to a considerably higher mortality than unilateral ones, whether cortical or subcortical.

  12. Oxaloacetate: a novel neuroprotective for acute ischemic stroke.

    PubMed

    Campos, Francisco; Sobrino, Tomás; Ramos-Cabrer, Pedro; Castillo, José

    2012-02-01

    It is well established that glutamate acts as an important mediator of neuronal degeneration during cerebral ischemia. Different kind of glutamate antagonists have been used to reduce the deleterious effects of glutamate. However, their preclinical success failed to translate into practical treatments. Far from the classical use of glutamate antagonists employed so far, the systemic administration of oxaloacetate represents a novel neuroprotective strategy to minimize the deleterious effect of glutamate in the brain tissue after ischemic stroke. The neuroprotective effect of oxaloacetate is based on the capacity of this molecule to reduce the brain and blood glutamate levels as a result of the activation of the blood-resident enzyme glutamate-oxaloacetate transaminase. Here we review the recent experimental and clinical results where it is demonstrated the potential applicability of oxaloacetate as a novel and powerful neuroprotective treatment against ischemic stroke.

  13. Partial Aortic Occlusion and Cerebral Venous Steal: Venous Effects of Arterial Manipulation in Acute Stroke

    PubMed Central

    Pranevicius, Osvaldas; Pranevicius, Mindaugas; Liebeskind, David S.

    2011-01-01

    Acute ischemic stroke therapy emphasizes early arterial clot lysis or removal. Partial aortic occlusion has recently emerged as an alternative hemodynamic approach to augment cerebral perfusion in acute ischemic stroke. The exact mechanism of cerebral flow augmentation with partial aortic occlusion remains unclear and may involve more than simple diversion of arterial blood flow from the lower body to cerebral collateral circulation. The cerebral venous steal hypothesis suggests that even a small increase in tissue pressure in the ischemic area will divert blood flow to surrounding regions with lesser tissue pressures. This may cause no-reflow (absence of flow after restoration of arterial patency) in the ischemic core and “luxury perfusion” in the surrounding regions. Such maldistribution may be reversed with increased venous pressure titrated to avoid changes in intracranial pressure. We propose that partial aortic occlusion enhances perfusion in the brain by offsetting cerebral venous steal. Partial aortic occlusion redistributes blood volume into the upper part of the body, manifest by an increase in central venous pressure. Increased venous pressure recruits the collapsed vascular network and, by eliminating cerebral venous steal, corrects perifocal perfusion maldistribution, analogous to positive end expiratory pressure recruitment of collapsed airways to decrease ventilation/perfusion mismatch in the lungs. PMID:21441149

  14. Exercise preconditioning exhibits neuroprotective effects on hippocampal CA1 neuronal damage after cerebral ischemia

    PubMed Central

    Shamsaei, Nabi; Khaksari, Mehdi; Erfani, Sohaila; Rajabi, Hamid; Aboutaleb, Nahid

    2015-01-01

    Recent evidence has suggested the neuroprotective effects of physical exercise on cerebral ischemic 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 through 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 exercise significantly 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. PMID:26487851

  15. Histone Acetylation and CREB Binding Protein Are Required for Neuronal Resistance against Ischemic Injury

    PubMed Central

    Yildirim, Ferah; Ji, Shengbo; Kronenberg, Golo; Barco, Angel; Olivares, Roman; Benito, Eva; Dirnagl, Ulrich; Gertz, Karen; Endres, Matthias

    2014-01-01

    Epigenetic transcriptional regulation by histone acetylation depends on the balance between histone acetyltransferase (HAT) and deacetylase activities (HDAC). Inhibition of HDAC activity provides neuroprotection, indicating that the outcome of cerebral ischemia depends crucially on the acetylation status of histones. In the present study, we characterized the changes in histone acetylation levels in ischemia models of focal cerebral ischemia and identified cAMP-response element binding protein (CREB)–binding protein (CBP) as a crucial factor in the susceptibility of neurons to ischemic stress. Both neuron-specific RNA interference and neurons derived from CBP heterozygous knockout mice showed increased damage after oxygen-glucose deprivation (OGD) in vitro. Furthermore, we demonstrated that ischemic preconditioning by a short (5 min) subthreshold occlusion of the middle cerebral artery (MCA), followed 24 h afterwards by a 30 min occlusion of the MCA, increased histone acetylation levels in vivo. Ischemic preconditioning enhanced CBP recruitment and histone acetylation at the promoter of the neuroprotective gene gelsolin leading to increased gelsolin expression in neurons. Inhibition of CBP's HAT activity attenuated neuronal ischemic preconditioning. Taken together, our findings suggest that the levels of CBP and histone acetylation determine stroke outcome and are crucially associated with the induction of an ischemia-resistant state in neurons. PMID:24748101

  16. Low-Power 2-MHz Pulsed-Wave Transcranial Ultrasound Reduces Ischemic Brain Damage in Rats.

    PubMed

    Alexandrov, Andrei V; Barlinn, Kristian; Strong, Roger; Alexandrov, Anne W; Aronowski, Jaroslaw

    2011-09-01

    It is largely unknown whether prolonged insonation with ultrasound impacts the ischemic brain tissue by itself. Our goal was to evaluate safety and the effect of high-frequency ultrasound on infarct volume in rats. Thirty-two Long-Evans rats with permanent middle cerebral and carotid artery occlusions received either 2-MHz ultrasound at two levels of insonation power (128 or 10 mW) or no ultrasound (controls). We measured cerebral hemorrhage, indirect and direct infarct volume as well as edema volume at 24 h. No cerebral hemorrhages were detected in all animals. Exposure to low-power (10 mW) ultrasound resulted in a significantly decreased indirect infarct volume (p = 0.0039), direct infarct volume (p = 0.0031), and brain edema volume (p = 0.01) compared with controls. High-power (128 mW) ultrasound had no significant effects. An additional experiment with India ink showed a greater intravascular penetration of dye into ischemic tissues exposed to low-power ultrasound. Insonation with high-frequency, low-power ultrasound reduces ischemic brain damage in rat. Its effect on edema reduction and possible promotion of microcirculation could be used to facilitate drug and nutrient delivery to ischemic areas.

  17. Rolipram stimulates angiogenesis and attenuates neuronal apoptosis through the cAMP/cAMP-responsive element binding protein pathway following ischemic stroke in rats

    PubMed Central

    HU, SHOUYE; CAO, QINGWEN; XU, PENG; JI, WENCHEN; WANG, GANG; ZHANG, YUELIN

    2016-01-01

    Rolipram, a phosphodiesterase-4 inhibitor, can activate the cyclic adenosine monophosphate (cAMP)/cAMP-responsive element binding protein (CREB) pathway to facilitate functional recovery following ischemic stroke. However, to date, the effects of rolipram on angiogenesis and cerebral ischemia-induced neuronal apoptosis are yet to be fully elucidated. In this study, the aim was to reveal the effect of rolipram on the angiogenesis and neuronal apoptosis following brain cerebral ischemia. Rat models of ischemic stroke were established following transient middle cerebral artery occlusion and rolipram was administered for three, seven and 14 days. The results were examined using behavioral tests, triphenyl tetrazolium chloride staining, immunostaining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) to evaluate the effects of rolipram therapy on functional outcome, angiogenesis and apoptosis. Western blot analysis was used to show the phosphorylated- (p-)CREB protein level in the ischemic hemisphere. The rolipram treatment group exhibited a marked reduction in infarct size and modified neurological severity score compared with the vehicle group, and rolipram treatment significantly promoted the microvessel density in the ischemic boundary region and increased p-CREB protein levels in the ischemic hemisphere. Furthermore, a significant reduction in the number of TUNEL-positive cells was observed in the rolipram group compared with the vehicle group. These findings suggest that rolipram has the ability to attenuate cerebral ischemic injury, stimulate angiogenesis and reduce neuronal apoptosis though the cAMP/CREB pathway. PMID:26998028

  18. Imaging acute ischemic stroke.

    PubMed

    González, R Gilberto; Schwamm, Lee H

    2016-01-01

    Acute ischemic stroke is common and often treatable, but treatment requires reliable information on the state of the brain that may be provided by modern neuroimaging. Critical information includes: the presence of hemorrhage; the site of arterial occlusion; the size of the early infarct "core"; and the size of underperfused, potentially threatened brain parenchyma, commonly referred to as the "penumbra." In this chapter we review the major determinants of outcomes in ischemic stroke patients, and the clinical value of various advanced computed tomography and magnetic resonance imaging methods that may provide key physiologic information in these patients. The focus is on major strokes due to occlusions of large arteries of the anterior circulation, the most common cause of a severe stroke syndrome. The current evidence-based approach to imaging the acute stroke patient at the Massachusetts General Hospital is presented, which is applicable for all stroke types. We conclude with new information on time and stroke evolution that imaging has revealed, and how it may open the possibilities of treating many more patients. PMID:27432672

  19. The relevance of hemodynamic factors to perioperative ischemic complications in childhood moyamoya disease.

    PubMed

    Iwama, T; Hashimoto, N; Yonekawa, Y

    1996-06-01

    Of 124 children younger than 15 years who underwent surgery for moyamoya disease, 21 (16.9%) experienced perioperative ischemic complications that could not be unequivocally attributed to the surgery. Eleven of the 21 patients experienced infarctions, and 10 experienced reversible ischemic neurological deficits without new lesions, as revealed by computed tomographic scans. An examination of the patients' perioperative clinical and laboratory data revealed that the mean values of intra- and postoperative minimum arterial carbon dioxide pressure, maximum arterial carbon dioxide pressure, and mean arterial pressure were similar in patients with and without ischemic complications. However, in patients with perioperative complications, the incidence of preoperative transient ischemic attacks (TIAs) and intra- and postoperative hypercapnia (maximum arterial carbon dioxide pressure > 45 mm Hg) was significantly higher. In addition, 7 of the 11 perioperative infarctions occurred in patients with frequent preoperative TIAs and intra- and postoperative hypercapnia. Cerebral blood flow studies with preoperative acetazolamide loading showed that the new infarctions were located in areas in which the cerebral blood flow had been compromised. Our results suggest that the occurrence of frequent preoperative TIA is an important indicator of the instability of the cerebral hemodynamics and of the risk of perioperative ischemic complications. To prevent these complications, preoperative management aimed at stabilizing the hemodynamic status is very important. Children who have moyamoya disease and who experience frequent preoperative TIAs are at risk for ischemic brain damage caused by hypercapnia as well as hypocapnia and hypotension. The establishment and maintenance of normocapnia with normotension are highly desirable for the perioperative management of moyamoya disease in children.

  20. Breakthrough: new guidance for silent cerebral ischemia and infarction in sickle cell disease.

    PubMed

    Quinn, Charles T

    2014-12-01

    Silent cerebral infarction (SCI) is a highly prevalent and morbid condition in sickle cell disease (SCD). SCI can occur beginning in the first year of life and becomes more common with increasing age. Potentially modifiable risk factors for SCI include anemia and blood pressure. Headache does not appear to be associated with SCI, so neurologically normal children with headache do not necessarily warrant screening MRI for SCI. SCI does affect cognition, but biological determinants of cognition are not more important than socioeconomic factors. The recent identification of acute silent cerebral ischemic events indicates that the total burden of ischemic injury to the brain in SCD is far greater than previously realized. Acute anemic events appear to increase the risk of acute silent cerebral ischemic events and SCI dramatically. The medical management of SCI is not yet defined, but documentation of the presence of SCI may qualify affected individuals for special resources because comprehensive interventions are needed to optimize patients' academic and vocational outcomes.

  1. Hypothermia inhibits the propagation of acute ischemic injury by inhibiting HMGB1.

    PubMed

    Lee, Jung Ho; Yoon, Eun Jang; Seo, Jeho; Kavoussi, Adriana; Chung, Yong Eun; Chung, Sung Phil; Park, Incheol; Kim, Chul Hoon; You, Je Sung

    2016-01-01

    Acute ischemic stroke causes significant chronic disability worldwide. We designed this study to clarify the mechanism by which hypothermia helps alleviate acute ischemic stroke. In a middle cerebral artery occlusion model (4 h ischemia without reperfusion), hypothermia effectively reduces mean infarct volume. Hypothermia also prevents neurons in the infarct area from releasing high mobility group box 1 (HMGB1), the most well-studied damage-associated molecular pattern protein. By preventing its release, hypothermia also prevents the typical middle cerebral artery occlusion-induced increase in serum HMGB1. We also found that both glycyrrhizin-mediated inhibition of HMGB1 and intracerebroventricular neutralizing antibody treatments before middle cerebral artery occlusion onset diminish infarct volume. This suggests a clear neuroprotective effect of HMGB1 inhibition by hypothermia in the brain. We next used real-time polymerase chain reaction to measure the levels of pro-inflammatory cytokines in peri-infarct regions. Although middle cerebral artery occlusion increases the expression of interleukin-1β and tissue necrosis factor-α, this elevation is suppressed by both hypothermia and glycyrrhizin treatment. We show that hypothermia reduces the production of inflammatory cytokines and helps salvage peri-infarct regions from the propagation of ischemic injury via HMGB1 blockade. In addition to suggesting a potential mechanism for hypothermia's therapeutic effects, our results suggest HMGB1 modulation may lengthen the therapeutic window for stroke treatments. PMID:27544687

  2. Augmenting collateral blood flow during ischemic stroke via transient aortic occlusion

    PubMed Central

    Winship, Ian R; Armitage, Glenn A; Ramakrishnan, Gomathi; Dong, Bin; Todd, Kathryn G; Shuaib, Ashfaq

    2014-01-01

    Collateral circulation provides an alternative route for blood flow to reach ischemic tissue during a stroke. Blood flow through the cerebral collaterals is a critical predictor of clinical prognosis after stroke and response to recanalization, but data on collateral dynamics and collateral therapeutics are lacking. Here, we investigate the efficacy of a novel approach to collateral blood flow augmentation to increase collateral circulation by optically recording blood flow in leptomeningeal collaterals in a clinically relevant model of ischemic stroke. Using high-resolution laser speckle contrast imaging (LSCI) during thromboembolic middle cerebral artery occlusion (MCAo), we demonstrate that transiently diverting blood flow from peripheral circulation towards the brain via intra-aortic catheter and balloon induces persistent increases in blood flow through anastomoses between the anterior and middle cerebral arteries. Increased collateral flow restores blood flow in the distal middle cerebral artery segments to baseline levels during aortic occlusion and persists for over 1 hour after removal of the aortic balloon. Given the importance of collateral circulation in predicting stroke outcome and response to treatment, and the potential of collateral flow augmentation as an adjuvant or stand-alone therapy for acute ischemic stroke, this data provide support for further development and translation of collateral therapeutics including transient aortic occlusion. PMID:24045399

  3. Safety of early initiation of rivaroxaban or dabigatran after thrombolysis in acute ischemic stroke.

    PubMed

    Ritzenthaler, T; Derex, L; Davenas, C; Bnouhanna, W; Farghali, A; Mechtouff, L; Cho, T-H; Nighoghossian, N

    2015-09-01

    The introduction of direct oral anticoagulants (DOA) in the early stage of cerebral infarction after thrombolysis may reduce the recurrence rate but raises safety concern. We sought to study the feasibility and safety of the introduction of rivaroxaban or dabigatran in this context. Thirty-four consecutive patients admitted for ischemic stroke related to non-valvular atrial fibrillation in whom DOA were given within the first two weeks following intravenous rt-PA were studied. A clinical and radiological monitoring protocol was established to ensure the safety of the prescription. None of the patients experienced symptomatic hemorrhagic transformation or a symptomatic recurrent ischemic event after early rivaroxaban or dabigatran introduction.

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

    SciTech Connect

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

    1982-04-01

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

  5. Lipocalin-2 as an Infection-Related Biomarker to Predict Clinical Outcome in Ischemic Stroke

    PubMed Central

    Hochmeister, Sonja; Engel, Odilo; Adzemovic, Milena Z.; Pekar, Thomas; Kendlbacher, Paul; Zeitelhofer, Manuel; Haindl, Michaela; Meisel, Andreas; Fazekas, Franz; Seifert-Held, Thomas

    2016-01-01

    Objectives From previous data in animal models of cerebral ischemia, lipocalin-2 (LCN2), a protein related to neutrophil function and cellular iron homeostasis, is supposed to have a value as a biomarker in ischemic stroke patients. Therefore, we examined LCN2 expression in the ischemic brain in an animal model and measured plasma levels of LCN2 in ischemic stroke patients. Methods In the mouse model of transient middle cerebral artery occlusion (tMCAO), LCN2 expression in the brain was analyzed by immunohistochemistry and correlated to cellular nonheme iron deposition up to 42 days after tMCAO. In human stroke patients, plasma levels of LCN2 were determined one week after ischemic stroke. In addition to established predictive parameters such as age, National Institutes of Health Stroke Scale and thrombolytic therapy, LCN2 was included into linear logistic regression modeling to predict clinical outcome at 90 days after stroke. Results Immunohistochemistry revealed expression of LCN2 in the mouse brain already at one day following tMCAO, and the amount of LCN2 subsequently increased with a maximum at 2 weeks after tMCAO. Accumulation of cellular nonheme iron was detectable one week post tMCAO and continued to increase. In ischemic stroke patients, higher plasma levels of LCN2 were associated with a worse clinical outcome at 90 days and with the occurrence of post-stroke infections. Conclusions LCN2 is expressed in the ischemic brain after temporary experimental ischemia and paralleled by the accumulation of cellular nonheme iron. Plasma levels of LCN2 measured in patients one week after ischemic stroke contribute to the prediction of clinical outcome at 90 days and reflect the systemic response to post-stroke infections. PMID:27152948

  6. [Cerebrolysin for acute ischemic stroke].

    PubMed

    iganshina, L E; Abakumova, T R

    2013-01-01

    The review discusses existing evidence of benefits and risks of cerebrolysin--a mixture of low-molecular-weight peptides and amino acids derived from pigs' brain tissue with proposed neuroprotective and neurotrophic properties, for acute ischemic stroke. The review presents results of systematic search and analysis of randomised clinical trials comparing cerebrolysin with placebo in patients with acute ischemic stroke. Only one trial was selected as meeting quality criteria. No difference in death and adverse events between cerebrolysin and placebo was established. The authors conclude about insufficiency of evidence to evaluate the effect of cerebrolysin on survival and dependency in people with acute ischemic stroke.

  7. Remote Ischemic Conditioning

    PubMed Central

    Heusch, Gerd; Bøtker, Hans Erik; Przyklenk, Karin; Redington, Andrew; Yellon, Derek

    2014-01-01

    In remote ischemic conditioning (RIC) brief, reversible episodes of ischemia with reperfusion in one vascular bed, tissue or organ confer a global protective phenotype and render remote tissues and organs resistant to ischemia/reperfusion injury. The peripheral stimulus can be chemical, mechanical or electrical and involves activation of peripheral sensory nerves. The signal transfer to the heart or other organs is through neuronal and humoral communications. Protection can be transferred, even across species, with plasma-derived dialysate and involves nitric oxide, stromal derived factor-1α, microRNA-144, but also other, not yet identified factors. Intracardiac signal transduction involves: adenosine, bradykinin, cytokines, and chemokines, which activate specific receptors; intracellular kinases; and mitochondrial function. RIC by repeated brief inflation/deflation of a blood pressure cuff protects against endothelial dysfunction and myocardial injury in percutaneous coronary interventions, coronary artery bypass grafting and reperfused acute myocardial infarction. RIC is safe and effective, noninvasive, easily feasible and inexpensive. PMID:25593060

  8. Ischemic bowel disease

    PubMed Central

    Castelli, M. F.; Qizilbash, A. H.; Salem, S.; Fyshe, T. G.

    1974-01-01

    The clinical, radiologic and pathologic features of 25 cases of ischemic bowel disease are presented. The majority of patients presented with the triad of abdominal pain, diarrhea and vomiting. In 13 patients the diarrhea was associated with the passage of bright red blood per rectum. There were 10 cases of infarction, 11 of enterocolitis and 4 had resulted in stricture formation. In five cases of enterocolitis the lesion was transient; symptoms improved with conservative medical management and the radiologic findings returned to normal. Barium enema examination yielded abnormal findings in the majority of the cases in which it was performed. Plain films of the abdomen, however, were not helpful. The actual mortality in this group of patients was 44%, 80% in those with infarction of the bowel and 20% in the other two groups. ImagesFIG. 1FIG. 2FIG. 3FIG. 4FIG. 5FIG. 6FIG. 7 PMID:4419659

  9. Protective effect of Spatholobus suberectus on brain tissues in cerebral ischemia

    PubMed Central

    Zhang, Rui; Liu, Cui; Liu, Xuejun; Guo, Yunliang

    2016-01-01

    Cerebral ischemia is the major causes the neuronal damages throughout the world. Present investigation evaluates the neuroprotective effect of (SS) in cerebral ischemic rat. All the rats were separated in to four group such as control group, ischemia/reperfusion (I/R) group and Spatholobus suberectus (100 and 200 mg/kg, p.o.) treated group which receives extract for 15 days prior to I/R. At the end of protocol all the rats were sacrificed and brain was isolated for the biochemical estimation. Further, oxidative stress was estimated by measuring the level of malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD) and glutathione peroxidase (GPX) in the brain tissue. Moreover other parameters like cytokine (IL-10 and TNF-α), nuclear factor kappa B p65 (NF-κB), caspase 3, brain ATP level and DNA damage by comet assay was estimated in the brain tissues of cerebral ischemic rats. Result of the study suggested that treatment with Spatholobus suberectus significantly (P<0.01) decreases the MDA and NO level and increases in the activity of SOD and GPX in the brain tissues of cerebral ischemic rats compared to I/R rats. Moreover, treatment with SS significantly increases the expressions of IL-10 and brain ATP and decreases the expressions of TNF-α, caspase 3 and NF-κB in the brain tissues of cerebral ischemic rats compared to I/R rats. Comet assay also postulates that SS treated rats brain shows less DNA damage than ischemic rats. Present study concludes the neuroprorective effect of Spatholobus suberectus in cerebral ischemic rats by its antioxidant, anti apoptotic and anti-inflammatory activity. PMID:27725876

  10. Proton-sensitive cation channels and ion exchangers in ischemic brain injury: new therapeutic targets for stroke?

    PubMed Central

    Leng, Tiandong; Shi, Yejie; Xiong, Zhi-Gang; Sun, Dandan

    2014-01-01

    Ischemic brain injury results from complicated cellular mechanisms. The present therapy for acute ischemic stroke is limited to thrombolysis with the recombinant tissue plasminogen activator (rtPA) and mechanical recanalization. Therefore, a better understanding of ischemic brain injury is needed for the development of more effective therapies. Disruption of ionic homeostasis plays an important role in cell death following cerebral ischemia. Glutamate receptor-mediated ionic imbalance and neurotoxicity have been well established in cerebral ischemia after stroke. However, non-NMDA receptor-dependent mechanisms, involving acid-sensing ion channel 1a (ASIC1a), transient receptor potential melastatin 7 (TRPM7), and Na+/H+ exchanger isoform 1 (NHE1), have recently emerged as important players in the dysregulation of ionic homeostasis in the CNS under ischemic conditions. These H+-sensitive channels and/or exchangers are expressed in the majority of cell types of the neurovascular unit. Sustained activation of these proteins causes excessive influx of cations, such as Ca2+, Na+, and Zn2+, and leads to ischemic reperfusion brain injury. In this review, we summarize recent pre-clinical experimental research findings on how these channels/exchangers are regulated in both in vitro and in vivo models of cerebral ischemia. The blockade or transgenic knockdown of these proteins was shown to be neuroprotective in these ischemia models. Taken together, these non-NMDA receptor-dependent mechanisms may serve as novel therapeutic targets for stroke intervention. PMID:24467911

  11. Vascular Protection Following Cerebral Ischemia and Reperfusion

    PubMed Central

    Palomares, Sara Morales; Cipolla, Marilyn J.

    2011-01-01

    Despite considerable research that has contributed to a better understanding of the pathophysiology of stroke, translation of this knowledge into effective therapies has largely failed. The only effective treatment for ischemic stroke is rapid recanalization of an occluded vessel by dissolving the clot with tissue plasminogen activator (tPA). However, stroke adversely affects vascular function as well that can cause secondary brain injury and limit treatment that depends on a patent vasculature. In middle cerebral arteries (MCA), ischemia/reperfusion (I/R) cause loss of myogenic tone, vascular paralysis, and endothelial dysfunction that can lead to loss of autoregulation. In contrast, brain parenchymal arterioles retain considerable tone during I/R that likely contributes to expansion of the infarct into the penumbra. Microvascular dysregulation also occurs during ischemic stroke that causes edema and hemorrhage, exacerbating the primary insult. Ischemic injury of vasculature is progressive with longer duration of I/R. Early postischemic reperfusion has beneficial effects on stroke outcome but can impair vascular function and exacerbate ischemic injury after longer durations of I/R. This review focuses on current knowledge on the effects of I/R on the structure and function of different vascular segments in the brain and highlight some of the more promising targets for vascular protection. PMID:22102980

  12. MRI of Blood–Brain Barrier Permeability in Cerebral Ischemia

    PubMed Central

    Ewing, James R.; Chopp, Michael

    2013-01-01

    Quantitative measurement of blood–brain barrier (BBB) permeability using MRI and its application to cerebral ischemia are reviewed. Measurement of BBB permeability using MRI has been employed to evaluate ischemic damage during acute and subacute phases of stroke and to predict hemorrhagic transformation. There is also an emerging interest on the development and use of MRI to monitor vascular structural changes and angiogenesis during stroke recovery. In this review, we describe MRI BBB permeability and susceptibility-weighted MRI measurements and its applications to evaluate ischemic damage during the acute and subacute phases of stroke and vascular remodeling during stroke recovery. PMID:23997835

  13. Employees with Cerebral Palsy

    MedlinePlus

    ... Resources Home | Accommodation and Compliance Series: Employees with Cerebral Palsy (CP) By Eddie Whidden, MA Preface Introduction Information About ... SOAR) at http://AskJAN.org/soar. Information about Cerebral Palsy (CP) What is CP? Cerebral palsy is a ...

  14. Cerebral Aneurysms Fact Sheet

    MedlinePlus

    ... Awards Enhancing Diversity Find People About NINDS Cerebral Aneurysms Fact Sheet See a list of all NINDS ... I get more information? What is a cerebral aneurysm? A cerebral aneurysm (also known as an intracranial ...

  15. Pravastatin acute neuroprotective effects depend on blood brain barrier integrity in experimental cerebral ischemia.

    PubMed

    Carone, D; Librizzi, L; Cattalini, A; Sala, G; Conti, E; Cuccione, E; Versace, A; Cai, R; Monza, L; de Curtis, M; Ferrarese, C; Beretta, S

    2015-07-30

    Statins have since long been reported to exert acute neuroprotection in experimental stroke models. However, crucial questions still need to be addressed as far as the timing of their cerebral effects after intravascular administration and the role played by the blood brain barrier (BBB) crossing properties. We tested the effects of an hydrophilic statin (pravastatin, 100 nM), which poorly crosses BBB under physiological conditions. Pravastatin was administered either 90 min before or immediately after transient middle cerebral artery occlusion in the in vitro isolated guinea pig brain preparation. A multi-modal outcome assessment was performed, through electrophysiological and cerebral vascular tone recordings, MAP-2 immunohistochemistry, BBB evaluation via ZO-1/FITC-albumin analysis, AKT and ERK activation and whole-cell antioxidant capacity. Pravastatin pre-ischemic administration did not produce any significant effect. Pravastatin post-ischemic administration significantly prevented MAP-2 immunoreactivity loss in ischemic areas, increased ERK phosphorylation in the ischemic hemisphere and enhanced whole-cell antioxidant capacity. Electrophysiological parameters, vascular tone and AKT signaling were unchanged. In all tested ischemic brains, ZO-1 fragmentation and FITC albumin extravasation was observed, starting 30 min from ischemia onset, indicating loss of BBB integrity. Our findings indicate that the rapid anti-ischemic effects of intravascular pravastatin are highly dependent on BBB increased permeability after stroke.

  16. Modulation of NADPH oxidase activation in cerebral ischemia/reperfusion injury in rats.

    PubMed

    Genovese, Tiziana; Mazzon, Emanuela; Paterniti, Irene; Esposito, Emanuela; Bramanti, Placido; Cuzzocrea, Salvatore

    2011-02-01

    NADPH oxidase is a major complex that produces reactive oxygen species (ROSs) during the ischemic period and aggravates brain damage and cell death after ischemic injury. Although many approaches have been tested for preventing production of ROSs by NADPH oxidase in ischemic brain injury, the regulatory mechanisms of NADPH oxidase activity after cerebral ischemia are still unclear. The aim of this study is identifying apocynin as a critical modulator of NADPH oxidase and elucidating its role as a neuroprotectant in an experimental model of brain ischemia in rat. Treatment of apocynin 5min before of reperfusion attenuated cerebral ischemia in rats. Administration of apocynin showed marked reduction in infarct size compared with that of control rats. Medial carotid artery occlusion (MCAo)-induced cerebral ischemia was also associated with an increase in, nitrotyrosine formation, as well as IL-1β expression, IκB degradation and ICAM expression in ischemic regions. These expressions were markedly inhibited by the treatment of apocynin. We also demonstrated that apocynin reduces levels of apoptosis (TUNEL, Bax and Bcl-2 expression) resulting in a reduction in the infarct volume in ischemia-reperfusion brain injury. This new understanding of apocynin induced adaptation to ischemic stress and inflammation could suggest novel avenues for clinical intervention during ischemic and inflammatory diseases. PMID:21138737

  17. [A case of Behçet disease developing recurrent ischemic stroke with fever and scrotal ulcers].

    PubMed

    Koike, Yuka; Sakai, Naoko; Umeda, Yoshitaka; Umeda, Maiko; Oyake, Mutsuo; Fujita, Nobuya

    2015-01-01

    A 30-year-old man, who was diagnosed with Behçet disease at 10 years of age, was hospitalized because of transient right hemiparesis after presenting with high fever and scrotal ulcers. Brain MRI revealed ischemic lesions in the area supplied by the anterior cerebral arteries. Analysis of cerebrospinal fluid (CSF) showed pleocytosis and a high interleukin-6 (IL-6) concentration (668 pg/ml). The patient was diagnosed with acute ischemic stroke associated with exacerbation of Behçet disease. After initiation of corticosteroid therapy, his clinical symptoms improved, and the CSF IL-6 concentration decreased. One year later, the patient developed high fever and scrotal ulcers after the onset of transient left upper limb plegia. Brain MRI showed an acute ischemic lesion in the right putamen, and CSF analysis showed an elevated IL-6 concentration (287 pg/ml). Brain CT angiography revealed stenosis of the left anterior cerebral artery and occlusion of the right anterior cerebral artery, which had been well visualized one year previously. Involvement of the intracranial cerebral arteries in Behçet disease is extremely rare. To the best of our knowledge, this is the first case report of a patient with recurrent symptomatic ischemic stroke associated with high fever and scrotal ulcers, which suggests exacerbation of Behçet disease.

  18. Complications following transfemoral cerebral angiography for cerebral ischemia. Report of 159 angiograms and correlation with surgical risk.

    PubMed

    Theodotou, B C; Whaley, R; Mahaley, M S

    1987-08-01

    One hundred fifty-nine transfemoral cerebral angiograms for patients with carotid stenosis who subsequently underwent carotid endarterectomy were reviewed. No patient with an asymptomatic carotid bruit developed cerebrovascular complications during angiography. Patients with transient ischemic attacks (TIAs) had a 4.5% incidence of complications. Patients with stroke in evolution had a complication rate of 7.7%. Patients with completed strokes had no angiographic complications. No complication lasted more than 1 hour; all occurred during angiography or immediately afterwards. Stroke in progress has too high a surgical and angiographic risk to warrant study. Transient ischemic attacks have an acceptable morbidity both surgically and angiographically. PMID:3603359

  19. Preterm Hypoxic–Ischemic Encephalopathy

    PubMed Central

    Gopagondanahalli, Krishna Revanna; Li, Jingang; Fahey, Michael C.; Hunt, Rod W.; Jenkin, Graham; Miller, Suzanne L.; Malhotra, Atul

    2016-01-01

    Hypoxic–ischemic encephalopathy (HIE) is a recognizable and defined clinical syndrome in term infants that results from a severe or prolonged hypoxic–ischemic episode before or during birth. However, in the preterm infant, defining hypoxic–ischemic injury (HII), its clinical course, monitoring, and outcomes remains complex. Few studies examine preterm HIE, and these are heterogeneous, with variable inclusion criteria and outcomes reported. We examine the available evidence that implies that the incidence of hypoxic–ischemic insult in preterm infants is probably higher than recognized and follows a more complex clinical course, with higher rates of adverse neurological outcomes, compared to term infants. This review aims to elucidate the causes and consequences of preterm hypoxia–ischemia, the subsequent clinical encephalopathy syndrome, diagnostic tools, and outcomes. Finally, we suggest a uniform definition for preterm HIE that may help in identifying infants most at risk of adverse outcomes and amenable to neuroprotective therapies. PMID:27812521

  20. PACAP38/PAC1 Signaling Induces Bone Marrow-Derived Cells Homing to Ischemic Brain

    PubMed Central

    Lin, Chen-Huan; Chiu, Lian; Lee, Hsu-Tung; Chiang, Chun-Wei; Liu, Shih-Ping; Hsu, Yung-Hsiang; Lin, Shinn-Zong; Hsu, Chung Y; Hsieh, Chia-Hung; Shyu, Woei-Cherng

    2015-01-01

    Understanding stem cell homing, which is governed by environmental signals from the surrounding niche, is important for developing effective stem cell-based repair strategies. The molecular mechanism by which the brain under ischemic stress recruits bone marrow-derived cells (BMDCs) to the vascular niche remains poorly characterized. Here we report that hypoxia-inducible factor-1α (HIF-1α) activation upregulates pituitary adenylate cyclase-activating peptide 38 (PACAP38), which in turn activates PACAP type 1 receptor (PAC1) under hypoxia in vitro and cerebral ischemia in vivo. BMDCs homing to endothelial cells in the ischemic brain are mediated by HIF-1α activation of the PACAP38-PAC1 signaling cascade followed by upregulation of cellular prion protein and α6-integrin to enhance the ability of BMDCs to bind laminin in the vascular niche. Exogenous PACAP38 confers a similar effect in facilitating BMDCs homing into the ischemic brain, resulting in reduction of ischemic brain injury. These findings suggest a novel HIF-1α-activated PACAP38-PAC1 signaling process in initiating BMDCs homing into the ischemic brain for reducing brain injury and enhancing functional recovery after ischemic stroke. Stem Cells 2015;33:1153–1172 PMID:25523790

  1. Interleukin-16 Polymorphism Is Associated with an Increased Risk of Ischemic Stroke

    PubMed Central

    Liu, Xiao-li; Du, Jian-zong; Zhou, Yu-miao; Shu, Qin-fen; Li, Ya-guo

    2013-01-01

    Clinical and experimental data have demonstrated that inflammation plays fundamental roles in the pathogenesis of ischemic stroke. Interleukin-16 (IL-16) is identified as a proinflammatory cytokine that is a key element in the ischemic cascade after cerebral ischemia. We aimed to examine the relationship between the IL-16 polymorphisms and the risk of ischemic stroke in a Chinese population. A total of 198 patients with ischemic stroke and 236 controls were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing method. We found that the rs11556218TG genotype and G allele of IL-16 were associated with significantly increased risks of ischemic stroke (TG versus TT, adjusted OR = 1.88; 95% CI, 1.15–3.07; G versus T, adjusted OR = 1.54; 95% CI, 1.05–2.27, resp.). However, there were no significant differences in the genotype and allele frequencies of IL-16 rs4778889 T/C and rs4072111 C/T polymorphisms between the two groups, even after stratification analyses by age, gender, and the presence or absence of hypertension, diabetes mellitus, hypercholesterolemia, and hypertriglyceridemia. These findings indicate that the IL-16 polymorphism may be related to the etiology of ischemic stroke in the Chinese population. PMID:24288444

  2. Systematic investigation of transcription factors critical in the protection against cerebral ischemia by Danhong injection.

    PubMed

    Wei, Junying; Zhang, Yanqiong; Jia, Qiang; Liu, Mingwei; Li, Defeng; Zhang, Yi; Song, Lei; Hu, Yanzhen; Xian, Minghua; Yang, Hongjun; Ding, Chen; Huang, Luqi

    2016-01-01

    Systematic investigations of complex pathological cascades during ischemic brain injury help to elucidate novel therapeutic targets against cerebral ischemia. Although some transcription factors (TFs) involved in cerebral ischemia, systematic surveys of their changes during ischemic brain injury have not been reported. Moreover, some multi-target agents effectively protected against ischemic stroke, but their mechanisms, especially the targets of TFs, are still unclear. Therefore, a comprehensive approach by integrating network pharmacology strategy and a new concatenated tandem array of consensus transcription factor response elements method to systematically investigate the target TFs critical in the protection against cerebral ischemia by a medication was first reported, and then applied to a multi-target drug, Danhong injection (DHI). High-throughput nature and depth of coverage, as well as high quantitative accuracy of the developed approach, make it more suitable for analyzing such multi-target agents. Results indicated that pre-B-cell leukemia transcription factor 1 and cyclic AMP-dependent transcription factor 1, along with six other TFs, are putative target TFs for DHI-mediated protection against cerebral ischemia. This study provides, for the first time, a systematic investigation of the target TFs critical to DHI-mediated protection against cerebral ischemia, as well as reveals more potential therapeutic targets for ischemic stroke. PMID:27431009

  3. Systematic investigation of transcription factors critical in the protection against cerebral ischemia by Danhong injection

    PubMed Central

    Wei, Junying; Zhang, Yanqiong; Jia, Qiang; Liu, Mingwei; Li, Defeng; Zhang, Yi; Song, Lei; Hu, Yanzhen; Xian, Minghua; Yang, Hongjun; Ding, Chen; Huang, Luqi

    2016-01-01

    Systematic investigations of complex pathological cascades during ischemic brain injury help to elucidate novel therapeutic targets against cerebral ischemia. Although some transcription factors (TFs) involved in cerebral ischemia, systematic surveys of their changes during ischemic brain injury have not been reported. Moreover, some multi-target agents effectively protected against ischemic stroke, but their mechanisms, especially the targets of TFs, are still unclear. Therefore, a comprehensive approach by integrating network pharmacology strategy and a new concatenated tandem array of consensus transcription factor response elements method to systematically investigate the target TFs critical in the protection against cerebral ischemia by a medication was first reported, and then applied to a multi-target drug, Danhong injection (DHI). High-throughput nature and depth of coverage, as well as high quantitative accuracy of the developed approach, make it more suitable for analyzing such multi-target agents. Results indicated that pre-B-cell leukemia transcription factor 1 and cyclic AMP-dependent transcription factor 1, along with six other TFs, are putative target TFs for DHI-mediated protection against cerebral ischemia. This study provides, for the first time, a systematic investigation of the target TFs critical to DHI-mediated protection against cerebral ischemia, as well as reveals more potential therapeutic targets for ischemic stroke. PMID:27431009

  4. Vascular remodeling after ischemic stroke: mechanisms and therapeutic potentials

    PubMed Central

    Liu, Jialing; Wang, Yongting; Akamatsu, Yosuke; Lee, Chih Cheng; Stetler, R Anne; Lawton, Michael T.; Yang, Guo-Yuan

    2014-01-01

    The brain vasculature has been increasingly recognized as a key player that directs brain development, regulates homeostasis, and contributes to pathological processes. Following ischemic stroke, the reduction of blood flow elicits a cascade of changes and leads to vascular remodeling. However, the temporal profile of vascular changes after stroke is not well understood. Growing evidence suggests that the early phase of cerebral blood volume (CBV) increase is likely due to the improvement in collateral flow, also known as arteriogenesis, whereas the late phase of CBV increase is attributed to the surge of angiogenesis. Arteriogenesis is triggered by shear fluid stress followed by activation of endothelium and inflammatory processes, while angiogenesis induces a number of pro-angiogenic factors and circulating endothelial progenitor cells (EPCs). The status of collaterals in acute stroke has been shown to have several prognostic implications, while the causal relationship between angiogenesis and improved functional recovery has yet to be established in patients. A number of interventions aimed at enhancing cerebral blood flow including increasing collateral recruitment are under clinical investigation. Transplantation of EPCs to improve angiogenesis is also underway. Knowledge in the underlying physiological mechanisms for improved arteriogenesis and angiogenesis shall lead to more effective therapies for ischemic stroke. PMID:24291532

  5. Thrombin exacerbates brain edema in focal cerebral ischemia.

    PubMed

    Hua, Y; Wu, J; Keep, R F; Hoff, J T; Xi, G

    2003-01-01

    Thrombin contributes to edema formation after intracerebral hemorrhage. Recent studies suggest that thrombin may also play a role in ischemic brain damage. In the present study, adult male Sprague-Dawley rats were anesthetized with pentobarbital. Middle cerebral artery (MCA) was occluded using the suture method. We found that brain thrombin activity was elevated after permanent MCA occlusion as was prothrombin messenger RNA expression. Intracerebral injection of a thrombin inhibitor, hirudin, reduced neurological deficits following cerebral ischemia. In contrast, intracerebral administration of exogenous thrombin (at a dose that is non-toxic to normal brain), markedly exacerbated brain edema after transient focal cerebral ischemia. These results indicate that extravascular thrombin inhibition may be a new therapeutic target for cerebral ischemia.

  6. Giant serpentine aneurysm of the distal anterior cerebral artery.

    PubMed

    Senbokuya, Nobuo; Kanemaru, Kazuya; Kinouchi, Hiroyuki; Horikoshi, Toru

    2012-11-01

    We report a case of a 38-year-old man with a giant serpentine aneurysm arising from the distal anterior cerebral artery. This aneurysm grew from a fusiform aneurysm to a huge aneurysm within 5 months before manifesting as a mass lesion. The aneurysm was largely filled with thrombus, and 4 distal branches arose from the aneurysm dome. Selective balloon test occlusion of the distal anterior cerebral artery using an intravascular technique was performed to confirm the tolerance of the brain tissue. The balloon test occlusion elicited adequate leptomeningeal collateral circulation and no neurologic symptoms; thus, the aneurysm was treated with trapping and resection. The patient had no ischemic complications after the surgery and returned to his job 1 month later. No ischemia developed in the 2 years after surgery. Selective balloon test occlusion of the distal cerebral artery using an intravascular technique can be a very useful tool in planning the therapeutic strategy for a complicated distal cerebral aneurysm.

  7. Vesicular antioxidants: role in age-related cerebral oxidative injury.

    PubMed

    Sarkar, Sibani; Mandal, Ardhendu Kumar; Das, Nirmalendu

    2013-01-01

    Oxidative stress, due to the generation of reactive oxygen species, is a major factor in cerebral ischemic damage and changes the activities of antioxidant enzymes and substantially influences the aging process. Free chemical antioxidant is almost ineffective to treat brain ischemia as blood-brain barrier exists in between blood and brain interstitial fluid, limiting component to pass from the circulation into cerebral region. Different compounds have been tested in vivo in different vesiculated forms to prevent cerebral ischemia. Nanoparticle-encapsulated drug treatment resulted in a significant protection of the antioxidant enzymes in both young and old rats. Nanocapsulated drug treatment causes a substantial protection against cerebral ischemia-reperfusion-induced oxidative damage to all parts of brain specifically hippocampal regions of all age groups of rat brain. PMID:23740123

  8. Cerebral salt-wasting syndrome due to hemorrhagic brain infarction: a case report

    PubMed Central

    2014-01-01

    Introduction Cerebral salt-wasting syndrome is a condition featuring hyponatremia and dehydration caused by head injury, operation on the brain, subarachnoid hemorrhage, brain tumor and so on. However, there are a few reports of cerebral salt-wasting syndrome caused by cerebral infarction. We describe a patient with cerebral infarction who developed cerebral salt-wasting syndrome in the course of hemorrhagic transformation. Case presentation A 79-year-old Japanese woman with hypertension and arrhythmia was admitted to our hospital for mild consciousness disturbance, conjugate deviation to right, left unilateral spatial neglect and left hemiparesis. Magnetic resonance imaging revealed a broad ischemic change in right middle cerebral arterial territory. She was diagnosed as cardiogenic cerebral embolism because atrial fibrillation was detected on electrocardiogram on admission. She showed hyponatremia accompanied by polyuria complicated at the same time with the development of hemorrhagic transformation on day 14 after admission. Based on her hypovolemic hyponatremia, she was evaluated as not having syndrome of inappropriate secretion of antidiuretic hormone but cerebral salt-wasting syndrome. She fortunately recovered with proper fluid replacement and electrolyte management. Conclusions This is a rare case of cerebral infarction and cerebral salt-wasting syndrome in the course of hemorrhagic transformation. It may be difficult to distinguish cerebral salt-wasting syndrome from syndrome of inappropriate antidiuretic hormone, however, an accurate assessment is needed to reveal the diagnosis of cerebral salt-wasting syndrome because the recommended fluid management is opposite in the two conditions. PMID:25055823

  9. Carotid endarterectomy and prevention of cerebral ischemia in symptomatic carotid stenosis

    SciTech Connect

    Mayberg, M.R.; Eskridge, J.; Winn, H.R.; Eskridge, J. ); Wilson, S.E. ); Yatsu, F. ); Weiss, D.G. ); Messina, L. ); Hershey, L.A. ); Colling, C. ); Deykin, D. )

    1991-12-18

    The objective of this study was to determine whether carotid endarterectomy provides protection against subsequent cerebral ischemia in men with ischemic symptoms in the distribution of significant ipsilateral internal carotid artery stenosis. The study group was comprised of men who presented within 120 days of onset of symptoms that were consistent with transient ischemic attacks, transient monocular blindness, or recent small completed strokes between July 1988 and February 1991. Among 5,000 patients screened, 189 individuals were randomized with angiographic internal carotid artery stenosis greater than 50% ipsilateral to the presenting symptoms. Forty-eight eligible patients who refused entry were followed up outside of the trial. For a selected cohort of men with symptoms of cerebral or retinal ischemia in the distribution of a high-grade internal carotid artery stenosis, carotid endarterectomy can effectively reduce the risk of subsequent ipsilateral cerebral ischemia. The risk of cerebral ischemia in this subgroup of patients is considerably higher than previously estimated.

  10. Moyamoya syndrome associated with γ knife surgery for cerebral arteriovenous malformation: case report.

    PubMed

    Uozumi, Yoichi; Sumitomo, Masaki; Maruwaka, Mikio; Araki, Yoshio; Izumi, Takashi; Miyachi, Shigeru; Kato, Takenori; Hasegawa, Toshinori; Kida, Yoshihisa; Okamoto, Sho; Wakabayashi, Toshihiko

    2012-01-01

    A 30-year-old female developed moyamoya syndrome after gamma knife surgery (GKS) for cerebral arteriovenous malformation (AVM), and was treated with bypass surgery. She suffered from flittering scotoma, right transient hemianopsia, and headache for 1 year. Cerebral angiography revealed a Spetzler-Martin grade III AVM located in the left occipital lobe. After staged embolization, GKS was performed with a minimum dose of 20 Gy to the periphery of the nidus at the 50% isodose level of the maximum target dose. Gradual nidus regression was achieved, and the clinical symptoms disappeared completely. However, at 30 months after GKS, the patient suffered transient ischemic attack. Cerebral angiography showed left middle cerebral artery occlusion with moyamoya vessels. The patient underwent direct and indirect bypass surgery. After surgery, the patient was free from ischemic symptoms. Chronic inflammation and long-term changes in expression of cytokines and growth factors after GKS may have triggered this case.

  11. Malignant Hemispheric Cerebral Infarction Associated with Idiopathic Systemic Capillary Leak Syndrome

    PubMed Central

    Miyata, Kei; Mikami, Takeshi; Mikuni, Nobuhiro; Aisaka, Wakiko; Irifune, Hideto; Narimatsu, Eichi

    2013-01-01

    Idiopathic systemic capillary leak syndrome (ISCLS) is a rare condition that is characterized by unexplained episodic capillary hyperpermeability due to a shift of fluid and protein from the intravascular to the interstitial space. This results in diffuse general swelling, fetal hypovolemic shock, hypoalbuminemia, and hemoconcentration. Although ISCLS rarely induces cerebral infarction, we experienced a patient who deteriorated and was comatose as a result of massive cerebral infarction associated with ISCLS. In this case, severe hypotensive shock, general edema, hemiparesis, and aphasia appeared after serious antecedent gastrointestinal symptoms. Progressive life-threatening ischemic cerebral edema required decompressive hemicraniectomy. The patient experienced another episode of severe hypotension and limb edema that resulted in multiple extremity compartment syndrome. Treatment entailed forearm and calf fasciotomies. Cerebral edema in the ischemic brain progresses rapidly in patients suffering from ISCLS. Strict control of fluid volume resuscitation and aggressive diuretic therapy may be needed during the post-leak phase of fluid remobilization. PMID:24163674

  12. Effectiveness of CT Computed Tomography Perfusion in Diagnostics of Acute Ischemic Stroke

    PubMed Central

    Menzilcioglu, Mehmet Sait; Mete, Ahmet; Ünverdi, Zeyni

    2015-01-01

    Summary Background Stroke is the third most common death reason after the cardiovascular disorders and cancer. Cerebral ischemia is a pathology that stems from a decrease in cerebral perfusion. Computed Tomography Perfusion (CTP) is an additional method to the conventional Computed Tomography (CT) that could be performed by using developed softwares, in a short period of time and with a low risk of complications. CTP not only allows early detection of cerebral ischemia but also gives valuable information on the ischemic penumbra which are very important in early diagnosis and treatment. Acute Ischemic Stroke (AIS) can be cured by trombolytic treapy within 3–6 hours after symptom onset. Since rapid screening and accurate diagnosis increase the success of the treatment, the role of neuroradiology in acute ischemia diagnostics and treatment has become more important. Our aim was to define CT skills in early diagnosis of AIS, to define its contribution to patient’s diagnosis and treatment and to define its importance regarding patient’s prognosis. Material/Methods We included 42 patients that presented to the emergency service and neurology outpatient clinic with the symptoms of acute cerebral incidence. Results In our study, we found that Cerebral Blood Flow (CBF) is 90.91% sensitive and 100% specific in examining ischemia. Conclusions Tissue hemodynamic data, especially sensitivity and specificity rates, which cannot be acquired by conventional CT and MRI methods, can be acquired by the CTP method. PMID:26740827

  13. Brain microvascular endothelial cell transplantation ameliorates ischemic white matter damage.

    PubMed

    Puentes, Sandra; Kurachi, Masashi; Shibasaki, Koji; Naruse, Masae; Yoshimoto, Yuhei; Mikuni, Masahiko; Imai, Hideaki; Ishizaki, Yasuki

    2012-08-21

    Ischemic insults affecting the internal capsule result in sensory-motor disabilities which adversely affect the patient's life. Cerebral endothelial cells have been reported to exert a protective effect against brain damage, so the transplantation of healthy endothelial cells might have a beneficial effect on the outcome of ischemic brain damage. In this study, endothelin-1 (ET-1) was injected into the rat internal capsule to induce lacunar infarction. Seven days after ET-1 injection, microvascular endothelial cells (MVECs) were transplanted into the internal capsule. Meningeal cells or 0.2% bovine serum albumin-Hank's balanced salt solution were injected as controls. Two weeks later, the footprint test and histochemical analysis were performed. We found that MVEC transplantation improved the behavioral outcome based on recovery of hind-limb rotation angle (P<0.01) and induced remyelination (P<0.01) compared with the control groups. Also the inflammatory response was repressed by MVEC transplantation, judging from fewer ED-1-positive activated microglial cells in the MVEC-transplanted group than in the other groups. Elucidation of the mechanisms by which MVECs ameliorate ischemic damage of the white matter may provide important information for the development of effective therapies for white matter ischemia.

  14. Brain microvascular endothelial cell transplantation ameliorates ischemic white matter damage.

    PubMed

    Puentes, Sandra; Kurachi, Masashi; Shibasaki, Koji; Naruse, Masae; Yoshimoto, Yuhei; Mikuni, Masahiko; Imai, Hideaki; Ishizaki, Yasuki

    2012-08-21

    Ischemic insults affecting the internal capsule result in sensory-motor disabilities which adversely affect the patient's life. Cerebral endothelial cells have been reported to exert a protective effect against brain damage, so the transplantation of healthy endothelial cells might have a beneficial effect on the outcome of ischemic brain damage. In this study, endothelin-1 (ET-1) was injected into the rat internal capsule to induce lacunar infarction. Seven days after ET-1 injection, microvascular endothelial cells (MVECs) were transplanted into the internal capsule. Meningeal cells or 0.2% bovine serum albumin-Hank's balanced salt solution were injected as controls. Two weeks later, the footprint test and histochemical analysis were performed. We found that MVEC transplantation improved the behavioral outcome based on recovery of hind-limb rotation angle (P<0.01) and induced remyelination (P<0.01) compared with the control groups. Also the inflammatory response was repressed by MVEC transplantation, judging from fewer ED-1-positive activated microglial cells in the MVEC-transplanted group than in the other groups. Elucidation of the mechanisms by which MVECs ameliorate ischemic damage of the white matter may provide important information for the development of effective therapies for white matter ischemia. PMID:22771710

  15. Bone marrow mesenchymal stem cell therapy in ischemic stroke: mechanisms of action and treatment optimization strategies.

    PubMed

    Li, Guihong; Yu, Fengbo; Lei, Ting; Gao, Haijun; Li, Peiwen; Sun, Yuxue; Huang, Haiyan; Mu, Qingchun

    2016-06-01

    Animal and clinical studies have confirmed the therapeutic effect of bone marrow mesenchymal stem cells on cerebral ischemia, but their mechanisms of action remain poorly understood. Here, we summarize the transplantation approaches, directional migration, differentiation, replacement, neural circuit reconstruction, angiogenesis, neurotrophic factor secretion, apoptosis, immunomodulation, multiple mechanisms of action, and optimization strategies for bone marrow mesenchymal stem cells in the treatment of ischemic stroke. We also explore the safety of bone marrow mesenchymal stem cell transplantation and conclude that bone marrow mesenchymal stem cell transplantation is an important direction for future treatment of cerebral ischemia. Determining the optimal timing and dose for the transplantation are important directions for future research. PMID:27482235

  16. Supratentorial arterial ischemic stroke following cerebellar tumor resection in two children.

    PubMed

    Catsman-Berrevoets, Coriene E; van Breemen, Melanie; van Veelen, Marie Lise; Appel, Inge M; Lequin, Maarten H

    2005-01-01

    We describe two children who developed ischemic strokes in the territory of the middle cerebral artery, one 7 days and one 11 days after resection of a cerebellar tumor. In the first child, another infarction occurred in the territory of the contralateral middle cerebral artery 5 days after the first stroke. No specific cause or underlying risk factor other than the surgical procedure was found. The subacute clinical course at stroke onset resembled that of the 'posterior fossa syndrome', suggesting a common underlying mechanism. PMID:16088257

  17. Bone marrow mesenchymal stem cell therapy in ischemic stroke: mechanisms of action and treatment optimization strategies

    PubMed Central

    Li, Guihong; Yu, Fengbo; Lei, Ting; Gao, Haijun; Li, Peiwen; Sun, Yuxue; Huang, Haiyan; Mu, Qingchun

    2016-01-01

    Animal and clinical studies have confirmed the therapeutic effect of bone marrow mesenchymal stem cells on cerebral ischemia, but their mechanisms of action remain poorly understood. Here, we summarize the transplantation approaches, directional migration, differentiation, replacement, neural circuit reconstruction, angiogenesis, neurotrophic factor secretion, apoptosis, immunomodulation, multiple mechanisms of action, and optimization strategies for bone marrow mesenchymal stem cells in the treatment of ischemic stroke. We also explore the safety of bone marrow mesenchymal stem cell transplantation and conclude that bone marrow mesenchymal stem cell transplantation is an important direction for future treatment of cerebral ischemia. Determining the optimal timing and dose for the transplantation are important directions for future research. PMID:27482235

  18. Cerebral Microdialysis.

    PubMed

    Young, Bethany; Kalanuria, Atul; Kumar, Monisha; Burke, Kathryn; Balu, Ramani; Amendolia, Olivia; McNulty, Kyle; Marion, BethAnn; Beckmann, Brittany; Ciocco, Lauren; Miller, Kimberly; Schuele, Donnamarie; Maloney-Wilensky, Eileen; Frangos, Suzanne; Wright, Danielle

    2016-03-01

    A variety of neuromonitoring techniques are available to aid in the care of neurocritically ill patients. However, traditional monitors lack the ability to measure brain biochemistry and may provide inadequate warning of potentially reversible deleterious conditions. Cerebral microdialysis (CMD) is a safe, novel method of monitoring regional brain biochemistry. Analysis of CMD analytes as part of a multimodal approach may help inform clinical decision making, guide medical treatments, and aid in prognostication of patient outcome. Its use is most frequently documented in traumatic brain injury and subarachnoid hemorrhage. Incorporating CMD into clinical practice is a multidisciplinary effort.

  19. Human neural stem cells promote proliferation of endogenous neural stem cells and enhance angiogenesis in ischemic rat brain

    PubMed Central

    Ryu, Sun; Lee, Seung-Hoon; Kim, Seung U.; Yoon, Byung-Woo

    2016-01-01

    Transplantation of human neural stem cells into the dentate gyrus or ventricle of rodents has been reportedly to enhance neurogenesis. In this study, we examined endogenous stem cell proliferation and angiogenesis in the ischemic rat brain after the transplantation of human neural stem cells. Focal cerebral ischemia in the rat brain was induced by middle cerebral artery occlusion. Human neural stem cells were transplanted into the subventricular zone. The behavioral performance of human neural stem cells-treated ischemic rats was significantly improved and cerebral infarct volumes were reduced compared to those in untreated animals. Numerous transplanted human neural stem cells were alive and preferentially localized to the ipsilateral ischemic hemisphere. Furthermore, 5-bromo-2′-deoxyuridine-labeled endogenous neural stem cells were observed in the subventricular zone and hippocampus, where they differentiated into cells immunoreactive for the neural markers doublecortin, neuronal nuclear antigen NeuN, and astrocyte marker glial fibrillary acidic protein in human neural stem cells-treated rats, but not in the untreated ischemic animals. The number of 5-bromo-2′-deoxyuridine-positive ⁄ anti-von Willebrand factor-positive proliferating endothelial cells was higher in the ischemic boundary zone of human neural stem cells-treated rats than in controls. Finally, transplantation of human neural stem cells in the brains of rats with focal cerebral ischemia promoted the proliferation of endogenous neural stem cells and their differentiation into mature neural-like cells, and enhanced angiogenesis. This study provides valuable insights into the effect of human neural stem cell transplantation on focal cerebral ischemia, which can be applied to the development of an effective therapy for stroke. PMID:27073384

  20. [A case of cerebral embolism due to cardiac myxoma presenting with multiple cerebral microaneurysms detected on first MRI scans].

    PubMed

    Sato, Takahiro; Saji, Naoki; Kobayashi, Kazuto; Shibazaki, Kensaku; Kimura, Kazumi

    2016-01-01

    A 64-year-old man developed right arm weakness and dysarthria, and was admitted to our hospital. Diffusion-weighted magnetic resonance imaging of the brain showed a high intensity area in the frontal lobe. T2*-weighted images showed multiple spotty low intensity lesions in bilateral cerebral hemispheres, mimicking cerebral microbleeds. Cerebral angiography showed multiple aneurysms in the anterior, middle, posterior cerebral arteries and cerebellar arteries. Transthoracic echocardiography revealed a floating structure in the left atrial chamber, indicating cardiac myxoma. We diagnosed cardioembolic ischemic stroke due to left atrial myxoma. Cardiac surgery for excision of a left atrial myxoma was performed on the 3rd hospital day. Multiple aneurysms should be taken into account for differential diagnosis in patients with cardiac myxoma and with atypical spotty low intensity on T2*-weighted images. PMID:26797485

  1. Noninvasive ventilatory correction as an adjunct to an experimental systemic reperfusion therapy in acute ischemic stroke.

    PubMed

    Barlinn, Kristian; Balucani, Clotilde; Palazzo, Paola; Zhao, Limin; Sisson, April; Alexandrov, Andrei V

    2010-01-01

    Background. Obstructive sleep apnea (OSA) is a common condition in patients with acute ischemic stroke and associated with early clinical deterioration and poor functional outcome. However, noninvasive ventilatory correction is hardly considered as a complementary treatment option during the treatment phase of acute ischemic stroke. Summary of Case. A 55-year-old woman with an acute middle cerebral artery (MCA) occlusion received intravenous tissue plasminogen activator (tPA) and enrolled into a thrombolytic research study. During tPA infusion, she became drowsy, developed apnea episodes, desaturated and neurologically deteriorated without recanalization, re-occlusion or intracerebral hemorrhage. Urgent noninvasive ventilatory correction with biphasic positive airway pressure (BiPAP) reversed neurological fluctuation. Her MCA completely recanalized 24 hours later. Conclusions. Noninvasive ventilatory correction should be considered more aggressively as a complementary treatment option in selected acute stroke patients. Early initiation of BiPAP can stabilize cerebral hemodynamics and may unmask the true potential of other therapies. PMID:21052540

  2. Brain protection against ischemic stroke using choline as a new molecular bypass treatment

    PubMed Central

    Jin, Xin; Wang, Ru-huan; Wang, Hui; Long, Chao-liang; Wang, Hai

    2015-01-01

    Aim: To determine whether administration of choline could attenuate brain injury in a rat model of ischemic stroke and the underlying mechanisms. Methods: A rat model of ischemic stroke was established through permanent middle cerebral artery occlusion (pMCAO). After the surgery, the rats were treated with choline or choline plus the specific α7 nAChR antagonist methyllycaconitine (MLA), or with the control drug nimodipine for 10 days. The neurological deficits, brain-infarct volume, pial vessel density and the number of microvessels in the cortex were assessed. Rat brain microvascular endothelial cells (rBMECs) cultured under hypoxic conditions were used in in vitro experiments. Results: Oral administration of choline (100 or 200 mg·kg−1·d−1) or nimodipine (20 mg·kg−1·d−1) significantly improved neurological deficits, and reduced infarct volume and nerve cell loss in the ischemic cerebral cortices in pMCAO rats. Furthermore, oral administration of choline, but not nimodipine, promoted the pial arteriogenesis and cerebral-cortical capillary angiogenesis in the ischemic regions. Moreover, oral administration of choline significantly augmented pMCAO-induced increases in the expression levels of α7 nAChR, HIF-1α and VEGF in the ischemic cerebral cortices as well as in the serum levels of VEGF. Choline-induced protective effects were prevented by co-treatment with MLA (1 mg·kg−1·d−1, ip). Treatment of rBMECs cultured under hypoxic conditions in vitro with choline (1, 10 and 100 μmol/L) dose-dependently promoted the endothelial-cell proliferation, migration and tube formation, as well as VEGF secretion, which were prevented by co-treatment with MLA (1 μmol/L) or by transfection with HIF-1α siRNA. Conclusion: Choline effectively attenuates brain ischemic injury in pMCAO rats, possibly by facilitating pial arteriogenesis and cerebral-cortical capillary angiogenesis via upregulating α7 nAChR levels and inducing the expression of HIF-1α and VEGF

  3. Behavioral effects of four antidepressants on an ischemic rat model of emotional disturbances.

    PubMed

    Bantsiele, Guy-Bernard; Bentué-Ferrer, Danièle; Saïkali, Stephan; Laviolle, Bruno; Bourin, Michel; Reymann, Jean-Michel

    2009-08-12

    The aim of this study was to examine the psychopharmacological effects of antidepressants on post-ischemic rats. Global transient cerebral ischemia was performing with the four-vessels occlusion method. Locomotor activity, neurological scores and activity during the 20 min forced swimming test (FST) session were comparatively evaluated in sham-operated and ischemic animals. Three doses of four antidepressants or saline were then intraperitoneally administered 23.5, 5 and 1h before the 5 min FST session, and 0.5h before the elevated plus-maze (EPM). Histological quantification of neuronal loss was performed at the end of the experiments. Results show that before treatment, ischemic animals present significantly greater spontaneous motor activity, a neurological score and an immobility time in the 20 min FST lower than sham-operated animals. After treatment, compared to the saline group, we show an antidepressant-like activity in the FST with all the molecules, except with the fluvoxamine, and an anxiolytic-like effect in the EPM, with at least one dose of each compounds. The observed effect is very similar according to whether or not the animals were ischemic, with a tendency to react more important for ischemic animals versus sham-operated. This difference is significant in the FST for the immobility time and in the EPM for the ratio of distance, of time, of number of entrances and non-protected head dips with the 45 mg dose of milnacipran. These results demonstrate that even though global transient cerebral ischemia induces important cerebral lesions, it modifies little the effects of the different antidepressants, whatever their primary pharmacological target, with a particular effectiveness with the dual serotonin and norepinephrine reuptake inhibitor milnacipran.

  4. Cerebral infarction in a 24-year-old pilot.

    PubMed

    Ohashi, Koichiro; Nakanishi, Kuniaki; Miyajima, Daijiro; Fukushima, Koji; Shirotani, Toshiki; Kuwamura, Keiichi; Tong, Andrew

    2003-10-01

    Ischemic stroke is a rare event in young adults. We report on a 24-yr-old pilot with cerebral infarction of undetermined etiology, temporally associated with chain smoking. The patient exhibited dysphasia, stupor (confused consciousness), and right facial-nerve palsy. Computed-tomography revealed a low-density area in the left insular cortex. Cerebroangiography showed severe stenosis in a branch of the left middle cerebral artery. After admission, the patient made a rapid and uneventful recovery within 72 h. MRI showed an area of hyperintensity on T2-weighted images 2 mo after the attack. Based on the hyperintense area on FLAIR (fluid attenuated inversion recovery sequence) images obtained in MRI performed 10 mo after the attack, we diagnosed a cerebral infarction. In the Japan Air Self-Defense Force, cerebral infarction is an aeromedically disqualifying condition. However, in the evaluation 2 mo after the attack, differentiation from reversible ischemic neurological deficit was difficult. We discuss the criteria used for diagnosis and the risk factors for cerebral infarction in young adults, as well as the aeromedical disposition of young pilots.

  5. Cerebral infarction in a 24-year-old pilot.

    PubMed

    Ohashi, Koichiro; Nakanishi, Kuniaki; Miyajima, Daijiro; Fukushima, Koji; Shirotani, Toshiki; Kuwamura, Keiichi; Tong, Andrew

    2003-10-01

    Ischemic stroke is a rare event in young adults. We report on a 24-yr-old pilot with cerebral infarction of undetermined etiology, temporally associated with chain smoking. The patient exhibited dysphasia, stupor (confused consciousness), and right facial-nerve palsy. Computed-tomography revealed a low-density area in the left insular cortex. Cerebroangiography showed severe stenosis in a branch of the left middle cerebral artery. After admission, the patient made a rapid and uneventful recovery within 72 h. MRI showed an area of hyperintensity on T2-weighted images 2 mo after the attack. Based on the hyperintense area on FLAIR (fluid attenuated inversion recovery sequence) images obtained in MRI performed 10 mo after the attack, we diagnosed a cerebral infarction. In the Japan Air Self-Defense Force, cerebral infarction is an aeromedically disqualifying condition. However, in the evaluation 2 mo after the attack, differentiation from reversible ischemic neurological deficit was difficult. We discuss the criteria used for diagnosis and the risk factors for cerebral infarction in young adults, as well as the aeromedical disposition of young pilots. PMID:14556575

  6. Safety of Direct Local Cooling (15° C) of the Cerebral Cortex with the Chillerstrip™ During Focal Cerebral Ischemia in Monkeys

    NASA Astrophysics Data System (ADS)

    Nemoto, Edwin M.; Jungreis, Charles; Jovin, Tudor; Rao, Gutti; Robinson, Timothy; Sanders, Todd; Casey, Kate; Kirkman, John

    Direct cooling of the cerebral cortex with the ChillerStrip™ to 15°C followed by spontaneous rewarming to 37°C is safe. Direct cooling of the brain reduces the severity of the ischemic insult as judged by the reduction in the hyperemia after reperfusion which appeared to be directly related to the temperature of the brain.

  7. Reversible Cerebral Vasoconstriction Syndrome: A Report on Three Cases.

    PubMed

    Roongpiboonsopit, Duangnapa; Kongbunkiat, Kannikar; Phanthumchinda, Kammant

    2016-01-01

    Reversible cerebral vasoconstriction syndrome (RCVS), a recently recognized syndrome, is defined as an intermittent segmental vasospasm of cerebral arteries accompanied by thunderclap headache. The major complications of RCVS include ischemic or hemorrhagic stroke, which may cause morbidity and mortality. It is important to detect RCVS in clinical practice because misdiagnosis may lead to inappropriate treatment. In Thailand, there are only two reported cases of RCVS, which may reflect an underdiagnosis of this syndrome. To raise awareness of RCVS, we reported a case series of three RCVS cases. Two of the presented cases had interesting precipitating factors, and two cases had an unusual delayed clinical course. PMID:27455831

  8. Cerebral malaria.

    PubMed

    Postels, Douglas G; Birbeck, Gretchen L

    2013-01-01

    Malaria, the most significant parasitic disease of man, kills approximately one million people per year. Half of these deaths occur in those with cerebral malaria (CM). The World Health Organization (WHO) defines CM as an otherwise unexplained coma in a patient with malarial parasitemia. Worldwide, CM occurs primarily in African children and Asian adults, with the vast majority (greater than 90%) of cases occurring in children 5 years old or younger in sub-Saharan Africa. The pathophysiology of the disease is complex and involves infected erythrocyte sequestration, cerebral inflammation, and breakdown of the blood-brain barrier. A recently characterized malarial retinopathy is visual evidence of Plasmodium falciparum's pathophysiological processes occurring in the affected patient. Treatment consists of supportive care and antimalarial administration. Thus far, adjuvant therapies have not been shown to improve mortality rates or neurological outcomes in children with CM. For those who survive CM, residual neurological abnormalities are common. Epilepsy, cognitive impairment, behavioral disorders, and gross neurological deficits which include motor, sensory, and language impairments are frequent sequelae. Primary prevention strategies, including bed nets, vaccine development, and chemoprophylaxis, are in varied states of development and implementation. Continuing efforts to find successful primary prevention options and strategies to decrease neurological sequelae are needed. PMID:23829902

  9. Clinical management of infectious cerebral vasculitides.

    PubMed

    Carod Artal, Francisco Javier

    2016-01-01

    A wide range of infections (virus, bacteria, parasite and fungi) may cause cerebral vasculitides. Headache, seizures, encephalopathy and stroke are common forms of presentation. Infection and inflammation of intracranial vessels may cause pathological vascular remodelling, vascular occlusion and ischemia. Vasculitis in chronic meningitis may cause ischemic infarctions, and is associated with poor outcome. Appropriate neuroimaging (CT-angiography, MR-angiography, conventional 4-vessel angiography) and laboratory testing (specific antibodies in blood and CSF, CSF culture and microscopy) and even brain biopsy are needed to quickly establish the aetiology. Enhancement of contrast, wall thickening and lumen narrowing are radiological signs pointing to an infectious vasculitis origin. Although corticosteroids and prophylactic antiplatelet therapy have been used in infectious cerebral vasculitis, there are no randomized clinical trials that have evaluated their efficacy and safety. Stable mycotic aneurysms can be treated with specific antimicrobial therapy. Endovascular therapy and intracranial surgery are reserved for ruptured aneurysms or enlarging unruptured aneurysms. PMID:26689107

  10. Successful Intra-Arterial Thrombolysis for Acute Ischemic Stroke in the Immediate Postpartum Period: Case Report

    SciTech Connect

    Mendez, Jose C. Masjuan, J.; Garcia, N.; Lecinana, M. de

    2008-01-15

    Stroke in pregnancy and the puerperium is a rare but potentially devastating event. We present the case of a previously healthy woman who underwent a cesarean delivery and experienced a middle cerebral artery thrombosis in the immediate postpartum period that was subsequently lysed with intra-arterial urokinase. The patient made a complete neurologic recovery. To the best of our knowledge, this is the first reported case of successful intra-arterial thrombolysis for ischemic stroke in the postpartum period.

  11. Prevention of ischemic complications during aneurysm surgery.

    PubMed

    Raabe, Andreas; Seidel, Kathleen

    2016-03-01

    Ischemic complications during aneurysm surgery are a frequent cause of postoperative infarctions and new neurological deficits. In this article, we discuss imaging and neurophysiological tools that may help the surgeon to detect intraoperative ischemia. The strength of intraoperative digital subtraction angiography (DSA) is the full view of the arterial and venous vessel. DSA is the gold standard in complex and giant aneurysms, but due to certain disadvantages, it cannot be considered standard of care. Microvascular Doppler sonography is probably the fastest diagnostic tool and can quickly aid diagnosis of large vessel occlusions. Intraoperative indocyanine green videoangiography is the best tool to assess flow in perforating and larger arteries, as well as occlusion of the aneurysm sac. Intraoperative neurophysiological monitoring with somatosensory and motor evoked potentials indirectly measures blood flow by recording neuronal function. It covers all causes of intraoperative ischemia, provided that ischemia occurs in the brain areas under surveillance. However, every method has advantages and disadvantages. No single method is superior to the others in every aspect. Therefore, it is very important for the neurosurgeon to know the strengths and weaknesses of each tool in order to have them available, to know how to use them for each individual situation, and to be ready to apply them within the time window for reversible cerebral ischemia.

  12. Systemic neutrophil activation in a mouse model of ischemic stroke and reperfusion.

    PubMed

    Morrison, Helena; McKee, Dana; Ritter, Leslie

    2011-04-01

    As a natural response to injury and disease, neutrophils activate, adhere to the microvasculature, migrate into brain tissue, and release toxic substances such as reactive oxygen species and proteases. This neutrophil response occurs when blood flow is returned to brain tissue (reperfusion) after ischemic stroke. Thus, the presence of activated systemic neutrophils increases the potential for tissue injury during reperfusion after ischemic stroke. Although experiments in rat models suggest that activated neutrophils play a pivotal role in cerebral ischemia reperfusion injury, little is known about systemic neutrophil activation during reperfusion following ischemic stroke in a mouse model. The purpose of this study was to characterize systemic leukocyte responses and neutrophil CD11b expression 15-min and 24-hr post-reperfusion in a mouse model of ischemic stroke. The intraluminal filament method of transient middle cerebral artery occlusion (tMCAO) with reperfusion or a sham procedure was performed in male C57Bl/6 mice. Automated leukocyte counts and manual white blood cell (WBC) differential counts were measured. Flow cytometry was used to assess systemic neutrophil surface CD11b expression. The data suggest that the damaging potential of systemic neutrophil activation begins as early as 15 min and remains evident at 24 hr after the initiation of reperfusion. In addition, because transgenic mouse models, bred on a C57Bl/6 background, are increasingly used to elucidate single mechanisms of reperfusion injury after ischemic stroke, findings from this study are foundational for future investigations examining the damaging potential of neutrophil responses post-reperfusion after ischemic stroke in genetically altered mouse models within this background strain. PMID:21044968

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

    PubMed

    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. PMID:27345710

  14. Bone marrow mesenchymal stem cells transplantation promotes the release of endogenous erythropoietin after ischemic stroke

    PubMed Central

    Lv, Wen; Li, Wen-yu; Xu, Xiao-yan; Jiang, Hong; Bang, Oh Yong

    2015-01-01

    This study investigated whether bone marrow mesenchymal stem cell (BMSC) transplantation protected ischemic cerebral injury by stimulating endogenous erythropoietin. The model of ischemic stroke was established in rats through transient middle cerebral artery occlusion. Twenty-four hours later, 1 × 106 human BMSCs (hBMSCs) were injected into the tail vein. Fourteen days later, we found that hBMSCs promoted the release of endogenous erythropoietin in the ischemic region of rats. Simultaneously, 3 μg/d soluble erythropoietin receptor (sEPOR) was injected into the lateral ventricle, and on the next 13 consecutive days. sEPOR blocked the release of endogenous erythropoietin. The neurogenesis in the subventricular zone was less in the hBMSCs + sEPOR group than in the hBMSCs + heat-denatured sEPOR group. The adhesive-removal test result and the modified Neurological Severity Scores (mNSS) were lower in the hBMSCs + sEPOR group than in the heat-denatured sEPOR group. The adhesive-removal test result and mNSS were similar between the hBMSCs + heat-denatured sEPOR group and the hBMSCs + sEPOR group. These findings confirm that BMSCs contribute to neurogenesis and improve neurological function by promoting the release of endogenous erythropoietin following ischemic stroke. PMID:26487854

  15. Treatment with Isorhamnetin Protects the Brain Against Ischemic Injury in Mice.

    PubMed

    Zhao, Jin-Jing; Song, Jin-Qing; Pan, Shu-Yi; Wang, Kai

    2016-08-01

    Ischemic stroke is a major cause of morbidity and mortality, yet lacks effective neuroprotective treatments. The aim of this work was to investigate whether treatment with isorhamnetin protected the brain against ischemic injury in mice. Experimental stroke mice underwent the filament model of middle cerebral artery occlusion with reperfusion. Treatment with isorhamnetin or vehicle was initiated immediately at the onset of reperfusion. It was found that treatment of experimental stroke mice with isorhamnetin reduced infarct volume and caspase-3 activity (a biomarker of apoptosis), and improved neurological function recovery. Treatment of experimental stroke mice with isorhamnetin attenuated cerebral edema, improved blood-brain barrier function, and upregulated gene expression of tight junction proteins including occludin, ZO-1, and claudin-5. Treatment of experimental stroke mice with isorhamnetin activated Nrf2/HO-1, suppressed iNOS/NO, and led to reduced formation of MDA and 3-NT in ipsilateral cortex. In addition, treatment of experimental stroke mice with isorhamnetin suppressed activity of MPO (a biomarker of neutrophil infiltration) and reduced protein levels of IL-1β, IL-6, and TNF-α in ipsilateral cortex. Furthermore, it was found that treatment of experimental stroke mice with isorhamnetin reduced mRNA and protein expression of NMDA receptor subunit NR1 in ipsilateral cortex. In conclusion, treatment with isorhamnetin protected the brain against ischemic injury in mice. Isorhamnetin could thus be envisaged as a countermeasure for ischemic stroke but remains to be tested in humans. PMID:27161367

  16. Differential diagnosis of regional cerebral hyperfixation of TC-99m HMPAO on SPECT imaging

    SciTech Connect

    Shirazi, P.; Konopka, L.; Crayton, J.W.

    1994-05-01

    Accurate diagnostic evaluation of patients with neurologic and neuropsychiatric disease is important because early treatment may halt disease progression and prevent impairment or disability. Cerebral hyperfixation of HMPAO has been ascribed to luxury perfusion following ischemic infarction. The present study sought to identify other conditions that also display radiotracer hyperfixation in order to develop a differential diagnosis of this finding on SPECT imaging. Two hundred fifty (n=250) successive cerebral SPECT images were reviewed for evidence of HMPAO hyperfixation. Hyperfixation was defined as enhanced focal perfusion surrounded by a zone of diminished or normal cerebral perfusion. All patients were scanned after intravenous injection of 25 mCi Tc-99m HMPAO. Volume-rendered and oblique images were obtained with a Trionix triple-head SPECT system using ultra high resolution fan beam collimators. Thirteen (13/250; 5%) of the patients exhibited regions of HMPAO hyperfixation. CT or MRI abnormalities were detected in 6/13 cases. Clinical diagnoses in these patients included intractable psychosis, post-traumatic stress disorder, alcohol and narcotic dependence, major depression, acute closed-head trauma, hypothyroidism, as well as subacute ischemic infarction. A wide variety of conditions may be associated with cerebral hyperfixation of HMPAO. These conditions include neurologic and psychiatric diagnoses, and extend the consideration of hyperfixation beyond ischemic infarction. Consequently, a differential diagnosis of HMPAO hyperfixation may be broader than originally considered, and this may suggest a fundamental role for local cerebral hyperperfusion. Elucidation of the fundamental mechanism(s) for cerebral hyperperfusion requires further investigation.

  17. Possible involvement of ubiquitin proteasome system and other proteases in acute and delayed aspects of ischemic preconditioning of brain in mice.

    PubMed

    Rehni, Ashish Kumar; Singh, Thakur Gurjeet; Behl, Nidhi; Arora, Sandeep

    2010-01-01

    The present study has been designed to investigate the potential role of ubiquitin proteasome system and other proteases in acute as well as delayed aspects of ischemic preconditioning induced reversal of ischemia-reperfusion injury in mouse brain. Bilateral carotid artery occlusion of 17 min followed by reperfusion for 24 h was employed in present study to produce ischemia and reperfusion induced cerebral injury in mice. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Memory was evaluated using elevated plus-maze test. Rota rod test was employed to assess motor incoordination. Bilateral carotid artery occlusion followed by reperfusion produced cerebral infarction and impaired memory and motor co-ordination. Three preceding episodes of bilateral carotid artery occlusion for 1 min and reperfusion of 1 min (ischemic preconditioning) both immediately before (for acute preconditioning) and 24 h before (for delayed preconditioning) global cerebral ischemia prevented markedly ischemia-reperfusion-induced cerebral injury as measured in terms of infarct size, loss of memory and motor coordination. Z-Leu-Leu-Phe-Chinese hamster ovary (CHO) (2 mg/kg, intraperitoneally (i.p.)), an inhibitor of ubiquitin proteasome system and other proteases attenuated the neuroprotective effect of both the acute as well as delayed ischemic preconditioning. It is concluded that the neuroprotective effect of both the acute as well as delayed phases of ischemic preconditioning may be due to the activation of ubiquitin proteasome system and other proteases.

  18. Ischemic Stroke after Heart Transplantation

    PubMed Central

    Acampa, Maurizio; Lazzerini, Pietro Enea; Guideri, Francesca; Tassi, Rossana; Martini, Giuseppe

    2016-01-01

    Cerebrovascular complications after orthotopic heart transplantation (OHT) are more common in comparison with neurological sequelae subsequent to routine cardiac surgery. Ischemic stroke and transient ischemic attack (TIA) are more common (with an incidence of up to 13%) than intracranial hemorrhage (2.5%). Clinically, ischemic stroke is manifested by the appearance of focal neurologic deficits, although sometimes a stroke may be silent or manifests itself by the appearance of encephalopathy, reflecting a diffuse brain disorder. Ischemic stroke subtypes distribution in perioperative and postoperative period after OHT is very different from classical distribution, with different pathogenic mechanisms. Infact, ischemic stroke may be caused by less common and unusual mechanisms, linked to surgical procedures and to postoperative inflammation, peculiar to this group of patients. However, many strokes (40%) occur without a well-defined etiology (cryptogenic strokes). A silent atrial fibrillation (AF) may play a role in pathogenesis of these strokes and P wave dispersion may represent a predictor of AF. In OHT patients, P wave dispersion correlates with homocysteine plasma levels and hyperhomocysteinemia could play a role in the pathogenesis of these strokes with multiple mechanisms increasing the risk of AF. In conclusion, stroke after heart transplantation represents a complication with considerable impact not only on mortality but also on subsequent poor functional outcome. PMID:26915504

  19. SLAP/SLAP2 prevent excessive platelet (hem)ITAM signaling in thrombosis and ischemic stroke in mice.

    PubMed

    Cherpokova, Deya; Bender, Markus; Morowski, Martina; Kraft, Peter; Schuhmann, Michael K; Akbar, Sarah M; Sultan, Cheryl S; Hughes, Craig E; Kleinschnitz, Christoph; Stoll, Guido; Dragone, Leonard L; Watson, Steve P; Tomlinson, Michael G; Nieswandt, Bernhard

    2015-01-01

    Glycoprotein VI and C-type lectin-like receptor 2 are essential platelet activating receptors in hemostasis and thrombo-inflammatory disease, which signal through a (hem)immunoreceptor tyrosine-based activation motif (ITAM)-dependent pathway. The adapter molecules Src-like adapter proteins (SLAP and SLAP2) are involved in the regulation of immune cell surface expression and signaling, but their function in platelets is unknown. In this study, we show that platelets expressed both SLAP isoforms and that overexpression of either protein in a heterologous cell line almost completely inhibited glycoprotein VI and C-type lectin-like receptor 2 signaling. In mice, single deficiency of SLAP or SLAP2 had only moderate effects on platelet function, whereas double deficiency of both adapters resulted in markedly increased signal transduction, integrin activation, granule release, aggregation, procoagulant activity, and thrombin generation in response to (hem)ITAM-coupled, but not G protein-coupled, receptor activation. In vivo, constitutive SLAP/SLAP2 knockout mice displayed accelerated occlusive arterial thrombus formation and a dramatically worsened outcome after focal cerebral ischemia. This was attributed to the absence of both adapter proteins in platelets, as demonstrated by adoptive transfer of Slap(-/-)/Slap2(-/-) platelets into wild-type mice. Our results establish SLAP and SLAP2 as critical inhibitors of platelet (hem)ITAM signaling in the setting of arterial thrombosis and ischemic stroke.

  20. Severe envenomation by Cerastes cerastes viper: an unusual mechanism of acute ischemic stroke.

    PubMed

    Rebahi, Houssam; Nejmi, Hicham; Abouelhassan, Taoufik; Hasni, Khadija; Samkaoui, Mohamed-Abdenasser

    2014-01-01

    Cerebral complications after snake bites--particularly ischemic complications--are rare. Very few cases of cerebral infarction resulting from a viper bite have been reported, and we call attention to this uncommon etiology. We discuss 3 authenticated reports of acute ischemic cerebrovascular accidents after 3 typical severe envenomations by Cerastes cerastes vipers. The 3 patients developed extensive local swelling and life-threatening systemic envenomation characterized by disseminated intravascular coagulopathy, increased fibrinolysis, thrombocytopenia, microangiopathic hemolytic anemia, and acute renal failure. This clinical picture involved atypical neurologic manifestations. These patients had either low Glasgow Coma Scale (GCS) or hemiparesis within hours to 4 days after being bitten, and they were found to have computed tomographic evidence of single or multiple ischemic (nonhemorrhagic) strokes of small- to large-vessel territories of the brain. One patient had good clinical recovery without neurologic deficits. Thrombotic complications occurred an average of 36 hours after being bitten, and their importance depends on the degree of envenomation. The possible mechanisms for cerebral infarction in these cases include generalized prothrombotic action of the venom (consumptive coagulopathy), toxin-induced vasculitis, and endothelial damage.

  1. Photodynamic impact induces ischemic tolerance in models in vivo and in vitro

    NASA Astrophysics Data System (ADS)

    Demyanenko, Svetlana; Sharifulina, Svetlana; Berezhnaya, Elena; Kovaleva, Vera; Neginskaya, Maria; Zhukovskaya, Ludmila

    2016-04-01

    Ischemic tolerance determines resistance to lethal ischemia gained by a prior sublethal stimulus (i.e., preconditioning). We reproduced this effect in two variants. In vitro the preliminary short (5 s) photodynamic treatment (PDT) (photosensitizer Photosens, 10 nM, 30 min preincubation; laser: 670 nm, 100 mW/cm2) significantly reduced the necrosis of neurons and glial cells in the isolated crayfish stretch receptor, which was caused by following 30-min PDT by 66% and 46%, respectively. In vivo PDT of the rat cerebral cortex with hydrophilic photosensitizer Rose Bengal (i.v. administration, laser irradiation: 532 nm, 60 mW/cm2, 3 mm beam diameter, 30 min) caused occlusion of small brain vessels and local photothrombotic infarct (PTI). It is a model of ischemic stroke. Cerebral tissue edema and global necrosis of neurons and glial cells occurred in the infarction core, which was surrounded by a 1.5 mm transition zone, penumbra. The maximal pericellular edema, hypo- and hyperchromia of neurons were observed in penumbra 24 h after PTI. The repeated laser irradiation of the contralateral cerebral cortex also caused PTI but lesser as compared with single PDT. Preliminary unilateral PTI provided ischemic tolerance: at 14 day after second exposure the PTI volume significantly decreased by 24% than in the case of a single exposure. Sensorimotor deficits in PDT-treated rats was registered using the behavioral tests. The preliminary PTI caused the preconditioning effect.

  2. Prevalence of intracranial artery stenosis in Iranian patients with acute ischemic stroke using transcranial Doppler ultrasonography

    PubMed Central

    Shariat, Abdolhamid; Niknam, Leila; Izadi, Sadegh; Salehi, Alireza

    2016-01-01

    Background: The aim of this study is to determine the frequency of intracranial artery stenosis in patients with acute ischemic stroke in Iran. Methods: A total of 169 patients with acute ischemic stroke were eligible to participate and were enrolled in this study from January 2012 to February 2013. All the patients were admitted to the Nemazee ‎Hospital, affiliated to Shiraz University of Medical Sciences, Iran. They underwent transcranial Doppler (TCD) ultrasonography. Mean flow velocity (MFV) of basilar artery, vertebral artery, middle cerebral artery (MCA), anterior cerebral artery (ACA), and posterior cerebral artery (PCA) were evaluated. Results: A mean of patients’ age was 67.80 ± 8.14 years. There were 83 men (49.1%) and 86 women (50.9%). Overall, 43 patients (25.4%), with a mean age of 66.7 ± 6.2 years, had intracranial stenosis. The number of men and women with intracranial stenosis was comparable (52.4% men vs. 47.6% women). Hypertension (P < 0.001), hyperlipidemia (P < 0.001), and diabetes mellitus (DM) (P < 0.001) were major risk factors for intracranial stenosis. Conclusion: The prevalence of intracranial artery stenosis in patients with acute ischemic stroke is 25.4% which is comparable with previous reports from Iran and other Middle East countries. PMID:27648174

  3. Neuroprotection by glutamate oxaloacetate transaminase in ischemic stroke: an experimental study.

    PubMed

    Campos, Francisco; Sobrino, Tomás; Ramos-Cabrer, Pedro; Argibay, Bárbara; Agulla, Jesús; Pérez-Mato, María; Rodríguez-González, Raquel; Brea, David; Castillo, José

    2011-06-01

    As ischemic stroke is associated with an excessive release of glutamate into the neuronal extracellular space, a decrease in blood glutamate levels could provide a mechanism to remove it from the brain tissue, by increasing the brain-blood gradient. In this regard, the ability of glutamate oxaloacetate transaminase (GOT) to metabolize glutamate in blood could represent a potential neuroprotective tool for ischemic stroke. This study aimed to determine the neuroprotective effects of GOT in an animal model of cerebral ischemia by means of a middle cerebral arterial occlusion (MCAO) following the Stroke Therapy Academic Industry Roundtable (STAIR) group guidelines. In this animal model, oxaloacetate-mediated GOT activation inhibited the increase of blood and cerebral glutamate after MCAO. This effect is reflected in a reduction of infarct size, smaller edema volume, and lower sensorimotor deficits with respect to controls. Magnetic resonance spectroscopy confirmed that the increase of glutamate levels in the brain parenchyma after MCAO is inhibited after oxaloacetate-mediated GOT activation. These findings show the capacity of the GOT to remove glutamate from the brain by means of blood glutamate degradation, and suggest the applicability of this enzyme as an efficient and novel neuroprotective tool against ischemic stroke.

  4. Classifiers for Ischemic Stroke Lesion Segmentation: A Comparison Study

    PubMed Central

    Maier, Oskar; Schröder, Christoph; Forkert, Nils Daniel; Martinetz, Thomas; Handels, Heinz

    2015-01-01

    Motivation Ischemic stroke, triggered by an obstruction in the cerebral blood supply, leads to infarction of the affected brain tissue. An accurate and reproducible automatic segmentation is of high interest, since the lesion volume is an important end-point for clinical trials. However, various factors, such as the high variance in lesion shape, location and appearance, render it a difficult task. Methods In this article, nine classification methods (e.g. Generalized Linear Models, Random Decision Forests and Convolutional Neural Networks) are evaluated and compared with each other using 37 multiparametric MRI datasets of ischemic stroke patients in the sub-acute phase in terms of their accuracy and reliability for ischemic stroke lesion segmentation. Within this context, a multi-spectral classification approach is compared against mono-spectral classification performance using only FLAIR MRI datasets and two sets of expert segmentations are used for inter-observer agreement evaluation. Results and Conclusion The results of this study reveal that high-level machine learning methods lead to significantly better segmentation results compared to the rather simple classification methods, pointing towards a difficult non-linear problem. The overall best segmentation results were achieved by a Random Decision Forest and a Convolutional Neural Networks classification approach, even outperforming all previously published results. However, none of the methods tested in this work are capable of achieving results in the range of the human observer agreement and the automatic ischemic stroke lesion segmentation remains a complicated problem that needs to be explored in more detail to improve the segmentation results. PMID:26672989

  5. Linear Accelerators

    SciTech Connect

    Sidorin, Anatoly

    2010-01-05

    In linear accelerators the particles are accelerated by either electrostatic fields or oscillating Radio Frequency (RF) fields. Accordingly the linear accelerators are divided in three large groups: electrostatic, induction and RF accelerators. Overview of the different types of accelerators is given. Stability of longitudinal and transverse motion in the RF linear accelerators is briefly discussed. The methods of beam focusing in linacs are described.

  6. Aqueous extract of Cordyceps alleviates cerebral ischemia-induced short-term memory impairment in gerbils.

    PubMed

    Lee, Sang-Hak; Ko, Il-Gyu; Kim, Sung-Eun; Hwang, Lakkyong; Jin, Jun-Jang; Choi, Hyun-Hee; Kim, Chang-Ju

    2016-04-01

    Cerebral ischemia is caused by reduced cerebral blood flow due to a transient or permanent cerebral artery occlusion. Ischemic injury in the brain leads to neuronal cell death, and eventually causes neurological impairments. Cordyceps, the name given to the fungi on insects, has abundant useful natural products with various biological activities. Cordyceps is known to have nephroprotective, hepatoprotective, anti-inflammatory, antioxidative, and antiapoptotic effects. We investigated the effects of Cordyceps on short-term memory, neuronal apoptosis, and cell proliferation in the hippocampal dentate gyrus following transient global ischemia in gerbils. For this study, a step-down avoidance test, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, immunohistochemistry for caspase-3 and 5-bromo-2'-de-oxyuridine, and western blot for Bax, Bcl-2, brain-derived neurotrophic factor (BDNF), and tyrosin kinase B were performed. In the present study, Cordyceps alleviated cerebral ischemia-induced short-term memory impairment. Cordyceps showed therapeutic effects through inhibiting cerebral ischemia-induced apoptosis in the hippocampus. Cordyceps suppressed cerebral ischemia-induced cell proliferation in the hippocampal dentate gyrus due to the reduced apoptotic neuronal cell death. Cordyceps treatment also enhanced BDNF and TrkB expressions in the hippocampus of ischemic gerbils. It can be suggested that Cordyceps overcomes cerebral ischemia-induced neuronal apoptosis, thus facilitates recovery following cerebral ischemia injury. PMID:27162767

  7. Aqueous extract of Cordyceps alleviates cerebral ischemia-induced short-term memory impairment in gerbils

    PubMed Central

    Lee, Sang-Hak; Ko, Il-Gyu; Kim, Sung-Eun; Hwang, Lakkyong; Jin, Jun-Jang; Choi, Hyun-Hee; Kim, Chang-Ju

    2016-01-01

    Cerebral ischemia is caused by reduced cerebral blood flow due to a transient or permanent cerebral artery occlusion. Ischemic injury in the brain leads to neuronal cell death, and eventually causes neurological impairments. Cordyceps, the name given to the fungi on insects, has abundant useful natural products with various biological activities. Cordyceps is known to have nephroprotective, hepatoprotective, anti-inflammatory, antioxidative, and antiapoptotic effects. We investigated the effects of Cordyceps on short-term memory, neuronal apoptosis, and cell proliferation in the hippocampal dentate gyrus following transient global ischemia in gerbils. For this study, a step-down avoidance test, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, immunohistochemistry for caspase-3 and 5-bromo-2′-de-oxyuridine, and western blot for Bax, Bcl-2, brain-derived neurotrophic factor (BDNF), and tyrosin kinase B were performed. In the present study, Cordyceps alleviated cerebral ischemia-induced short-term memory impairment. Cordyceps showed therapeutic effects through inhibiting cerebral ischemia-induced apoptosis in the hippocampus. Cordyceps suppressed cerebral ischemia-induced cell proliferation in the hippocampal dentate gyrus due to the reduced apoptotic neuronal cell death. Cordyceps treatment also enhanced BDNF and TrkB expressions in the hippocampus of ischemic gerbils. It can be suggested that Cordyceps overcomes cerebral ischemia-induced neuronal apoptosis, thus facilitates recovery following cerebral ischemia injury. PMID:27162767

  8. [Cerebral palsy].

    PubMed

    Malagón Valdez, Jorge

    2007-01-01

    The term cerebral palsy (CP), is used for a great number of clinical neurological syndromes. The syndromes are characterized by having a common cause, motor defects. It is important, because they can cause a brain damage by presenting motor defects and some associated deficiencies, such as mental deficiency, epilepsy, language and visual defects and pseudobulbar paralysis, with the non-evolving fact. Some authors prefer using terms such as "non-evolving encephalopathies". In the treatment the utility of prevention programs of early stimulation and special rehabilitation methods, and treatment of associated deficiencies such as epilepsy, mental deficiency, language, audition and visual problems, and the attention deficit improve the prognosis in an important way. The prognosis depends on the severity of the disease and the associated manifestations. PMID:18422084

  9. Activation of RXR/PPARγ underlies neuroprotection by bexarotene in ischemic stroke.

    PubMed

    Certo, Michelangelo; Endo, Yasuyuki; Ohta, Kiminori; Sakurada, Shinobu; Bagetta, Giacinto; Amantea, Diana

    2015-12-01

    The identification of novel drug targets for the treatment of ischemic stroke is currently an urgent challenge. Recent experimental findings have highlighted the neuroprotective potential of immunomodulatory strategies, based on polarization of myeloid cells toward non-inflammatory, beneficial phenotypes. Given the role of retinoid X receptors (RXR) in myeloid cells differentiation and polarization, here we have explored the neuroprotective potential of the RXR agonist bexarotene in mice subjected to focal cerebral ischemia. Acute administration of bexarotene significantly reduced blood brain barrier leakage, brain infarct damage and neurological deficit produced by transient middle cerebral artery occlusion in mice, without affecting cerebral blood flow. The rexinoid exerted neuroprotection with a wide time-window, being effective when administered up to 4.5h after the insult. The amelioration of histological outcome, as well as the ability of bexarotene to revert middle cerebral artery occlusion (MCAo)-induced spleen atrophy, was antagonised by BR1211, a pan-RXR antagonist, or by the selective peroxisome proliferator-activated receptor (PPAR)γ antagonist bisphenol A diglycidyl ether (BADGE), highlighting the involvement of the RXR/PPARγ heterodimer in the beneficial effects exerted by the drug. Immunofluorescence analysis revealed that bexarotene elevates Ym1-immunopositive N2 neutrophils both in the ipsilateral hemisphere and in the spleen of mice subjected to transient middle cerebral artery occlusion, pointing to a major role for peripheral neutrophil polarization in neuroprotection. Thus, our findings suggest that the RXR agonist bexarotene exerts peripheral immunomodulatory effects under ischemic conditions to be effectively repurposed for the acute therapy of ischemic stroke. PMID:26546745

  10. [Pregnancy and acute ischemic stroke].

    PubMed

    Bereczki, Dániel

    2016-05-15

    Pregnancy-related ischemic strokes play an important role in both maternal and fetal morbidity and mortality. Changes in hemostaseology and hemodynamics as well as risk factors related to or independent from pregnancy contribute to the increased stroke-risk during gestation and the puerperium. Potential teratogenic effects make diagnostics, acute therapy and prevention challenging. Because randomized, controlled trials are not available, a multicenter registry of patients with gestational stroke would be desirable. Until definite guidelines emerge, management of acute ischemic stroke during pregnancy remains individual, involving experts and weighing the risks and benefits.

  11. Movement disorders in ischemic stroke: clinical study of 22 patients.

    PubMed

    D'Olhaberriague, L; Arboix, A; Martí-Vilalta, J L; Moral, A; Massons, J

    1995-12-01

    Movement disorders (bemichorea-hemiballismus, hemidystonia and isolated tremor) are an uncommon clinical manifestation in ischemic stroke (IS), and their anatomical basis is poorly understood. We analyzed the clinical and neuroimaging characteristics of 22 consecutive patients who bad movement disorders associated with cerebral infarction (MDCI), studied at four institutions over 8 years. In one institution (from the La Alianza-Central Hospital of Barcelona Stroke Registry) nine patients with MDCI were identified among 1099 consecutive first ever stroke patients (0.8%) (908 with IS, 1%). Fifteen out of 22 patients (68%) had hemichorea-hemiballismus, five (23%) hemidystonia and two (9%) isolated tremor. MDCI were more often left sided (n = 15, 68%), being bilateral in one patient (4.5%). A lesion was found on neuroimaging (CT and/or MRI) in 15 patients (68%), in the territory of the posterior cerebral artery (n = 8) and middle cerebral artery (six deep and one superficial). The most commonly involved structure was the thalamus (n = 8, 36.5%). IS subtypes were; presumed lacunar infarcts in 14 patients (64%), atherothrombotic infarcts in two patients (9%), cardioembolic infarcts in two patients (9%) and infarcts of unknown etiology in four patients (18%). Hemichorea-hemiballismus was the most common type of MDCI in our study, usually being the result of a thalamic infarction. The thalamus was the most frequently damaged structure underlying all types of MDCI. There was a striking propensity of MDCI which resulted from nondominant deep hemispheric small vessel infarctions.

  12. Dynamic change of collateral flow varying with distribution of regional blood flow in acute ischemic rat cortex

    NASA Astrophysics Data System (ADS)

    Wang, Zhen; Luo, Weihua; Zhou, Fangyuan; Li, Pengcheng; Luo, Qingming

    2012-12-01

    Cerebral blood flow (CBF) is critical for the maintenance of cerebral function by guaranteed constant oxygen and glucose supply to brain. Collateral channels (CCs) are recruited to provide alternatives to CBF to ischemic regions once the primary vessel is occluded during ischemic stroke. However, the knowledge of the relationship between dynamic evolution of collateral flow and the distribution of regional blood flow remains limited. In this study, laser speckle imaging was used to assess dynamic changes of CCs and regional blood flow in a rat cortex with permanent middle cerebral artery occlusion (MCAo). We found that CCs immediately provided blood flow to ischemic territories after MCAo. More importantly, there were three kinds of dynamic changes of CCs during acute stroke: persistent CC, impermanent CC, and transient CC, respectively, related to different distributions of regional blood flow. Although there was the possible occurrence of peri-infarct depolarization (PID) during ischemia, there was no obvious significance about the onset time and duration of CCs between rats with and without PID. These results suggest that the initial arising of CCs does not ensure their persistence, and that collateral flow could be varied with distribution of regional blood flow in acute ischemic stroke, which may facilitate the understanding of collateral recruitment and promote the development of collateral therapeutics in the future.

  13. Angiogenesis in Ischemic Stroke and Angiogenic Effects of Chinese Herbal Medicine

    PubMed Central

    Seto, Sai-Wang; Chang, Dennis; Jenkins, Anita; Bensoussan, Alan; Kiat, Hosen

    2016-01-01

    Stroke is one of the major causes of death and adult disability worldwide. The underlying pathophysiology of stroke is highly complicated, consisting of impairments of multiple signalling pathways, and numerous pathological processes such as acidosis, glutamate excitotoxicity, calcium overload, cerebral inflammation and reactive oxygen species (ROS) generation. The current treatment for ischemic stroke is limited to thromolytics such as recombinant tissue plasminogen activator (tPA). tPA has a very narrow therapeutic window, making it suitable to only a minority of stroke patients. Hence, there is great urgency to develop new therapies that can protect brain tissue from ischemic damage. Recent studies have shown that new vessel formation after stroke not only replenishes blood flow to the ischemic area of the brain, but also promotes neurogenesis and improves neurological functions in both animal models and patients. Therefore, drugs that can promote angiogenesis after ischemic stroke can provide therapeutic benefits in stroke management. In this regard, Chinese herbal medicine (CHM) has a long history in treating stroke and the associated diseases. A number of studies have demonstrated the pro-angiogenic effects of various Chinese herbs and herbal formulations in both in vitro and in vivo settings. In this article, we present a comprehensive review of the current knowledge on angiogenesis in the context of ischemic stroke and discuss the potential use of CHM in stroke management through modulation of angiogenesis. PMID:27275837

  14. Global profiling of influence of intra-ischemic brain temperature on gene expression in rat brain.

    PubMed

    Kobayashi, Megumi Sugahara; Asai, Satoshi; Ishikawa, Koichi; Nishida, Yayoi; Nagata, Toshihito; Takahashi, Yasuo

    2008-06-01

    Mild to moderate differences in brain temperature are known to greatly affect the outcome of cerebral ischemia. The impact of brain temperature on ischemic disorders has been mainly evaluated through pathological analysis. However, no comprehensive analyses have been conducted at the gene expression level. Using a high-density oligonucleotide microarray, we screened 24000 genes in the hippocampus under hypothermic (32 degrees C), normothermic (37 degrees C), and hyperthermic (39 degrees C) conditions in a rat ischemia-reperfusion model. When the ischemic group at each intra-ischemic brain temperature was compared to a sham-operated control group, genes whose expression levels changed more than three-fold with statistical significance could be detected. In our screening condition, thirty-three genes (some of them novel) were obtained after screening, and extensive functional surveys and literature reviews were subsequently performed. In the hypothermic condition, many neuroprotective factor genes were obtained, whereas cell death- and cell damage-associated genes were detected as the brain temperature increased. At all intra-ischemic brain temperatures, multiple molecular chaperone genes were obtained. The finding that intra-ischemic brain temperature affects the expression level of many genes related to neuroprotection or neurotoxicity coincides with the different pathological outcomes at different brain temperatures, demonstrating the utility of the genetic approach.

  15. Angiogenesis in Ischemic Stroke and Angiogenic Effects of Chinese Herbal Medicine.

    PubMed

    Seto, Sai-Wang; Chang, Dennis; Jenkins, Anita; Bensoussan, Alan; Kiat, Hosen

    2016-01-01

    Stroke is one of the major causes of death and adult disability worldwide. The underlying pathophysiology of stroke is highly complicated, consisting of impairments of multiple signalling pathways, and numerous pathological processes such as acidosis, glutamate excitotoxicity, calcium overload, cerebral inflammation and reactive oxygen species (ROS) generation. The current treatment for ischemic stroke is limited to thromolytics such as recombinant tissue plasminogen activator (tPA). tPA has a very narrow therapeutic window, making it suitable to only a minority of stroke patients. Hence, there is great urgency to develop new therapies that can protect brain tissue from ischemic damage. Recent studies have shown that new vessel formation after stroke not only replenishes blood flow to the ischemic area of the brain, but also promotes neurogenesis and improves neurological functions in both animal models and patients. Therefore, drugs that can promote angiogenesis after ischemic stroke can provide therapeutic benefits in stroke management. In this regard, Chinese herbal medicine (CHM) has a long history in treating stroke and the associated diseases. A number of studies have demonstrated the pro-angiogenic effects of various Chinese herbs and herbal formulations in both in vitro and in vivo settings. In this article, we present a comprehensive review of the current knowledge on angiogenesis in the context of ischemic stroke and discuss the potential use of CHM in stroke management through modulation of angiogenesis.

  16. The Quest for Arterial Recanalization in Acute Ischemic Stroke-The Past, Present and the Future

    PubMed Central

    L.L.Yeo, Leonard; Sharma, Vijay K

    2013-01-01

    Ischemic stroke is one of the major causes of mortality and long-term disability. In the recent past, only very few treatment options were available and a considerable proportion of stroke survivors remained permanently disabled. However, over the last 2 decades rapid advances in acute stroke care have resulted in a corresponding improvement in mortality rates and functional outcomes. In this review, we describe the evolution of systemic thrombolytic agents and various interventional devices, their current status as well as some of the future prospects. We reviewed literature pertaining to acute ischemic stroke reperfusion treatment. We explored the current accepted treatment strategies to attain cerebral reperfusion via intravenous modalities and compare and contrast them within the boundaries of their clinical trials. Subsequently we reviewed the trials for interventional devices for acute ischemic stroke, categorizing them into thrombectomy devices, aspiration devices, clot disruption devices and thrombus entrapment devices. Finally we surveyed several of the alternative reperfusion strategies available. We also shed some light on the controversies surrounding the current strategies of treatment of acute ischemic stroke. Acute invasive interventional strategies continue to improve along with the noninvasive modalities. Both approaches appear promising. We conducted a comprehensive chronological review of the existing treatments as well as upcoming remedies for acute ischemic stroke. PMID:23864913

  17. Neuroprotective effect of oxaloacetate in a focal brain ischemic model in the rat.

    PubMed

    Knapp, L; Gellért, L; Kocsis, K; Kis, Z; Farkas, T; Vécsei, L; Toldi, J

    2015-01-01

    During an ischemic event, the well-regulated glutamate (Glu) homeostasis is disturbed, which gives rise to extremely high levels of this excitatory neurotransmitter in the brain tissues. It was earlier reported that the administration of oxaloacetate (OxAc) as a Glu scavenger reduces the Glu level in the brain by enhancing the brain-to-blood Glu efflux. Here, we studied the neuroprotective effect of OxAc administration in a new focal ischemic model in rats. Occlusion of the middle cerebral artery resulted in immediate reduction of the somatosensory-evoked responses (SERs), and the amplitudes remained at the reduced level throughout the whole ischemic period. On reperfusion, the SERs started to increase, but never reached the control level. OxAc proved to be protective, since the amplitudes started to recover even during the ischemia, and finally fully regained the control level. The findings of the histological measurements were in accordance with the electrophysiological data. After Fluoro Jade C staining, significantly fewer labeled cells were detected in the OxAc-treated group relative to the control. These results provide new evidence of the neuroprotective effect of OxAc against ischemic injury, which strengthens the likelihood of its future applicability as a novel neuroprotective agent for the treatment of ischemic stroke patients.

  18. Rhucin, a recombinant C1 inhibitor for the treatment of hereditary angioedema and cerebral ischemia.

    PubMed

    Longhurst, Hilary

    2008-03-01

    Pharming NV and Esteve are developing Rhucin, a recombinant human C1 esterase inhibitor. Rhucin is currently undergoing phase III clinical trials in North America and is awaiting regulatory approval in Western Europe for the treatment of prophylactic and acute hereditary angioedema. Pharming is also investigating Rhucin for the potential treatment of cerebral ischemic injury.

  19. [Regional vasoactive and metabolic therapy of patients with severe cranio-cerebral traumas].

    PubMed

    Lapshin, V N; Shakh, B N; Teplov, V M; Smirnov, D B

    2012-01-01

    In patients with severe cranio-cerebral traumas an investigation was performed of the efficiency of using vasoactive therapy in complex treatment directed to earlier recovery of the microcirculatory blood flow and aerobic metabolism in ischemic parts of the brain. PMID:22880433

  20. Rhucin, a recombinant C1 inhibitor for the treatment of hereditary angioedema and cerebral ischemia.

    PubMed

    Longhurst, Hilary

    2008-03-01

    Pharming NV and Esteve are developing Rhucin, a recombinant human C1 esterase inhibitor. Rhucin is currently undergoing phase III clinical trials in North America and is awaiting regulatory approval in Western Europe for the treatment of prophylactic and acute hereditary angioedema. Pharming is also investigating Rhucin for the potential treatment of cerebral ischemic injury. PMID:18311668

  1. Duplication of the Posterior Cerebral Artery and the ‘True Fetal’ Variant

    PubMed Central

    Masoud, Hesham; Nguyen, Thanh N.; Thatcher, Joshua; Barest, Glenn; Norbash, Alexander M.

    2015-01-01

    We present a rare case of bilateral posterior cerebral artery variant anatomy seen in a patient presenting with acute ischemic stroke. An embryological explanation of the variant configuration is discussed along with demonstrative radiologic images and a display of the vascular territory supplied. PMID:26600800

  2. Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cerebral ischemia is caused by an interruption of blood flow to the brain which generally leads to irreversible brain damage. Ischemic injury is associated with vascular leakage, inflammation, tissue injury, and cell death. Cellular changes associated with ischemia include impairment of metabolism, ...

  3. Cerebral Hypoperfusion Precedes Nausea During Centrifugation

    NASA Technical Reports Server (NTRS)

    Serrador, Jorge M.; Schlegel, Todd T.; Black, F. Owen; Wood, Scott J.

    2004-01-01

    Nausea and motion sickness are important operational concerns for aviators and astronauts. Understanding underlying mechanisms associated with motion sickness may lead to new treatments. The goal of this work was to determine if cerebral blood flow changes precede the development of nausea in motion sick susceptible subjects. Cerebral flow velocity in the middle cerebral artery (transcranial Doppler), blood pressure (Finapres) and end-tidal CO2 were measured while subjects were rotated on a centrifuge (250 degrees/sec). Following 5 min of rotation, subjects were translated 0.504 m off-center, creating a +lGx centripetal acceleration in the nasal-occipital plane. Ten subjects completed the protocol without symptoms while 5 developed nausea (4 while 6ff-center and 1 while rotating on-center). Prior to nausea, subjects had significant increases in blood pressure (+13plus or minus 3 mmHg, P less than 0.05) and cerebrovascular resistance (+46 plus or minus 17%, P less than 0.05) and decreases in cerebral flow velocity both in the second (-13 plus or minus 4%) and last minute (-22 plus or minus 5%) before symptoms (P less than 0.05). In comparison, controls demonstrated no change in blood pressure or cerebrovascular resistance in the last minute of off-center rotation and only a 7 plus or minus 2% decrease in cerebral flow velocity. All subjects had significant hypocapnia (-3.8 plus or minus 0.4 mmHg, P less than 0.05), however this hypocapnia could not fully explain the cerebral hypoperfusion associated with the development of nausea. These data indicate that reductions in cerebral blood flow precede the development of nausea. Further work is necessary to determine what role cerebral hypoperfusion plays in motion sickness and whether cerebral hypoperfusion can be used to predict the development of nausea in susceptible individuals.

  4. Melatonin suppresses cerebral edema caused by middle cerebral artery occlusion/reperfusion in rats assessed by magnetic resonance imaging.

    PubMed

    Torii, Kunio; Uneyama, Hisayuki; Nishino, Hitoo; Kondoh, Takashi

    2004-01-01

    Melatonin, a pineal secretory product synthesized from tryptophan, has been found to be effective against neurotoxicity. The present study was aimed at demonstrating the effectiveness of melatonin in vivo in reducing ischemia-induced cerebral edema using magnetic resonance imaging (MRI). Rats were subjected to middle cerebral artery (MCA) occlusion/reperfusion surgery. Melatonin was administered twice (6.0 mg/kg, p.o.) just prior to 1 hr of MCA occlusion and 1 day after the surgery. T2-weighted multislice spin-echo images were acquired 1 day after the surgery. In the saline-treated control rats, increases in T2-weighted signals (water content) were clearly observed in the striatum and in the cerebral cortex. In the melatonin-treated group, total volume of edema was reduced by 51.6% compared with control group (P < 0.01). The protective effect of melatonin against edema was more clearly observed in the cerebral cortex (reduced by 59.8%, P < 0.01) than in the striatum (reduced by 34.2%, P < 0.05). Edema volume in a coronal slice was the greatest at the level of the bregma. Suppression of cerebral edema by melatonin was more effective posterior than anterior to the bregma. Melatonin appeared to reduce the volume of the edematous sites rather than to shift the signal intensity distribution. The present MRI study clearly demonstrates the effectiveness of melatonin against cerebral edema formation in ischemic animals in vivo, especially in the cerebral cortex. Melatonin may be highly useful in preventing cortical dysfunctions such as motor, sensory, memory, and psychological impairments associated with ischemic stroke.

  5. Whole-Brain CT Perfusion to Quantify Acute Ischemic Penumbra and Core.

    PubMed

    Lin, Longting; Bivard, Andrew; Krishnamurthy, Venkatesh; Levi, Christopher R; Parsons, Mark W

    2016-06-01

    Purpose To validate the use of perfusion computed tomography (CT) with whole-brain coverage to measure the ischemic penumbra and core and to compare its performance to that of limited-coverage perfusion CT. Materials and Methods Institutional ethics committee approval and informed consent were obtained. Patients (n = 296) who underwent 320-detector CT perfusion within 6 hours of the onset of ischemic stroke were studied. First, the ischemic volume at CT perfusion was compared with the penumbra and core reference values at magnetic resonance (MR) imaging to derive CT perfusion penumbra and core thresholds. Second, the thresholds were tested in a different group of patients to predict the final infarction at diffusion-weighted imaging 24 hours after CT perfusion. Third, the change in ischemic volume delineated by the optimal penumbra and core threshold was determined as the brain coverage was gradually reduced from 160 mm to 20 mm. The Wilcoxon signed-rank test, concordance correlation coefficient (CCC), and analysis of variance were used for the first, second, and third steps, respectively. Results CT perfusion at penumbra and core thresholds resulted in the least volumetric difference from MR imaging reference values with delay times greater than 3 seconds and delay-corrected cerebral blood flow of less than 30% (P = .34 and .33, respectively). When the thresholds were applied to the new group of patients, prediction of the final infarction was allowed with delay times greater than 3 seconds in patients with no recanalization of the occluded artery (CCC, 0.96 [95% confidence interval: 0.92, 0.98]) and with delay-corrected cerebral blood flow less than 30% in patients with complete recanalization (CCC, 0.91 [95% confidence interval: 0.83, 0.95]). However, the ischemic volume with a delay time greater than 3 seconds was underestimated when the brain coverage was reduced to 80 mm (P = .04) and the core volume measured as cerebral blood flow less than 30% was

  6. Can Accelerators Accelerate Learning?

    NASA Astrophysics Data System (ADS)

    Santos, A. C. F.; Fonseca, P.; Coelho, L. F. S.

    2009-03-01

    The 'Young Talented' education program developed by the Brazilian State Funding Agency (FAPERJ) [1] makes it possible for high-schools students from public high schools to perform activities in scientific laboratories. In the Atomic and Molecular Physics Laboratory at Federal University of Rio de Janeiro (UFRJ), the students are confronted with modern research tools like the 1.7 MV ion accelerator. Being a user-friendly machine, the accelerator is easily manageable by the students, who can perform simple hands-on activities, stimulating interest in physics, and getting the students close to modern laboratory techniques.

  7. Can Accelerators Accelerate Learning?

    SciTech Connect

    Santos, A. C. F.; Fonseca, P.; Coelho, L. F. S.

    2009-03-10

    The 'Young Talented' education program developed by the Brazilian State Funding Agency (FAPERJ)[1] makes it possible for high-schools students from public high schools to perform activities in scientific laboratories. In the Atomic and Molecular Physics Laboratory at Federal University of Rio de Janeiro (UFRJ), the students are confronted with modern research tools like the 1.7 MV ion accelerator. Being a user-friendly machine, the accelerator is easily manageable by the students, who can perform simple hands-on activities, stimulating interest in physics, and getting the students close to modern laboratory techniques.

  8. Hyperpolarized 129Xe magnetic resonance imaging of a rat model of transient Ischemic Stroke

    NASA Astrophysics Data System (ADS)

    Walvick, Ronn P.; Bastan, Birgul; Reno, Austin; Mansour, Joey; Sun, Yanping; Zhou, Xin; Mazzani, Mary; Fisher, Marc; Sotak, Christopher H.; Albert, Mitchell S.

    2009-02-01

    Ischemic stroke accounts for nearly 80% of all stroke cases. Although proton diffusion and perfusion magnetic resonance imaging (MRI) are the gold standards in ischemic stroke diagnostics, the use of hyperpolarized 129Xe MRI has a potential role to contribute to the diagnostic picture. The highly lipophilic hyperpolarized 129Xe can be non-invasively delivered via inhalation into the lungs where it is dissolved into the blood and delivered to other organs such as the brain. As such, we expect hyperpolarized 129Xe to act as a perfusion tracer which will result in a signal deficit in areas of blood deprived tissue. In this work, we present imaging results from an animal model of transient ischemic stroke characterized through 129Xe MRI. In this model, a suture is used to occlude the middle cerebral artery (MCA) in the rat brain, thus causing an ischemic event. After a period of MCA occlusion, the suture can then be removed to reperfuse the ischemic area. During the ischemic phase of the stroke, a signal void was observed in the MCA territory; which was subsequently restored by normal 129Xe MRI signal once perfusion was reinstated. Further, a higher resolution one-dimensional chemical shift image shows a sharp signal drop in the area of ischemia. Validation of ischemic damage was shown through both proton diffusion-weighted MRI (DWI) and by 2,3,5-triphenyltetrazoliumchloride (TTC) staining. The results show the potential of 129Xe to act as a perfusion tracer; information that may add to the diagnostic and prognostic utility of the clinical picture of stroke.

  9. Polyhydroxylated fullerene nanoparticles attenuate brain infarction and oxidative stress in rat model of ischemic stroke

    PubMed Central

    Vani, Javad Rasouli; Mohammadi, Mohammad Taghi; Foroshani, Mahsa Sarami; Jafari, Mahvash

    2016-01-01

    Oxidative stress is the common underlying mechanism of damage in ischemic stroke. Therefore, we aimed to evaluate the possible protective effects of polyhydroxylated fullerene derivatives on brain infarction and oxidative/nitrosative stress in a rat model of ischemic stroke. The experiment was performed by four groups of rats (each; n=12); Sham, Control ischemia, and ischemic treatment groups (Pretreatment and Posttreatment). Brain ischemia was induced by 90 min middle cerebral artery occlusion (MCAO) followed by 24 hours reperfusion. Rats received fullerene nanoparticles at dose of 1 mg/kg 30 min before MCAO and immediately after beginning of reperfusion. Infarct volume, contents of malondialdehyde (MDA), glutathione (GSH) and nitrate as well as superoxide dismutase (SOD) activity were assessed 24 hours after termination of MCAO. Brain infarct volume was 310 ± 21 mm3 in control group. Administration of fullerene nanoparticles before and after MCAO significantly decreased the infarct volume by 53 % (145 ± 45 mm3) and 81 % (59 ± 13 mm3), respectively. Ischemia also enhanced MDA and nitrate contents of ischemic hemispheres by 45 % and 25 % , respectively. Fullerene nanoparticles considerably reduced the MDA and nitrate contents of ischemic hemispheres before MCAO by 58 % and 17 % , respectively, and after MCAO by 38 % and 21 % , respectively. Induction of MCAO significantly decreased GSH content (19 % ) and SOD activity (52 % ) of ischemic hemispheres, whereas fullerene nanoparticles increased the GSH content and SOD activity of ischemic hemispheres by 19 % and 52 % before MCAO, respectively, and 21 % and 55 % after MCAO, respectively. Our findings indicate that fullerene nanoparticles, as a potent scavenger of free radicals, protect the brain cells against ischemia/reperfusion injury and inhibit brain oxidative/nitrosative damage. PMID:27540350

  10. [Phenomenon of heart ischemic postconditioning].

    PubMed

    Maslov, L N; Mrochek, A G; Hanus, L; Pei, J -M; Zhang, Y; Wang, H; Naryzhnaia, N V

    2012-08-01

    Authors of review analyzed papers on problem of heart ischemic postconditioning. In the review, it was demonstrated that postconditioning decreased an infarct size, prevented cardiomyocytes apoptosis, improved cardiac contractility in reperfusion period, augmented cardiac tolerance to arrhythmogenic impact ofreperfusion, prevented neutrophil invasion into the reperfused heart, abolished reperfusion endothelial dysfunction and suppressed reperfusion oxidative stress in myocardium. PMID:23155619

  11. A Review of the Mechanisms of Blood-Brain Barrier Permeability by Tissue-Type Plasminogen Activator Treatment for Cerebral Ischemia

    PubMed Central

    Suzuki, Yasuhiro; Nagai, Nobuo; Umemura, Kazuo

    2016-01-01

    Cerebrovascular homeostasis is maintained by the blood-brain barrier (BBB), which forms a mechanical and functional barrier between systemic circulation and the central nervous system (CNS). In patients with ischemic stroke, the recombinant tissue-type plasminogen activator (rt-PA) is used to accelerate recanalization of the occluded vessels. However, rt-PA is associated with a risk of increasing intracranial bleeding (ICB). This effect is thought to be caused by the increase in cerebrovascular permeability though various factors such as ischemic reperfusion injury and the activation of matrix metalloproteinases (MMPs), but the detailed mechanisms are unknown. It was recently found that rt-PA treatment enhances BBB permeability not by disrupting the BBB, but by activating the vascular endothelial growth factor (VEGF) system. The VEGF regulates both the dissociation of endothelial cell (EC) junctions and endothelial endocytosis, and causes a subsequent increase in vessel permeability through the VEGF receptor-2 (VEGFR-2) activation in ECs. Here, we review the possibility that rt-PA increases the penetration of toxic molecules derived from the bloodstream including rt-PA itself, without disrupting the BBB, and contributes to these detrimental processes in the cerebral parenchyma. PMID:26834557

  12. [Progress on Hypoxic-ischemic Brain Damage Associated with CCR2 and CCL2].

    PubMed

    Luo, Yu-jia; Li, Ru-bo; Ma, Shi-yu; Lü, Meng-yan

    2016-02-01

    Hypoxic-ischemic brain damage (HIBD) is referred to a common type of cerebral damage, which is caused by injury, leading to shallow bleeding in the cortex with intact cerebral pia mater. In recent years, studies show that a various kinds of immune cells and immune cellular factors are involved in the occurrence of HIBD. CC chemokine receptor 2 (CCR2) is a representative of CC chemokine receptor, and is widely distributed in cerebral neuron, astrocyte, and microglial cells, and is the main chemo-tactic factor receptor in brain tissue. CC chemokine ligand 2 (CCL2) is a kind of basophilic protein and the ligand of CCR2, and plays an important role in inflammation. In order to provide evidence for correlational studies in HIBD, this review will introduce the biological characteristics of CCR2 and CCL2, and illustrate the relationship between the immunoreactivity and HIBD. PMID:27295859

  13. Conventional protein kinase Cβ-mediated phosphorylation inhibits collapsin response-mediated protein 2 proteolysis and alleviates ischemic injury in cultured cortical neurons and ischemic stroke-induced mice.

    PubMed

    Yang, Xuan; Zhang, Xinxin; Li, Yun; Han, Song; Howells, David W; Li, Shujuan; Li, Junfa

    2016-05-01

    We previously reported that conventional protein kinase C (cPKC)β participated in hypoxic preconditioning-induced neuroprotection against cerebral ischemic injury, and collapsin response-mediated protein 2 (CRMP2) was identified as a cPKCβ interacting protein. In this study, we explored the regulation of CRMP2 phosphorylation and proteolysis by cPKCβ, and their role in ischemic injury of oxygen-glucose deprivation (OGD)-treated cortical neurons and brains of mice with middle cerebral artery occlusion-induced ischemic stroke. The results demonstrated that cPKCβ-mediated CRMP2 phosphorylation via the cPKCβ-selective activator 12-deoxyphorbol 13-phenylacetate 20-acetate (DOPPA) and inhibition of calpain-mediated CRMP2 proteolysis by calpeptin and a fusing peptide containing TAT peptide and the calpain cleavage site of CRMP2 (TAT-CRMP2) protected neurons against OGD-induced cell death through inhibiting CRMP2 proteolysis in cultured cortical neurons. The OGD-induced nuclear translocation of the CRMP2 breakdown product was inhibited by DOPPA, calpeptin, and TAT-CRMP2 in cortical neurons. In addition, both cPKCβ activation and CRMP2 proteolysis inhibition by hypoxic preconditioning and intracerebroventricular injections of DOPPA, calpeptin, and TAT-CRMP2 improved the neurological deficit in addition to reducing the infarct volume and proportions of cells with pyknotic nuclei in the peri-infact region of mice with ischemic stroke. These results suggested that cPKCβ modulates CRMP2 phosphorylation and proteolysis, and cPKCβ activation alleviates ischemic injury in the cultured cortical neurons and brains of mice with ischemic stroke through inhibiting CRMP2 proteolysis by phosphorylation. Focal cerebral ischemia induces a large flux of Ca(2+) to activate calpain which cleaves collapsin response mediator (CRMP) 2 into breakdown product (BDP). Inhibition of CRMP2 cleavage by calpeptin and TAT-CRMP2 alleviates ischemic injury. Conventional protein kinase C (c

  14. Ligustrazine monomer against cerebral ischemia/reperfusion injury.

    PubMed

    Gao, Hai-Jun; Liu, Peng-Fei; Li, Pei-Wen; Huang, Zhuo-Yan; Yu, Feng-Bo; Lei, Ting; Chen, Yong; Cheng, Ye; Mu, Qing-Chun; Huang, Hai-Yan

    2015-05-01

    Ligustrazine (2,3,5,6-tetramethylpyrazine) is a major active ingredient of the Szechwan lovage rhizome and is extensively used in treatment of ischemic cerebrovascular disease. The mechanism of action of ligustrazine use against ischemic cerebrovascular diseases remains unclear at present. This study summarizes its protective effect, the optimum time window of administration, and the most effective mode of administration for clinical treatment of cerebral ischemia/reperfusion injury. We examine the effects of ligustrazine on suppressing excitatory amino acid release, promoting migration, differentiation and proliferation of endogenous neural stem cells. We also looked at its effects on angiogenesis and how it inhibits thrombosis, the inflammatory response, and apoptosis after cerebral ischemia. We consider that ligustrazine gives noticeable protection from cerebral ischemia/reperfusion injury. The time window of ligustrazine administration is limited. The protective effect and time window of a series of derivative monomers of ligustrazine such as 2-[(1,1-dimethylethyl)oxidoimino]methyl]-3,5,6-trimethylpyrazine, CXC137 and CXC195 after cerebral ischemia were better than ligustrazine. PMID:26109963

  15. Ozone Therapy on Cerebral Blood Flow: A Preliminary Report

    PubMed Central

    2004-01-01

    Ozone therapy is currently being used in the treatment of ischemic disorders, but the underlying mechanisms that result in successful treatment are not well known. This study assesses the effect of ozone therapy on the blood flow in the middle cerebral and common carotid arteries. Seven subjects were recruited for the therapy that was performed by transfusing ozone-enriched autologous blood on 3 alternate days over 1 week. Blood flow quantification in the common carotid artery (n = 14) was performed using color Doppler. Systolic and diastolic velocities in the middle cerebral artery (n = 14) were estimated using transcranial Doppler. Ultrasound assessments were conducted at the following three time points: 1) basal (before ozone therapy), 2) after session #3 and 3) 1 week after session #3. The common carotid blood flow had increased by 75% in relation to the baseline after session #3 (P < 0.001) and by 29% 1 week later (P = 0.039). In the middle cerebral artery, the systolic velocity had increased by 22% after session #3 (P = 0.001) and by 15% 1 week later (P = 0.035), whereas the diastolic velocity had increased by 33% after session #3 (P < 0.001) and by 18% 1 week later (P = 0.023). This preliminary Doppler study supports the clinical experience of achieving improvement by using ozone therapy in peripheral ischemic syndromes. Its potential use as a complementary treatment in cerebral low perfusion syndromes merits further clinical evaluation. PMID:15841265

  16. Cerebral Contusions and Lacerations

    MedlinePlus

    ... Stretch Additional Content Medical News Cerebral Contusions and Lacerations By James E. Wilberger, MD, Derrick A. Dupre, ... a direct, strong blow to the head. Cerebral lacerations are tears in brain tissue, caused by a ...

  17. Cerebral aneurysm (image)

    MedlinePlus

    ... area within the vessel wall. If a cerebral (brain) aneurysm ruptures, the escaping blood within the brain may cause severe neurologic complications or death. A person who has a ruptured cerebral aneurysm may complain of the sudden onset of "the ...

  18. United Cerebral Palsy

    MedlinePlus

    ... be sure to follow us on Twitter . United Cerebral Palsy UCP educates, advocates and provides support services to ... Partners Merz Logo Sprint Relay Copyright © 2015 United Cerebral Palsy 1825 K Street NW Suite 600 Washington, DC ...

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

    PubMed Central

    Lan, Zujian; Xu, Xiaoyu; Xu, Wenkai; Li, Jin; Liang, Zengrong; Zhang, Xuefei; Lei, Ming; Zhao, Chunshun

    2015-01-01

    To develop novel anti-ischemic stroke agents with better therapeutic efficacy and bioavailability, we designed and synthesized a series of 3-alkyl-2,3-dihydro-1H-isoindol-1-ones compounds (3a–i) derivatives, one of which (3d) exhibited the strongest inhibitory activity for the adenosine diphosphate-induced and arachidonic acid-induced platelet aggregation. This activity is superior to that of 3-n-butylphthalide and comparable with aspirin and edaravone. Meanwhile, 3d not only exhibited a potent activity in scavenging free radicals and improving the survival of HT22 cells against the reactive oxygen species-mediated cytotoxicity in vitro but also significantly attenuated the ischemia/reperfusion-induced oxidative stress in ischemic rat brains. Results from transient middle cerebral artery occlusion and permanent middle cerebral artery occlusion model, indicated that 3d could significantly reduce infarct size, improve neurobehavioral deficits, and prominently decrease attenuation of cerebral damage. Most importantly, 3d possessed a very high absolute bioavailability and was rapidly distributed in brain tissue to keep high plasma drug concentration for the treatment of ischemic strokes. In conclusion, our findings suggest that 3-alkyl-2,3-dihydro-1H-isoindol-1-ones, a novel series of compounds, might be candidate drugs for the treatment of acute ischemic strokes, and 3d may be a promising therapeutic agent for the primary and secondary prevention of ischemic stroke. PMID:26170623

  20. Hemodynamic and metabolic effects of cerebral revascularization.

    PubMed

    Leblanc, R; Tyler, J L; Mohr, G; Meyer, E; Diksic, M; Yamamoto, L; Taylor, L; Gauthier, S; Hakim, A

    1987-04-01

    Pre- and postoperative positron emission tomography (PET) was performed in six patients undergoing extracranial to intracranial bypass procedures for the treatment of symptomatic extracranial carotid occlusion. The six patients were all men, aged 52 to 68 years. Their symptoms included transient ischemic attacks (five cases), amaurosis fugax (two cases), and completed stroke with good recovery (one case). Positron emission tomography was performed within 4 weeks prior to surgery and between 3 to 6 months postoperatively, using oxygen-15-labeled CO, O2, and CO2 and fluorine-18-labeled fluorodeoxyglucose. Cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolic rates for oxygen and glucose (CMRO2 and CMRGlu), and the oxygen extraction fraction (OEF) were measured in both hemispheres. Preoperatively, compared to five elderly control subjects, patients had increased CBV, a decreased CBF/CBV ratio, and decreased CMRO2, indicating reduced cerebral perfusion pressure and depressed oxygen metabolism. The CBF was decreased in only one patient who had bilateral carotid occlusions; the OEF, CMRGlu, and CMRO2/CMRGlu and CMRGlu/CBF ratios were not significantly different from control measurements. All bypasses were patent and all patients were asymptomatic following surgery. Postoperative PET revealed decreased CBV and an increased CBF/CBV ratio, indicating improved hemodynamic function and oxygen hypometabolism. This was associated with increased CMRO2 in two patients in whom the postoperative OEF was also increased. The CMRGlu and CMRGlu/CBF ratio were increased in five patients. Changes in CBF and the CMRO2/CMRGlu ratio were variable. One patient with preoperative progressive mental deterioration, documented by serial neuropsychological testing and decreasing CBF and CMRO2, had improved postoperative CBF and CMRO2 concomitant with improved neuropsychological functioning. It is concluded that symptomatic carotid occlusion is associated with altered

  1. Aging and Cerebral Palsy.

    ERIC Educational Resources Information Center

    Networker, 1993

    1993-01-01

    This special edition of "The Networker" contains several articles focusing on aging and cerebral palsy (CP). "Aging and Cerebral Palsy: Pathways to Successful Aging" (Jenny C. Overeynder) reports on the National Invitational Colloquium on Aging and Cerebral Palsy held in April 1993. "Observations from an Observer" (Kathleen K. Barrett) describes…

  2. White Matter Ischemic Changes in Hyperacute Ischemic Stroke

    PubMed Central

    Trouard, Theodore P; Lafleur, Scott R.; Krupinski, Elizabeth A.; Salamon, Noriko; Kidwell, Chelsea S.

    2015-01-01

    Background and Purpose— The purpose of this study was to evaluate changes in fractional anisotropy (FA), as measured by diffusion tensor imaging, of white matter (WM) infarction and hypoperfusion in patients with acute ischemic stroke using a quantitative voxel-based analysis. Methods— In this prospective study, diffusion tensor imaging and dynamic susceptibility contrast perfusion sequences were acquired in 21 patients with acute ischemic stroke who presented within 6 hours of symptom onset. The coregistered FA, apparent diffusion coefficient, and dynamic susceptibility contrast time to maximum (Tmax) maps were used for voxel-based quantification using a region of interest approach in the ipsilateral affected side and in the homologous contralateral WM. The regions of WM infarction versus hypoperfusion were segmented using a threshold method. Data were analyzed by regression and ANOVA. Results— There was an overall significant mean difference (P<0.001) for the apparent diffusion coefficient, Tmax, and FA values between the normal, hypoperfused, and infarcted WM. The mean±SD of FA was significantly higher (P<0.001) in hypoperfused WM (0.397±0.019) and lower (P<0.001) in infarcted WM (0.313±0.037) when compared with normal WM (0.360±0.020). Regression tree analysis of hypoperfused WM showed the largest mean FA difference at Tmax above versus below 5.4 s with a mean difference of 0.033 (P=0.0096). Conclusions— Diffusion tensor imaging-FA was decreased in regions of WM infarction and increased in hypoperfused WM in patients with hyperacute acute ischemic stroke. The significantly increased FA values in the hypoperfused WM with Tmax≥5.4 s are suggestive of early ischemic microstructural changes. PMID:25523053

  3. Complete occlusion of the right middle cerebral artery associated with Mycoplasma pneumoniae pneumonia

    PubMed Central

    Kang, Ben; Kim, Dong Hyun; Hong, Young Jin; Son, Byong Kwan; Lim, Myung Kwan; Choe, Yon Ho

    2016-01-01

    We report a case of a 5-year-old girl who developed left hemiparesis and left facial palsy, 6 days after the initiation of fever and respiratory symptoms due to pneumonia. Chest radiography, conducted upon admission, showed pneumonic infiltration and pleural effusion in the left lung field. Brain magnetic resonance imaging showed acute ischemic infarction in the right middle cerebral artery territory. Brain magnetic resonance angiography and transfemoral cerebral angiography revealed complete occlusion of the right middle cerebral artery. Mycoplasma pneumoniae infection was identified by a 4-fold increase in IgG antibodies to M. pneumoniae between acute and convalescent sera by enzyme-linked immunosorbent assay. Fibrinogen and D-dimer levels were elevated, while laboratory exams in order to identify other predisposing factors of pediatric stroke were all negative. This is the first reported pediatric case in English literature of a M. pneumoniae-associated cerebral infarction involving complete occlusion of the right middle cerebral artery. PMID:27186223

  4. The influence of the amyloid ß-protein and its precursor in modulating cerebral hemostasis.

    PubMed

    Van Nostrand, William E

    2016-05-01

    Ischemic and hemorrhagic strokes are a significant cause of brain injury leading to vascular cognitive impairment and dementia (VCID). These deleterious events largely result from disruption of cerebral hemostasis, a well-controlled and delicate balance between thrombotic and fibrinolytic pathways in cerebral blood vessels and surrounding brain tissue. Ischemia and hemorrhage are both commonly associated with cerebrovascular deposition of amyloid ß-protein (Aß). In this regard, Aß directly and indirectly modulates cerebral thrombosis and fibrinolysis. Further, major isoforms of the Aß precursor protein (AßPP) function as a potent inhibitor of pro-thrombotic proteinases. The purpose of this review article is to summarize recent research on how cerebral vascular Aß and AßPP influence cerebral hemostasis. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia, edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. PMID:26519139

  5. [Two Cases of Ruptured Cerebral Aneurysm Complicated with Delayed Coil Protrusion after Coil Embolization].

    PubMed

    Furukawa, Takashi; Ogata, Atsushi; Ebashi, Ryo; Takase, Yukinori; Masuoka, Jun; Kawashima, Masatou; Abe, Tatsuya

    2016-07-01

    We report two cases of delayed coil protrusion after coil embolization for ruptured cerebral aneurysms. Case 1:An 82-year-old woman with a subarachnoid hemorrhage due to a ruptured small anterior communicating artery aneurysm underwent successful coil embolization. Eighteen days after the procedure, coil protrusion from the aneurysm into the right anterior cerebral artery was observed without any symptoms. Further coil protrusion did not develop after 28 days. Case 2:A 78-year-old woman with a subarachnoid hemorrhage due to a ruptured small left middle cerebral artery aneurysm underwent successful coil embolization. Twenty days after the procedure, coil protrusion from the aneurysm into the left middle cerebral artery was observed, with a transient ischemic attack. Further coil protrusion did not develop. Both patients recovered with antithrombotic treatment. Even though delayed coil protrusion after coil embolization is rare, it should be recognized as a long-term complication of coil embolization for cerebral aneurysms. PMID:27384117

  6. Role of Histamine and Its Receptors in Cerebral Ischemia

    PubMed Central

    2012-01-01

    Histamine is recognized as a neurotransmitter or neuromodulator in the brain, and it plays a major role in the pathogenic progression after cerebral ischemia. Extracellular histamine increases gradually after ischemia, and this may come from histaminergic neurons or mast cells. Histamine alleviates neuronal damage and infarct volume, and it promotes recovery of neurological function after ischemia; the H1, H2, and H3 receptors are all involved. Further studies suggest that histamine alleviates excitotoxicity, suppresses the release of glutamate and dopamine, and inhibits inflammation and glial scar formation. Histamine may also affect cerebral blood flow by targeting to vascular smooth muscle cells, and promote neurogenesis. Moreover, endogenous histamine is an essential mediator in the cerebral ischemic tolerance. Due to its multiple actions, affecting neurons, glia, vascular cells, and inflammatory cells, histamine is likely to be an important target in cerebral ischemia. But due to its low penetration of the blood-brain barrier and its wide actions in the periphery, histamine-related agents, like H3 antagonists and carnosine, show potential for cerebral ischemia therapy. However, important questions about the molecular aspects and pathophysiology of histamine and related agents in cerebral ischemia remain to be answered to form a solid scientific basis for therapeutic application. PMID:22860191

  7. Cerebral vascular regulation and brain injury in preterm infants.

    PubMed

    Brew, Nadine; Walker, David; Wong, Flora Y

    2014-06-01

    Cerebrovascular lesions, mainly germinal matrix hemorrhage and ischemic injury to the periventricular white matter, are major causes of adverse neurodevelopmental outcome in preterm infants. Cerebrovascular lesions and neuromorbidity increase with decreasing gestational age, with the white matter predominantly affected. Developmental immaturity in the cerebral circulation, including ongoing angiogenesis and vasoregulatory immaturity, plays a major role in the severity and pattern of preterm brain injury. Prevention of this injury requires insight into pathogenesis. Cerebral blood flow (CBF) is low in the preterm white matter, which also has blunted vasoreactivity compared with other brain regions. Vasoreactivity in the preterm brain to cerebral perfusion pressure, oxygen, carbon dioxide, and neuronal metabolism is also immature. This could be related to immaturity of both the vasculature and vasoactive signaling. Other pathologies arising from preterm birth and the neonatal intensive care environment itself may contribute to impaired vasoreactivity and ineffective CBF regulation, resulting in the marked variations in cerebral hemodynamics reported both within and between infants depending on their clinical condition. Many gaps exist in our understanding of how neonatal treatment procedures and medications have an impact on cerebral hemodynamics and preterm brain injury. Future research directions for neuroprotective strategies include establishing cotside, real-time clinical reference values for cerebral hemodynamics and vasoregulatory capacity and to demonstrate that these thresholds improve long-term outcomes for the preterm infant. In addition, stimulation of vascular development and repair with growth factor and cell-based therapies also hold promise.

  8. The emotional stress and risk of ischemic stroke.

    PubMed

    Kotlęga, Dariusz; Gołąb-Janowska, Monika; Masztalewicz, Marta; Ciećwież, Sylwester; Nowacki, Przemysław

    2016-01-01

    Stroke is the second leading cause of death worldwide, and the leading cause of acquired disability in adults in most regions. There have been distinguished modifiable and non-modifiable risk factors of stroke. Among them the emotional stress was presented as a risk factor. The aim of this review was to present available data regarding the influence of acute and chronic mental stress on the risk of ischemic stroke as well as discussing the potential pathomechanisms of such relationship. There is an evident association between both acute and chronic emotional stress and risk of stroke. Several potential mechanisms are discussed to be the cause. Stress can increase the cerebrovascular disease risk by modulating symphaticomimetic activity, affecting the blood pressure reactivity, cerebral endothelium, coagulation or heart rhythm. The emotional stress seems to be still underestimated risk factor in neurological practice and research. Further studies and analyses should be provided for better understanding of this complex, not fully known epidemiological problem.

  9. [The neurovascular unit in health and ischemic stroke].

    PubMed

    Ago, Tetsuro

    2016-04-01

    The neurovascular unit (NVU), a minimal unit to exert neurological functions, is composed of neurons, astrocytes, endothelial cells, pericytes, and extracellular matrix proteins forming basal membranes. The cell components interact with one another and function cooperatively under both physiological and pathological conditions. Pericytes and astrocytes participate crucially in the formation and maintenance of the blood-brain barrier (BBB), the tight junction formed by endothelial cells, and regulate cerebral blood flow in response to neurological activities. The BBB actively regulate molecular import and export. The concept of the NVU is also useful for understanding pathogenesis and exploring therapeutic targets in various CNS disorders. In this review, recent research advances regarding the NVU and its components in health and ischemic stroke are summarized. PMID:27333744

  10. Ischemic stroke injury is mediated by aberrant Cdk5.

    PubMed

    Meyer, Douglas A; Torres-Altoro, Melissa I; Tan, Zhenjun; Tozzi, Alessandro; Di Filippo, Massimiliano; DiNapoli, Vincent; Plattner, Florian; Kansy, Janice W; Benkovic, Stanley A; Huber, Jason D; Miller, Diane B; Greengard, Paul; Calabresi, Paolo; Rosen, Charles L; Bibb, James A

    2014-06-11

    Ischemic stroke is one of the leading causes of morbidity and mortality. Treatment options are limited and only a minority of patients receive acute interventions. Understanding the mechanisms that mediate neuronal injury and death may identify targets for neuroprotective treatments. Here we show that the aberrant activity of the protein kinase Cdk5 is a principal cause of neuronal death in rodents during stroke. Ischemia induced either by embolic middle cerebral artery occlusion (MCAO) in vivo or by oxygen and glucose deprivation in brain slices caused calpain-dependent conversion of the Cdk5-activating cofactor p35 to p25. Inhibition of aberrant Cdk5 during ischemia protected dopamine neurotransmission, maintained field potentials, and blocked excitotoxicity. Furthermore, pharmacological inhibition or conditional knock-out (CKO) of Cdk5 prevented neuronal death in response to ischemia. Moreover, Cdk5 CKO dramatically reduced infarctions following MCAO. Thus, targeting aberrant Cdk5 activity may serve as an effective treatment for stroke.

  11. Guidelines for the prevention of stroke in patients with stroke or transient ischemic attack: a guideline for healthcare professionals from the american heart association/american stroke association.

    PubMed

    Furie, Karen L; Kasner, Scott E; Adams, Robert J; Albers, Gregory W; Bush, Ruth L; Fagan, Susan C; Halperin, Jonathan L; Johnston, S Claiborne; Katzan, Irene; Kernan, Walter N; Mitchell, Pamela H; Ovbiagele, Bruce; Palesch, Yuko Y; Sacco, Ralph L; Schwamm, Lee H; Wassertheil-Smoller, Sylvia; Turan, Tanya N; Wentworth, Deidre

    2011-01-01

    The aim of this updated statement is to provide comprehensive and timely evidence-based recommendations on the prevention of ischemic stroke among survivors of ischemic stroke or transient ischemic attack. Evidence-based recommendations are included for the control of risk factors, interventional approaches for atherosclerotic disease, antithrombotic treatments for cardioembolism, and the use of antiplatelet agents for noncardioembolic stroke. Further recommendations are provided for the prevention of recurrent stroke in a variety of other specific circumstances, including arterial dissections; patent foramen ovale; hyperhomocysteinemia; hypercoagulable states; sickle cell disease; cerebral venous sinus thrombosis; stroke among women, particularly with regard to pregnancy and the use of postmenopausal hormones; the use of anticoagulation after cerebral hemorrhage; and special approaches to the implementation of guidelines and their use in high-risk populations.

  12. Heart Failure in Acute Ischemic Stroke

    PubMed Central

    Cuadrado-Godia, Elisa; Ois, Angel; Roquer, Jaume

    2010-01-01

    Heart failure (HF) is a complex clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood. Due to the aging of the population it has become a growing public health problem in recent decades. Diagnosis of HF is clinical and there is no diagnostic test, although some basic complementary testing should be performed in all patients. Depending on the ejection fraction (EF), the syndrome is classified as HF with low EF or HF with normal EF (HFNEF). Although prognosis in HF is poor, HFNEF seems to be more benign. HF and ischemic stroke (IS) share vascular risk factors such as age, hypertension, diabetes mellitus, coronary artery disease and atrial fibrillation. Persons with HF have higher incidence of IS, varying from 1.7% to 10.4% per year across various cohort studies. The stroke rate increases with length of follow-up. Reduced EF, independent of severity, is associated with higher risk of stroke. Left ventricular mass and geometry are also related with stroke incidence, with concentric hypertrophy carrying the greatest risk. In HF with low EF, the stroke mechanism may be embolism, cerebral hypoperfusion or both, whereas in HFNEF the mechanism is more typically associated with chronic endothelial damage of the small vessels. Stroke in patients with HF is more severe and is associated with a higher rate of recurrence, dependency, and short term and long term mortality. Cardiac morbidity and mortality is also high in these patients. Acute stroke treatment in HF includes all the current therapeutic options to more carefully control blood pressure. For secondary prevention, optimal control of all vascular risk factors is essential. Antithrombotic therapy is mandatory, although the choice of a platelet inhibitor or anticoagulant drug depends on the cardiac disease. Trials are ongoing to evaluate anticoagulant therapy for prevention of embolism in patients with low EF who are at

  13. Dietary Sutherlandia and Elderberry Mitigate Cerebral Ischemia-Induced Neuronal Damage and Attenuate p47phox and Phospho-ERK1/2 Expression in Microglial Cells

    PubMed Central

    Chuang, Dennis Y.; Cui, Jiankun; Simonyi, Agnes; Engel, Victoria A.; Chen, Shanyan; Fritsche, Kevin L.; Thomas, Andrew L.; Applequist, Wendy L.; Folk, William R.; Lubahn, Dennis B.; Sun, Albert Y.; Sun, Grace Y.

    2014-01-01

    Sutherlandia (Sutherlandia frutescens) and elderberry (Sambucus spp.) are used to promote health and for treatment of a number of ailments. Although studies with cultured cells have demonstrated antioxidative and anti-inflammatory properties of these botanicals, little is known about their ability to mitigate brain injury. In this study, C57BL/6 J male mice were fed AIN93G diets without or with Sutherlandia or American elderberry for 2 months prior to a 30-min global cerebral ischemia induced by occlusion of the bilateral common carotid arteries (BCCAs), followed by reperfusion for 3 days. Accelerating rotarod assessment at 24 h after BCCA occlusion showed amelioration of sensorimotor impairment in the mice fed the supplemented diets as compared with the ischemic mice fed the control diet. Quantitative digital pathology assessment of brain slides stained with cresyl violet at 3 days after ischemia/reperfusion (I/R) revealed significant reduction in neuronal cell death in both dietary groups. Immunohistochemical staining for ionized calcium-binding adapter molecule-1 demonstrated pronounced activation of microglia in the hippocampus and striatum in the ischemic brains 3 days after I/R, and microglial activation was significantly reduced in animals fed supplemented diets. Mitigation of microglial activation by the supplements was further supported by the decrease in expression of p47phox, a cytosolic subunit of NADPH oxidase, and phospho-ERK1/2, a mitogen-activated protein kinase known to mediate a number of cytoplasmic processes including oxidative stress and neuroinflammatory responses. These results demonstrate neuroprotective effect of Sutherlandia and American elderberry botanicals against oxidative and inflammatory responses to cerebral I/R. PMID:25324465

  14. Middle cerebral-anterior cerebral-radial artery interposition graft bypass for proximal anterior cerebral artery aneurysm.

    PubMed

    Kazumata, Ken; Asaoka, Katsuyuki; Yokoyama, Yuka; Osanai, Toshiya; Sugiyama, Taku; Itamoto, Kouji

    2011-01-01

    A 74-year-old man underwent pterional craniotomy to treat a left proximal anterior cerebral artery (ACA) aneurysm. The orifice of the aneurysm was located at the origin of the proximal segment of the ACA, and the right A(1) segment of ACA was hypoplastic. After failed attempts at neck plasty with fenestrated clips, trapping and bypass were performed. Superficial temporal to left frontopolar artery bypass was performed to secure minimal blood supply. The radial artery (RA) was then harvested, and middle cerebral artery (MCA) to A(1) segment of the ACA bypass was performed using the RA interposition graft. Trapping of the aneurysm was successfully achieved without ischemic event. Intracranial-intracranial bypass has been employed in the treatment of complex cerebral aneurysm in an increasing number of selected patients. The present case shows that MCA-ACA-RA interposition graft bypass is an effective procedure to provide blood supply to the ACA territory if a proximal A(1) lesion requires trapping with incompetent contralateral A(1).

  15. ORTHO-LBNP: A new apparatus for assessing autocontrol mechanisms of the heart-vessel system in pilots undergoing training in conditions of ischemic hypoxia and orthostatic stress

    NASA Astrophysics Data System (ADS)

    Truszczynski, Olaf; Skibniewski, Franciszek; Dziuda, Lukasz; Gacek, Adam; Krej, Mariusz; Sobotnicki, Aleksander; Rajchel, Jan; Bylinka, Marek; Burek, Michal

    The authors present a new system for examining the behaviour of the human body and cerebral circulation in conditions of ischemic hypoxia and orthostatic stress that can cause orthostatic hypotension. Ischemic hypoxia affects mainly pilots of highly manoeuvrable aircraft, where long-lasting G forces not seldom reach 6-8 +Gz and can exceed the gravitational acceleration by ten times or more. Additionally, pilots are subjected to orthostatic hypotension in which abnormally low blood pressure is caused by pressure adjustment disorder and decreased stroke volume when changing body position rapidly. For several decades, these effects have been deeply investigated using human centrifuges or lower body negative pressure (LBNP) chambers. The latter method involves significantly less financial resources to carry out experiments and training, whereas the effects exerted on pilots, and the results of the training can be comparable. A group of researchers from the Military Institute of Aviation Medicine, Warszawa, Poland, and the Institute of Medical Technology and Equipment ITAM, Zabrze, Poland, are developing the innovative ORTHO-LBNP device based on the cradle principle and the LBNP method. The system will be implemented in a modern programme for training cadets of the Polish Air Force Academy, Dęblin, Poland. Together with other equipment such as a high-G centrifuge, pressure chambers, flight and spatial disorientation simulators as well as gymnastic training equipment for pilots (GTEP), the ORTHO-LBNP apparatus will be an element of the selection system of candidates for aviation. It is expected that the experimental studies will result in developing new indicators providing an objective assessment, whether examined persons possess the traits necessary for performing tasks related to the job of a pilot. It is highly probable that those indicators can be incorporated into routine checks for pilots, which in turn, can lead to improving the safety of flight operations and

  16. Current trends in the management of acute ischemic stroke.

    PubMed

    Paramasivam, Srinivasan

    2015-01-01

    Stroke is the leading cause of disability and most of the cases are those of ischemic stroke. Management strategies especially for large vessel occlusive stroke have undergone a significant change in the recent years that include widespread use of thrombolytic medications followed by endovascular clot removal. For successful treatment by endovascular thrombectomy, the important factors are patient selection based on clinical criterion including age, time of onset, premorbid clinical condition, co-morbidities, National Institute of Health Stroke Scale, and imaging criterion including computed tomography (CT) head, CT angiogram and CT perfusion. Patients presenting within 4.5 hours of onset are considered for intravenous (IV) recombinant tissue plasminogen activator treatment. Mechanical clot retrieval devices have evolved over the past decade. The Mechanical Embolus Removal in Cerebral Ischemia device was approved first followed by the penumbra revascularization system. They have proven in various studies to improve recanalization with acceptable rates of symptomatic intra-cerebral hemorrhage. Introduction of stent retrievers has led to a new era in the interventional management of acute ischemic stroke (AIS). Recent trials namely MRCLEAN, ESCAPE, SWIFT PRIMEs, and EXTEND-IA have used the stent retriever predominantly and have shown unequivocal benefit in the outcome at 90 days for AIS patients with large vessel occlusion. More recently, a new catheter namely 5 MAX ACE was introduced along with improvement in the suction device. This has led to a direct aspiration first pass technique resulting in faster recanalization. Advancements in the endovascular management of AIS with large vessel occlusion have resulted in a paradigm shift in the way this disease is managed. Improvements in patient selection using clinical and imaging criterion along with technical and technological advancements in mechanical thrombectomy have made possible a significantly improved outcome

  17. Current trends in the management of acute ischemic stroke.

    PubMed

    Paramasivam, Srinivasan

    2015-01-01

    Stroke is the leading cause of disability and most of the cases are those of ischemic stroke. Management strategies especially for large vessel occlusive stroke have undergone a significant change in the recent years that include widespread use of thrombolytic medications followed by endovascular clot removal. For successful treatment by endovascular thrombectomy, the important factors are patient selection based on clinical criterion including age, time of onset, premorbid clinical condition, co-morbidities, National Institute of Health Stroke Scale, and imaging criterion including computed tomography (CT) head, CT angiogram and CT perfusion. Patients presenting within 4.5 hours of onset are considered for intravenous (IV) recombinant tissue plasminogen activator treatment. Mechanical clot retrieval devices have evolved over the past decade. The Mechanical Embolus Removal in Cerebral Ischemia device was approved first followed by the penumbra revascularization system. They have proven in various studies to improve recanalization with acceptable rates of symptomatic intra-cerebral hemorrhage. Introduction of stent retrievers has led to a new era in the interventional management of acute ischemic stroke (AIS). Recent trials namely MRCLEAN, ESCAPE, SWIFT PRIMEs, and EXTEND-IA have used the stent retriever predominantly and have shown unequivocal benefit in the outcome at 90 days for AIS patients with large vessel occlusion. More recently, a new catheter namely 5 MAX ACE was introduced along with improvement in the suction device. This has led to a direct aspiration first pass technique resulting in faster recanalization. Advancements in the endovascular management of AIS with large vessel occlusion have resulted in a paradigm shift in the way this disease is managed. Improvements in patient selection using clinical and imaging criterion along with technical and technological advancements in mechanical thrombectomy have made possible a significantly improved outcome

  18. Dynamic imaging of cerebral blood flow in rat reperfused mini-stroke model using laser speckle temporal contrast analysis

    NASA Astrophysics Data System (ADS)

    Wang, Zhen; Luo, Weihua; Li, Pengcheng; Zeng, Shaoqun; Luo, Qingming

    2007-05-01

    Laser speckle temporal contrast analysis (LSTCA) was used to image the cerebral blood flow (CBF) of ischemic area in reperfused mini-stroke model in rats. Focal cortical ischemia in male Sprague-Dawley rats (n=20) was induced by deliberate ligation of multiple branches of the middle cerebral artery (MCA) together with a nylon ring and the dura. LSTCA was used to monitor the spatio-temporal characteristics of cerebral blood flow dynamics in the rat somatosensory cortex in the ischemic and reperfused stages. The infarction volume was measured by 2, 3, 5- triphenyltetrazolium chloride (TTC) staining 24 hours after reperfusion. The distribution of changes in cerebral blood flow which outlined by the laser speckle imaging represented the relative CBF gradient (21.98+/-1.96%, 67.2+/-1.67 %, 107.24+/-4.71 % of the baseline) from ischemic core, penumbra zone to normal tissue immediately after cortical ischemia, in which a central ischemic core had little or no perfusion surrounded by a penumbral region with reduced perfusion, in addition, we had shown the existence of a surrounding region of hyperemic tissue; Thereafter a postrecanalization hyperperfusion occurred in the same infarct core since 24 hours after reperfusion (242.62+/-18.52% of the baseline). Histology of the ischemic regions at 24 hours after reperfusion revealed small focal infarcts that were typically 3~4 mm in diameter, approximately equal to the nylon ring in size and position and essentially accordant with the spatial distribution of the ischemic cortex with below 30% residual CBF of the pre-ischemic baseline. It was demonstrated that this technique of LSTCA was easy to implement and availably used to image the spatial and temporal evolution of CBF changes with high resolution in rat reperfused mini-stroke model.

  19. Multivariate Analysis of Risk Factors of Cerebral Infarction in 439 Patients Undergoing Thoracic Endovascular Aneurysm Repair

    PubMed Central

    Kanaoka, Yuji; Ohki, Takao; Maeda, Koji; Baba, Takeshi; Fujita, Tetsuji

    2016-01-01

    Abstract The aim of the study is to identify the potential risk factors of cerebral infarction associated with thoracic endovascular aneurysm repair (TEVAR). TEVAR was developed as a less invasive surgical alternative to conventional open repair for thoracic aortic aneurysm treatment. However, outcomes following TEVAR of aortic and distal arch aneurysms remain suboptimal. Cerebral infarction is a major concern during the perioperative period. We included 439 patients who underwent TEVAR of aortic aneurysms at a high-volume teaching hospital between July 2006 and June 2013. Univariate and multivariate logistic regression analyses were performed to identify perioperative cerebral infarction risk factors. Four patients (0.9%) died within 30 days of TEVAR; 17 (3.9%) developed cerebral infarction. In univariate analysis, history of ischemic heart disease and cerebral infarction and concomitant cerebrovascular disease were significantly associated with cerebral infarction. “Shaggy aorta” presence, left subclavian artery coverage, carotid artery debranching, and pull-through wire use were identified as independent risk factors of cerebral infarction. In multivariate analysis, history of ischemic heart disease (odds ratio [OR] 6.49, P = 0.046) and cerebral infarction (OR 43.74, P = 0.031), “shaggy aorta” (OR 30.32, P < 0.001), pull-through wire use during surgery (OR 7.196, P = 0.014), and intraoperative blood loss ≥800 mL (OR 24.31, P = 0.017) were found to be independent risk factors of cerebral infarction. This study identified patient- and procedure-related risk factors of cerebral infarction following TEVAR. These results indicate that patient outcomes could be improved through the identification and management of procedure-related risk factors. PMID:27082585

  20. Astrocytic Toll-Like Receptor 3 Is Associated with Ischemic Preconditioning- Induced Protection against Brain Ischemia in Rodents

    PubMed Central

    Li, Yang; Xu, Xu-lin; Guo, Lian-jun; Lu, Qing; Wang, Jian

    2014-01-01

    Background Cerebral ischemic preconditioning (IPC) protects brain against ischemic injury. Activation of Toll-like receptor 3 (TLR3) signaling can induce neuroprotective mediators, but whether astrocytic TLR3 signaling is involved in IPC-induced ischemic tolerance is not known. Methods IPC was modeled in mice with three brief episodes of bilateral carotid occlusion. In vitro, IPC was modeled in astrocytes by 1-h oxygen-glucose deprivation (OGD). Injury and components of the TLR3 signaling pathway were measured after a subsequent protracted ischemic event. A neutralizing antibody against TLR3 was used to evaluate the role of TLR3 signaling in ischemic tolerance. Results IPC in vivo reduced brain damage from permanent middle cerebral artery occlusion in mice and increased expression of TLR3 in cortical astrocytes. IPC also reduced damage in isolated astrocytes after 12-h OGD. In astrocytes, IPC or 12-h OGD alone increased TLR3 expression, and 12-h OGD alone increased expression of phosphorylated NFκB (pNFκB). However, IPC or 12-h OGD alone did not alter the expression of Toll/interleukin receptor domain-containing adaptor-inducing IFNβ (TRIF) or phosphorylated interferon regulatory factor 3 (pIRF3). Exposure to IPC before OGD increased TRIF and pIRF3 expression but decreased pNFκB expression. Analysis of cytokines showed that 12-h OGD alone increased IFNβ and IL-6 secretion; 12-h OGD preceded by IPC further increased IFNβ secretion but decreased IL-6 secretion. Preconditioning with TLR3 ligand Poly I:C increased pIRF3 expression and protected astrocytes against ischemic injury; however, cells treated with a neutralizing antibody against TLR3 lacked the IPC- and Poly I:C-induced ischemic protection and augmentation of IFNβ. Conclusions The results suggest that IPC-induced ischemic tolerance is mediated by astrocytic TLR3 signaling. This reprogramming of TLR3 signaling by IPC in astrocytes may play an important role in suppression of the post-ischemic

  1. Arterial ischemic stroke in HIV

    PubMed Central

    Bryer, Alan; Lucas, Sebastian; Stanley, Alan; Allain, Theresa J.; Joekes, Elizabeth; Emsley, Hedley; Turnbull, Ian; Downey, Colin; Toh, Cheng-Hock; Brown, Kevin; Brown, David; Ison, Catherine; Smith, Colin; Corbett, Elizabeth L.; Nath, Avindra; Heyderman, Robert S.; Connor, Myles D.; Solomon, Tom

    2016-01-01

    HIV infection, and potentially its treatment, increases the risk of an arterial ischemic stroke. Multiple etiologies and lack of clear case definitions inhibit progress in this field. Several etiologies, many treatable, are relevant to HIV-related stroke. To fully understand the mechanisms and the terminology used, a robust classification algorithm to help ascribe the various etiologies is needed. This consensus paper considers the strengths and limitations of current case definitions in the context of HIV infection. The case definitions for the major etiologies in HIV-related strokes were refined (e.g., varicella zoster vasculopathy and antiphospholipid syndrome) and in some instances new case definitions were described (e.g., HIV-associated vasculopathy). These case definitions provided a framework for an algorithm to help assign a final diagnosis, and help classify the subtypes of HIV etiology in ischemic stroke. PMID:27386505

  2. Sex stratified neuronal cultures to study ischemic cell death pathways.

    PubMed

    Fairbanks, Stacy L; Vest, Rebekah; Verma, Saurabh; Traystman, Richard J; Herson, Paco S

    2013-01-01

    Sex differences in neuronal susceptibility to ischemic injury and neurodegenerative disease have long been observed, but the signaling mechanisms responsible for those differences remain unclear. Primary disassociated embryonic neuronal culture provides a simplified experimental model with which to investigate the neuronal cell signaling involved in cell death as a result of ischemia or disease; however, most neuronal cultures used in research today are mixed sex. Researchers can and do test the effects of sex steroid treatment in mixed sex neuronal cultures in models of neuronal injury and disease, but accumulating evidence suggests that the female brain responds to androgens, estrogens, and progesterone differently than the male brain. Furthermore, neonate male and female rodents respond differently to ischemic injury, with males experiencing greater injury following cerebral ischemia than females. Thus, mixed sex neuronal cultures might obscure and confound the experimental results; important information might be missed. For this reason, the Herson Lab at the University of Colorado School of Medicine routinely prepares sex-stratified primary disassociated embryonic neuronal cultures from both hippocampus and cortex. Embryos are sexed before harvesting of brain tissue and male and female tissue are disassociated separately, plated separately, and maintained separately. Using this method, the Herson Lab has demonstrated a male-specific role for the ion channel TRPM2 in ischemic cell death. In this manuscript, we share and discuss our protocol for sexing embryonic mice and preparing sex-stratified hippocampal primary disassociated neuron cultures. This method can be adapted to prepare sex-stratified cortical cultures and the method for embryo sexing can be used in conjunction with other protocols for any study in which sex is thought to be an important determinant of outcome. PMID:24378980

  3. Suppression of Etk/Bmx protects against ischemic brain injury.

    PubMed

    Chen, Kai-Yun; Wu, Chung-Che; Chang, Cheng-Fu; Chen, Yuan-Hao; Chiu, Wen-Ta; Lou, Ya-Hsin; Chen, Yen-Hua; Shih, Hsiu-Ming; Chiang, Yung-Hsiao

    2012-01-01

    Etk/Bmx (epithelial and endothelial tyrosine kinase, also known as BMX), a member of the Tec (tyrosine kinase expressed in hepatocellular carcinoma) family of protein-tyrosine kinases, is an important regulator of signal transduction for the activation of cell growth, differentiation, and development. We have previously reported that activation of Etk leads to apoptosis in MDA-MB-468 cells. The purpose of this study was to examine the role of Etk in neuronal injury induced by H(2)O(2) or ischemia. Using Western blot analysis and immunohistochemistry, we found that treatment with H(2)O(2) significantly enhanced phosphorylation of Etk and its downstream signaling molecule Stat1 in primary cortical neurons. Inhibiting Etk activity by LFM-A13 or knocking down Etk expression by a specific shRNA increased the survival of primary cortical neurons. Similarly, at 1 day after a 60-min middle cerebral artery occlusion (MCAo) in adult rats, both phosphorylated Etk and Stat1 were coexpressed with apoptotic markers in neurons in the penumbra. Pretreatment with LFM-A13 or an adenoviral vector encoding the kinase deletion mutant Etkk attenuated caspase-3 activity and infarct volume in ischemic brain. All together, our data suggest that Etk is activated after neuronal injury. Suppressing Etk activity protects against neurodegeneration in ischemic brain. PMID:21929872

  4. [Therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy].

    PubMed

    Gulczyńska, Ewa; Gadzinowski, Janusz

    2012-03-01

    Hypoxia-ischemia in the perinatal period is a serious condition affecting infants, which can result in death and cerebral palsy and associated disabilities. There has been significant research progress in hypoxic-ischemic encephalopathy over the last 2 decades. Many new molecular mechanisms of asphyxia have been identified. Despite all these advances, therapeutic interventions in HIE remain to be limited. Recently it has been revealed that mild therapeutic hypothermia is the only modality shown to improve neurologic outcome. The authors present a summary of pathogenesis of HIE, animal studies of cooling for hypoxic and ischemic models, and first publications on human therapeutic hypothermia trials. The diagnosis of encephalopathy in full-term neonates and enrollment criteria for hypothermia are also discussed. The current data from randomized control trials of hypothermia as neuroprotection for full and near-term infants are presented along with the results of meta-analyses of these trials. Finally the status of ongoing neonatal hypothermia trials as well as status of therapeutic hypothermia in Poland is summarized.

  5. Glucose modulation of ischemic brain injury: review and clinical recommendations.

    PubMed

    Wass, C T; Lanier, W L

    1996-08-01

    Ischemic brain injury is the third-leading cause of death among Americans and the leading cause of serious disability. Based on studies of animal models, a substantial amount of experimental evidence shows that hyperglycemia at the onset of brain ischemia worsens postischemic neurologic outcome. Consistent with these observations, hyperglycemia also is associated with a worsening of postischemic brain injury in humans. In humans, however, data are often difficult to interpret because of problems in determining the timing of hyperglycemia relative to a critical ischemic event and in elucidating the effect of coexisting pathophysiologic processes (for example, a stress response) on outcome. Glucose modulation of neurologic injury is observed when ischemia is either global (for example, that accompanying cardiac arrest or severe systemic hypotension) or focal (for example, that accompanying thrombotic or embolic stroke). Toxicity is probably the result of an intracellular lactic acidosis. Specifically, the associated hydrogen ions are injurious to neurons and glia. On the basis of these factors, we recommend diligent monitoring of blood glucose concentrations in patients who are at increased risk for new-onset, ongoing, or recurring cerebral ischemia. In such patients, the use of fluid infusions, corticosteroid drugs, and insulin, as well as stress management, should be tailored to treat preexisting hyperglycemia and prevent new-onset hyperglycemia. Maintenance of normoglycemia is recommended. When one attempts to treat preexisting hyperglycemia, care should be taken to avoid rapid fluid shifts, electrolyte abnormalities, and hypoglycemia, all of which can be detrimental to the brain.

  6. Plasminogen Activators and Ischemic Stroke: Conditions for Acute Delivery

    PubMed Central

    del Zoppo, Gregory J

    2013-01-01

    Appropriate acute treatment with plasminogen activators (PAs) can significantly increase the probability of minimal or no disability in selected ischemic stroke patients. There is a great deal of evidence showing that intravenous recombinant tissue PAs (rt-PA) infusion accomplishes this goal, recanalization with other PAs has also been demonstrated in the development of this treatment. Recanalization of symptomatic, documented carotid or vertebrobasilar arterial territory occlusions have also been achieved by local intra-arterial PA delivery, although only a single prospective double-blinded randomized placebo-controlled study has been reported. The increase in intracerebral hemorrhage with these agents by either delivery approach underscores the need for careful patient selection, dose-appropriate safety and efficacy, proper clinical trial design, and an understanding of the evolution of cerebral tissue injury due to focal ischemia. Principles underlying the evolution of focal ischemia have been expanded by experience with acute PA intervention. Several questions remain open that concern the manner in which PAs can be applied acutely in ischemic stroke and how injury development can be limited. PMID:23539414

  7. Acute ethanol effects on focal cerebral ischemia in fasted rats.

    PubMed

    Zhao, Y J; Yang, G Y; Ben-Joseph, O; Ross, B D; Chenevert, T L; Domino, E F

    1998-05-01

    The effects of acute ethanol intoxication were investigated in a rat model of unilateral middle cerebral artery occlusion. Groups of 5 to 8 male Sprague-Dawley rats were subjected to 4 hr of left middle cerebral artery occlusion. All groups were deprived of food overnight and were pretreated intraperitoneally with 5% dextrose solution (10 ml/kg), 20% ethyl alcohol in 5% dextrose solution (2 g/kg), or 30% ethyl alcohol in a 5% dextrose solution (3 g/kg) 1 hr before middle cerebral artery occlusion. Regional cerebral blood flow during ipsilateral occlusion was approximately 9.1 to 10% of baseline in all groups. The mean % brain water content in control, 2 g/kg ethanol-treated groups, and 3 g/kg ethanol-treated groups were: in the ischemic core--81.6, 81.2, and 82.4; intermediate zone--80.5, 80.6, and 81.7; and outer zone--79.7, 79.7, and 80.8, respectively. Brain Na+ and K+ content in the three groups was related to water content, but much greater with ethanol pretreatment. The water content of the intermediate zones in the 3 g/kg ethanol-treated animals was significantly greater than in the control (p < 0.01 and 0.001) and the 2 g/kg ethanol-treated groups. One-way analysis of variance indicated a significant dose-effect relationship in which the lower dose of ethanol tended to reduce ischemic core water content, and the larger dose increased ischemic core water, compared with the control. None of the overnight fasted groups had any significant hyperglycemia. The group given 3 g/kg i.p. ethanol 1 hr before had exacerbated edema formation with a mean whole blood level of ethanol of approximately 230 mg/dl. The neurotoxic effects of high concentrations of ethanol were unrelated to any change in plasma glucose concentrations.

  8. Focal embolic cerebral ischemia in the rat

    PubMed Central

    Zhang, Li; Zhang, Rui Lan; Jiang, Quan; Ding, Guangliang; Chopp, Michael; Zhang, Zheng Gang

    2015-01-01

    Animal models of focal cerebral ischemia are well accepted for investigating the pathogenesis and potential treatment strategies for human stroke. Occlusion of the middle cerebral artery (MCA) with an endovascular filament is a widely used model to induce focal cerebral ischemia. However, this model is not amenable to thrombolytic therapies. As thrombolysis with recombinant tissue plasminogen activator (rtPA) is a standard of care within 4.5 hours of human stroke onset, suitable animal models that mimic cellular and molecular mechanisms of thrombosis and thrombolysis of stroke are required. By occluding the MCA with a fibrin-rich allogeneic clot, we have developed an embolic model of MCA occlusion in the rat, which recapitulates the key components of thrombotic development and of thrombolytic therapy of rtPA observed from human ischemic stroke. The surgical procedures of our model can be typically completed within approximately 30 min and are highly adaptable to other strains of rats as well as mice for both genders. Thus, this model provides a powerful tool for translational stroke research. PMID:25741989

  9. Hyperacute management of ischemic stroke.

    PubMed

    Song, Sarah

    2013-11-01

    Stroke is a devastating disease and currently the fourth leading cause of death in this country. Acute ischemic stroke is an emergency and requires effective triage, diagnosis, and critical management. The hyperacute management of ischemic stroke begins in the field, with recognition of stroke symptoms by emergency medical systems (EMS) personnel. The EMS is an important component to an effective stroke system of care, which also includes primary stroke centers, routing protocols for acute ischemic stroke, and telemedicine. Following the arrival of a potential stroke patient to the emergency room setting, patients should be stabilized and undergo assessment for potential intravenous alteplase (IV tPA) treatment. Assessments include diagnostic tests, neuroimaging, and standardized stroke evaluations. After these assessments have been performed, IV tPA, the only medication for acute stroke approved by the U.S. Food and Drug Administration, can be considered using a variety of inclusion and exclusion criteria. Previously time restrictions limited the usage of IV tPA to 3 hours, but this time window has now been extended for eligible candidates to 4.5 hours. The administration of IV tPA has specific requirements for monitoring and should be standardized via protocol across hospitals.

  10. [Ischemic cerebrovascular accidents in childhood].

    PubMed

    Pascual Pascual, S I; Pascual Castroviejo, I; Vélez, A

    1988-04-01

    Authors review 53 children, aged 0 to 14 years, affected with cerebrovascular ischemic strokes. Largest aetiological groups were: a) congenital heart disease, 16 patients; b) arteritis of unknown cause, 11; c) idiopathic arterial occlusion without arteritis images on angiography, 7; d) moyamoya disease, 6; and d) local or systemic infections, 5. The mode of onset was as completed stroke in 72% and stroke in evolution in 24%. After acute stage 17.6% of patients presented other definitive strokes, 11.7% suffered only transient ischemic strokes (TIA), and 4% reversible ischemic neurologic deficits (RIND). Mean follow-up was 4.36 years, 9.8% of patients died, 11.8% recovered completely and 52.9% improved after initial stroke. Poor global evolution was associated with heart disease (p less than 0.05) and with onset of strokes before age 2 (p less than 0.05). Most important sequelae, besides motor impairment, were epilepsy (49%) and mental retardation (50% got less than IQ 80). Late epilepsy was associated with seizures at onset (p less than 0.05). Clinical factors of adverse mental development were: a) seizures at onset, b) late epilepsy and c) stroke before age 2. 66% of cases had two or more arterial lesions in the same or in different arterial trees. Therefore, embolic and arteritic factors probably play an important role in infancy and childhood stroke. PMID:3400936

  11. Patterns and dynamics of subventricular zone neuroblast migration in the ischemic striatum of the adult mouse

    PubMed Central

    Zhang, Rui L; Chopp, Michael; Gregg, Sara R; Toh, Yier; Roberts, Cindi; LeTourneau, Yvonne; Buller, Benjamin; Jia, Longfei; Davarani, Siamak P Nejad; Zhang, Zheng G

    2009-01-01

    The migratory behavior of neuroblasts after a stroke is poorly understood. Using time-lapse microscopy, we imaged migration of neuroblasts and cerebral vessels in living brain slices of adult doublecortin (DCX, a marker of neuroblasts) enhanced green fluorescent protein (eGFP) transgenic mice that were subjected to 7 days of stroke. Our results show that neuroblasts originating in the subventricular zone (SVZ) of adult mouse brain laterally migrated in chains or individually to reach the ischemic striatum. The chains were initially formed at the border between the SVZ and the striatum by neuroblasts in the SVZ and then extended to the striatum. The average speed of DCX-eGFP-expressing cells within chains was 28.67±1.04 μm/h, which was significantly faster (P < 0.01) than the speed of the cells in the SVZ (17.98±0.57 μm/h). Within the ischemic striatum, individual neuroblasts actively extended or retracted their processes, suggestive of probing the immediate microenvironment. The neuroblasts close to cerebral blood vessels exhibited multiple processes. Our data suggest that neuroblasts actively interact with the microenvironment to reach the ischemic striatum by multiple migratory routes. PMID:19436318

  12. Memory deficit associated with increased brain proinflammatory cytokine levels and neurodegeneration in acute ischemic stroke.

    PubMed

    Silva, Bruno; Sousa, Larissa; Miranda, Aline; Vasconcelos, Anilton; Reis, Helton; Barcelos, Lucíola; Arantes, Rosa; Teixeira, Antonio; Rachid, Milene Alvarenga

    2015-08-01

    The present study aimed to investigate behavioral changes and neuroinflammatory process following left unilateral common carotid artery occlusion (UCCAO), a model of cerebral ischemia. Post-ischemic behavioral changes following 15 min UCCAO were recorded 24 hours after reperfusion. The novel object recognition task was used to assess learning and memory. After behavioral test, brains from sham and ischemic mice were removed and processed to evaluate central nervous system pathology by TTC and H&E techniques as well as inflammatory mediators by ELISA. UCCAO promoted long-term memory impairment after reperfusion. Infarct areas were observed in the cerebrum by TTC stain. Moreover, the histopathological analysis revealed cerebral necrotic cavities surrounded by ischemic neurons and hippocampal neurodegeneration. In parallel with memory dysfunction, brain levels of TNF-a, IL-1b and CXCL1 were increased post ischemia compared with sham-operated group. These findings suggest an involvement of central nervous system inflammatory mediators and brain damage in cognitive impairment following unilateral acute ischemia.

  13. Functional genomics indicate that schizophrenia may be an adult vascular-ischemic disorder

    PubMed Central

    Moises, H W; Wollschläger, D; Binder, H

    2015-01-01

    In search for the elusive schizophrenia pathway, candidate genes for the disorder from a discovery sample were localized within the energy-delivering and ischemia protection pathway. To test the adult vascular-ischemic (AVIH) and the competing neurodevelopmental hypothesis (NDH), functional genomic analyses of practically all available schizophrenia-associated genes from candidate gene, genome-wide association and postmortem expression studies were performed. Our results indicate a significant overrepresentation of genes involved in vascular function (P<0.001), vasoregulation (that is, perivascular (P<0.001) and shear stress (P<0.01), cerebral ischemia (P<0.001), neurodevelopment (P<0.001) and postischemic repair (P<0.001) among schizophrenia-associated genes from genetic association studies. These findings support both the NDH and the AVIH. The genes from postmortem studies showed an upregulation of vascular-ischemic genes (P=0.020) combined with downregulated synaptic (P=0.005) genes, and ND/repair (P=0.003) genes. Evidence for the AVIH and the NDH is critically discussed. We conclude that schizophrenia is probably a mild adult vascular-ischemic and postischemic repair disorder. Adult postischemic repair involves ND genes for adult neurogenesis, synaptic plasticity, glutamate and increased long-term potentiation of excitatory neurotransmission (i-LTP). Schizophrenia might be caused by the cerebral analog of microvascular angina. PMID:26261884

  14. Functional genomics indicate that schizophrenia may be an adult vascular-ischemic disorder.

    PubMed

    Moises, H W; Wollschläger, D; Binder, H

    2015-08-11

    In search for the elusive schizophrenia pathway, candidate genes for the disorder from a discovery sample were localized within the energy-delivering and ischemia protection pathway. To test the adult vascular-ischemic (AVIH) and the competing neurodevelopmental hypothesis (NDH), functional genomic analyses of practically all available schizophrenia-associated genes from candidate gene, genome-wide association and postmortem expression studies were performed. Our results indicate a significant overrepresentation of genes involved in vascular function (P < 0.001), vasoregulation (that is, perivascular (P < 0.001) and shear stress (P < 0.01), cerebral ischemia (P < 0.001), neurodevelopment (P < 0.001) and postischemic repair (P < 0.001) among schizophrenia-associated genes from genetic association studies. These findings support both the NDH and the AVIH. The genes from postmortem studies showed an upregulation of vascular-ischemic genes (P = 0.020) combined with downregulated synaptic (P = 0.005) genes, and ND/repair (P = 0.003) genes. Evidence for the AVIH and the NDH is critically discussed. We conclude that schizophrenia is probably a mild adult vascular-ischemic and postischemic repair disorder. Adult postischemic repair involves ND genes for adult neurogenesis, synaptic plasticity, glutamate and increased long-term potentiation of excitatory neurotransmission (i-LTP). Schizophrenia might be caused by the cerebral analog of microvascular angina.

  15. Atorvastatin attenuates cognitive deficits through Akt1/caspase-3 signaling pathway in ischemic stroke.

    PubMed

    Yang, Jie; Pan, Ying; Li, Xuejing; Wang, Xianying

    2015-12-10

    Neuronal damage in the hippocampal formation is more sensitive to ischemic stimulation and easily injured, causing severe learning and memory impairment. Therefore, protection of hippocampal neuronal damage is the main contributor for learning and memory impairment during cerebral ischemia. Atorvastatin has been reported to ameliorate ischemic brain damage after ischemia reperfusion (I/R). However, its molecular mechanism has not been elucidated clearly. In this study, we established four-vessel occlusion model in rats with cerebral ischemia. Here, we demonstrated that atorvastatin significantly improves the behavior of I/R-rat in open field tasks. We also found that atorvastatin significantly shortens the distance and time of loading onto the hidden platform in the positioning navigation process, decreases the latency in the space exploration process when cognitive testing with Morris water maze was performed during ischemic stroke in rats. Furthermore, the survival rate of neurons in the CA1 area of the hippocampus and the phosphorylation of Akt (Ser473) in the neurons are increased, whereas the expression of caspase-3 are inhibited by atorvastatin. However, after an intracerebroventricular injection of LY294002 (an inhibitor of Akt1), the above neuroprotective effects of atorvastatin are attenuated. In summary, our results imply atorvastatin may improve the survival rate of hippocampal neurons and reduce the impairment of learning and memory by downregulating the activation of the caspase-3 via increasing the phosphorylation of Akt1 during ischemia/reperfusion. PMID:26597376

  16. Early treatment of hypertension in acute ischemic and intracerebral hemorrhagic stroke: progress achieved, challenges, and perspectives.

    PubMed

    Feldstein, Carlos A

    2014-03-01

    Hypertension is the leading risk factor for ischemic and intracerebral hemorrhagic subtypes of stroke. Additionally, high blood pressure (BP) in the acute cerebrovascular event is associated with poor outcome, and a high percentage of stroke survivors have inadequate control of hypertension. The present is a systematic review of prospective, randomized, and controlled trials carried out on safety and efficacy of antihypertensive treatment of both subtypes of acute stroke. Six trials involving 7512 patients were included, which revealed controversies on the speed and the goals of treatment. These controversies could be due at least in part, from the fact that some studies analyzed the results of antihypertensive treatment in ischemic and intracerebral hemorrhagic subtypes of acute stroke together, and from a different prevalence of past-stroke in the randomized groups. Further research is necessary to establish whether standard antihypertensive treatment provides greater benefit than simple observation in patients with ischemic acute stroke and Stage 2 hypertension of JNC 7, albeit they were not candidates for acute reperfusion. In that case, the target reduction in BP could be 10% to 15% within 24 hours. The recently published INTERACT 2 has provided evidence that patients with hemorrhagic stroke may receive intensive antihypertensive treatment safely with the goal of reducing systolic BP to levels no lower than 130 mm Hg. It is important to take into account that marked BP lowering in acute stroke increases the risk of poor outcome by worsening cerebral ischemia from deterioration of cerebral blood flow autoregulation. PMID:24220549

  17. [Structural and functional changes of external and intracranial arteries in elderly patients of different ethnic groups with ischemic heart disease].

    PubMed

    Fedorets, V N; Abramov, E A; Bartosh-Zelenaia, S Iu; Naĭden, T V

    2014-01-01

    The present article discusses the problem of structural and functional changes in extra-and intracranial arteries in elderly patients with ischemic heart disease (CHD) belonging to different ethnic groups before the upcoming coronary arteriography research and planned operative intervention. We examined 120 elderly patients with ischemic heart disease, including 50 patients of Korean nationality and 70 patients of Slavic ethnicity. Average values of IMT of the right and left CCA patients of South Asian group were significantly lower than those of Slavic ethnicity. Elderly patients with CHD the violation of cerebral circulation were due to atherosclerotic lesions of the extracranial vessels and local hemodynamic disturbances in their area of pathological tortuosity. Korean ethnicity elderly patients with CHD were observed more pronounced signs of stenosis and deformation of the main arteries of the neck, as well as lower collateral reserve of cerebral circulation.

  18. Magnetic resonance imaging of post-ischemic blood-brain barrier damage with PEGylated iron oxide nanoparticles

    NASA Astrophysics Data System (ADS)

    Liu, Dong-Fang; Qian, Cheng; An, Yan-Li; Chang, Di; Ju, Sheng-Hong; Teng, Gao-Jun

    2014-11-01

    Blood-brain barrier (BBB) damage during ischemia may induce devastating consequences like cerebral edema and hemorrhagic transformation. This study presents a novel strategy for dynamically imaging of BBB damage with PEGylated supermagnetic iron oxide nanoparticles (SPIONs) as contrast agents. The employment of SPIONs as contrast agents made it possible to dynamically image the BBB permeability alterations and ischemic lesions simultaneously with T2-weighted MRI, and the monitoring could last up to 24 h with a single administration of PEGylated SPIONs in vivo. The ability of the PEGylated SPIONs to highlight BBB damage by MRI was demonstrated by the colocalization of PEGylated SPIONs with Gd-DTPA after intravenous injection of SPION-PEG/Gd-DTPA into a mouse. The immunohistochemical staining also confirmed the leakage of SPION-PEG from cerebral vessels into parenchyma. This study provides a novel and convenient route for imaging BBB alteration in the experimental ischemic stroke model.

  19. Acute ischemic stroke treated with intravenous tissue plasminogen activator in a patient taking dabigatran with radiographic evidence of recanalization.

    PubMed

    Sangha, Navdeep; El Khoury, Ramy; Misra, Vivek; Lopez, George

    2012-11-01

    Dabigatran etexelate is a new oral direct thrombin inhibitor that has been approved by the US Food and Drug Administration to prevent stroke in patients with nonvalvular atrial fibrillation. A 51-year-old man with a history of atrial fibrillation who was taking dabigatran presented with an acute ischemic stroke. The patient had a normal international normalized ratio, activated partial thromboplastin time, and an elevated thrombin time of 26.4 seconds. Recanalization of the middle cerebral artery with intravenous tissue plasminogen activator was apparent on digital subtraction angiography, and there was no evidence of intracerebral hemorrhage on the repeat computed tomographic scan. This is the first report of a patient who was taking dabigatran etexilate and who had an ischemic stroke caused by a middle cerebral artery occlusion, with an elevated thrombin time and radiographic recanalization with intravenous tissue plasminogen activator without evidence of hemorrhagic transformation. PMID:22683118

  20. The TRIF-dependent signaling pathway is not required for acute cerebral ischemia/reperfusion injury in mice

    SciTech Connect

    Hua, Fang; Wang, Jun; Sayeed, Iqbal; Ishrat, Tauheed; Atif, Fahim; Stein, Donald G.

    2009-12-18

    TIR domain-containing adaptor protein (TRIF) is an adaptor protein in Toll-like receptor (TLR) signaling pathways. Activation of TRIF leads to the activation of interferon regulatory factor 3 (IRF3) and nuclear factor kappa B (NF-{kappa}B). While studies have shown that TLRs are implicated in cerebral ischemia/reperfusion (I/R) injury and in neuroprotection against ischemia afforded by preconditioning, little is known about TRIF's role in the pathological process following cerebral I/R. The present study investigated the role that TRIF may play in acute cerebral I/R injury. In a mouse model of cerebral I/R induced by transient middle cerebral artery occlusion, we examined the activation of NF-{kappa}B and IRF3 signaling in ischemic cerebral tissue using ELISA and Western blots. Neurological function and cerebral infarct size were also evaluated 24 h after cerebral I/R. NF-{kappa}B activity and phosphorylation of the inhibitor of kappa B (I{kappa}B{alpha}) increased in ischemic brains, but IRF3, inhibitor of {kappa}B kinase complex-{epsilon} (IKK{epsilon}), and TANK-binding kinase1 (TBK1) were not activated after cerebral I/R in wild-type (WT) mice. Interestingly, TRIF deficit did not inhibit NF-{kappa}B activity or p-I{kappa}B{alpha} induced by cerebral I/R. Moreover, although cerebral I/R induced neurological and functional impairments and brain infarction in WT mice, the deficits were not improved and brain infarct size was not reduced in TRIF knockout mice compared to WT mice. Our results demonstrate that the TRIF-dependent signaling pathway is not required for the activation of NF-{kappa}B signaling and brain injury after acute cerebral I/R.

  1. Echocardiographic assessment of ischemic mitral regurgitation.

    PubMed

    Dudzinski, David M; Hung, Judy

    2014-01-01

    Ischemic mitral regurgitation is an important consequence of LV remodeling after myocardial infarction. Echocardiographic diagnosis and assessment of ischemic mitral regurgitation are critical to gauge its adverse effects on prognosis and to attempt to tailor rational treatment strategy. There is no single approach to the echocardiographic assessment of ischemic mitral regurgitation: standard echocardiographic measures of mitral regurgitation severity and of LV dysfunction are complemented by assessments of displacement of the papillary muscles and quantitative indices of mitral valve deformation. Development of novel approaches to understand mitral valve geometry by echocardiography may improve understanding of the mechanism, clinical trajectory, and reparability of ischemic mitral regurgitation.

  2. Houshiheisan compound prescription protects neurovascular units after cerebral ischemia

    PubMed Central

    Wang, Haizheng; Wang, Lei; Zhang, Nan; Zhang, Qi; Zhao, Hui; Zhang, Qiuxia

    2014-01-01

    Houshiheisan is composed of wind-dispelling (chrysanthemun flower, divaricate saposhnikovia root, Manchurian wild ginger, cassia twig, Szechwan lovage rhizome, and platycodon root) and deficiency-nourishing (ginseng, Chinese angelica, large-head atractylodes rhizome, Indian bread, and zingiber) drugs. In this study, we assumed these drugs have protective effects against cerebral ischemia, on neurovascular units. Houshiheisan was intragastrically administered in a rat model of focal cerebral ischemia. Hematoxylin-eosin staining, transmission electron microscopy, immunofluorescence staining, and western blot assays showed that Houshiheisan reduced pathological injury to the ischemic penumbra, protected neurovascular units, visibly up-regulated neuronal nuclear antigen expression, and down-regulated amyloid precursor protein and amyloid-β 42 expression. Wind-dispelling and deficiency-nourishing drugs maintained NeuN expression to varying degrees, but did not affect amyloid precursor protein or amyloid-β 42 expression in the ischemic penumbra. Our results suggest that the compound prescription Houshiheisan effectively suppresses abnormal amyloid precursor protein accumulation, reduces amyloid substance deposition, maintains stabilization of the internal environment of neurovascular units, and minimizes injury to neurovascular units in the ischemic penumbra. PMID:25206882

  3. Mn-SOD Upregulation by Electroacupuncture Attenuates Ischemic Oxidative Damage via CB1R-Mediated STAT3 Phosphorylation.

    PubMed

    Sun, Sisi; Chen, Xiyao; Gao, Yang; Liu, Zhaoyu; Zhai, Qian; Xiong, Lize; Cai, Min; Wang, Qiang

    2016-01-01

    Electroacupuncture (EA) pretreatment elicits the neuroprotective effect against cerebral ischemic injury through cannabinoid receptor type 1 receptor (CB1R). In current study, we aimed to investigate whether the signal transducer and activator of transcription 3 (STAT3) and manganese superoxide dismutase (Mn-SOD) were involved in the antioxidant effect of EA pretreatment through CB1R. At 2 h after EA pretreatment, focal cerebral ischemic injury was induced by transient middle cerebral artery occlusion for 60 min in C57BL/6 mice. The expression of Mn-SOD in the penumbra was assessed by Western blot and immunoflourescent staining at 2 h after reperfusion. In the presence or absence of Mn-SOD small interfering RNA (siRNA), the neurological deficit score, the infarct volume, the terminal deoxynucleotidyl transferase-mediated dUDP-biotin nick end labeling (TUNEL) staining, and oxidative stress were evaluated. Furthermore, the Mn-SOD protein expression and phosphorylation of STAT3 at Y705 were also determined in the presence and absence of CB1R antagonists (AM251, SR141716) and CB1R agonists (arachidonyl-2-chloroethylamide (ACEA), WIN 55,212-2). EA pretreatment upregulated the Mn-SOD protein expression and Mn-SOD-positive neuronal cells at 2 h after reperfusion. EA pretreatment also attenuated oxidative stress, inhibited cellular apoptosis, and induced neuroprotection against ischemic damage, whereas these beneficial effects of EA pretreatment were reversed by knockdown of Mn-SOD. Mn-SOD upregulation and STAT3 phosphorylation by EA pretreatment were abolished by two CB1R antagonists, while pretreatment with two CB1R agonists increased the expression of Mn-SOD and phosphorylation level of STAT3. Mn-SOD upregulation by EA attenuates ischemic oxidative damage through CB1R-mediated STAT3 phosphorylation in stroke mice, which may represent one new mechanism of EA pretreatment-induced neuroprotection against cerebral ischemia.

  4. Posterior cerebral artery territory infarctions.

    PubMed

    Cereda, Carlo; Carrera, Emmanuel

    2012-01-01

    Infarctions in the territory of the posterior cerebral artery (PCA) occur in about 5-10% of all ischemic strokes. The PCA can be divided into 'deep' (P1 and P2 segments) and 'superficial' (P3 and P4) segments. Occlusion of paramedian perforating arteries arising from P1 causes rostral midbrain infarction with or without thalamic lesion. The classical clinical triad after thalamomesencephalic infarcts is hypersomnolence, cognitive deficits and vertical oculomotor paresis. Two main arterial groups arise from P2: infarction in the territory of the thalamogeniculate arteries causes severe contralateral hypesthesia and ataxia, whereas infarction in the territory of the posterior choroidal arteries results in sectoranopia with involvement of the lateral geniculate body. After superficial PCA infarcts, visual field defects and somatosensory deficits are the most frequent signs. Additionally, disorders of reading may be seen after unilateral left infarction and disorientation for place and visual neglect after right lesion. After bilateral PCA infarcts, amnesia, cortical blindness (the patient cannot see but pretend he can) may occur. Acute thrombolysis is as useful after PCA infarctions as after anterior circulation strokes. Mortality after PCA strokes is low, but long-term behavioral and cognitive deficits are underestimated.

  5. Evaluation of cerebral ischemia using near-infrared spectroscopy with oxygen inhalation

    NASA Astrophysics Data System (ADS)

    Ebihara, Akira; Tanaka, Yuichi; Konno, Takehiko; Kawasaki, Shingo; Fujiwara, Michiyuki; Watanabe, Eiju

    2012-09-01

    Conventional methods presently used to evaluate cerebral hemodynamics are invasive, require physical restraint, and employ equipment that is not easily transportable. Therefore, it is difficult to take repeated measurements at the patient's bedside. An alternative method to evaluate cerebral hemodynamics was developed using near-infrared spectroscopy (NIRS) with oxygen inhalation. The bilateral fronto-temporal areas of 30 normal volunteers and 33 patients with cerebral ischemia were evaluated with the NIRS system. The subjects inhaled oxygen through a mask for 2 min at a flow rate of 8 L/min. Principal component analysis (PCA) was applied to the data, and a topogram was drawn using the calculated weights. NIRS findings were compared with those of single-photon-emission computed tomography (SPECT). In normal volunteers, no laterality of the PCA weights was observed in 25 of 30 cases (83%). In patients with cerebral ischemia, PCA weights in ischemic regions were lower than in normal regions. In 28 of 33 patients (85%) with cerebral ischemia, NIRS findings agreed with those of SPECT. The results suggest that transmission of the changes in systemic SpO2 were attenuated in ischemic regions. The method discussed here should be clinically useful because it can be used to measure cerebral ischemia easily, repeatedly, and noninvasively.

  6. Protection mechanism of early hyperbaric oxygen therapy in rats with permanent cerebral ischemia.

    PubMed

    Yu, Min; Xue, Yixue; Liang, Weidi; Zhang, Yupeng; Zhang, Zhiqiang

    2015-10-01

    [Purpose] The purpose of this study was to investigate whether early hyperbaric oxygen is useful in rats with permanent cerebral ischemia, and whether its mechanism relates to the inhibition of the tumor necrosis factor-alpha-protein kinase C-alpha pathway. [Subjects] Healthy, male Sprague-Dawley rats (N = 108) were the subjects. [Methods] After middle cerebral artery occlusion models were successfully made, rats were randomly divided into sham-operated, cerebral ischemia, and hyperbaric oxygen groups. At 4 and 12 hours after modeling, the volume of cerebral infarction was determined by triphenyltetrazolium chloride staining, and brain water content was measured using the dry and wet method. The expression of tumor necrosis factor-alpha and protein kinase C-alpha in the ischemic penumbra tissue was measured using Western blot analysis. [Results] The data showed that at 4 and 12 hours after modeling, cerebral infarct volume and brain water content decreased in the hyperbaric oxygen group, and expression of tumor necrosis factor-alpha and phospho-protein kinase C-alpha in the ischemic penumbra tissue also decreased. [Conclusion] Our study demonstrates that early hyperbaric oxygen therapy has protective effects on brain tissue after cerebral ischemia, possibly via inhibition of tumor necrosis factor-alpha and phospho-protein kinase C-alpha.

  7. Intravascular Perfusion of Carbon Black Ink Allows Reliable Visualization of Cerebral Vessels

    PubMed Central

    Hasan, Mohammad R.; Herz, Josephine; Hermann, Dirk M.; Doeppner, Thorsten R.

    2013-01-01

    The anatomical structure of cerebral vessels is a key determinant for brain hemodynamics as well as the severity of injury following ischemic insults. The cerebral vasculature dynamically responds to various pathophysiological states and it exhibits considerable differences between strains and under conditions of genetic manipulations. Essentially, a reliable technique for intracranial vessel staining is essential in order to study the pathogenesis of ischemic stroke. Until recently, a set of different techniques has been employed to visualize the cerebral vasculature including injection of low viscosity resin, araldite F, gelatin mixed with various dyes1 (i.e. carmine red, India ink) or latex with2 or without3 carbon black. Perfusion of white latex compound through the ascending aorta has been first reported by Coyle and Jokelainen3. Maeda et al.2 have modified the protocol by adding carbon black ink to the latex compound for improved contrast visualization of the vessels after saline perfusion of the brain. However, inefficient perfusion and inadequate filling of the vessels are frequently experienced due to high viscosity of the latex compound4. Therefore, we have described a simple and cost-effective technique using a mixture of two commercially available carbon black inks (CB1 and CB2) to visualize the cerebral vasculature in a reproducible manner5. We have shown that perfusion with CB1+CB2 in mice results in staining of significantly smaller cerebral vessels at a higher density in comparison to latex perfusion5. Here, we describe our protocol to identify the anastomotic points between the anterior (ACA) and middle cerebral arteries (MCA) to study vessel variations in mice with different genetic backgrounds. Finally, we demonstrate the feasibility of our technique in a transient focal cerebral ischemia model in mice by combining CB1+CB2-mediated vessel staining with TTC staining in various degrees of ischemic injuries. PMID:23328838

  8. Perinatal ischemic stroke: a five-year retrospective study in a level-III maternity

    PubMed Central

    Machado, Virgínia; Pimentel, Sónia; Pinto, Filomena; Nona, José

    2015-01-01

    Objective To study the incidence, clinical presentation, risk factors, imaging diagnosis, and clinical outcome of perinatal stroke. Methods Data was retrospectively collected from full-term newborns admitted to the neonatal unit of a level III maternity in Lisbon with cerebral stroke, from January 2007 to December 2011. Results There were 11 cases of stroke: nine were arterial ischemic stroke and two were cerebral venous sinus thrombosis. We estimated an incidence of arterial ischemic stroke of 1.6/5,000 births and of cerebral venous sinus thrombosis of 7.2/100,000 births. There were two cases of recurrent stroke. Eight patients presented with symptoms while the remaining three were asymptomatic and incidentally diagnosed. The most frequently registered symptoms (8/11) were seizures; in that, generalized clonic (3/8) and focal clonic (5/8). Strokes were more commonly left-sided (9/11), and the most affected artery was the left middle cerebral artery (8/11). Transfontanelle ultrasound was positive in most of the patients (10/11), and stroke was confirmed by cerebral magnetic resonance in all patients. Electroencephalographic recordings were carried out in five patients and were abnormal in three (focal abnormalities n=2, burst-suppression pattern n=1). Eight patients had previously identified risk factors for neonatal stroke which included obstetric and neonatal causes. Ten patients were followed up at outpatients setting; four patients developed motor deficits and one presented with epilepsy. Conclusions Although a modest and heterogeneous sample, this study emphasizes the need for a high level of suspicion when it comes to neonatal stroke, primarily in the presence of risk factors. The prevalence of neurological sequelae in our series supports the need of long-term follow-up and early intervention strategies. PMID:25993071

  9. Effects of Tannic Acid on the Ischemic Brain Tissue of Rats.

    PubMed

    Sen, Halil Murat; Ozkan, Adile; Guven, Mustafa; Akman, Tarık; Aras, Adem Bozkurt; Sehitoglu, Ibrahim; Alacam, Hasan; Silan, Coskun; Cosar, Murat; Ozisik Karaman, Handan Isın

    2015-08-01

    Many studies of brain ischemia have shown the role played by massive ischemia-induced production of reactive oxygen species, the main mechanism of neuronal death. However, currently, there is no treatment choice to prevent cell death triggered by reactive oxygen species. In our study, we researched the effects of tannic acid, an antioxidant, on the ischemic tissue of rats with induced middle cerebral artery occlusion. The animals were divided into three groups of eight animals. The sham group were only administered 10 % ethanol intraperitoneally, the second group had middle cerebral artery occlusion induced and were given 10 % ethanol intraperitoneally, while the third group had middle cerebral artery occlusion with 10 mg/kg dose tannic acid dissolved in 10 % ethanol administered within half an hour intraperitoneally. The rats were sacrificed 24 h later, and brain tissue was examined biochemically and histopathologically. Biochemical evaluation of brain tissue found that comparing the ischemic group with no treatment with the tannic acid-treated ischemia group; the superoxide dismutase (SOD) levels were higher, malondialdehyde (MDA) levels were lower, and nuclear respiratory factor-1 (NRF-1) was higher in the tannic acid-treated group. Histopathological examination showed that the histopathological results of the tannic acid group were better than the group not given tannic acid. Biochemical and histopathological results showed that tannic acid administration had an antioxidant effect on the negative effects of ischemia in brain tissue.

  10. Serum Levels of Substance P and Mortality in Patients with a Severe Acute Ischemic Stroke.

    PubMed

    Lorente, Leonardo; Martín, María M; Almeida, Teresa; Pérez-Cejas, Antonia; Ramos, Luis; Argueso, Mónica; Riaño-Ruiz, Marta; Solé-Violán, Jordi; Hernández, Mariano

    2016-01-01

    Substance P (SP), a member of tachykinin family, is involved in the inflammation of the central nervous system and in the appearance of cerebral edema. Higher serum levels of SP have been found in 18 patients with cerebral ischemia compared with healthy controls. The aim of our multi-center study was to analyze the possible association between serum levels of SP and mortality in ischemic stroke patients. We included patients with malignant middle cerebral artery infarction (MMCAI) and a Glasgow Coma Scale (GCS) lower than 9. Non-surviving patients at 30 days (n = 31) had higher serum concentrations of SP levels at diagnosis of severe MMCAI than survivors (n = 30) (p < 0.001). We found in multiple regression an association between serum concentrations of SP higher than 362 pg/mL and mortality at 30 days (Odds Ratio = 5.33; 95% confidence interval = 1.541-18.470; p = 0.008) after controlling for age and GCS. Thus, the major novel finding of our study was the association between serum levels of SP and mortality in patients suffering from severe acute ischemic stroke. PMID:27338372

  11. Galectin-1-secreting neural stem cells elicit long-term neuroprotection against ischemic brain injury

    PubMed Central

    Wang, Jiayin; Xia, Jinchao; Zhang, Feng; Shi, Yejie; Wu, Yun; Pu, Hongjian; Liou, Anthony K. F.; Leak, Rehana K.; Yu, Xinguang; Chen, Ling; Chen, Jun

    2015-01-01

    Galectin-1 (gal-1), a special lectin with high affinity to β-galactosides, is implicated in protection against ischemic brain injury. The present study investigated transplantation of gal-1-secreting neural stem cell (s-NSC) into ischemic brains and identified the mechanisms underlying protection. To accomplish this goal, secretory gal-1 was stably overexpressed in NE-4C neural stem cells. Transient cerebral ischemia was induced in mice by middle cerebral artery occlusion for 60 minutes and s-NSCs were injected into the striatum and cortex within 2 hours post-ischemia. Brain infarct volume and neurological performance were assessed up to 28 days post-ischemia. s-NSC transplantation reduced infarct volume, improved sensorimotor and cognitive functions, and provided more robust neuroprotection than non-engineered NSCs or gal-1-overexpressing (but non-secreting) NSCs. White matter injury was also ameliorated in s-NSC-treated stroke mice. Gal-1 modulated microglial function in vitro, by attenuating secretion of pro-inflammatory cytokines (TNF-α and nitric oxide) in response to LPS stimulation and enhancing production of anti-inflammatory cytokines (IL-10 and TGF-β). Gal-1 also shifted microglia/macrophage polarization toward the beneficial M2 phenotype in vivo by reducing CD16 expression and increasing CD206 expression. In sum, s-NSC transplantation confers robust neuroprotection against cerebral ischemia, probably by alleviating white matter injury and modulating microglial/macrophage function. PMID:25858671

  12. Serum Levels of Substance P and Mortality in Patients with a Severe Acute Ischemic Stroke

    PubMed Central

    Lorente, Leonardo; Martín, María M.; Almeida, Teresa; Pérez-Cejas, Antonia; Ramos, Luis; Argueso, Mónica; Riaño-Ruiz, Marta; Solé-Violán, Jordi; Hernández, Mariano

    2016-01-01

    Substance P (SP), a member of tachykinin family, is involved in the inflammation of the central nervous system and in the appearance of cerebral edema. Higher serum levels of SP have been found in 18 patients with cerebral ischemia compared with healthy controls. The aim of our multi-center study was to analyze the possible association between serum levels of SP and mortality in ischemic stroke patients. We included patients with malignant middle cerebral artery infarction (MMCAI) and a Glasgow Coma Scale (GCS) lower than 9. Non-surviving patients at 30 days (n = 31) had higher serum concentrations of SP levels at diagnosis of severe MMCAI than survivors (n = 30) (p < 0.001). We found in multiple regression an association between serum concentrations of SP higher than 362 pg/mL and mortality at 30 days (Odds Ratio = 5.33; 95% confidence interval = 1.541–18.470; p = 0.008) after controlling for age and GCS. Thus, the major novel finding of our study was the association between serum levels of SP and mortality in patients suffering from severe acute ischemic stroke. PMID:27338372

  13. Detrimental effects of tropisetron on permanent ischemic stroke in the rat

    PubMed Central

    Candelario-Jalil, Eduardo; Muñoz, Eduardo; Fiebich, Bernd L

    2008-01-01

    Background Recent in vitro evidence indicates that blockade of 5-hydroxytryptamine (5-HT) receptor 3 (5-HT3) is able to confer protection in different models of neuronal injury. The purpose of the present study was to investigate the effect of tropisetron, a 5-HT3 receptor antagonist, on infarct size and neurological score in a model of ischemic stroke induced by permanent middle cerebral artery occlusion (pMCAO) in the rat. Methods Two different doses of tropisetron (5 and 10 mg/kg) or vehicle were administered intraperitoneally 30 min before pMCAO. Neurological deficit scores, mortality rate and infarct volume were determined 24 h after permanent focal cerebral ischemia. Results Tropisetron failed to reduce cerebral infarction. Animals receiving tropisetron showed a significant increase (p < 0.05) in neurological deficits and mortality rate. Conclusion Data from this study indicate that blockade of 5-HT3 receptors with tropisetron worsens ischemic brain injury induced by pMCAO. These findings could have important clinical implications. Patients taking tropisetron, and possibly other 5-HT3 antagonists, could potentially have a worse outcome following a brain infarct. PMID:18254974

  14. Sex differences in ischemic stroke sensitivity are influenced by gonadal hormones, not by sex chromosome complement.

    PubMed

    Manwani, Bharti; Bentivegna, Kathryn; Benashski, Sharon E; Venna, Venugopal Reddy; Xu, Yan; Arnold, Arthur P; McCullough, Louise D

    2015-02-01

    Epidemiologic studies have shown sex differences in ischemic stroke. The four core genotype (FCG) mouse model, in which the testes determining gene, Sry, has been moved from Y chromosome to an autosome, was used to dissociate the effects of sex hormones from sex chromosome in ischemic stroke outcome. Middle cerebral artery occlusion (MCAO) in gonad intact FCG mice revealed that gonadal males (XXM and XYM) had significantly higher infarct volumes as compared with gonadal females (XXF and XYF). Serum testosterone levels were equivalent in adult XXM and XYM, as was serum estrogen in XXF and XYF mice. To remove the effects of gonadal hormones, gonadectomized FCG mice were subjected to MCAO. Gonadectomy significantly increased infarct volumes in females, while no change was seen in gonadectomized males, indicating that estrogen loss increases ischemic sensitivity. Estradiol supplementation in gonadectomized FCG mice rescued this phenotype. Interestingly, FCG male mice were less sensitive to effects of hormones. This may be due to enhanced expression of the transgene Sry in brains of FCG male mice. Sex differences in ischemic stroke sensitivity appear to be shaped by organizational and activational effects of sex hormones, rather than sex chromosomal complement.

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

    PubMed

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

    2016-05-15

    Hypertriglyceridemia (HTG) is a weak risk factor in primary ischemic stroke prevention. However, clinical studies have found a counterintuitive association between a good prognosis after ischemic stroke and HTG. This "HTG paradox" requires confirmation and further explanation. The aim of this study was to experimentally assess this paradox relationship using the gene-modified mice model of extreme HTG. We first used the human Apolipoprotein CIII transgenic (Tg-ApoCIII) mice and non-transgenic (Non-Tg) littermates to examine the effect of HTG on stroke. To our surprise, infarct size, neurological deficits, brain edema, BBB permeability, neuron density and lipid peroxidation were the same in Tg-ApoCIII mice and Non-Tg mice after temporary middle cerebral artery occlusion (tMCAO). In the late phase (21 days after surgery), no differences were found in brain atrophy, neurological dysfunctions, weight and mortality between the two groups. To confirm the results in Tg-ApoCIII mice, Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1(GPIHBP1) knockout mice, another severe HTG mouse model, were used and yielded similar results. Our study demonstrates for the first time that extreme HTG does not affect ischemic brain injuries in the tMCAO mouse model, indicating that the association between HTG and good outcomes after ischemic stroke probably represents residual unmeasured confounding. Further clinical and prospective population-based studies are needed to explore variables that contribute to the paradox. PMID:26970521

  16. Angiopoietin-like 4: A double-edged sword in atherosclerosis and ischemic stroke?

    PubMed

    Xu, Liang; Guo, Zhen-Ni; Yang, Yi; Xu, Jun; Burchell, Sherrefa R; Tang, Jiping; Zhang, Jianmin; Xu, Jing; Zhang, John H

    2015-10-01

    Ischemic stroke is one of the leading causes of death in the world, and thus is a major public health concern. Atherosclerosis, also known as atherogenesis, is a crucial risk factor for cerebral ischemia, yet how it develops remains largely unknown. It has been found, however, that angiopoietin-like protein 4 (ANGPTL4), a protein expressed in vascular endothelial cells, plays a role in the pathophysiology of atherosclerosis and may therefore be involved in ischemic stroke. ANGPTL4 activity is associated with endothelial cell integrity, inflammation, oxidative stress, and lipid metabolism. ANGPTL4 also serves as a potent inhibitor of the lipoprotein lipase, and may inhibit atherogenesis via regulating inflammatory signaling and lipid metabolism. In addition, ANGPTL4 plays a role in the regulation of oxidative stress. However, there currently exists a controversy on the role of ANGPTL4 in endothelial cells. Some studies indicate that ANGPTL4 can protect the integrity of endothelial cells, while others have shown that it can be destructive to the endothelium, thereby leading to the initiation of atherosclerosis. Thus, the effects of ANGPTL4 on development of atherosclerosis and thereby ischemic stroke, are undefined. Further research is needed to better understand ANGPTL4-mediated signaling pathways in endothelial function and to determine its potentials as therapeutic target for atherosclerosis and ischemic stroke. PMID:26033474

  17. Blood-Brain Barrier Alterations Provide Evidence of Subacute Diaschisis in an Ischemic Stroke Rat Model

    PubMed Central

    Garbuzova-Davis, Svitlana; Rodrigues, Maria C. O.; Hernandez-Ontiveros, Diana G.; Tajiri, Naoki; Frisina-Deyo, Aric; Boffeli, Sean M.; Abraham, Jerry V.; Pabon, Mibel; Wagner, Andrew; Ishikawa, Hiroto; Shinozuka, Kazutaka; Haller, Edward; Sanberg, Paul R.; Kaneko, Yuji; Borlongan, Cesario V.

    2013-01-01

    Background 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. Methodology/Principal Findings 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. Conclusions/Significance 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. PMID:23675488

  18. Pioglitazone after Ischemic Stroke or Transient Ischemic Attack

    PubMed Central

    Kernan, W.N.; Viscoli, C.M.; Furie, K.L.; Young, L.H.; Inzucchi, S.E.; Gorman, M.; Guarino, P.D.; Lovejoy, A.M.; Peduzzi, P.N.; Conwit, R.; Brass, L.M.; Schwartz, G.G.; Adams, H.P.; Berger, L.; Carolei, A.; Clark, W.; Coull, B.; Ford, G.A.; Kleindorfer, D.; O’Leary, J.R.; Parsons, M.W.; Ringleb, P.; Sen, S.; Spence, J.D.; Tanne, D.; Wang, D.; Winder, T.R.

    2016-01-01

    BACKGROUND Patients with ischemic stroke or transient ischemic attack (TIA) are at increased risk for future cardiovascular events despite current preventive therapies. The identification of insulin resistance as a risk factor for stroke and myocardial infarction raised the possibility that pioglitazone, which improves insulin sensitivity, might benefit patients with cerebrovascular disease. METHODS In this multicenter, double-blind trial, we randomly assigned 3876 patients who had had a recent ischemic stroke or TIA to receive either pioglitazone (target dose, 45 mg daily) or placebo. Eligible patients did not have diabetes but were found to have insulin resistance on the basis of a score of more than 3.0 on the homeostasis model assessment of insulin resistance (HOMA-IR) index. The primary outcome was fatal or nonfatal stroke or myocardial infarction. RESULTS By 4.8 years, a primary outcome had occurred in 175 of 1939 patients (9.0%) in the pioglitazone group and in 228 of 1937 (11.8%) in the placebo group (hazard ratio in the pioglitazone group, 0.76; 95% confidence interval [CI], 0.62 to 0.93; P = 0.007). Diabetes developed in 73 patients (3.8%) and 149 patients (7.7%), respectively (hazard ratio, 0.48; 95% CI, 0.33 to 0.69; P<0.001). There was no significant between-group difference in all-cause mortality (hazard ratio, 0.93; 95% CI, 0.73 to 1.17; P = 0.52). Pioglitazone was associated with a greater frequency of weight gain exceeding 4.5 kg than was placebo (52.2% vs. 33.7%, P<0.001), edema (35.6% vs. 24.9%, P<0.001), and bone fracture requiring surgery or hospitalization (5.1% vs. 3.2%, P = 0.003). CONCLUSIONS In this trial involving patients without diabetes who had insulin resistance along with a recent history of ischemic stroke or TIA, the risk of stroke or myocardial infarction was lower among patients who received pioglitazone than among those who received placebo. Pioglitazone was also associated with a lower risk of diabetes but with higher risks of

  19. Pre-treatment with LCZ696, an orally active angiotensin receptor neprilysin inhibitor, prevents ischemic brain damage.

    PubMed

    Bai, Hui-Yu; Mogi, Masaki; Nakaoka, Hirotomo; Kan-No, Harumi; Tsukuda, Kana; Chisaka, Toshiyuki; Wang, Xiao-Li; Kukida, Masayoshi; Shan, Bao-Shuai; Yamauchi, Toshifumi; Higaki, Akinori; Iwanami, Jun; Horiuchi, Masatsugu

    2015-09-01

    Angiotensin II receptor blockers (ARBs) are known to prevent ischemic brain damage after stroke. Natriuretic peptides, which are increased by a neprilysin inhibitor, are also reported to protect against brain damage. Therefore, we investigated the possible protective effect of valsartan (VAL) compared with LCZ696 (VAL+ neprilysin inhibitor; 1:1) after middle cerebral artery (MCA) occlusion. Eight-week-old male C57BL/6J mice were treated with VAL (3mg/kg per day) or LCZ696 (6mg/kg per day) for 2 weeks before MCA occlusion. Blood pressure and heart rate were measured by telemetry. Cerebral blood flow (CBF) was determined by laser-Doppler flowmetry. Ischemic area was evaluated by triphenytetrasodium chloride staining, and oxidative stress was determined by dihydroethidium staining. Blood pressure and heart rate were not significantly different before and after treatment. Pre-treatment with LCZ696 or VAL reduced the ischemic area, and this effect of LCZ696 was more marked than that of VAL pre-treatment. The decrease in CBF in the peripheral region of the ischemic area was significantly attenuated by pre-treatment with LCZ696 or VAL, without any significant effect on CBF in the core region. VAL or LCZ696 pre-treatment significantly decreased the increase of superoxide anion production in the cortex on the ischemic side. However, no significant difference in CBF and superoxide anion production was observed between VAL and LCZ696 pre-treatment. The preventive effect of LCZ696 on ischemic brain damage after stroke was more marked than that of VAL. LCZ696 could be used as a new approach to prevent brain damage after stroke. (246 words). PMID:26057694

  20. Ischemic stroke assessment with near-infrared spectroscopy

    NASA Astrophysics Data System (ADS)

    Chen, Weiguo; Li, Pengcheng; Zeng, Shaoqun; Luo, Qingming; Hu, Bo

    1999-09-01

    Many authors have elucidated the theory about oxygenated hemoglobin, deoxygenated hemoglobin absorption in near-infrared spectrum. And the theory has opened a window to measure the hemodynamic changes caused by stroke. However, no proper animal model still has established to confirm the theory. The aim of this study was to validate near-infrared cerebral topography (NCT) as a practical tool and to try to trace the focal hemodynamic changes of ischemic stroke. In the present study, middle cerebral artery occlusion model and the photosensitizer induced intracranial infarct model had been established. NCT and functional magnetic resonance image (fMRI) were obtained during pre- and post-operation. The geometric shape and infarct area of NCT image was compared with the fMRI images and anatomical samples of each rat. The results of two occlusion models in different intervene factors showed the NCT for infarct focus matched well with fMRI and anatomic sample of each rats. The instrument might become a practical tool for short-term prediction of stroke and predicting the rehabilitation after stroke in real time.

  1. Radix Ilicis Pubescentis total flavonoids ameliorates neuronal damage and reduces lesion extent in a mouse model of transient ischemic attack.

    PubMed

    Miao, Ming-San; Guo, Lin; Li, Rui-Qi; Zhang, Xiao-Lei

    2016-03-01

    Flavonoids are a major component in the traditional Chinese medicine Radix Ilicis Pubescentis. Previous studies have shown that the administration of Radix Ilicis Pubescentis total flavonoids is protective in cerebral ischemia. However, to our knowledge, no studies have examined whether the total flavonoids extracted from Radix Ilicis Pubescentis prevent or ameliorate neuronal damage following transient ischemic attacks. Therefore, Radix Ilicis Pubescentis total flavonoids question and the potential underlying mechanisms. Thus, beginning 3 days before the induction of a mouse model of transient ischemic attack using tert-butyl hydroperoxide injections, mice were intragastrically administered 0.3, 0.15, or 0.075 g/kg of Radix Ilicis Pubescentis total flavonoids daily for 10 days. The results of spectrophotometric analyses demonstrated that Radix Ilicis Pubescentis total flavonoids enhanced oxygen free radical scavenging and reduced pathological alterations in the brain. Hematoxylin-eosin staining results showed that Radix Ilicis Pubescentis total flavonoids reduced hippocampal neuronal damage and cerebral vascular injury in this mouse model of transient ischemic attack. These results suggest that the antioxidant effects of Radix Ilicis Pubescentis total flavonoids alleviate the damage to brain tissue caused by transient ischemic attack.

  2. Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack: a statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke: co-sponsored by the Council on Cardiovascular Radiology and Intervention: the American Academy of Neurology affirms the value of this guideline.

    PubMed

    Sacco, Ralph L; Adams, Robert; Albers, Greg; Alberts, Mark J; Benavente, Oscar; Furie, Karen; Goldstein, Larry B; Gorelick, Philip; Halperin, Jonathan; Harbaugh, Robert; Johnston, S Claiborne; Katzan, Irene; Kelly-Hayes, Margaret; Kenton, Edgar J; Marks, Michael; Schwamm, Lee H; Tomsick, Thomas

    2006-02-01

    The aim of this new statement is to provide comprehensive and timely evidence-based recommendations on the prevention of ischemic stroke among survivors of ischemic stroke or transient ischemic attack. Evidence-based recommendations are included for the control of risk factors, interventional approaches for atherosclerotic disease, antithrombotic treatments for cardioembolism, and the use of antiplatelet agents for noncardioembolic stroke. Further recommendations are provided for the prevention of recurrent stroke in a variety of other specific circumstances, including arterial dissections; patent foramen ovale; hyperhomocysteinemia; hypercoagulable states; sickle cell disease; cerebral venous sinus thrombosis; stroke among women, particularly with regard to pregnancy and the use of postmenopausal hormones; the use of anticoagulation after cerebral hemorrhage; and special approaches for the implementation of guidelines and their use in high-risk populations.

  3. Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack: a statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke: co-sponsored by the Council on Cardiovascular Radiology and Intervention: the American Academy of Neurology affirms the value of this guideline.

    PubMed

    Sacco, Ralph L; Adams, Robert; Albers, Greg; Alberts, Mark J; Benavente, Oscar; Furie, Karen; Goldstein, Larry B; Gorelick, Philip; Halperin, Jonathan; Harbaugh, Robert; Johnston, S Claiborne; Katzan, Irene; Kelly-Hayes, Margaret; Kenton, Edgar J; Marks, Michael; Schwamm, Lee H; Tomsick, Thomas

    2006-03-14

    The aim of this new statement is to provide comprehensive and timely evidence-based recommendations on the prevention of ischemic stroke among survivors of ischemic stroke or transient ischemic attack. Evidence-based recommendations are included for the control of risk factors, interventional approaches for atherosclerotic disease, antithrombotic treatments for cardioembolism, and the use of antiplatelet agents for noncardioembolic stroke. Further recommendations are provided for the prevention of recurrent stroke in a variety of other specific circumstances, including arterial dissections; patent foramen ovale; hyperhomocysteinemia; hypercoagulable states; sickle cell disease; cerebral venous sinus thrombosis; stroke among women, particularly with regard to pregnancy and the use of postmenopausal hormones; the use of anticoagulation after cerebral hemorrhage; and special approaches for the implementation of guidelines and their use in high-risk populations.

  4. Parameters of diffusional kurtosis imaging for the diagnosis of acute cerebral infarction in different brain regions

    PubMed Central

    Guo, Yue-Lin; Li, Su-Juan; Zhang, Zhong-Ping; Shen, Zhi-Wei; Zhang, Gui-Shan; Yan, Gen; Wang, Yan-Ting; Rao, Hai-Bing; Zheng, Wen-Bin; Wu, Ren-Hua

    2016-01-01

    Diffusional kurtosis imaging (DKI) is a new type diffusion-weighted sequence which measures the non-Gaussianity of water diffusion. The present study aimed to investigate whether the parameters of DKI could distinguish between differences in water molecule diffusion in various brain regions under the conditions of acute infarction and to identify the optimal DKI parameter for locating ischemic lesions in each brain region. A total of 28 patients with acute ischemic stroke in different brain regions were recruited for the present study. The relative values of DKI parameters were selected as major assessment indices, and the homogeneity of background image and contrast of adjacent structures were used as minor assessment indices. According to the brain region involved in three DKI parametric maps, including mean kurtosis (MK), axial kurtosis (Ka) and radial kurtosis (Kr), 112 groups of regions of interest were outlined in the following regions: Corpus callosum (n=17); corona radiata (n=26); thalamus (n=21); subcortical white matter (n=24); and cerebral cortex (n=24). For ischemic lesions in the corpus callosum and corona radiata, significant increases in relative Ka were detected, as compared with the other parameters (P<0.05). For ischemic lesions in the thalamus, subcortical white matter and cerebral cortices, an increase in the three parameters was detected, however this difference was not significant. Minor assessment indices demonstrated that Ka lacked tissue contrast and the background of Kr was heterogeneous; thus, MK was the superior assessment parameter for ischemic lesions in these regions. In conclusion, Ka is better suited for the diagnosis of acute ischemic lesions in highly anisotropic brain regions, such as the corpus callosum and corona radiate. MK may be appropriate for the lesions in low anisotropic or isotropic brain regions, such as the thalamus, subcortical white matter and cerebral cortices. PMID:27446298

  5. Future accelerators (?)

    SciTech Connect

    John Womersley

    2003-08-21

    I describe the future accelerator facilities that are currently foreseen for electroweak scale physics, neutrino physics, and nuclear structure. I will explore the physics justification for these machines, and suggest how the case for future accelerators can be made.

  6. Assessment of arterial collateralization and its relevance to intra-arterial therapy for acute ischemic stroke.

    PubMed

    Ramaiah, Siva Seeta; Mitchell, Peter; Dowling, Richard; Yan, Bernard

    2014-03-01

    Evidence from recent randomized controlled studies comparing intra-arterial (IA) therapy with intravenous tissue plasminogen activator highlighted the mismatch between recanalization success and clinical outcomes in patients presenting with acute ischemic stroke. There is emerging interest in the impact of arterial collateralization, as determined by leptomeningeal anastomoses (LMAs), on the treatment outcomes of IA therapy. The system of LMA constitutes the secondary network of cerebral collateral circulation apart from the Circle of Willis. Both anatomic and angiographic studies confirmed significant interindividual variability in LMA. This review aims to outline the current understanding of arterial collateralization and its impact on outcomes after IA therapy for acute ischemic stroke, underpinning the possible role of arterial collateralization assessment as a selection tool for patients most likely to benefit from IA therapy.

  7. Transient ischemic attack as an unusual initial manifestation of acute promyelocytic leukemia.

    PubMed

    Liu, Lifeng; Yuan, Xiaoling

    2016-07-01

    Patients with acute promyelocytic leukemia (APL) are prone to both bleeding and thrombosis. Both of these have a significant impact on the morbidity and mortality of patients with this disease. Here we report a case of a 41-year-old male, who presented with transient ischemic attack (TIA) and early neurological deterioration (END) as initial manifestations prior to an ultimate diagnosis of APL. This patient had no cerebrovascular risk factors or familial cerebrovascular disease. The patient experienced an acute ischemic stroke, verified by magnetic resonance imaging (MRI), in less than 24 h after his second hospital admission. Some APL patients suffer from cerebral ischemia as an initial manifestation or during induction therapy, and patients presenting this condition may continue to deteriorate until their death during hospitalization. Thus, APL should be considered as a possible underlying disease in patients with TIA without cerebrovascular risk factors. Delayed diagnosis and treatment of APL can be fatal.

  8. Pilocarpine-Induced Status Epilepticus in Rats Involves Ischemic and Excitotoxic Mechanisms

    PubMed Central

    Fabene, Paolo Francesco; Merigo, Flavia; Galiè, Mirco; Benati, Donatella; Bernardi, Paolo; Farace, Paolo; Nicolato, Elena; Marzola, Pasquina; Sbarbati, Andrea

    2007-01-01

    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. PMID:17971868

  9. Meta-Analysis of Local Endovascular Therapy for Acute Ischemic Stroke.

    PubMed

    Kennedy, Sean A; Baerlocher, Mark O; Baerlocher, Felix; Socko, Daniel; Sacks, David; Nikolic, Boris; Wojak, Joan C; Haskal, Ziv J

    2016-03-01

    A meta-analysis was performed to assess randomized controlled trials comparing local endovascular therapy (with and without intravenous thrombolysis) versus standard care (intravenous thrombolysis alone when appropriate) for acute ischemic stroke. Local endovascular therapy showed a significant improvement in functional independence versus standard care (odds ratio, 1.779; 95% confidence interval, 1.262-2.507; P < .001). This benefit strengthened further on subgroup analyses of trials in which a majority of cases used stent retrievers, trials with intravenous thrombolysis use in both arms when appropriate, and trials that required preprocedural imaging of all patients. There were no significant differences between arms in terms of mortality, hemicraniectomy, intracranial hemorrhage, and cerebral edema rates (P > .05). In conclusion, in the treatment of acute ischemic stroke, local endovascular therapy leads to improved functional independence compared with standard care. PMID:26803573

  10. [Dystypia after ischemic stroke: a disturbance of linguistic processing for Romaji (Romanized Japanese)?].

    PubMed

    Suzuki, Yukiko; Inatomi, Yuichiro; Yonehara, Toshiro; Hirano, Teruyuki

    2015-01-01

    "Dystypia", characterized by an impairment of typing on a keyboard, is a unique neurobehavioral syndrome. A 77-year-old right-handed woman developed a relatively selective impairment of typing after ischemic stroke. The MRI documented new scattered ischemic lesions in the middle cerebral artery territory of the left hemisphere and an old infarct lesion in the frontal area of the right hemisphere. The standard neuropsychological tests showed no aphasia, normal praxis, intact visuospatial ability, and a mild visual memory disturbance. The detailed analysis documented severe impairment of writing and reading abilities for Romaji (Romanized Japanese), spelled by alphabet letters and the most common way to input Japanese into computers. The writing and reading abilities for other Japanese linguistic modalities such as kanji (morphogram: Chinese character), kana (syllabogram: Japanese proper character), and alphabet letters, were not or minimally impaired. A disturbance of linguistic processing for Romaji may be the main underlying neural mechanism for dystypia in this patient. PMID:25672858

  11. Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia.

    PubMed

    Panickar, Kiran S; Jang, Saebyeol

    2013-08-01

    Cerebral ischemia is caused by an interruption of blood flow to the brain which generally leads to irreversible brain damage. Ischemic injury is associated with vascular leakage, inflammation, tissue injury, and cell death. Cellular changes associated with ischemia include impairment of metabolism, energy failure, free radical production, excitotoxicity, altered calcium homeostasis, and activation of proteases all of which affect brain functioning and also contribute to longterm disabilities including cognitive decline. Inflammation, mitochondrial dysfunction, increased oxidative/nitrosative stress, and intracellular calcium overload contribute to brain injury including cell death and brain edema. However, there is a paucity of agents that can effectively reduce cerebral damage and hence considerable attention has focused on developing newer agents with more efficacy and fewer side-effects. Polyphenols are natural compounds with variable phenolic structures and are rich in vegetables, fruits, grains, bark, roots, tea, and wine. Most polyphenols have antioxidant, anti-inflammatory, and anti-apoptotic properties and their protective effects on mitochondrial functioning, glutamate uptake, and regulating intracellular calcium levels in ischemic injury in vitro have been demonstrated. This review will assess the current status of the potential effects of polyphenols in reducing cerebral injury and improving cognitive function in ischemia in animal and human studies. In addition, the review will also examine available patents in nutrition and agriculture that relates to cerebral ischemic injury with an emphasis on plant polyphenols.

  12. microRNAs: innovative targets for cerebral ischemia and stroke

    PubMed Central

    Ouyang, Yi-Bing; Stary, Creed M.; Yang, Guo-Yuan; Giffard, Rona

    2013-01-01

    Stroke is one of the leading causes of death and disability worldwide. Because stroke is a multifactorial disease with a short therapeutic window many clinical stroke trials have failed and the only currently approved therapy is thrombolysis. MicroRNAs (miRNA) are endogenously expressed noncoding short single-stranded RNAs that play a role in the regulation of gene expression at the post-transcriptional level, via degradation or translational inhibition of their target mRNAs. The study of miRNAs is rapidly growing and recent studies have revealed a significant role of miRNAs in ischemic disease. miRNAs are especially important candidates for stroke therapeutics because of their ability to simultaneously regulate many target genes and since to date targeting single genes for therapeutic intervention has not yet succeeded in the clinic. Although there are already quite a few review articles about miRNA in ischemic heart disease, much less is currently known about miRNAs in cerebral ischemia. This review summarizes current knowledge about miRNAs and cerebral ischemia, focusing on the role of miRNAs in ischemia, both changes in expression and identification of potential targets, as well as the potential of miRNAs as biomarkers and therapeutic targets in cerebral ischemia. PMID:23170800

  13. Cerebral infarction in diabetes: Clinical pattern, stroke subtypes, and predictors of in-hospital mortality

    PubMed Central

    Arboix, Adrià; Rivas, Antoni; García-Eroles, Luis; de Marcos, Lourdes; Massons, Joan; Oliveres, Montserrat

    2005-01-01

    Background To compare the characteristics and prognostic features of ischemic stroke in patients with diabetes and without diabetes, and to determine the independent predictors of in-hospital mortality in people with diabetes and ischemic stroke. Methods Diabetes was diagnosed in 393 (21.3%) of 1,840 consecutive patients with cerebral infarction included in a prospective stroke registry over a 12-year period. Demographic characteristics, cardiovascular risk factors, clinical events, stroke subtypes, neuroimaging data, and outcome in ischemic stroke patients with and without diabetes were compared. Predictors of in-hospital mortality in diabetic patients with ischemic stroke were assessed by multivariate analysis. Results People with diabetes compared to people without diabetes presented more frequently atherothrombotic stroke (41.2% vs 27%) and lacunar infarction (35.1% vs 23.9%) (P < 0.01). The in-hospital mortality in ischemic stroke patients with diabetes was 12.5% and 14.6% in those without (P = NS). Ischemic heart disease, hyperlipidemia, subacute onset, 85 years old or more, atherothrombotic and lacunar infarcts, and thalamic topography were independently associated with ischemic stroke in patients with diabetes, whereas predictors of in-hospital mortality included the patient's age, decreased consciousness, chronic nephropathy, congestive heart failure and atrial fibrillation Conclusion Ischemic stroke in people with diabetes showed a different clinical pattern from those without diabetes, with atherothrombotic stroke and lacunar infarcts being more frequent. Clinical factors indicative of the severity of ischemic stroke available at onset have a predominant influence upon in-hospital mortality and may help clinicians to assess prognosis more accurately. PMID:15833108

  14. A type-II positive allosteric modulator of α7 nAChRs reduces brain injury and improves neurological function after focal cerebral ischemia in rats.

    PubMed

    Sun, Fen; Jin, Kunlin; Uteshev, Victor V

    2013-01-01

    In the absence of clinically-efficacious therapies for ischemic stroke there is a critical need for development of new therapeutic concepts and approaches for prevention of brain injury secondary to cerebral ischemia. This study tests the hypothesis that administration of PNU-120596, a type-II positive allosteric modulator (PAM-II) of α7 nicotinic acetylcholine receptors (nAChRs), as long as 6 hours after the onset of focal cerebral ischemia significantly reduces brain injury and neurological deficits in an animal model of ischemic stroke. Focal cerebral ischemia was induced by a transient (90 min) middle cerebral artery occlusion (MCAO). Animals were then subdivided into two groups and injected intravenously (i.v.) 6 hours post-MCAO with either 1 mg/kg PNU-120596 (treated group) or vehicle only (untreated group). Measurements of cerebral infarct volumes and neurological behavioral tests were performed 24 hrs post-MCAO. PNU-120596 significantly reduced cerebral infarct volume and improved neurological function as evidenced by the results of Bederson, rolling cylinder and ladder rung walking tests. These results forecast a high therapeutic potential for PAMs-II as effective recruiters and activators of endogenous α7 nAChR-dependent cholinergic pathways to reduce brain injury and improve neurological function after cerebral ischemic stroke. PMID:23951360

  15. How to Perfuse: Concepts of Cerebral Protection during Arch Replacement

    PubMed Central

    Habertheuer, Andreas; Wiedemann, Dominik; Kocher, Alfred; Laufer, Guenther; Vallabhajosyula, Prashanth

    2015-01-01

    Arch surgery remains undoubtedly among the most technically and strategically challenging endeavors in cardiovascular surgery. Surgical interventions of thoracic aneurysms involving the aortic arch require complete circulatory arrest in deep hypothermia (DHCA) or elaborate cerebral perfusion strategies with varying degrees of hypothermia to achieve satisfactory protection of the brain from ischemic insults, that is, unilateral/bilateral antegrade cerebral perfusion (ACP) and retrograde cerebral perfusion (RCP). Despite sophisticated and increasingly individualized surgical approaches for complex aortic pathologies, there remains a lack of consensus regarding the optimal method of cerebral protection and circulatory management during the time of arch exclusion. Many recent studies argue in favor of ACP with various degrees of hypothermic arrest during arch reconstruction and its advantages have been widely demonstrated. In fact ACP with more moderate degrees of hypothermia represents a paradigm shift in the cardiac surgery community and is widely adopted as an emergent strategy; however, many centers continue to report good results using other perfusion strategies. Amidst this important discussion we review currently available surgical strategies of cerebral protection management and compare the results of recent European multicenter and single-center data. PMID:26713319

  16. Urinary kallidinogenase for the treatment of cerebral arterial stenosis

    PubMed Central

    Zhao, Liandong; Zhao, Ying; Wan, Qi; Zhang, Haijun

    2015-01-01

    Aim Urinary kallidinogenase (UK) has shown promise in improving cerebral perfusion. This study aimed to examine how UK affects cognitive status and serum levels of amyloid betas (Aβs) 1-40 and 1-42 in patients with cerebral arterial stenosis. Methods Ninety patients with cerebral arterial stenosis were enrolled, of whom 45 patients received UK + conventional treatment (UK group), and 45 patients received conventional treatment alone as control group. Cognitive status and Aβ1-40 and Aβ1-42 serum levels were determined before treatment and at 4 weeks and 8 weeks after treatment. Results At 4 weeks after treatment, cognitive status in patients treated with UK clearly improved accompanied by Aβ1-40 serum levels decreasing while there was no change of Aβ1-42. Cognitive status in patients receiving UK continued to improve, Aβ1-40 serum levels declined further as well as Aβ1-42 serum levels began to decrease dramatically at 8 weeks after treatment. Conclusion UK could improve cognitive status and decrease both Aβ1-40 and Aβ1-42 serum levels to prevent ischemic cerebral injury, which represents a good option for patients with cerebral arterial stenosis. PMID:26508834

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

    PubMed Central

    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