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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

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

    2015-11-01

    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 Preconditioning: the Road So Far….

    PubMed

    Thushara Vijayakumar, N; Sangwan, Amit; Sharma, Bhargy; Majid, Arshad; Rajanikant, G K

    2016-05-01

    Cerebral preconditioning constitutes the brain's adaptation to lethal ischemia when first exposed to mild doses of a subtoxic stressor. The phenomenon of preconditioning has been largely studied in the heart, and data from in vivo and in vitro models from past 2-3 decades have provided sufficient evidence that similar machinery exists in the brain as well. Since preconditioning results in a transient protective phenotype labeled as ischemic tolerance, it can open many doors in the medical warfare against stroke, a debilitating cerebrovascular disorder that kills or cripples thousands of people worldwide every year. Preconditioning can be induced by a variety of stimuli from hypoxia to pharmacological anesthetics, and each, in turn, induces tolerance by activating a multitude of proteins, enzymes, receptors, transcription factors, and other biomolecules eventually leading to genomic reprogramming. The intracellular signaling pathways and molecular cascades behind preconditioning are extensively being investigated, and several first-rate papers have come out in the last few years centered on the topic of cerebral ischemic tolerance. However, translating the experimental knowledge into the clinical scaffold still evades practicality and faces several challenges. Of the various preconditioning strategies, remote ischemic preconditioning and pharmacological preconditioning appears to be more clinically relevant for the management of ischemic stroke. In this review, we discuss current developments in the field of cerebral preconditioning and then examine the potential of various preconditioning agents to confer neuroprotection in the brain. PMID:26081149

  3. Immune mechanisms in cerebral ischemic tolerance

    PubMed Central

    Garcia-Bonilla, Lidia; Benakis, Corinne; Moore, Jamie; Iadecola, Costantino; Anrather, Josef

    2014-01-01

    Stressor-induced tolerance is a central mechanism in the response of bacteria, plants, and animals to potentially harmful environmental challenges. This response is characterized by immediate changes in cellular metabolism and by the delayed transcriptional activation or inhibition of genetic programs that are not generally stressor specific (cross-tolerance). These programs are aimed at countering the deleterious effects of the stressor. While induction of this response (preconditioning) can be established at the cellular level, activation of systemic networks is essential for the protection to occur throughout the organs of the body. This is best signified by the phenomenon of remote ischemic preconditioning, whereby application of ischemic stress to one tissue or organ induces ischemic tolerance (IT) in remote organs through humoral, cellular and neural signaling. The immune system is an essential component in cerebral IT acting simultaneously both as mediator and target. This dichotomy is based on the fact that activation of inflammatory pathways is necessary to establish IT and that IT can be, in part, attributed to a subdued immune activation after index ischemia. Here we describe the components of the immune system required for induction of IT and review the mechanisms by which a reprogrammed immune response contributes to the neuroprotection observed after preconditioning. Learning how local and systemic immune factors participate in endogenous neuroprotection could lead to the development of new stroke therapies. PMID:24624056

  4. Hemodilution increases cerebral blood flow in acute ischemic stroke

    SciTech Connect

    Vorstrup, S.; Andersen, A.; Juhler, M.; Brun, B.; Boysen, G.

    1989-07-01

    We measured cerebral blood flow in 10 consecutive, but selected, patients with acute ischemic stroke (less than 48 hours after onset) before and after hemodilution. Cerebral blood flow was measured by xenon-133 inhalation and emission tomography, and only patients with focal hypoperfusion in clinically relevant areas were included. Hemodilution was done according to the hematocrit level: for a hematocrit greater than or equal to 42%, 500 ml whole blood was drawn and replaced by the same volume of dextran 40; for a hematocrit between 37% and 42%, only 250 ml whole blood was drawn and replaced by 500 cc of dextran 40. Mean hematocrit was reduced by 16%, from 46 +/- 5% (SD) to 39 +/- 5% (SD) (p less than 0.001). Cerebral blood flow increased in both hemispheres by an average of 20.9% (p less than 0.001). Regional cerebral blood flow increased in the ischemic areas in all cases, on an average of 21.4 +/- 12.0% (SD) (p less than 0.001). In three patients, a significant redistribution of flow in favor of the hypoperfused areas was observed, and in six patients, the fractional cerebral blood flow increase in the hypoperfused areas was of the same magnitude as in the remainder of the brain. In the last patient, cerebral blood flow increased relatively less in the ischemic areas. Our findings show that cerebral blood flow increases in the ischemic areas after hemodilution therapy in stroke patients. The marked regional cerebral blood flow increase seen in some patients could imply an improved oxygen delivery to the ischemic tissue.

  5. Obesity Exacerbates Rat Cerebral Ischemic Injury through Enhancing Ischemic Adiponectin-Containing Neuronal Apoptosis.

    PubMed

    Wu, Ming-Hsiu; Chio, Chung-Ching; Tsai, Kuen-Jer; Chang, Ching-Ping; Lin, Nan-Kai; Huang, Chao-Ching; Lin, Mao-Tsun

    2016-08-01

    A diet consisting of high levels of saturated fat has been linked to a dramatic rise in obesity. Long-term exposure to high fat, "Western diet" (WD), is detrimental to ischemic brain injury. Adiponectin receptor 1 (ADR-1) activation is also shown to exacerbate ischemic neuronal death. However, it is not known whether increasing percentages of adiponectin (APN)-containing neurons attenuates ischemic neuronal apoptosis by modulating ADRS. To explore the role of APN and its ADRs in the development of acute cerebral injury, we subjected WD and control diet (CD) rats to 1 h of middle cerebral artery occlusion followed by 23 h of reperfusion. Compared with CD rats, WD rats exhibited higher levels of brain infarct, neurologic deficits, brain edema, and apoptosis of APN-containing neurons; upregulation of both ADR-1 and P38 mitogen-activated protein kinase (P38MAPK); and downregulation of ADR-2 in ischemic brain tissues including frontal cortex, striatum, and hippocampus. Increasing percentages of APN-containing neurons by baculovirus-mediated administration of APN, in addition to reducing apoptosis of APN-containing neurons in ischemic brain tissues, significantly attenuated brain infarct and edema, neurologic deficits, and altered expression of ADR-1, P38MAPK, and ADR-2 in both WD and CD group rats. These data suggest a negative correlation between percentages of APN-containing neurons and cerebral ischemic injury. Obesity could exacerbate rat cerebral ischemic injury by enhancing apoptosis of APN-containing neurons in ischemic brain tissues probably via modulating ADRs and P38MAPK. PMID:26126515

  6. 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.

  7. Early exercise training improves ischemic outcome in rats by cerebral hemodynamics.

    PubMed

    Tian, Shan; Zhang, Youcan; Tian, Song; Yang, Xiaojiao; Yu, Kewei; Zhang, Yuling; Shen, Xiafeng; Zhang, Liping; Sun, Yu; Xie, Hongyu; He, Zhijie; Guo, Zhenzhen; Jia, Jie; Wu, Yi; Bai, Yulong; Zhu, Yulian; Cheng, Yong; Wang, Xinggang; Wu, Junfa; Wang, Nianhong; Yu, Huixian; Hu, Yongshan

    2013-10-01

    This study examined whether very early initiated physical rehabilitation (VEIPR), as a recommended therapy for postischemia, could improve motor performance and cerebral blood flow (CBF). Adult male rats with ischemic injury caused by middle cerebral artery occlusion (MCAO) were trained to run on a treadmill for 30min per day at 12m/min. Through such exercise training for 3 days, the ischemic rats exhibited increased motor function and decreased infarct volume, as measured by a behavioral score and 2,3,5-triphenyltetrazolium chloride (TTC) staining method, as well as accelerated CBF, as detected with laser speckle imaging (LSI). Furthermore, to determine whether the observed improved CBF provided the protective factor for motor function recovery, we investigated the apoptosis of ischemic rat brain microvascular endothelial cells (rBMECs), which accepted the mechanical force of CBF directly, under flow intervention. The findings indicated that a modest flow decreased cell apoptosis in the ischemic condition and that this effect is magnitude dependent, as excessive flow increased apoptosis. PMID:23948104

  8. [Ischemic insult in the anterior and posterior cerebral circulation].

    PubMed

    Smajlović, Dzevdet; Ibrahimagić, Omer; Dostović, Zikrija

    2003-01-01

    In the everyday practice among clinical and etiological classifications for ischemic stroke, the terms strokes in the anterior and posterior cerebral circulation are also in use. The aim of this study was to analyze the frequency of ischemic strokes in the anterior and posterior circulation, their age and sex distribution, risk factors and hospital mortality. In the study it was analyzed 1772 patients with acute ischemic stroke hospitalized at the Department of Neurology Tuzla, Bosnia and Herzegovina, between January 1st 1996 and December 31st 2000. The mean age was 65.5 years (+9.9), 942 (55%) were females. Ischemic strokes for all patients were confirmed with computed tomography, while other data were collected from the standard patients' history charts. Anterior circulation stroke (ACS) had 1408 patients (81.8%), the rest of 314 (18.2%) had posterior circulation stroke (PCS). In the both types females were slightly overrepresented: 784 (56%) in ACS, and 158 (50.5%) in PCS. Moreover, females were significantly older than males: 67 (+9.8) versus 64 (+10) years in ACS (p < 0.001), 67.5 (+10.3) versus 63.5 (+9.2) in PCS (p < 0.001). Hypertension was the major risk factor occurring in 67% patients with ACS and 71 with PCS; heart diseases 54% in the both types, and diabetes in 23% patients with ACS and 20% with PCS. The cortical ischemic lesion was verified in 46% patients with ACS, 41% with PCS; subcortical in 12.5% and 14.5%; and lacunar in 41.5% and 44.5%, respectively. Hospital mortality was 30% (430 patients) for ACS, and 32% (101 patients) for PCS. Hospital mortality was considerably higher among females: 33% versus 28% for ACS (p = 0.03), 38% versus 27% for PCS (p = 0.03). On the basis of our study we can conclude that ischemic strokes in the anterior cerebral circulation are 4/5 of all ischemic strokes at the Department of Neurology Tuzla. Both, anterior and posterior circulation strokes are more frequent in females, witches were in average older than males

  9. 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

  10. 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

  11. 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

  12. Cerebral ischemic events in patients with pancreatic cancer

    PubMed Central

    Bonnerot, Mathieu; Humbertjean, Lisa; Mione, Gioia; Lacour, Jean-Christophe; Derelle, Anne-Laure; Sanchez, Jean-Charles; Riou-Comte, Nolwenn; Richard, Sébastien

    2016-01-01

    Abstract Stroke is a dramatic complication of pancreatic cancer with mechanisms related to oncological disease. A better description of the characteristics of cerebrovascular events would help better understand the pathogeny and protect vulnerable patients. We thus conducted a descriptive analysis of clinical, biological, and radiological features of patients from our centers and literature. We reviewed consecutive cases of patients who presented cerebrovascular events and pancreatic cancer in 4 stroke units in Lorrain (France) between January 1, 2009 and March 31, 2015, and all reported cases of literature. We identified 17 cases in our centers and 18 reported cases. Fifty-seven per cent of patients were male. Median age was 63 ± 14 years and ranged from 23 to 81 years. All cerebral events were ischemic. At the onset of stroke, pancreatic cancer had already been diagnosed in 59% of the patients in our centers for a mean time of 5.4 months. Five of them (29%) were being treated with gemcitabine and 2 (12%) with folfirinox. Adenocarcinoma at metastatic stage was reported in 82% of cases overall. Brain imaging revealed disseminated infarctions in 64%. High median levels of D-dimer (7600 ± 5 × 107 μg/L), C-reactive protein (63 ± 43 mg/L), and elevated prothrombin time (19 ± 6 seconds) were found. Thirty-six per cent of patients explored with echocardiography were diagnosed with nonbacterial thrombotic endocarditis. Ten of our patients received anticoagulant therapy as secondary stroke prevention without any documented recurrence. Nevertheless, outcome was poor with a median survival time of 28 ± 14 days after stroke onset. Cerebral ischemic events occur at advanced stages of pancreatic cancer, most likely by a thromboembolic mechanism. Disseminated infarctions and high D-dimer, C-reactive protein levels, and a high prothrombin time are the most constant characteristics found in this context. All patients should be screened for

  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. PMID:24792782

  14. Interleukin-1 exacerbates focal cerebral ischemia and reduces ischemic brain temperature in the rat.

    PubMed

    Parry-Jones, Adrian R; Liimatainen, Timo; Kauppinen, Risto A; Gröhn, Olli H J; Rothwell, Nancy J

    2008-06-01

    The proinflammatory cytokine interleukin-1 (IL-1) is a key mediator of inflammation in cerebral ischemia, but its precise mechanisms of action remain elusive. Temperature is critical to outcome in brain injury and given the importance of IL-1 in pyrogenesis this has clear mechanistic implications. IL-1 exacerbates ischemia independently of core (rectal) temperature. However, it is temperature in the ischemic brain that influences outcome and rectal temperature is likely to be a poor surrogate marker. This study tested the hypothesis that IL-1 exacerbates cerebral ischemia by increasing ischemic brain temperature. Wistar rats undergoing transient middle cerebral artery occlusion received either 4 microg/kg IL-1 (n=9) or vehicle (n=10) intraperitoneally. NMR-generated maps of brain temperature, tissue perfusion, and the trace of the diffusion tensor were collected during occlusion, early reperfusion, and at 24 hr. IL-1 significantly increased ischemic damage at 24 hr by 35% but rectal temperature did not vary significantly between groups. However, ischemic brain was 1.7 degrees C cooler on reperfusion in IL-1-treated animals (vs. vehicle) and a corresponding reduction in cerebral blood flow was identified in the ischemic striatum. Contrary to the stated hypothesis, IL-1 reduced ischemic brain temperature during reperfusion and this may be due to a reduction in tissue perfusion. PMID:18421691

  15. Sex, Aging, and Preexisting Cerebral Ischemic Disease in Patients With Aortic Stenosis

    PubMed Central

    Wang, Ping; Acker, Michael A.; Bilello, Michel; Melhem, Elias R.; Stambrook, Elizabeth; Ratcliffe, Sarah J.; Floyd, Thomas F.

    2011-01-01

    Background Patients undergoing cardiac surgery have a high frequency of preexisting cerebral ischemic lesions, the presence of which appears to predict cognitive sequelae. Patients undergoing aortic valve replacement for aortic stenosis (AS) incur an exceptionally high risk for perioperative cerebral ischemia. The extreme risk in this subgroup may arise from the preexisting burden of cerebral ischemic disease. We tested the hypotheses that increasing age, female sex, coronary artery disease, and the severity of AS are predictive of the severity of preexisting cerebral ischemic lesions. Methods A total of 95 subjects were included in this study. Subjects were imaged on 1.5 Tesla magnetic resonance imaging scanners to obtain multimodal image sets which were used for the automatic segmentation of cerebral lesion volume. The dependence of lesion volume upon age, sex, coronary artery disease, and the severity of AS were tested. Results The results demonstrate a strong correlation between aging, female sex, and white matter and ischemia-like lesion volume in patients with aortic stenosis. Conclusions Women and those of advanced age presenting for aortic valve replacement for AS may incur a particularly high risk for postoperative neurologic sequelae due to an exceptional preexisting burden of cerebral ischemic disease. PMID:20868818

  16. 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

  17. 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

  18. 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

  19. Ischemic postconditioning in cerebral ischemia: Differences between the immature and mature brain?

    PubMed

    Leger, Pierre-Louis; Bonnin, Philippe; Renolleau, Sylvain; Baud, Olivier; Charriaut-Marlangue, Christiane

    2015-10-01

    Ischemic postconditioning (postC), defined as serial mechanical interruptions of blood flow at reperfusion, effectively reduces myocardial infarct size in all species tested so far, including humans. In the brain, ischemic postC leads to controversial results regardless of variations in factors such as onset time of beginning, the duration of ischemia and/or reperfusion, and the number of cycles of occlusion/reperfusion. Thus, many major issues remain to be resolved regarding its protective effects. Future studies should aim to identify the parameters that yield the strongest protection, as well as to understand why the efficacy of ischemic postC differs between models. This review will focus on initial hemodynamic changes and their consequences, and on specific features such as NO-dependent vascular tone and/or prolonged acidosis in cerebral ischemia-reperfusion in order to better understand the dynamics of ischemic postC in the developing brain. PMID:25777940

  20. Activation of cerebral sodium-glucose transporter type 1 function mediated by post-ischemic hyperglycemia exacerbates the development of cerebral ischemia.

    PubMed

    Yamazaki, Y; Ogihara, S; Harada, S; Tokuyama, S

    2015-12-01

    The regulation of post-ischemic hyperglycemia plays an important role in suppressing neuronal damage in therapeutic strategies for cerebral ischemia. We previously reported that the cerebral sodium-glucose transporter (SGLT) was involved in the post-ischemic hyperglycemia-induced exacerbation of cerebral ischemic neuronal damage. Cortical SGLT-1, one of the cerebral SGLT isoforms, is dramatically increased by focal cerebral ischemia. In this study, we focused on the involvement of cerebral SGLT-1 in the development of cerebral ischemic neuronal damage. It was previously reported that activation of 5'-adenosine monophosphate-activated protein kinase (AMPK) increases SGLT-1 expression. Moreover, ischemic stress-induced activation of AMPK exacerbates cerebral ischemic neuronal damage. Therefore, we directly confirmed the relationship between cerebral SGLT-1 and cerebral AMPK activation using in vitro primary culture of mouse cortical neurons. An in vivo mouse model of focal cerebral ischemia was generated using a middle cerebral artery occlusion (MCAO). The development of infarct volume and behavioral abnormalities on day 3 after MCAO were ameliorated in cerebral SGLT-1 knock down mice. Cortical and striatal SGLT-1 expression levels were significantly increased at 12h after MCAO. Immunofluorescence revealed that SGLT-1 and the neuronal nuclear antigen (NeuN) were co-localized in the cortex and striatum of MCAO mice. In the in vitro study, primary cortical neurons were cultured for five days before each treatment with reagents. Concomitant treatment with hydrogen peroxide and glucose induced the elevation of SGLT-1 and phosphorylated AMPK/AMPK ratio, and this elevation was suppressed by compound C, an AMPK inhibitor in primary cortical neurons. Moreover, compound C suppressed neuronal cell death induced by concomitant hydrogen peroxide/glucose treatment in primary cortical neurons. Therefore, we concluded that enhanced cerebral SGLT-1 function mediated by post-ischemic

  1. 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.

  2. [On the quantitative analysis of focal ischemic cerebral infarction by TTC staining].

    PubMed

    Feng, Chunyan; Fan, Xiaonong; Zhang, Chunhong; Shi, Xuemin

    2009-12-01

    It is known that ischemic cerebrovascular disease is causing enormous harm to human health on account of the resultant high morbidity and disability rate. In this connexion, the anticipated target is to control the size of focal ischemic cerebral infarction, which is also an important method for judgment of therapeutic efficacy. The key question is to survey the size accurately and objectively; at the same time, the quantitative analysis of focal ischemic cerebral infarction is the pivotal question affecting the experiment conclusion and the reliability level. In this paper are introduced and summarized the methods being recently and commonly used in survey and computation, and the studies made on quantitative analysis of focal ischemic cerebral infarction by 2, 3, 5-triphenyltetrazolium chloride (TTC) staining method. Also are summarized the principles of dyeing in TTC method, the preparatory work, and the commonly used method of surveying and computation. It is the intent of this review to provide relevant data and suggestion for research workers. PMID:20095504

  3. 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.

  4. Ameliorative effects of Gualou Guizhi decoction on inflammation in focal cerebral ischemic-reperfusion injury

    PubMed Central

    ZHANG, YUQIN; ZHANG, SHENGNAN; LI, HUANG; HUANG, MEI; XU, WEI; CHU, KEDAN; CHEN, LIDIAN; CHEN, XIANWEN

    2015-01-01

    Gualou Guizhi decoction (GLGZD) is a well-established Traditional Chinese Medicinal formulation which has long been used to treat stroke in a clinical setting in China. The present study investigated the ameliorative effects of GLGZD on inflammation in focal cerebral ischemic-reperfusion injury. A rat model of middle cerebral artery occlusion (MCAO) was employed. Rats were administrated GLGZD (7.2 and 14.4 g/kg per day) or saline as control 2 h after reperfusion and daily over the following seven days. Neurological deficit score and screen test were evaluated at 1, 3, 5 and 7 days after MCAO. Brain infarct size and brain histological changes were observed via 2,3,5-triphenyltetrazolium chloride staining and regular hematoxylin & eosin staining. Furthermore, inflammation mediators and nuclear factor-κB (NF-κB) were investigated using ELISA and immunohistochemistry. GLGZD treatment significantly improved neurological function, ameliorated histological changes to the brain and decreased infarct size in focal cerebral ischemic-reperfusion injury. GLGZD was found to significantly reduce interleukin (IL)-1, tumor necrosis factor-α and NF-κB levels, while increasing levels of IL-10. In conclusion, the present study suggested that GLGZD has a neuroprotective effect on focal cerebral ischemic-reperfusion injury and this effect is likely to be associated with the anti-inflammatory function of GLGZD. PMID:25815894

  5. Cerebral aspergillosis in a diabetic patient leading to cerebral artery occlusion and ischemic stroke: a case report and literature review.

    PubMed

    Li, Wentao; Shafi, Neelofer; Periakaruppan, Ramayee; Valyi-Nagy, Tibor; Groth, John; Testai, Fernando D

    2015-01-01

    Cerebral aspergillosis is a rare and highly fatal hematogenous infection most commonly found in immune compromised patients. From the onset of neurologic symptoms, the median reported rate of survival is between 5 and 9 days. Compounded with increased hemorrhagic risks and the lack of specificity in both clinical presentation and traditional imaging, a fast and noninvasive method of definitive diagnosis is necessary if there is to be any hope for positive outcomes. We describe the case of a 50-year-old female diabetic with a history of otitis media, an uncharacterized inflammatory nasopharyngeal process, and prior ischemic strokes who presented with a new cerebral infarction in the setting of an angioinvasive fungal infection of the large cerebral arteries. We also present a literature review of aspergillosis detection and treatment in hopes that future cases will be diagnosed in a timely manner and more patients may be saved. PMID:25444026

  6. 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

  7. 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

  8. 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

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

    PubMed

    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

  10. 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

  11. 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

  12. Resveratrol preconditioning protects against cerebral ischemic injury via Nrf2

    PubMed Central

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

    2015-01-01

    Background and Purpose Nuclear erythroid 2 related factor 2 (Nrf2) is an astrocyte-enriched transcription factor that has previously been shown to upregulate cellular antioxidant systems in response to ischemia. While resveratrol preconditioning (RPC) has emerged as a potential neuroprotective therapy, the involvement of Nrf2 in RPC-induced neuroprotection and mitochondrial reactive oxygen species (ROS) production following cerebral ischemia remains unclear. The goal of our study was to study the contribution of Nrf2 to RPC and its effects on mitochondrial function. Methods We used rodent astrocyte cultures and an in vivo stroke model with RPC. An Nrf2 DNA-binding ELISA and protein analysis via Western blotting of downstream Nrf2 targets were performed to determine RPC-induced activation of Nrf2 in rat and mouse astrocytes. Following RPC, mitochondrial function was determined by measuring ROS production and mitochondrial respiration in both wild-type (WT) and Nrf2−/− mice. Infarct volume was measured to determine neuroprotection, while protein levels were measured by immunoblotting. Results We report that Nrf2 is activated by RPC in rodent astrocyte cultures, and that loss of Nrf2 reduced RPC-mediated neuroprotection in a mouse model of focal cerebral ischemia. In addition, we observed that wild-type and Nrf2−/− cortical mitochondria exhibited increased uncoupling and ROS production following RPC treatments, Finally, Nrf2−/− astrocytes exhibited decreased mitochondrial antioxidant expression and were unable to upregulate cellular antioxidants following RPC treatment. Conclusion Nrf2 contributes to RPC-induced neuroprotection through maintaining mitochondrial coupling and antioxidant protein expression. PMID:25908459

  13. Normobaric hyperoxia delays and attenuates early nitric oxide production in focal cerebral ischemic rats.

    PubMed

    Yuan, Zhongrui; Liu, Wenlan; Liu, Baoyi; Schnell, Aaron; Liu, Ke Jian

    2010-09-17

    Overproduction of neuronal nitric oxide synthase (nNOS)-derived NO is detrimental during cerebral ischemia. Normobaric hyperoxia (NBO) has been shown to be neuroprotective, extending the therapeutic time window for ischemic stroke, but the mechanism is not fully understood. In the present study, using a rat model of ischemic stroke, we investigated the effect of early NBO treatment on neuronal NO production. Male Sprague-Dawley rats were given normoxia (30% O(2)) or NBO (95% O(2)) during 10, 30, 60 or 90min filament occlusion of the middle cerebral artery. NO(x)(-) (nitrite plus nitrate) and 3-nitrotyrosine were measured in the ischemic cortex. Ischemia caused a rapid increase in the production of NO(x)(-), with a peak at 10min after ischemia onset, then gradually declining to the baseline level at 60min. NBO treatment delayed the NO(x)(-) production peak to 30min and attenuated the total amount of NO(x)(-). Ischemia also increased 3-nitrotyrosine formation, which was significantly reduced by NBO treatment. Inhibition of nNOS by pre-treatment with 7-nitroindazole had similar effect as NBO treatment on NO(x)(-) and 3-nitrotyrosine production, and when combined with NBO, no further reduction in NO production was observed. Furthermore, NBO treatment significantly decreased brain infarct volume. Taken together, our findings demonstrate that delaying and attenuating the early NO release from nNOS may be an important mechanism accounting for NBO's neuroprotection. PMID:20633543

  14. 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

  15. 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

  16. Cerebral hemodynamics in human acute ischemic stroke: a study with diffusion- and perfusion-weighted magnetic resonance imaging and SPECT.

    PubMed

    Liu, Y; Karonen, J O; Vanninen, R L; Ostergaard, L; Roivainen, R; Nuutinen, J; Perkiö, J; Könönen, M; Hämäläinen, A; Vanninen, E J; Soimakallio, S; Kuikka, J T; Aronen, H J

    2000-06-01

    Nineteen patients with acute ischemic stroke (<24 hours) underwent diffusion-weighted and perfusion-weighted (PWI) magnetic resonance imaging at the acute stage and 1 week later. Eleven patients also underwent technetium-99m ethyl cysteinate dimer single-photon emission computed tomography (SPECT) at the acute stage. Relative (ischemic vs. contralateral control) cerebral blood flow (relCBF), relative cerebral blood volume, and relative mean transit time were measured in the ischemic core, in the area of infarct growth, and in the eventually viable ischemic tissue on PWI maps. The relCBF was also measured from SPECT. There was a curvilinear relationship between the relCBF measured from PWI and SPECT (r = 0.854; P < 0.001). The tissue proceeding to infarction during the follow-up had significantly lower initial CBF and cerebral blood volume values on PWI maps (P < 0.001) than the eventually viable ischemic tissue had. The best value for discriminating the area of infarct growth from the eventually viable ischemic tissue was 48% for PWI relCBF and 87% for PWI relative cerebral blood volume. Combined diffusion and perfusion-weighted imaging enables one to detect hemodynamically different subregions inside the initial perfusion abnormality. Tissue survival may be different in these subregions and may be predicted. PMID:10894174

  17. Dehydroascorbic Acid Attenuates Ischemic Brain Edema and Neurotoxicity in Cerebral Ischemia: An in vivo Study

    PubMed Central

    Song, Juhyun; Park, Joohyun; Kim, Jae Hwan; Choi, Ja Yong; Kim, Jae Young; Lee, Kyoung Min

    2015-01-01

    Ischemic stroke results in the diverse phathophysiologies including blood brain barrier (BBB) disruption, brain edema, neuronal cell death, and synaptic loss in brain. Vitamin C has known as the potent anti-oxidant having multiple functions in various organs, as well as in brain. Dehydroascorbic acid (DHA) as the oxidized form of ascorbic acid (AA) acts as a cellular protector against oxidative stress and easily enters into the brain compared to AA. To determine the role of DHA on edema formation, neuronal cell death, and synaptic dysfunction following cerebral ischemia, we investigated the infarct size of ischemic brain tissue and measured the expression of aquaporin 1 (AQP-1) as the water channel protein. We also examined the expression of claudin 5 for confirming the BBB breakdown, and the expression of bcl 2 associated X protein (Bax), caspase-3, inducible nitric oxide synthase (iNOS) for checking the effect of DHA on the neurotoxicity. Finally, we examined postsynaptic density protein-95 (PSD-95) expression to confirm the effect of DHA on synaptic dysfunction following ischemic stroke. Based on our findings, we propose that DHA might alleviate the pathogenesis of ischemic brain injury by attenuating edema, neuronal loss, and by improving synaptic connection. PMID:25792869

  18. 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

  19. Neuroprotective potential of cerium oxide nanoparticles for focal cerebral ischemic stroke.

    PubMed

    Zhou, Da; Fang, Ting; Lu, Lin-Qing; Yi, Li

    2016-08-01

    During the previous years, with the emerging of nanotechnology, the enormous capabilities of nanoparticles have drawn great attention from researchers in terms of their potentials in various aspects of pharmacology. Cerium oxide nanoparticles (nanoceria), considered as one of the most widely used nanomaterials, due to its tempting catalytic antioxidant properties, show a promising potential in diverse disorders, such as cerebral ischemic stroke (CIS), cancer, neurodegenerative and inflammatory diseases. Overwhelming generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) during cerebral ischemia and reperfusion periods is known to aggravate brain damage via sophisticated cellular and molecular mechanisms, and therefore exploration of the antioxidant capacities of nanoceria becomes a new approach in reducing cerebral ischemic injury. Furthermore, utilizing nanoceria as a drug carrier might display the propensity to overcome limitations or inefficacy of other conceivable neuroprotectants and exhibit synergistic effects. In this review, we emphasize on the principle features of nanoceria and current researches concerning nanoceria as a potential therapeutic agent or carrier in improving the prognosis of CIS. PMID:27465320

  20. 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

  1. 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

  2. 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

  3. Imaging Evidence for Cerebral Hyperperfusion Syndrome after Intravenous Tissue Plasminogen Activator for Acute Ischemic Stroke

    PubMed Central

    Zhang, Yi

    2016-01-01

    Background. Cerebral hyperperfusion syndrome (CHS), a rare complication after cerebral revascularization, is a well-described phenomenon after carotid endarterectomy or carotid artery stenting. However, the imaging evidence of CHS after intravenous tissue plasminogen activator (iv tPA) for acute ischemic stroke (AIS) has not been reported. Case Report. Four patients were determined to have manifestations of CHS with clinical deterioration after treatment with iv tPA, including one patient who developed seizure, one patient who had a deviation of the eyes toward lesion with worsened mental status, and two patients who developed worsened hemiparesis. In all four patients, postthrombolysis head CT examinations were negative for hemorrhage; CT angiogram showed patent cervical and intracranial arterial vasculature; CT perfusion imaging revealed hyperperfusion with increased relative cerebral blood flow and relative cerebral blood volume and decreased mean transit time along with decreased time to peak in the clinically related artery territory. Vascular dilation was also noted in three of these four cases. Conclusions. CHS should be considered in patients with clinical deterioration after iv tPA and imaging negative for hemorrhage. Cerebral angiogram and perfusion studies can be useful in diagnosing CHS thereby helping with further management. PMID:27242938

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

    PubMed Central

    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. PMID:24064492

  5. Intranasal administration of aTf protects and repairs the neonatal white matter after a cerebral hypoxic-ischemic event.

    PubMed

    Guardia Clausi, Mariano; Paez, Pablo M; Campagnoni, Anthony T; Pasquini, Laura A; Pasquini, Juana M

    2012-10-01

    Our previous studies showed that the intracerebral injection of apotransferrin (aTf) attenuates white matter damage and accelerates the remyelination process in a neonatal rat model of cerebral hypoxia-ischemia (HI) injury. However, the intracerebral injection of aTf might not be practical for clinical treatments. Therefore, the development of less invasive techniques capable of delivering aTf to the central nervous system would clearly aid in its effective clinical use. In this work, we have determined whether intranasal (iN) administration of human aTf provides neuroprotection to the neonatal mouse brain following a cerebral hypoxic-ischemic event. Apotransferrin was infused into the naris of neonatal mice and the HI insult was induced by right common carotid artery ligation followed by exposure to low oxygen concentration. Our results showed that aTf was successfully delivered into the neonatal HI brain and detected in the olfactory bulb, forebrain and posterior brain 30 min after inhalation. This treatment successfully reduced white matter damage, neuronal loss and astrogliosis in different brain regions and enhanced the proliferation and survival of oligodendroglial progenitor cells (OPCs) in the subventricular zone and corpus callosum (CC). Additionally, using an in vitro hypoxic model, we demonstrated that aTf prevents oligodendrocyte progenitor cell death by promoting their differentiation. In summary, these data suggest that iN administration of aTf has the potential to be used for clinical treatment to protect myelin and to induce remyelination in demyelinating hypoxic-ischemic events in the neonatal brain. PMID:22736466

  6. [Research progress in the study of protective effect of tanshinone IIA on cerebral ischemic stroke].

    PubMed

    Li, De-chuan; Bao, Xiu-qi; Sun, Hua; Zhang, Dan

    2015-06-01

    Danshen is one of the traditional Chinese herbal medicines and nas a long history or being used clinically in the treatment of cardiovascular and cerebrovascular conditions such as coronary heart disease and angina pectoris. Tanshinone IIA is a derivative of phenanthrene-quinone isolated from Danshen. It has been reported to be the major bioactive compound of Danshen and has diverse biological effects. Recent studies demonstrated that tanshinone IIA had neuroprotective effects on experimental ischemic stroke through its antiinflammatory, anti-oxidant, anti-apoptosis effects and its inhibitory effect on excitatory amino acid toxicity. In this review, we summarized all the recent progresses on the protective effect of tanshinone IIA on cerebral ischemic stroke. Hopefully, this article will throw some light on further study and application of tanshinone IIA. PMID:26521431

  7. 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.

  8. 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

  9. 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.

  10. 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

  11. [Hemodynamic and methabolic aspects of sodium nitroprusside pharmacodynamics during buccal administration in patients with arterial hypertension of cerebral ischemic genesis].

    PubMed

    Vizir, V A; Kechin, I L; Fedorova, E P

    2006-01-01

    The authors presented in the article efficiency of new formulation of Natrium Nitroprusodum used buccaly in patients with cerebral-ischemic form of arterial hypertention and stage II hypertention. It has been shown both in an acute experiment and after monothrerapy having been used. The medication proved to have positive effect on brachiocephalic vessel blood flow indices in patients of both groups using pulse doplergraphy. The use of Natrium Nitroprussidum used buccaly in patients with cerebral-ischemic form of arterial hypertention and hyportensive disease differentiates in terms of indices characterising the formation, transport and utilisation of energetic products, products of POL and antioxidant ferments. PMID:16689085

  12. Trigeminal neuralgia increases cerebral blood flow in a focal cerebral ischemic model in rats

    PubMed Central

    Wang, Wei; Zhao, Weiliang; Liu, Zhenxiu; Xia, Jianhua; Wu, Jingru; Shi, Xueyin

    2015-01-01

    Objective: To investigate the influences of trigeminal neuropathic pain on the cerebral blood flow in a ET-1 focal cerebral ischemia model. Methods: Male Sprague-Dawley (SD) rats (220-260 g) were randomly divided into a model group (trigeminal neuralgia, TN group) and a sham operation group (sham group). The TN group received bilateral infraorbital nerve chronic constriction surgery, and the sham group only underwent exposure of the infraorbital nerve. The mechanical pain threshold of the rats was continuously monitored for 30 days post surgery. On postoperative day 30, the animals were anesthetized, and 3 μL (120 pM/μL) ET-1 was injected into the surroundings of the middle cerebral artery (MCA) to establish a cerebral focal ischemia-reperfusion injury model in rats. The changes in cerebral blood flow of these two groups were monitored 30 min after the injection of ET-1. Results: The mechanic pain threshold values between rats in the two groups were not significantly different (P>0.05). The threshold value in the TN group on postoperative day 9 significantly decreased compared with that before surgery (P<0.01). Between postoperative days 9 and 30, the pain threshold values in the TN group were significantly lower than those in the sham group (P<0.01). From postoperative day 10, the mean arterial pressure in the TN group significantly increased compared with that before surgery (P<0.05), and the blood pressure (BP) in the TN group was higher than that in the sham group between postoperative days 10 and 30 (P<0.05). After 75 min of ET-1 microinjection, the cerebral blood flow in the rat frontal cortex exhibited reperfusion, and the cerebral blood flow in the TN group was significantly higher than that in the sham group (P<0.05). In addition, the content of calcitonin gene-related peptide (CGRP) in the blood of rats in the TN group was significantly higher than that in the sham group (P<0.05). Conclusions: Trigeminal neuropathic pain may increase the mean arterial

  13. 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

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

    PubMed Central

    Zhang, Jun; Zhu, Wusheng; Xiao, Lulu; Cao, Qinqin; Zhang, Hao; Wang, Huaiming; Ye, Zusen; Hao, Yonggang; Dai, Qiliang; Sun, Wen; Liu, Xinfeng; Ye, Ruidong

    2016-01-01

    Caveolin-1 (Cav-1) plays pivotal roles in the endothelial damage following stroke. The present study aimed to investigate whether serum Cav-1 level is associated with the presence of cerebral small vessel disease (cSVD) in patients with acute ischemic stroke. To this end, 156 patients were consecutively enrolled. Cranial magnetic resonance imaging was analyzed to determine the surrogates of cSVD, including cerebral microbleeds (CMBs), silent lacunar infarcts (SLIs), and white matter hyperintensities (WMHs). After adjusting for potential confounders, patients with low Cav-1 level had a higher risk of CMBs than patients with high Cav-1 level (OR: 4.05, 95% CI: 1.77–9.30). However, there was no relationship between Cav-1 and the presence of SLIs or WMHs. When CMBs were stratified by location and number, a similar association was found in patients with deep or infratentorial CMBs (OR: 4.04, 95% CI: 1.59–10.25) and with multiple CMBs (OR: 3.18, 95% CI: 1.16–8.72). These results suggest lower serum Cav-1 levels may be associated with CMBs, especially those that are multiple and located in deep brain or infratentorial structures, in patients with acute ischemic stroke. Cav-1 may be involved in the pathophysiology of CMBs, and may act as a potential target for treating cSVD. PMID:27119011

  15. Neuroprotective effect of osthole against acute ischemic stroke on middle cerebral ischemia occlusion in rats.

    PubMed

    Chao, Xiaodong; Zhou, Jun; Chen, Tao; Liu, Wenbo; Dong, Wenpeng; Qu, Yan; Jiang, Xiaofan; Ji, Xituan; Zhen, Haining; Fei, Zhou

    2010-12-01

    Osthole, a natural coumarin derivative, has taken considerable attention because of its diverse pharmacological functions. It has been reported to be useful in the treatment of chronic cerebral hypoperfusion and neuronal damage. In the present study, we examined the neuroprotective effect of osthole and its potential mechanisms against acute ischemic stroke induced by middle cerebral artery occlusion (MCAO) in rats. The rats were pretreated with osthole 10, 20 and 40 mg/kg 30 min before MCAO. The neuroprotective effect of osthole against acute ischemic stroke was evaluated by neurological deficit score (NDS), dry-wet weight and 2,3,5-triphenyltetrazolium chloride (TTC) staining. The contents of malondialdehyde (MDA) and glutathione (GSH), activity of myeloperoxidase (MPO) and the level of interleukin (IL)-1β and IL-8 after 2h of MCAO in rats were detected to investigate its anti-oxidative action and anti-inflammatory property. Pretreatment with osthole significantly increased in GSH, and decreased the volume of infarction, NDS, edema, MDA, MPO, IL-1β and IL-8 compared with rats in the MCAO group at 24h after MCAO. The study suggests the neuroprotective effect of osthole in the MCAO model of rats. The anti-oxidative action and anti-inflammatory property of osthole may contribute to a beneficial effect against stroke. PMID:20869955

  16. Reduction of focal cerebral ischemic damage by delayed treatment with nitric oxide donors.

    PubMed

    Zhang, F; Iadecola, C

    1994-07-01

    We studied whether delayed posttreatment with the nitric oxide donor 3-morpholinosydnonimine (SIN-1) is effective in reducing the size of the infarct produced by occlusion of the middle cerebral artery (MCA) in spontaneously hypertensive rats (SHRs). SHRs were anesthetized with halothane and intubated transorally. The left MCA was occluded at the level of the inferior cerebral vein. Cerebral blood flow (CBF) was monitored in the ischemic hemisphere by a laser-Doppler flowmeter, and an electroencephalogram (EEG) was recorded. SIN-1 was infused into the left internal carotid artery for 60 min starting 3, 15, 30, 60 or 120 min after MCA occlusion. The hypotension associated with SIN-1 administration was controlled by i.v. administration of phenylephrine. At the end of the infusion, rats were extubated and allowed to recover. Infarct size was measured 24 h later on thionein-stained coronal brain sections by computer-assisted planimetry. SIN-1 infusion 3 min after MCA occlusion enhanced the recovery of CBF and EEG amplitude and reduced the size of the infarct by 30 +/- 11% (p < 0.05, analysis of variance). The reduction in infarct size by SIN-1 was still seen when SIN-1 was administered 15, 30, and 60 min after MCA occlusion (p < 0.05). However, administration of SIN-1 2 h after MCA occlusion did not affect the size of the infarct (p > 0.05). We conclude that posttreatment with SIN-1 is effective in reducing focal ischemic damage if this agent is administered up to 60 min after MCA occlusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8014203

  17. 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

  18. Ischemic Postconditioning Decreases Cerebral Edema and Brain Blood Barrier Disruption Caused by Relief of Carotid Stenosis in a Rat Model of Cerebral Hypoperfusion

    PubMed Central

    Yang, Fuwei; Zhang, Xiaojie; Sun, Ying; Wang, Boyu; Zhou, Chuibing; Luo, Yinan; Ge, Pengfei

    2013-01-01

    Background and Purpose Complications due to brain edema and breakdown of blood brain barrier are an important factor affecting the treatment effects of patients with severe carotid stenosis. In this study, we investigated the protective effects of ischemic postconditioning on brain edema and disruption of blood brain barrier via establishing rat model of hypoperfusion due to severe carotid stenosis. Methods Wistar rat model of hypoperfusion due to severe carotid stenosis was established by binding a stainless microtube to both carotid arteries. Ischemic postconditioning procedure consisted of three cycles of 30 seconds ischemia and 30 seconds reperfusion. Brain edema was evaluated by measuring cerebral water content, and blood brain barrier permeability was assayed by examining cerebral concentration of Evans' Blue (EB) and fluorescein sodium (NaF). ELISA was used to analyze the expression of MMP-9, claudin-5 and occludin. The activity and location of MMP-9 was analyzed by gelatin zymography and in situ zymography, respectively. The distribution of tight junction proteins claudin-5 and occludin was observed by immunohistochemistry. Results The increased brain water content and cerebral concentration of EB and NaF were suppressed by administration of ischemic postconditioning prior to relief of carotid stenosis. Zymographic studies showed that MMP-9 was mainly located in the cortex and its activity was significantly improved by relief of carotid stenosis and, but the elevated MMP-9 activity was inhibited markedly by ischemic postconditioning. Immunohistochemistry revealed that ischemic postconditioning improved the discontinuous distribution of claudin-5 and occludin. ELISA detected that the expression of up-regulated MMP-9 and down-regulated claudin-5 and occludin caused by carotid relief were all attenuated by ischemic postconditioning. Conclusions Ischemic postconditioning is an effective method to prevent brain edema and improve BBB permeability and could be

  19. Effect of delta opioid receptor activation on spatial cognition and neurogenesis in cerebral ischemic rats.

    PubMed

    Wang, Shu-Yan; Duan, Ya-Le; Zhao, Bing; Wang, Xiang-Rui; Zhao, Zheng; Zhang, Guang-Ming

    2016-05-01

    This study aimed to investigate whether a selective delta opioid receptor agonist, [D-Ala2, D-Leu5]-Enkephalin (DADLE), regulates neurogenesis in the hippocampus of ischemic rats. Using an intracerebral cannula, rats were subjected to cerebral ischemia using the standard four-vessel occlusion. DADLE (2.5nmol), DADLE (2.5nmol) with naltrindole (NAL) (2.5nmol), or vehicle was administered at the onset of reperfusion. Bromodeoxyuridine (BrdU, 100mg/kg, intraperitoneal) was used to label newly formed cells from days 1 to 7 after ischemia. Immunohistochemistry was used to evaluate cell proliferation and apoptosis and differentiation 7days 28 days, respectively, after ischemia. Morris water maze test was conducted to test spatial learning and memory 23-27 days after ischemia. We found that DADLE treatment improved performance in the Morris water maze test, promoted proliferation and differentiation of newly formed neurons, and inhibited differentiation into astrocytes in a rat model of cerebral ischemia. Furthermore, the protective effects of DADLE were significantly reversed by co-administration of NAL (P<0.05), a highly potent and selective delta opioid receptor antagonist. Our findings suggest that DADLE promotes spatial cognitive function recovery and regulates neurogenesis after ischemia, which may provide a promising therapeutic strategy for cerebral ischemia. PMID:27016387

  20. 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

  1. Cerebrovascular dysfunction and microcirculation rarefaction precede white matter lesions in a mouse genetic model of cerebral ischemic small vessel disease

    PubMed Central

    Joutel, Anne; Monet-Leprêtre, Marie; Gosele, Claudia; Baron-Menguy, Céline; Hammes, Annette; Schmidt, Sabine; Lemaire-Carrette, Barbara; Domenga, Valérie; Schedl, Andreas; Lacombe, Pierre; Hubner, Norbert

    2010-01-01

    Cerebral ischemic small vessel disease (SVD) is the leading cause of vascular dementia and a major contributor to stroke in humans. Dominant mutations in NOTCH3 cause cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a genetic archetype of cerebral ischemic SVD. Progress toward understanding the pathogenesis of this disease and developing effective therapies has been hampered by the lack of a good animal model. Here, we report the development of a mouse model for CADASIL via the introduction of a CADASIL-causing Notch3 point mutation into a large P1-derived artificial chromosome (PAC). In vivo expression of the mutated PAC transgene in the mouse reproduced the endogenous Notch3 expression pattern and main pathological features of CADASIL, including Notch3 extracellular domain aggregates and granular osmiophilic material (GOM) deposits in brain vessels, progressive white matter damage, and reduced cerebral blood flow. Mutant mice displayed attenuated myogenic responses and reduced caliber of brain arteries as well as impaired cerebrovascular autoregulation and functional hyperemia. Further, we identified a substantial reduction of white matter capillary density. These neuropathological changes occurred in the absence of either histologically detectable alterations in cerebral artery structure or blood-brain barrier breakdown. These studies provide in vivo evidence for cerebrovascular dysfunction and microcirculatory failure as key contributors to hypoperfusion and white matter damage in this genetic model of ischemic SVD. PMID:20071773

  2. 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

  3. Dynamic Cerebral Autoregulation Is Heterogeneous in Different Subtypes of Acute Ischemic Stroke

    PubMed Central

    Xing, Yingqi; Yan, Shuo; Lv, Cunling; Jin, Hang; Yang, Yi

    2014-01-01

    Background and Purpose Stroke of large-artery atherosclerosis and small-artery occlusion are two main subtypes of stroke according to TOAST classification. The underlying mechanisms of how these two subtypes affect dynamic cerebral autoregulation (dCA) might be heterogeneous, resulting in varied clinical conditions and outcomes. We therefore studied the pattern of dCA in these two subtypes. Methods Forty-one patients with acute unilateral middle cerebral artery (MCA) territory stroke (15 with ipsilateral large-artery atherosclerosis and 26 with small-artery occlusion) and 20 healthy volunteers were enrolled. Non-invasive continuous cerebral blood flow velocity and arterial blood pressure were recorded simultaneously from each subject in supine position using transcranial Doppler on MCA bilaterally and servo-controlled plethysmograph on the middle finger, respectively. Transfer function analysis was applied to derive autoregulatory parameters, gain, phase difference (PD), and slope of step response. Results In the large-artery atherosclerosis group, PD in affected hemisphere was 42.9±18.5 degree, which is significantly lower than the unaffected hemisphere (72.4±29.9 degree, P<0.01), and the healthy group (P<0.01). However, PD is similar in the unaffected hemisphere and healthy group (P>0.1). In the small-artery occlusion group, PD in the affected hemisphere was similar to that in the contralateral hemisphere (33.8±17.9 vs. 32.6±21.1 degree, P>0.1), both sides were significantly lower than the healthy group (all P<0.001).The results of the slope of step response agree with the findings in PD. Conclusions DCA in different subtypes of acute ischemic stroke is heterogeneous, which might be attributed to the varied pathologic changes of cerebral blood vessels. PMID:24671155

  4. [Advance in study on pharmacological mechanisms of Qingkailing injection in intervention of ischemic cerebral injury].

    PubMed

    Chen, Yin-Ying; Wang, Zhong

    2012-11-01

    As a severe threat to human health, ischemic brain injury has a very complex pathological mechanism involving excitotoxic amino acids, oxygen free radical formation, nitric oxide (NO), Ca2+ overload and inflammation. Traditional Chinese medicine Qingkailing injection have shown good clinical efficacy in the treatment of cerebrovascular disease, and thus it is very significant to studies on its pharmacological mechanism. This essay summarizes relevant studies on pharmacological mechanism of a new compound traditional Chinese medicine Jingzhiqiangkailing (JZQKL) injection in treatment on cerebral ischemia, and explains the pharmacological mechanism of its single effective compounds and their compatibility in treatment of schemic brain injury in the aspects of regulating inflammatory response, neurotrophic factors, vascular protection, blood-brain barrier (BBB) protection and others, and thus providing information for further studies. PMID:23397712

  5. Prokineticins are neuroprotective in models of cerebral ischemia and ischemic tolerance in vitro.

    PubMed

    Landucci, Elisa; Lattanzi, Roberta; Gerace, Elisabetta; Scartabelli, Tania; Balboni, Gianfranco; Negri, Lucia; Pellegrini-Giampietro, Domenico E

    2016-09-01

    Bv8/prokineticin 2 (PK2) is a member of a bioactive family of peptides that regulate multiple functions in the CNS including hyperalgesia, neurogenesis, neuronal survival and inflammation. Recent studies have associated PK2 and prokineticin receptors (PKR) with human diseases, but because their role in neuropathology is still debated we examined whether prokineticins exert a protective or deleterious role in models of cerebral ischemia and ischemic tolerance in vitro. In order to mimic cerebral ischemia, we exposed primary murine cortical cell cultures or rat organotypic hippocampal slices to appropriate periods of oxygen-glucose deprivation (OGD), which leads to neuronal damage 24 h later. Ischemic tolerance was induced by exposing hippocampal slices to a preconditioning subtoxic pharmacological stimulus (3 μM NMDA for 1 h) 24 h before the exposure to OGD. Bv8 (10-100 nM) attenuated OGD injury in cortical cultures and hippocampal slices, and the effect was prevented by the PKR antagonist PC7. The development of OGD tolerance was associated with an increase in the expression of PK2, PKR1 and PKR2 mRNA and proteins and was prevented by addition of the antagonist PC7 into the medium during preconditioning. Both Bv8 at protective concentrations and the NMDA preconditioning stimulus promoted the phosphorylation of ERK1/2 and Akt. These findings indicate that the prokineticin system can be up-regulated by a defensive preconditioning subtoxic NMDA stimulus and that PK2 may act as an endogenous neuroprotective factor through the activation of the ERK1/2 and Akt transduction pathways. PMID:27140692

  6. CT perfusion cerebral blood volume does not always predict infarct core in acute ischemic stroke.

    PubMed

    d'Esterre, Christopher D; Roversi, Gloria; Padroni, Marina; Bernardoni, Andrea; Tamborino, Carmine; De Vito, Alessandro; Azzini, Cristiano; Marcello, Onofrio; Saletti, Andrea; Ceruti, Stefano; Lee, Ting Yim; Fainardi, Enrico

    2015-10-01

    We investigated the practical clinical utility of the CT perfusion (CTP) cerebral blood volume (CBV) parameter for differentiating salvageable from non-salvageable tissue in acute ischemic stroke (AIS). Fifty-five patients with AIS were imaged within 6 h from onset using CTP. Admission CBV defect (CBVD) volume was outlined using previously established gray and white matter CBV thresholds for infarct core. Admission cerebral blood flow (CBF) hypoperfusion and CBF/CBV mismatch were visually evaluated. Truncation of the ischemic time-density curve (ITDC) and hypervolemia status at admission, recanalization at 24-h CT angiography, hemorrhagic transformation (HT) at 24 h and/or 7-day non-contrast CT (NCCT), final infarct volume as indicated by 3-month NCCT defect (NCCTD) and 3-month modified Rankin Score were determined. Patients with recanalization and no truncation had the highest correlation (R = 0.81) and regression slope (0.80) between CBVD and NCCTD. Regression slopes were close to zero for patients with admission hypervolemia with/without recanalization. Hypervolemia underestimated (p = 0.02), while recanalization and ITDC truncation overestimated (p = 0.03) the NCCTD. Among patients with confirmed recanalization at 24 h, 38 % patients had an admission CBF/CBV mismatch within normal appearing areas on respective NCCT. 83 % of these patients developed infarction in admission hypervolemic CBF/CBV mismatch tissue. A reduction in CBV is a valuable predictor of infarct core when the acquisition of ITDC data is complete and hypervolemia is absent within the tissue destined to infarct. Raised or normal CBV is not always indicative of salvageable tissue, contrary to the current definition of penumbra. PMID:25981225

  7. Impact of Coexisting Coronary Artery Disease on the Occurrence of Cerebral Ischemic Lesions after Carotid Stenting

    PubMed Central

    Huang, Kuo-Lun; Chang, Yeu-Jhy; Chang, Chien-Hung; Chang, Ting-Yu; Liu, Chi-Hung; Hsieh, I-Chang; Wong, Ho-Fai; Wai, Yau-Yau; Chen, Yu-Wei; Yip, Bak-Sau; Lee, Tsong-Hai

    2014-01-01

    Background Coronary artery disease (CAD) may coexist with extracranial carotid artery stenosis (ECAS), but the influence of CAD on procedure-related complications after carotid artery stenting (CAS) has not been well investigated. The study aimed to determine the impact of CAD on the occurrence of peri-CAS cerebral ischemic lesions on diffusion-weighted imaging (DWI) scanning. Methods Coronary angiography was performed within six months before CAS. DWI scanning was repetitively done within 1 week before and after CAS. Clinical outcome measures were stroke, angina, myocardial infarction and death within 30 days. Results Among 126 patients (69.5±9.0 years) recruited for unilateral protected CAS, 33 (26%) patients had peri-CAS DWI-positive lesions. CAD was noted in 79% (26 in 33) and 48% (45 in 93) of patients with and without peri-CAS DWI-positive lesions (OR, 4.0; 95% CI, 1.6–10.0; P = .0018), and the number of concomitant CAD on coronary angiography was positively correlated with the risk for peri-CAS DWI-positive lesions (P = .0032). In patients with no CAD (n = 55), asymptomatic CAD (n = 41) and symptomatic CAD (n = 30), the occurrence rates of peri-CAS DWI-positive lesions were 13%, 41% and 30% (P = .0048), and the peri-CAS stroke rates were 2%, 7% and 0% (P = .2120). Conclusions The severity of morphological CAD and the presence of either symptomatic or asymptomatic CAD are associated with the occurrence of peri-CAS cerebral ischemic lesions. PMID:24732408

  8. 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.

  9. Modulation of ischemic-induced damage to cerebral adenylate cyclase in gerbils by calcium channel blockers.

    PubMed

    Christie-Pope, B C; Palmer, G C

    1986-12-01

    It has been previously established that prolonged bilateral carotid occlusion followed by recirculation produces damage to the synaptic enzyme adenylate cyclase in the frontal cortex of the gerbil. Since calcium entrance into the brain may account in part for the deleterious consequences of stroke, the present study examined whether pretreatment with calcium channel blockers would modify the effects of 60 min of bilateral ischemia plus 40 min of reflow on various parameters of cortical adenylate cyclase activation. In this context activation of cerebral homogenates by norepinephrine with or without 5'-guanylyl imidodiphosphate was preserved by pretreatment of ischemic gerbils with verapamil but worsened by flunarizine. In contrast, in particulate fractions (treated with EGTA to reduce metallic ion levels) the damage to the Mn2+-sensitive catalytic site of adenylate cyclase was prevented only by flunarizine. Pretreatment with the two calcium channel blockers resulted in an elevated basal activity of the enzyme, thereby reducing the response in the homogenate preparation to forskolin. Gerbils pretreated with verapamil tended to have an increased ability for survival resulting from the ischemic episode. Under in vitro conditions the enzyme preparations were not markedly influenced by either drug. PMID:3508245

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

    SciTech Connect

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

    1989-04-01

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

  11. 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)

  12. 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

  13. Zinc finger protein 667 expression is upregulated by cerebral ischemic preconditioning and protects cells from oxidative stress

    PubMed Central

    YUAN, DUN; HUANG, JUN; YUAN, XIANRUI; ZHAO, JIE; JIANG, WEIXI

    2013-01-01

    Brain ischemic injury is associated with clinical emergencies such as acute ischemic and hemorrhagic stroke, head trauma, prolonged severe hypotension and cardiac arrest. Ischemic preconditioning (IPC) is the most powerful endogenous mechanism against ischemic injury. However, the majority of IPC treatments are invasive and thus impractical in the clinical setting. Identifying the endogenous neuroprotective mechanism induced by IPC is important for developing new strategies to reduce stroke severity. Zinc finger protein 667 (ZNF667) is a novel zinc finger protein that is upregulated by myocardial IPC. However, its functional role in neuronal ischemia has not been elucidated. In this study, the changes of ZNF667 expression on cerebral IPC and its potential neuroprotective function were investigated. The cerebral ischemia model was established by ameliorated four-vessel occlusion in rats. The northern blot results demonstrated that ZNF667 expression was increased in the hippocampus and cortex at 12 and 24 h after cerebral ischemic pretreatment. To investigate the neuroprotective function of ZNF667, enhanced green fluorescent protein (EGFP)-ZNF667 fusion protein was expressed in C2C12 and brain astrocytoma cells and its subcellular localization was detected by confocal microscopy. EGFP-ZNF667 fusion proteins were localized in the nucleus of C2C12 and brain astrocytoma cells, indicating that ZNF667 may act as a transcription factor in neural cells. To mimic oxidative stress associated with ischemia/reperfusion injury, hydrogen peroxide (H2O2) was used to treat cells. Cell viability was measured by the lactate dehydrogenase (LDH) and WST-1 assays. A decrease in viability was detected in C2C12 and astrocytoma cells following H2O2 treatment, whereas ZNF667 gene overexpression significantly improved cell viability following H2O2 treatment. These results suggested that ZNF667 plays a neuroprotective role by acting as a transcription factor in cerebral IPC. PMID:24648981

  14. 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

  15. The role of the cerebral capillaries in acute ischemic stroke: the extended penumbra model

    PubMed Central

    Østergaard, Leif; Jespersen, Sune Nørhøj; Mouridsen, Kim; Mikkelsen, Irene Klærke; Jonsdottír, Kristjana Ýr; Tietze, Anna; Blicher, Jakob Udby; Aamand, Rasmus; Hjort, Niels; Iversen, Nina Kerting; Cai, Changsi; Hougaard, Kristina Dupont; Simonsen, Claus Z; Von Weitzel-Mudersbach, Paul; Modrau, Boris; Nagenthiraja, Kartheeban; Riisgaard Ribe, Lars; Hansen, Mikkel Bo; Bekke, Susanne Lise; Dahlman, Martin Gervais; Puig, Josep; Pedraza, Salvador; Serena, Joaquín; Cho, Tae-Hee; Siemonsen, Susanne; Thomalla, Götz; Fiehler, Jens; Nighoghossian, Norbert; Andersen, Grethe

    2013-01-01

    The pathophysiology of cerebral ischemia is traditionally understood in relation to reductions in cerebral blood flow (CBF). However, a recent reanalysis of the flow-diffusion equation shows that increased capillary transit time heterogeneity (CTTH) can reduce the oxygen extraction efficacy in brain tissue for a given CBF. Changes in capillary morphology are typical of conditions predisposing to stroke and of experimental ischemia. Changes in capillary flow patterns have been observed by direct microscopy in animal models of ischemia and by indirect methods in humans stroke, but their metabolic significance remain unclear. We modeled the effects of progressive increases in CTTH on the way in which brain tissue can secure sufficient oxygen to meet its metabolic needs. Our analysis predicts that as CTTH increases, CBF responses to functional activation and to vasodilators must be suppressed to maintain sufficient tissue oxygenation. Reductions in CBF, increases in CTTH, and combinations thereof can seemingly trigger a critical lack of oxygen in brain tissue, and the restoration of capillary perfusion patterns therefore appears to be crucial for the restoration of the tissue oxygenation after ischemic episodes. In this review, we discuss the possible implications of these findings for the prevention, diagnosis, and treatment of acute stroke. PMID:23443173

  16. 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

  17. Cellular correlates of longitudinal diffusion tensor imaging of axonal degeneration following hypoxic–ischemic cerebral infarction in neonatal rats

    PubMed Central

    Tuor, Ursula I.; Morgunov, Melissa; Sule, Manasi; Qiao, Min; Clark, Darren; Rushforth, David; Foniok, Tadeusz; Kirton, Adam

    2014-01-01

    Ischemically damaged brain can be accompanied by secondary degeneration of associated axonal connections e.g. Wallerian degeneration. Diffusion tensor imaging (DTI) is widely used to investigate axonal injury but the cellular correlates of many of the degenerative changes remain speculative. We investigated the relationship of DTI of directly damaged cerebral cortex and secondary axonal degeneration in the cerebral peduncle with cellular alterations in pan-axonal neurofilament staining, myelination, reactive astrocytes, activation of microglia/macrophages and neuronal cell death. DTI measures (axial, radial and mean diffusivity, and fractional anisotropy (FA)) were acquired at hyperacute (3 h), acute (1 and 2 d) and chronic (1 and 4 week) times after transient cerebral hypoxia with unilateral ischemia in neonatal rats. The tissue pathology underlying ischemic and degenerative responses had a complex relationship with DTI parameters. DTI changes at hyperacute and subacute times were smaller in magnitude and tended to be transient and/or delayed in cerebral peduncle compared to cerebral cortex. In cerebral peduncle by 1 d post-insult, there were reductions in neurofilament staining corresponding with decreases in parallel diffusivity which were more sensitive than mean diffusivity in detecting axonal changes. Ipsilesional reductions in FA within cerebral peduncle were robust in detecting both early and chronic degenerative responses. At one or four weeks post-insult, radial diffusivity was increased ipsilaterally in the cerebral peduncle corresponding to pathological evidence of a lack of ontogenic myelination in this region. The detailed differences in progression and magnitude of DTI and histological changes reported provide a reference for identifying the potential contribution of various cellular responses to FA, and, parallel, radial, and mean diffusivity. PMID:25379414

  18. 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

  19. Pharmacokinetics of 21 active components in focal cerebral ischemic rats after oral administration of the active fraction of Xiao-Xu-Ming decoction.

    PubMed

    Wang, Caihong; Jia, Zhixin; Wang, Zhe; Hu, Ting; Qin, Hailin; Du, Guanhua; Wu, Caisheng; Zhang, Jinlan

    2016-04-15

    The Xiao-Xu-Ming decoction (XXMD) is a traditional Chinese medicine prescription that is clinically used for the treatment of stroke. The active fraction of XXMD (AF-XXMD) exhibits pharmacological effects that are similar to those of XXMD. In this study, 21 primary compounds of AF-XXMD with potential anti-ischemic-stroke activities were selected as effective candidates to perform comparisons of their pharmacokinetic differences between control and cerebral ischemic rats and to characterize their pharmacokinetic behaviors in cerebral ischemic rats. After oral administration of AF-XXMD to control and cerebral ischemic rats, plasma and brain were harvested and analyzed using liquid chromatography coupled with tandem mass spectrometry. Reverse molecular docking results indicate that 21 AF-XXMD-derived compounds exert potential neuroprotection, anti- inflammation, and vascular dilation effects via interaction with multiple targets in stroke-related pathways. The blood-brain permeability, cerebral exposure and brain region distribution of these compounds were found to change in cerebral ischemic models. Flavonoids were identified as the predominant form in plasma, whereas chromones were found to be the major form in the brain, and alkaloids possessed moderate blood-brain permeability. Collectively, the cerebral pharmacokinetic behaviors of chromones, flavonoids and alkaloids were found to change under pathological conditions. The efficacy of AF-XXMD against cerebral ischemia is relevant to the synergistic effects of these compounds in targeting different receptors and pathways. Chromones exhibit relatively high brain permeability, and their activity and mechanism warrant further investigation. PMID:26852160

  20. 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

  1. 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

  2. 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

  3. 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

  4. Dynamic cerebral autoregulation is transiently impaired for one week after large-vessel acute ischemic stroke

    PubMed Central

    Petersen, Nils H.; Ortega-Gutierrez, Santiago; Reccius, Andres; Masurkar, Arjun; Huang, Amy; Marshall, Randolph S

    2016-01-01

    Background Dynamic cerebral autoregulation (DCA) is the continuous counterregulation of cerebral blood flow to fluctuations in blood pressure. DCA can become impaired after acute stroke, but it remains unclear to what extent and over what interval this occurs. Methods We included 28 patients (NIHSS=12±6.5, age=68.4±17.1, 16F) with acute large-vessel ischemic stroke in the middle cerebral artery territory and 29 healthy controls (mean age 54.9±9, 16F). DCA was assessed by simultaneous measurement of blood pressure together with blood flow velocities using finger plethysmography/arterial catheter and transcranial Doppler over three 10-minute recordings on days 0–2, 3–6 and >=7 days after stroke. Transfer function analysis was applied to calculate average phase shift (PS) in the low frequency range (0.06–0.12 Hz). Less PS indicated poorer autoregulation. The affected side was compared with the unaffected side and controls. Univariate comparisons of data were performed using t-tests at single time points, and generalized estimating equations with an exchangeable correlation matrix to examine the change in PS over time. Results At mean 1.3±0.5 days after stroke the average PS in the affected hemisphere was 29.6±10.5 degrees versus 42.5±13 degrees in the unaffected hemisphere (p=0.004). At 4.1±1 days, the PS in affected and unaffected hemisphere was 23.2±19.1 vs. 41.7±18.5 degrees, respectively (p=0.003). At mean 9.75±2.2 days stroke there was no difference between affected and unaffected hemisphere (53.2±28.2 versus 50.7±29.2 degrees, p=0.69). Control subjects had an average PS=47.9±16.8, significantly different from patients’ affected hemisphere at the first two measurements (p=0.001), but not the third (p=0.37). The PS in controls remained unchanged on repeat testing after an average 19.1 days (48.4±17.1, p=0.61). Using the last recording as the reference, the average PS in the affected hemisphere was −23.54 (−44.1, −3) degrees lower on

  5. 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

  6. 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

  7. 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

  8. HCaRG Accelerates Tubular Repair after Ischemic Kidney Injury

    PubMed Central

    Matsuda, Hiroyuki; Lavoie, Julie L.; Gaboury, Louis; Hamet, Pavel

    2011-01-01

    The repair of the kidney after ischemia/reperfusion injury involves proliferation of proximal tubular epithelial cells as well as cell migration and differentiation. Immediately after reperfusion, expression of hypertension-related calcium-regulated gene (HCaRG/COMMD5) decreases, but its expression increases even higher than baseline during repair. HCaRG inhibits proliferation and accelerates wound healing and differentiation in cultured cells, but whether HCaRG can stimulate renal repair after ischemia/reperfusion injury is unknown. Here, transgenic mice overexpressing human HCaRG survived longer and recovered renal function faster than littermate controls after ischemia/reperfusion (64% versus 25% survival at 7 days). Proliferation of proximal tubular epithelial cells stopped earlier after ischemia/reperfusion injury, E-cadherin levels recovered more rapidly, and vimentin induction abated faster in transgenic mice. HCaRG overexpression also reduced macrophage infiltration and inflammation after injury. Taken together, these data suggest that HCaRG accelerates repair of renal proximal tubules by modulating cell proliferation of resident tubular epithelial cells and by facilitating redifferentiation. PMID:21921141

  9. Measurement of ischemic changes in cerebral blood flow by the hydrogen clearance technique and brain cortical temperature. Influence of flunarizine.

    PubMed

    Marrannes, R; Edmonds, H L; Wauquier, A; Melis, W; Van Loon, J

    1986-06-01

    In dogs global cerebral ischemia was produced by clamping reversibly the left subclavian and brachiocephalic arteries, supplying the head. The intercostal arteries were ligated permanently. Cerebral blood flow (CBF) was measured discontinuously using a hydrogen saturation-desaturation technique. Clamping of the former two vessels caused an increase in systemic blood pressure. When this increase was not blunted by previous splenectomy and blood withdrawal a still important CBF remained during the clamp. However, if this rise in blood pressure was impaired, CBF decreased to 9 +/- 8% (mean +/- S.D., n = 14) of the pre-ischemic value. Flunarizine is known to have anti-hypoxic/ischemic properties. The influence of this drug (0.1 mg/kg i.v.), injected 10 min after the beginning of a 30-min ischemia period, on the post-ischemic CBF was investigated. Two-three hour after ischemia CBF was significantly lower in the solvent-treated animals than in the flunarizine-treated group, in which CBF approached the preischemic values. Changes in CBF were also followed continuously by measurement of the variations of brain versus aortic temperature. It was analyzed what information this can provide on CBF. PMID:3753102

  10. High incidence of adverse cerebral blood flow responses to spreading depolarization in the aged ischemic rat brain.

    PubMed

    Menyhárt, Ákos; Makra, Péter; Szepes, Borbála É; Tóth, Orsolya M; Hertelendy, Péter; Bari, Ferenc; Farkas, Eszter

    2015-12-01

    Spreading depolarizations (SDs) occur spontaneously in the brain after stroke, exacerbate ischemic injury, and thus emerge as a potential target of intervention. Aging predicts worse outcome from stroke; yet, the impact of age on SD evolution is not clear. Cerebral ischemia was induced by bilateral common carotid artery occlusion in young (8-9 weeks old, n = 8) and old (2 year olds, n = 6) anesthetized rats. Sham-operated animals of both age groups served as control (n = 12). Electrocorticogram, direct current potential, and cerebral blood flow (CBF) variations were acquired via a small craniotomy above the parietal cortex. SDs were elicited by KCl through a second craniotomy distal to the recording site. Ischemia and age delayed the recovery from SD. CBF decreased progressively during ischemia in the old animals selectively, and inverse neurovascular coupling with SD evolved in the old but not in the young ischemic group. We propose that (mal)adaptation of cerebrovascular function with aging impairs the SD-related CBF response, which is implicated in the intensified expansion of ischemic damage in the old brain. PMID:26346140

  11. 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. PMID:26454372

  12. Anti-Neuroinflammatory Effects of Uncaria sinensis in LPS-Stimulated BV2 Microglia Cells and Focal Cerebral Ischemic Mice.

    PubMed

    Kang, Bo Kyung; Kim, Mi Kyoung; Kim, So Young; Lee, Seung Jin; Choi, Young Whan; Choi, Byung Tae; Shin, Hwa Kyoung

    2015-01-01

    Uncaria sinensis (US) has long been used as a traditional Korean medicine to treat cardiovascular and central nervous system diseases, including hypertension and cerebral ischemia. Several recent studies have indicated that US has neuroprotective and cerebrovascular protective effects in ischemic brain injury; however, little is known about the anti-inflammatory effects of US. Therefore, the present study was designed to validate the anti-inflammatory effects of US. The anti-neuroinflammatory properties of US on pro-inflammatory mediators were investigated in lipopolysaccharide (LPS)-stimulated murine BV2 microglia and injured brains induced by photothrombotic cortical ischemia. Hexane extracts of US (HEUS) significantly suppressed the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in LPS-stimulated BV2 microglia and inhibited LPS-induced expression of iNOS and COX-2 in a dose-dependent manner without causing cytotoxicity in BV2 cells. In addition, HEUS significantly reduced the generation of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6. Moreover, HEUS treatment inhibited the transcriptional activity and nuclear translocation of NF-κB in LPS-stimulated BV2 cells. In an in vivo study, treatment of HEUS resulted in significantly reduced infarct volume and improved neurological function 48 h after ischemic brain injury, possibly through the inhibition of the production of pro-inflammatory cytokines. HEUS inhibits LPS-stimulated production of pro-inflammatory mediators and prevents cerebral ischemic damage, suggesting that US may have therapeutic potential for the prevention and treatment of ischemic stroke accompanied by microglia activation. PMID:26364663

  13. Interleaved imaging of cerebral hemodynamics and blood flow index to monitor ischemic stroke and treatment in rat by volumetric diffuse optical tomography.

    PubMed

    Lin, Zi-Jing; Ren, Ming; Li, Lin; Liu, Yueming; Su, Jianzhong; Yang, Shao-Hua; Liu, Hanli

    2014-01-15

    Diffuse optical tomography (DOT) has been used by several groups to assess cerebral hemodynamics of cerebral ischemia in humans and animals. In this study, we combined DOT with an indocyanine green (ICG)-tracking method to achieve interleaved images of cerebral hemodynamics and blood flow index (BFI) using two middle cerebral artery occlusion (MCAO) rat models. To achieve volumetric images with high-spatial resolution, we first integrated a depth compensation algorithm (DCA) with a volumetric mesh-based rat head model to generate three-dimensional (3D) DOT on a rat brain atlas. Then, the experimental DOT data from two rat models were collected using interleaved strategy for cerebral hemodynamics and BFI during and after ischemic stroke, with and without a thrombolytic therapy for the embolic MCAO model. The acquired animal data were further analyzed using the integrated rat-atlas-guided DOT method to form time-evolving 3D images of both cerebral hemodynamics and BFI. In particular, we were able to show and identify therapeutic outcomes of a thrombolytic treatment applied to the embolism-induced ischemic model. This paper demonstrates that volumetric DOT is capable of providing high-quality, interleaved images of cerebral hemodynamics and blood perfusion in small animals during and after ischemic stroke, with excellent 3D visualization and quantifications. PMID:23872158

  14. Interleaved imaging of cerebral hemodynamics and blood flow index to monitor ischemic stroke and treatment in rat by volumetric diffuse optical tomography

    PubMed Central

    Lin, Zi-Jing; Ren, Ming; Li, Lin; Liu, Yueming; Su, Jianzhong; Yang, Shao-Hua; Liu, Hanli

    2013-01-01

    Diffuse optical tomography (DOT) has been used by several groups to assess cerebral hemodynamics of cerebral ischemia in humans and animals. In this study, we combined DOT with an indocyanine green (ICG)-tracking method to achieve interleaved images of cerebral hemodynamics and blood flow index (BFI) using two middle cerebral artery occlusion (MCAO) rat models. To achieve volumetric images with high-spatial resolution, we first integrated a depth compensation algorithm (DCA) with a volumetric mesh-based rat head model to generate three-dimensional (3D) DOT on a rat brain atlas. Then, the experimental DOT data from two rat models were collected using interleaved strategy for cerebral hemodynamics and BFI during and after ischemic stroke, with and without a thrombolytic therapy for the embolic MCAO model. The acquired animal data were further analyzed using the integrated rat-atlas-guided DOT method to form time-evolving 3D images of both cerebral hemodynamics and BFI. In particular, we were able to show and identify therapeutic outcomes of a thrombolytic treatment applied to the embolism-induced ischemic model. This paper demonstrates that volumetric DOT is capable of providing high-quality, interleaved images of cerebral hemodynamics and blood perfusion in small animals during and after ischemic stroke, with excellent 3D visualization and quantifications. PMID:23872158

  15. NQDI-1, an inhibitor of ASK1 attenuates acute perinatal hypoxic-ischemic cerebral injury by modulating cell death

    PubMed Central

    HAO, HU; LI, SITAO; TANG, HUI; LIU, BINGQING; CAI, YAO; SHI, CONGCONG; XIAO, XIN

    2016-01-01

    Apoptosis signal-regulating kinase 1 (ASK1) is a ubiquitously expressed protein kinase, which regulates cell fate in numerous injury conditions. Therefore, ASK1 may be a promising novel therapeutic target for injury. However, the expression and distribution of ASK1 in the perinatal brain following hypoxia-ischemia (HI) remains to be elucidated. In the present study, western blotting and immunofluorescence were used to determine the expression and distribution of ASK1 and any associated downstream targets in the perinatal rat brain following HI. NQDI-1, a specific inhibitor of ASK1 was intracerebroventricularly injected following neonatal rats brain insult for neuroprotection. The results revealed an increased expression of ASK1 and this expression was localized to the neurons and astrocytes, compared with the sham controls. Additionally, it was demonstrated that the ASK1/c-Jun N-terminal kinases (JNK) pathway was involved in the brain damage following HI in neonatal rats. Notably, NQDI-1 significantly inhibited the in vivo expression levels of ASK1, phosphorylated (p-)JNK, p-c-Jun, p53 and caspase 3. Reduced acute hypoxic-ischemic cerebral injury and cell apoptosis was observed following the injection of NQDI-1. Collectively, NQDI-1 attenuated acute perinatal hypoxic-ischemic cerebral injury by inhibiting the expression of ASK1 and cell apoptosis. This may be a promising novel neuroprotective inhibitor for perinatal cerebra injury. PMID:27081917

  16. 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

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

    NASA Astrophysics Data System (ADS)

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

    2013-02-01

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

  18. Cerebrolysin adjuvant treatment in Broca's aphasics following first acute ischemic stroke of the left middle cerebral artery

    PubMed Central

    Muresanu, DF; Bajenaru, O; Popescu, BO; Deme, SM; Moessler, H; Meinzingen, SZ; Petrica, L; Serpe, M; Ursoniu, S

    2010-01-01

    Background: The aim of our study was to assess the efficacy of Cerebrolysin administration in Broca's aphasics with acute ischemic stroke. Methods: We registered 2,212 consecutive Broca's aphasics following an acute ischemic stroke admitted in four departments of neurology in Romania, between September 2005 and September 2009. Language was evaluated with the Romanian version of the Western Aphasia Battery (WAB). The following inclusion criteria were used for this study: age 20%75 years, admission in the hospital within 12 hours from the onset of the symptoms, diagnosis of first acute left middle cerebral artery (MCA) ischemic stroke, presence of large artery disease (LAD) stroke, a NIHSS score of 5%22 points, and a therapeutic time window within 72 h. Fifty two patients were treated with Cerebrolysin (Cerebrolysin group) as an adjunctive treatment. A placebo group, which received saline infusions (n=104 patients) were matched to the NIHSS and WAB scores, gender and age of the Cerebrolysin group at baseline. We assessed spontaneous speech (SS), comprehension (C), repetition (R), naming (N), and Aphasia Quotient (AQ) scores of the two groups in an open label design, over 90 days, the mRS scores and mortality. Results: The Cerebrolysin and the placebo groups had similar age (66+/%8 versus 65+/%8 years) and sex ratio (14/38 versus 30/74). The mean AQ scores and the mean subscores for 3 subtests of WAB (SS, R, N) were similar at baseline and improved in the Cerebrolysin group significantly (p<0.05) over placebo group at all study time points. The mRS score at 90 days was also lower in the Cerebrolysin group than in the placebo group. Cerebrolysin and placebo were both tolerated and safe, and no difference in the mortality rate was seen (3.8% in each group). Conclusion: Cerebrolysin is effective for the treatment of Broca's aphasics with a first acute ischemic stroke of the left MCA territory. PMID:20945821

  19. 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.

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

    PubMed Central

    Kim, Ji Hyun; Park, Sun Haeng; Kim, Young Whan; Ha, Jung Min; Bae, Sun Sik; Lee, Guem San; Cho, Su In; Choi, Byung Tae; Shin, Hwa Kyoung

    2011-01-01

    Dangkwisoo-San (DS) is an herbal extract that is widely used in traditional Korean medicine to treat traumatic ecchymosis and pain by promoting blood circulation and relieving blood stasis. However, the effect of DS in cerebrovascular disease has not been examined experimentally. The protective effects of DS on focal ischemic brain were investigated in a mouse model. DS stimulated nitric oxide (NO) production in human brain microvascular endothelial cells (HBMECs). DS (10–300 μg/mL) produced a concentration-dependent relaxation in mouse aorta, which was significantly attenuated by the nitric oxide synthase (NOS) inhibitor L-NAME, suggesting that DS causes vasodilation via a NO-dependent mechanism. DS increased resting cerebral blood flow (CBF), although it caused mild hypotension. To investigate the effect of DS on the acute cerebral injury, C57/BL6J mice received 90 min of middle cerebral artery occlusion followed by 22.5 h of reperfusion. DS administered 3 days before arterial occlusion significantly reduced cerebral infarct size by 53.7% compared with vehicle treatment. However, DS did not reduce brain infarction in mice treated with the relatively specific endothelial NOS (eNOS) inhibitor, N5-(1-iminoethyl)-L-ornithine, suggesting that the neuroprotective effect of DS is primarily endothelium-dependent. This correlated with increased phosphorylation of eNOS in the brains of DS-treated mice. DS acutely improves CBF in eNOS-dependent vasodilation and reduces infarct size in focal cerebral ischemia. These data provide causal evidence that DS is cerebroprotective via the eNOS-dependent production of NO, which ameliorates blood circulation. PMID:21423636

  1. Predictors of Cerebral Arteriopathy in Children with Arterial Ischemic Stroke: Results of the International Pediatric Stroke Study

    PubMed Central

    Amlie-Lefond, Catherine; Bernard, Timothy J.; Sébire, Guillaume; Friedman, Neil R.; Heyer, Geoffrey L.; Lerner, Norma B.; deVeber, Gabrielle; Fullerton, Heather J.

    2012-01-01

    Background Cerebral arteriopathies, including an idiopathic focal cerebral arteriopathy of childhood (FCA), are common in children with arterial ischemic stroke (AIS) and strongly predictive of recurrence. To better understand these lesions, we measured predictors of arteriopathy within a large international series of children with AIS. Methods and Results Between 1/2003 and 7/2007, 30 centers within the International Pediatric Stroke Study (IPSS) enrolled 667 children (29 days-19 years of age) with AIS and abstracted clinical and radiographic data. Cerebral arteriopathy and its subtypes were defined using published definitions; FCA was defined as cerebral arterial stenosis not attributed to specific diagnoses such as moyamoya, arterial dissection, vasculitis, or post-varicella angiopathy. We used multivariate logistic regression techniques to determine predictors of arteriopathy and FCA among those subjects who received vascular imaging. The authors had full access to and take full responsibility for the integrity of the data. All authors have read and agree to the manuscript as written. Of 667 subjects, 525 had known vascular imaging results, and 53% of those (n=277) had an arteriopathy. The most common arteriopathies were FCA (n=69, 25%), moyamoya (n=61, 22%), and arterial dissection (n=56; 20%). Predictors of arteriopathy include early school age (5-9 years), recent upper respiratory infections (URI), and sickle cell disease, while prior cardiac disease and sepsis reduced the risk of arteriopathy. The only predictor of FCA was recent URI. Conclusions Arteriopathy is prevalent among children with AIS, particularly those presenting in early school age, and those with a history of sickle cell disease. Recent URI predicted cerebral arteriopathy, and FCA in particular, suggesting a possible role for infection in the pathogenesis of these lesions. PMID:19255344

  2. 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. PMID:25891441

  3. Tumor necrosis factor-α inhibition attenuates middle cerebral artery remodeling but increases cerebral ischemic damage in hypertensive rats

    PubMed Central

    Girgla, Saavia S.; Moreno, Guillermo; McClain, Jonathon L.; Dorrance, Anne M.

    2014-01-01

    Hypertension causes vascular inflammation evidenced by an increase in perivascular macrophages and proinflammatory cytokines in the arterial wall. Perivascular macrophage depletion reduced tumor necrosis factor (TNF)-α expression in cerebral arteries of hypertensive rats and attenuated inward remodeling, suggesting that TNF-α might play a role in the remodeling process. We hypothesized that TNF-α inhibition would improve middle cerebral artery (MCA) structure and reduce damage after cerebral ischemia in hypertensive rats. Six-week-old male stroke-prone spontaneously hypertensive rats (SHRSP) were treated with the TNF-α inhibitor etanercept (ETN; 1.25 mg·kg−1·day−1 ip daily) or PBS (equivolume) for 6 wk. The myogenic tone generation, postischemic dilation, and passive structure of MCAs were assessed by pressure myography. Cerebral ischemia was induced by MCA occlusion (MCAO). Myogenic tone was unchanged, but MCAs from SHRSP + ETN had larger passive lumen diameter and reduced wall thickness and wall-to-lumen ratio. Cerebral infarct size was increased in SHRSP + ETN after transient MCAO, despite an improvement in dilation of nonischemic MCA. The increase in infarct size was linked to a reduction in the number of microglia in the infarct core and upregulation of markers of classical macrophage/microglia polarization. There was no difference in infarct size after permanent MCAO or when untreated SHRSP subjected to transient MCAO were given ETN at reperfusion. Our data suggests that TNF-α inhibition attenuates hypertensive MCA remodeling but exacerbates cerebral damage following ischemia/reperfusion injury likely due to inhibition of the innate immune response of the brain. PMID:25015967

  4. Monocarboxylate transporter 4 plays a significant role in the neuroprotective mechanism of ischemic preconditioning in transient cerebral ischemia.

    PubMed

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

    2015-10-01

    Monocarboxylate transporters (MCTs), which carry monocarboxylates such as lactate across biological membranes, have been associated with cerebral ischemia/reperfusion process. In this study, we studied the effect of ischemic preconditioning (IPC) on MCT4 immunoreactivity after 5 minutes of transient cerebral ischemia in the gerbil. Animals were randomly designated to four groups (sham-operated group, ischemia only group, IPC + sham-operated group and IPC + ischemia group). A serious loss of neuron was found in the stratum pyramidale of the hippocampal CA1 region (CA1), not CA2/3, of the ischemia-only group at 5 days post-ischemia; however, in the IPC + ischemia groups, neurons in the stratum pyramidale of the CA1 were well protected. Weak MCT4 immunoreactivity was found in the stratum pyramidale of the CA1 in the sham-operated group. MCT4 immunoreactivity in the stratum pyramidale began to decrease at 2 days post-ischemia and was hardly detected at 5 days post-ischemia; at this time point, MCT4 immunoreactivity was newly expressed in astrocytes. In the IPC + sham-operated group, MCT4 immunoreactivity in the stratum pyramidale of the CA1 was increased compared with the sham-operated group, and, in the IPC + ischemia group, MCT4 immunoreactivity was also increased in the stratum pyramidale compared with the ischemia only group. Briefly, present findings show that IPC apparently protected CA1 pyramidal neurons and increased or maintained MCT4 expression in the stratum pyramidale of the CA1 after transient cerebral ischemia. Our findings suggest that MCT4 appears to play a significant role in the neuroprotective mechanism of IPC in the gerbil with transient cerebral ischemia. PMID:26692857

  5. Monocarboxylate transporter 4 plays a significant role in the neuroprotective mechanism of ischemic preconditioning in transient cerebral ischemia

    PubMed Central

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

    2015-01-01

    Monocarboxylate transporters (MCTs), which carry monocarboxylates such as lactate across biological membranes, have been associated with cerebral ischemia/reperfusion process. In this study, we studied the effect of ischemic preconditioning (IPC) on MCT4 immunoreactivity after 5 minutes of transient cerebral ischemia in the gerbil. Animals were randomly designated to four groups (sham-operated group, ischemia only group, IPC + sham-operated group and IPC + ischemia group). A serious loss of neuron was found in the stratum pyramidale of the hippocampal CA1 region (CA1), not CA2/3, of the ischemia-only group at 5 days post-ischemia; however, in the IPC + ischemia groups, neurons in the stratum pyramidale of the CA1 were well protected. Weak MCT4 immunoreactivity was found in the stratum pyramidale of the CA1 in the sham-operated group. MCT4 immunoreactivity in the stratum pyramidale began to decrease at 2 days post-ischemia and was hardly detected at 5 days post-ischemia; at this time point, MCT4 immunoreactivity was newly expressed in astrocytes. In the IPC + sham-operated group, MCT4 immunoreactivity in the stratum pyramidale of the CA1 was increased compared with the sham-operated group, and, in the IPC + ischemia group, MCT4 immunoreactivity was also increased in the stratum pyramidale compared with the ischemia only group. Briefly, present findings show that IPC apparently protected CA1 pyramidal neurons and increased or maintained MCT4 expression in the stratum pyramidale of the CA1 after transient cerebral ischemia. Our findings suggest that MCT4 appears to play a significant role in the neuroprotective mechanism of IPC in the gerbil with transient cerebral ischemia. PMID:26692857

  6. 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

  7. 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

  8. Angiogenesis and stem cell transplantation as potential treatments of cerebral ischemic stroke.

    PubMed

    Wei, Ling; Keogh, Christine L; Whitaker, Vivian Riley; Theus, Michelle Hedrick; Yu, Shan Ping

    2005-07-01

    Ischemic stroke is a leading cause of human death and disability. Although stroke survivors may gain spontaneous partial functional recovery, they often suffer from sensory-motor dysfunctions, behavioral/neurological alterations, and various degrees of paralysis. Currently, limited clinical intervention is available to prevent ischemic damage and restore lost function in stroke victims. In addition to the extensive research on protective maneuvers against ischemia-induced cell death, increasing attention has been focused on potential strategies of promoting tissue repair and functional recovery in the damaged post-ischemic brain. Angiogenesis, or the growth of new blood vessels, may contribute to cell survival and functional recovery of the area of insult. The study of angiogenesis will increase the understanding of the mechanism underlying post-ischemia neurovascular plasticity and regeneration. Additionally, stem cell transplantation has emerged in the last few years as a potential therapy for ischemic stroke, because of their capability to differentiate into multiple cell types and the possibility that they may provide trophic support for cell survival, tissue repair, and functional recovery. PMID:15927824

  9. 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

  10. 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.

  11. [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. PMID:26856268

  12. 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

  13. 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

  14. 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

  15. Hypothermia-induced ischemic tolerance is associated with Drp1 inhibition in cerebral ischemia-reperfusion injury of mice.

    PubMed

    Tang, Yingying; Liu, Xiaojie; Zhao, Jie; Tan, Xueying; Liu, Bing; Zhang, Gaofeng; Sun, Lixin; Han, Dengyang; Chen, Huailong; Wang, Mingshan

    2016-09-01

    Excessive mitochondrial fission activation has been implicated in cerebral ischemia-reperfusion (IR) injury. Hypothermia is effective in preventing cerebral ischemic damage. However, effects of hypothermia on ischemia-induced mitochondrial fission activation is not well known. Therefore, the aim of this study was to investigate whether hypothermia protect the brain by inhibiting mitochondrial fission-related proteins activation following cerebral IR injury. Adult male C57BL/6 mice were subjected to transient forebrain ischemia induced by 15min of bilateral common carotid artery occlusion (BCCAO). Mice were divided into three groups (n=48 each): Hypothermia (HT) group, with mild hypothermia (32-34°C) for 4h; Normothermia (NT) group, similarly as HT group except for cooling; Sham group, with vessels exposed but without occlusion or cooling. Hematoxylin and eosin (HE), Nissl staining, Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining and behavioral testing (n=6 each) demonstrated that hypothermia significantly decreased ischemia-induced neuronal injury. The expressions of Dynamin related protein 1 (Drp1) and Cytochrome C (Cyto C) (n=6 each) in mice hippocampus were measured at 3, 6, 24, and 72h of reperfusion. IR injury significantly increased expressions of total Drp1, phosphorylated Drp1 (P-Drp1 S616) and Cyto C under normothermia. However, mild hypothermia inhibited Drp1 activation and Cyto C cytosolic release, preserved neural cells integrity and reduced neuronal necrosis and apoptosis. These findings indicated that mild hypothermia-induced neuroprotective effects against ischemia-reperfusion injury is associated with suppressing mitochondrial fission-related proteins activation and apoptosis execution. PMID:27235868

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

    PubMed Central

    Meulman, T. J.; Bakker, J.; van den Bos, E. J.

    2015-01-01

    Khat is a stimulating agent used by many people in the Horn of Africa and the Arabian peninsula. Khat chewing is a known cardiovascular risk factor and is thought to cause vasoconstriction, systemic hypertension, and thrombogenicity. A 33-year-old Somalian man initially presented with loss of neurological function of the left arm, hazy vision, and headache. He smokes tobacco and chews two bundles of khat a week for more than 10 years. His ECG on admission showed a Q wave in V1 and V2 and 2 mm ST-elevations in V1, V2, and V3 and a terminal negative T wave in I, aVL, V2, V3, and V4, consistent with a recent, evolving anterior infarction. A noncontrast enhanced CT of the brain showed ischemia in the right middle cerebral artery vascular territory. An MRI showed recent ischemia in the vascular territory of the posterior division of the right middle cerebral artery. Coronary angiography showed a 70% stenosis with haziness of the proximal left anterior descending artery. Diagnostic tests and imaging are consistent with recent myocardial infarction in the LAD vascular territory because of coronary spasm and cerebral infarction in the middle cerebral artery vascular territory probably related to khat chewing. PMID:25815235

  17. Pediatric Cerebral Stroke: Susceptibility-Weighted Imaging May Predict Post-Ischemic Malignant Edema

    PubMed Central

    Bosemani, Thangamadhan; Poretti, Andrea; Orman, Gunes; Meoded, Avner; Huisman, Thierry A.G.M.

    2013-01-01

    Summary Susceptibility-weighted imaging (SWI) is an advanced MRI technique providing information on the blood oxygenation level. Deoxyhemoglobin is increased in hypoperfused tissue characterized by SWI-hypointensity, while high oxyhemoglobin concentration within hyperperfused tissue results in a SWI iso- or hyperintensity compared to healthy brain tissue. We describe a child with a stroke, where SWI in addition to excluding hemorrhage and delineating the thrombus proved invaluable in determining regions of hyperperfusion or luxury perfusion, which contributed further to the prognosis including an increased risk of developing post-ischemic malignant edema. PMID:24199819

  18. 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

  19. 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

  20. 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

  1. 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

  2. Immunohistochemical Analysis of Cerebral Thrombi Retrieved by Mechanical Thrombectomy from Patients with Acute Ischemic Stroke

    PubMed Central

    Schuhmann, Michael K.; Gunreben, Ignaz; Kleinschnitz, Christoph; Kraft, Peter

    2016-01-01

    Mechanical thrombectomy is a novel treatment option for patients with acute ischemic stroke (AIS). Only a few studies have previously suggested strategies to categorize retrieved clots according to their histologic composition. However, these reports did not analyze potential biomarkers that are of importance in stroke-related inflammation. We therefore histopathologically investigated 37 intracerebral thrombi mechanically retrieved from patients with AIS, and focused on the composition of immune cells and platelets. We also conducted correlation analyses of distinctive morphologic patterns (erythrocytic, serpentine, layered, red, white, mixed appearance) with clinical parameters. Most T cells and monocytes were detected in erythrocytic and red clots, in which the distribution of these cells was random. In contrast, von Willebrand factor (vWF)-positive areas co-localized with regions of fibrin and collagen. While clots with huge amounts of vWF seem to be associated with a high National Institute of Health Stroke Scale score at admission, histologic findings could not predict the clinical outcome at discharge. In summary, we provide the first histologic description of mechanically retrieved intracerebral thrombi regarding biomarkers relevant for inflammation in ischemic stroke. PMID:26927082

  3. Immunohistochemical Analysis of Cerebral Thrombi Retrieved by Mechanical Thrombectomy from Patients with Acute Ischemic Stroke.

    PubMed

    Schuhmann, Michael K; Gunreben, Ignaz; Kleinschnitz, Christoph; Kraft, Peter

    2016-01-01

    Mechanical thrombectomy is a novel treatment option for patients with acute ischemic stroke (AIS). Only a few studies have previously suggested strategies to categorize retrieved clots according to their histologic composition. However, these reports did not analyze potential biomarkers that are of importance in stroke-related inflammation. We therefore histopathologically investigated 37 intracerebral thrombi mechanically retrieved from patients with AIS, and focused on the composition of immune cells and platelets. We also conducted correlation analyses of distinctive morphologic patterns (erythrocytic, serpentine, layered, red, white, mixed appearance) with clinical parameters. Most T cells and monocytes were detected in erythrocytic and red clots, in which the distribution of these cells was random. In contrast, von Willebrand factor (vWF)-positive areas co-localized with regions of fibrin and collagen. While clots with huge amounts of vWF seem to be associated with a high National Institute of Health Stroke Scale score at admission, histologic findings could not predict the clinical outcome at discharge. In summary, we provide the first histologic description of mechanically retrieved intracerebral thrombi regarding biomarkers relevant for inflammation in ischemic stroke. PMID:26927082

  4. 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

  5. Noninvasive cerebral oximetry during endovascular therapy for acute ischemic stroke: an observational study.

    PubMed

    Hametner, Christian; Stanarcevic, Predrag; Stampfl, Sibylle; Rohde, Stefan; Veltkamp, Roland; Bösel, Julian

    2015-11-01

    Implementing endovascular stroke care often impedes neurologic assessment in patients who need sedation or general anesthesia. Cerebral near-infrared spectroscopy (NIRS) may help physicians monitor cerebral tissue viability, but data in hyperacute stroke patients receiving endovascular treatment are sparse. In this observational study, the NIRS index regional oxygen saturation (rSO2) was measured noninvasively before, during, and after endovascular therapy via bilateral forehead NIRS optodes. During the study period, 63 patients were monitored with NIRS; 43 qualified for analysis. Before recanalization, 10 distinct rSO2 decreases occurred in 11 patients with respect to time to intubation. During recanalization, two kinds of unilateral rSO2 changes occurred in the affected hemisphere: small peaks throughout the treatment (n=14, 32.6%) and sustained increases immediately after recanalization (n=2, 4.7%). Lower area under the curve 10% below baseline was associated with better reperfusion status (thrombolysis in cerebral infarction ≥ 2b, P=0.009). At the end of the intervention, lower interhemispheric rSO2 difference predicted death within 90 days (P=0.037). After the intervention, higher rSO2 variability predicted poor outcome (modified Rankin scale > 3, P=0.032). Our findings suggest that bi-channel rSO2-NIRS has potential for guiding neuroanesthesia and predicting outcome. To better monitor local revascularization, an improved stroke-specific set-up in future studies is necessary. PMID:26243709

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

    PubMed

    Zhang, Pengyue; Zhang, Yuling; Zhang, Jie; Wu, Yi; Jia, Jie; Wu, Junfa; Hu, Yongshan

    2013-01-01

    Early exercise is an effective strategy for stroke treatment, but the underlying mechanism remains poorly understood. Apoptosis plays a critical role after stroke. However, it is unclear whether early exercise inhibits apoptosis after stroke. The present study investigated the effect of early exercise on apoptosis induced by ischemia. Adult SD rats were subjected to transient focal cerebral ischemia by middle cerebral artery occlusion model (MCAO) and were randomly divided into early exercise group, non-exercise group and sham group. Early exercise group received forced treadmill training initiated at 24 h after operation. Fourteen days later, the cell apoptosis were detected by TdT-mediated dUTP-biotin nick-end labeling (TUNEL) and Fluoro-Jade-B staining (F-J-B). Caspase-3, cleaved caspase-3 and Bcl-2 were determined by western blotting. Cerebral infarct volume and motor function were evaluated by cresyl violet staining and foot fault test respectively. The results showed that early exercise decreased the number of apoptotic cells (118.74 ± 6.15 vs. 169.65 ± 8.47, p < 0.05, n = 5), inhibited the expression of caspase-3 and cleaved caspase-3 (p < 0.05, n = 5), and increased the expression of Bcl-2 (p < 0.05, n = 5). These data were consistent with reduced infarct volume and improved motor function. These results suggested that early exercise could provide neuroprotection through inhibiting neuron apoptosis. PMID:23502470

  7. 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

  8. 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

  9. 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

  10. 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.

  11. 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. PMID:27526150

  12. 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

  13. External Counterpulsation Reduces Beat-to-Beat Blood Pressure Variability When Augmenting Blood Pressure and Cerebral Blood Flow in Ischemic Stroke

    PubMed Central

    Tian, Ge; Xiong, Li; Lin, Wenhua; Han, Jinghao; Chen, Xiangyan; Leung, Thomas Wai Hong; Soo, Yannie Oi Yan

    2016-01-01

    Background and Purpose External counterpulsation (ECP) is a noninvasive method used to enhance cerebral perfusion by elevating the blood pressure in ischemic stroke. However, the response of the beat-to-beat blood pressure variability (BPV) in ischemic stroke patients during ECP remains unknown. Methods We enrolled recent ischemic stroke patients and healthy controls. Changes in the blood flow velocities in bilateral middle cerebral arteries and the continuous beat-to-beat blood pressure before, during, and after ECP were monitored. Power spectral analysis revealed that the BPV included oscillations at very low frequency (VLF; <0.04 Hz), low frequency (LF; 0.04–0.15 Hz), and high frequency (HF; 0.15–0.40 Hz), and the total power spectral density (TP; <0.40 Hz) and LF/HF ratio were calculated. Results We found that ECP significantly increased the systolic and diastolic blood pressures in both stroke patients and controls. ECP decreased markedly the systolic and diastolic BPVs at VLF and LF and the TP, and the diastolic BPV at HF when compared with baseline. The decreases in diastolic and systolic BPV reached 37.56% and 23.20%, respectively, at VLF, 21.15% and 12.19% at LF, 8.76% and 16.59% at HF, and 31.92% and 23.62% for the total TP in stroke patients, which did not differ from those in healthy controls. The change in flow velocity on the contralateral side was positively correlated with the total TP systolic BPV change induced by ECP (r=0.312, p=0.035). Conclusions ECP reduces the beat-to-beat BPV when increasing the blood pressure and cerebral blood flow velocity in ischemic stroke patients. ECP might be able to improve the clinical outcome by decreasing the beat-to-beat BPV in stroke patients, and this should be explored further in future studies. PMID:27095525

  14. 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.

  15. 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

  16. The Prediction of Clinical Outcome Using HbA1c in Acute Ischemic Stroke of the Deep Branch of Middle Cerebral Artery

    PubMed Central

    Shin, Sung Bong; Kim, Tae Uk; Hyun, Jung Keun

    2015-01-01

    Objective To elucidate the association between glycemic control status and clinical outcomes in patients with acute ischemic stroke limited to the deep branch of the middle cerebral artery (MCA). Methods We evaluated 65 subjects with first-ever ischemic stroke of the deep branches of the MCA, which was confirmed by magnetic resonance angiography. All subjects had blood hemoglobin A1c (HbA1c) measured at admission. They were classified into two groups according to the level of HbA1c (low <7.0% or high ≥7.0%). Neurological impairment and functional status were evaluated using the National Institutes of Health Stroke Scale (NIHSS), Functional Independence Measure (FIM), Korean version of Modified Barthel Index (K-MBI), Korean version of Mini-Mental State Examination (MMSE-K), and the Loewenstein Occupational Therapy Cognitive Assessment (LOTCA) at admission and discharge. Body mass index, serum glucose, homocysteine and cholesterol levels were also measured at admission. Results The two groups did not show any difference in the NIHSS, FIM, K-MBI, MMSE-K, and LOTCA scores at any time point. Body mass index and levels of blood homocysteine and cholesterol were not different between the two groups. The serum blood glucose level at admission was negatively correlated with all outcome measures. Conclusion We found that HbA1c cannot be used for predication of clinical outcome in patients with ischemic stroke of the deep branch of the middle cerebral artery. PMID:26798617

  17. Extravasation into brain and subsequent spread beyond the ischemic core of a magnetic resonance contrast agent following a step-down infusion protocol in acute cerebral ischemia

    PubMed Central

    2014-01-01

    Background Limiting expansion of the ischemic core lesion by reinstating blood flow and protecting the penumbral cells is a priority in acute stroke treatment. However, at present, methods are not available for effective drug delivery to the ischemic penumbra. To address these issues this study compared the extravasation and subsequent interstitial spread of a magnetic resonance contrast agent (MRCA) beyond the ischemic core into the surrounding brain in a rat model of ischemia-reperfusion for bolus injection and step-down infusion (SDI) protocols. Methods Male Wistar rats underwent middle cerebral artery (MCA) occlusion for 3 h followed by reperfusion. Perfusion-diffusion mismatched regions indicating the extent of spread were identified by measuring cerebral blood flow (CBF) deficits by arterial spin-labeled magnetic resonance imaging and the extent of the ischemic core by mapping the apparent diffusion coefficient (ADC) of water with diffusion-weighted imaging. Vascular injury was assessed via MRCA, gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) penetration, by Look-Locker T1-weighted MR imaging after either a bolus injection (n = 8) or SDI (n = 6). Spatial and temporal expansion of the MRCA front during a 25 min imaging period was measured from images obtained at 2.5 min intervals. Results The mean ADC lesion was 20 ± 7% of the hemispheric area whereas the CBF deficit area was 60 ± 16%, with the difference between the areas suggesting the possible presence of a penumbra. The bolus injection led to MRCA enhancement with an area that initially spread into the ischemic core and then diminished over time. The SDI produced a gradual increase in the area of MRCA enhancement that slowly enlarged to occupy the core, eventually expanded beyond it into the surrounding tissue and then plateaued. The integrated area from SDI extravasation was significantly larger than that for the bolus (p = 0.03). The total number of pixels covered by the

  18. Cerebral changes and cognitive impairment after an ischemic heart disease: a multimodal MRI study.

    PubMed

    Bernard, Charlotte; Catheline, Gwénaëlle; Dilharreguy, Bixente; Couffinhal, Thierry; Ledure, Sylvain; Lassalle-Lagadec, Saioa; Callaert, Dorothée; Allard, Michèle; Sibon, Igor

    2016-09-01

    Three to 6 months after an acute coronary syndrome (ACS), cognitive impairment is observed in more than 30 % of the patients, mainly in executive functioning. The aim of this study was to investigate, using multimodal MRI, cerebral anatomo-functional substratum of executive dysfunction. Thirty-three patients were recruited 4 ± 1 months after a first ACS. Executive functions were evaluated with the Trail-Making-Test-B (TMTB) at baseline (ie 4 ± 1 months after ACS) and 6 months later (ie 10 ± 1 months after ACS). Using both time-points, we identified 3 groups of patients according to normative data based on age, gender and education level: 15 'cognitively normal' patients without impairment at each follow-up, 10 'transient impaired' patients with an impairment only at baseline and 8 'impairing' patients with an impairment only at follow-up. We explored, in the whole-brain, the structural integrity using Voxel-Based Morphometry and Tract-Based Spatial Statistics and the resting-state functional connectivity using Network-Based Statistics. No structural difference was observed between impaired and cognitively normal patients. At the functional level, compared to the 'cognitively normal' group, the 'transient impaired' patients presented an increased functional connectivity in a network centered on middle-orbito-frontal regions, whereas the 'impairing' patients presented only a non-significant decrease of functional connectivity. Executive dysfunction in ACS patients is associated to functional but no structural characteristics, particularly to an increased functional connectivity in cognitive networks in transient impaired patients. Further studies with larger sample size are needed to confirm these results and to determine if these patients could be at higher risk for developing permanent cognitive disorders. PMID:26589710

  19. 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

  20. 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 ...

  1. Hyperthermic preconditioning severely accelerates neuronal damage in the gerbil ischemic hippocampal dentate gyrus via decreasing SODs expressions.

    PubMed

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

    2015-11-15

    It is well known that neurons in the dentate gyrus (DG) of the hippocampus are resistant to short period of ischemia. Hyperthermia is a proven risk factor for cerebral ischemia and can produce more extensive brain damage related with mortality rates. The aim of this study was to examine the effect of hyperthermic conditioning (H) on neuronal death, gliosis and expressions of SODs as anti-oxidative enzymes in the gerbil DG following 5 min-transient cerebral ischemia. The animals were randomly assigned to 4 groups: 1) (N+sham)-group was given sham-operation with normothermia (N); 2) (N+ischemia)-group was given 5 min-transient ischemia with N; 3) (H+sham)-group was given sham-operation with H; and 4) (H+ischemia)-group was given 5 min-transient cerebral ischemia with H. H (39±0.5°C) was induced by subjecting the animals to a heating pad for 30 min before and during the operation. In the (N+ischemia)-groups, a significant neuronal death was observed in the polymorphic layer (PL) from 1 day after ischemia-reperfusion. In the (H+ischemia)-groups, neuronal death was also observed in the PL from 1day post-ischemia; the degree of the neuronal death was severer than that in the (N+ischemia)-groups. In addition, we examined the gliosis of astrocytes and microglia using anti-glial fibrillary acidic protein (GFAP) and anti- ionized calcium-binding adapter molecule 1 (Iba-1). GFAP(+) and Iba-1(+) glial cells were much more activated in the (H+ischemia)-groups than those in the (N+ischemia)-groups. On the other hand, immunoreactivities and levels of SOD1 rather than SOD2 were significantly lower in the (H+ischemia)-groups than those in the (N+ischemia)-groups. In brief, on the basis of our findings, we suggest that cerebral ischemic insult with hyperthermic conditioning brings up severer neuronal damage and gliosis in the polymorphic layer through reducing SOD1 expression rather than SOD2 expression in the DG. PMID:26365286

  2. Neuroprotection of Ischemic Preconditioning is Mediated by Anti-inflammatory, Not Pro-inflammatory, Cytokines in the Gerbil Hippocampus Induced by a Subsequent Lethal Transient Cerebral Ischemia.

    PubMed

    Kim, Dong Won; Lee, Jae-Chul; Cho, Jeong-Hwi; Park, Joon Ha; Ahn, Ji Hyeon; Chen, Bai Hui; Shin, Bich-Na; Tae, Hyun-Jin; Seo, Jeong Yeol; Cho, Jun Hwi; Kang, Il Jun; Hong, Seongkweon; Kim, Young-Myeong; Won, Moo-Ho; Kim, In Hye

    2015-09-01

    Ischemic preconditioning (IPC) induced by sublethal transient cerebral ischemia could reduce neuronal damage/death following a subsequent lethal transient cerebral ischemia. We, in this study, compared expressions of interleukin (IL)-2 and tumor necrosis factor (TNF)-α as pro-inflammatory cytokines, and IL-4 and IL-13 as anti-inflammatory cytokines in the gerbil hippocampal CA1 region between animals with lethal ischemia and ones with IPC followed by lethal ischemia. In the animals with lethal ischemia, pyramidal neurons in the stratum pyramidale (SP) of the hippocampal CA1 region were dead at 5 days post-ischemia; however, IPC protected the CA1 pyramidal neurons from lethal ischemic injury. Expressions of all cytokines were significantly decreased in the SP after lethal ischemia and hardly detected in the SP at 5 days post-ischemia because the CA1 pyramidal neurons were dead. IPC increased expressions of anti-inflammatory cytokines (IL-4 and IL-13) in the stratum pyramidale of the CA1 region following no lethal ischemia (sham-operation), and the increased expressions of IL-4 and IL-13 by IPC were continuously maintained is the SP of the CA1 region after lethal ischemia. However, pro-inflammatory cytokines (IL-2 and TNF-α) in the SP of the CA1 region were similar those in the sham-operated animals with IPC, and the IL-4 and IL-13 expressions in the SP were maintained after lethal ischemia. In conclusion, this study shows that anti-inflammatory cytokines significantly increased and longer maintained by IPC and this might be closely associated with neuroprotection after lethal transient cerebral ischemia. PMID:26290267

  3. Autophagy protects human brain microvascular endothelial cells against methylglyoxal-induced injuries, reproducible in a cerebral ischemic model in diabetic rats.

    PubMed

    Fang, Lili; Li, Xue; Zhong, Yinbo; Yu, Jing; Yu, Lina; Dai, Haibin; Yan, Min

    2015-10-01

    Cerebral microvascular endothelial cells (ECs) are crucial for brain vascular repair and maintenance, but their physiological function may be impaired during ischemic stroke and diabetes. Methylglyoxal (MGO), a reactive dicarbonyl produced during glucose metabolism, could exacerbate ischemia-induced EC injury and dysfunction. We investigated the protective effect of autophagy on cultured human brain microvascular endothelial cells (HBMEC) that underwent MGO treatment. A further study was conducted to explore the underlying mechanisms of the protective effect. Autophagic activity was assessed by evaluating protein levels, using western blot. 3-methyladenine (3-MA), bafilomycin A1, ammonium chloride (AC), Beclin 1 siRNA, and chloroquine (CQ) were used to cause autophagy inhibition. Alarmar blue assay and lactate dehydrogenase release assay were used to evaluate cell viability. Streptozotocin was administered to induce type I diabetes in rats and post-permanent middle cerebral artery occlusion was performed to elicit cerebral ischemia. Blood-brain barrier permeability was also assessed. Our study found that MGO reduced HBMEC cell viability in a concentration- and time-dependent manner, and triggered the responsive autophagy activation. Autophagy inhibitors bafilomycin A1, AC, 3-MA, and BECN1 siRNA exacerbated MGO-induced HBMEC injury. FAK phosphorylation inhibitor PF573228 inhibited MGO-triggered autophagy and enhanced lactate dehydrogenase release. Meanwhile, similar autophagy activation in brain vascular ECs was observed during permanent middle cerebral artery occlusion-induced cerebral ischemia in diabetic rats, while chloroquine-induced autophagy inhibition enhanced blood-brain barrier permeability. Taken together, our study indicates that autophagy triggered by MGO defends HBMEC against injuries. PMID:26251121

  4. Resveratrol protects CA1 neurons against focal cerebral ischemic reperfusion-induced damage via the ERK-CREB signaling pathway in rats.

    PubMed

    Li, Zhen; Fang, Fang; Wang, Yuanyin; Wang, Liecheng

    2016-01-01

    Ischemic stroke is a primary cause of mortality and disability in the aged population. Resveratrol (Res), a natural polyphenol enriched in plants, presents diverse biological activities, e.g., antiinflammatory and anti-oxidation effects. Here, we evaluated whether Res pretreatment influenced focal cerebral ischemia-induced cognitive impairment, and we explored the underlying mechanisms in rats. The results showed that a single administration of Res (30mg/kg, i.p.) at 1 or 4h, but not at 24h before focal cerebral ischemia exerted significant neuroprotective effects, including a reduction in hippocampal CA1 neuronal death and spatial cognition deficits caused by ischemia. The neuroprotective effects of Res were suppressed by pretreatment with MK801, an NMDA receptor blocker, or U0126, an extracellular signal regulated kinase 1/2 (ERK1/2) kinase inhibitor. A western blot analysis revealed that Res treatment at 1h before ischemia significantly increased ERK1/2 phosphorylation and cyclic-AMP response element binding protein (CREB) phosphorylation in the CA1 region of the hippocampus, which can be prevented with U0126 pretreatment. The results showed that the NMDA receptor-mediated ERK-CREB signaling pathway might participates in Res-induced neuroprotection in rats with focal cerebral ischemia. PMID:27143440

  5. Preconditioning with recombinant high-mobility group box 1 induces ischemic tolerance in a rat model of focal cerebral ischemia-reperfusion.

    PubMed

    Wang, Chen; Liu, Xiao-Xi; Huang, Kai-Bin; Yin, Su-Bing; Wei, Jing-Jing; Hu, Ya-Fang; Gu, Yong; Zheng, Guo-Qing

    2016-05-01

    Preconditioning with ligands of toll-like receptors (TLRs) is a powerful neuroprotective approach whereby a low dose of stimulus confers significant protection against subsequent substantial brain damage by reprogramming the ischemia-activated TLRs signaling. Herein, we aim to explore whether preconditioning with recombinant high-mobility group box 1 (rHMGB1), one of the TLRs ligands, decreases cerebral ischemia-reperfusion injury (IRI). Rats were intracerebroventricularly pretreated with rHMGB1, 1 or 3 days before induction of middle cerebral artery occlusion. Results showed that preconditioning with rHMGB1 1 day, but not 3 days, prior to ischemia dramatically reduced neurological deficits, infarct size, brain swelling, cell apoptosis, and blood-brain barrier permeability. Interleukin-1R-associated kinase-M (IRAK-M), a critical negative regulator of TLRs signaling, was robustly increased in response to brain IRI and was further elevated by rHMGB1 pretreatment, indicating its role associated with the rHMGB1 preconditioning-mediated ischemic tolerance. In vitro and in vivo assays indicated that the induced IRAK-M expression was localized in microglia. In addition, TLR4 specific inhibitor TAK-242 abolished the neuroprotective effects and the induction of IRAK-M offered by rHMGB1 preconditioning. Collectively, our study demonstrates that rHMGB1 preconditioning is neuroprotective during cerebral IRI, which is associated with activated TLR4/IRAK-M signaling in microglia. We found that high-mobility group box 1 (HMGB1) pretreatment conditioned the brain against subsequent ischemia-reperfusion injury. We propose the following mechanism for HMGB1 preconditioning-mediated ischemic tolerance: through toll-like receptor TLR4, HMGB1 preconditioning magnifies the up-regulation of interleukin-1R-associated kinase-M (IRAK-M) induced by ischemia-reperfusion in microglia, resulting in the decreased phosphorylation of IRAK-1. These findings are helpful in understanding the

  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. 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.

  8. 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

  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 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

  10. Cerebral Blood Volume ASPECTS Is the Best Predictor of Clinical Outcome in Acute Ischemic Stroke: A Retrospective, Combined Semi-Quantitative and Quantitative Assessment

    PubMed Central

    Padroni, Marina; Bernardoni, Andrea; Tamborino, Carmine; Roversi, Gloria; Borrelli, Massimo; Saletti, Andrea; De Vito, Alessandro; Azzini, Cristiano; Borgatti, Luca; Marcello, Onofrio; d’Esterre, Christopher; Ceruti, Stefano; Casetta, Ilaria; Lee, Ting-Yim; Fainardi, Enrico

    2016-01-01

    Introduction The capability of CT perfusion (CTP) Alberta Stroke Program Early CT Score (ASPECTS) to predict outcome and identify ischemia severity in acute ischemic stroke (AIS) patients is still questioned. Methods 62 patients with AIS were imaged within 8 hours of symptom onset by non-contrast CT, CT angiography and CTP scans at admission and 24 hours. CTP ASPECTS was calculated on the affected hemisphere using cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) maps by subtracting 1 point for any abnormalities visually detected or measured within multiple cortical circular regions of interest according to previously established thresholds. MTT-CBV ASPECTS was considered as CTP ASPECTS mismatch. Hemorrhagic transformation (HT), recanalization status and reperfusion grade at 24 hours, final infarct volume at 7 days and modified Rankin scale (mRS) at 3 months after onset were recorded. Results Semi-quantitative and quantitative CTP ASPECTS were highly correlated (p<0.00001). CBF, CBV and MTT ASPECTS were higher in patients with no HT and mRS≤2 and inversely associated with final infarct volume and mRS (p values: from p<0.05 to p<0.00001). CTP ASPECTS mismatch was slightly associated with radiological and clinical outcomes (p values: from p<0.05 to p<0.02) only if evaluated quantitatively. A CBV ASPECTS of 9 was the optimal semi-quantitative value for predicting outcome. Conclusions Our findings suggest that visual inspection of CTP ASPECTS recognizes infarct and ischemic absolute values. Semi-quantitative CBV ASPECTS, but not CTP ASPECTS mismatch, represents a strong prognostic indicator, implying that core extent is the main determinant of outcome, irrespective of penumbra size. PMID:26824672

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

    PubMed

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

    2016-06-01

    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. 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

  13. 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

  14. First autologous cell therapy of cerebral palsy caused by hypoxic-ischemic brain damage in a child after cardiac arrest-individual treatment with cord blood.

    PubMed

    Jensen, A; Hamelmann, E

    2013-01-01

    Each year, thousands of children incur brain damage that results in lifelong sequelae. Therefore, based on experimental evidence, we explored the therapeutic potential of human cord blood, known to contain stem cells, to examine the functional neuroregeneration in a child with cerebral palsy after cardiac arrest. The boy, whose cord blood was stored at birth, was 2.5 years old and normally developed when global ischemic brain damage occurred resulting in a persistent vegetative state. Nine weeks later, he received autologous cord blood (91.7 mL, cryopreserved, 5.75 × 10e8 mononuclear cells) intravenously. Active rehabilitation (physio- and ergotherapy) was provided daily, follow-up at 2, 5, 12, 24, 30, and 40 months. At 2-months follow-up the boy's motor control improved, spastic paresis was largely reduced, and eyesight was recovered, as did the electroencephalogram. He smiled when played with, was able to sit and to speak simple words. At 40 months, independent eating, walking in gait trainer, crawling, and moving from prone position to free sitting were possible, and there was significantly improved receptive and expressive speech competence (four-word sentences, 200 words). This remarkable functional neuroregeneration is difficult to explain by intense active rehabilitation alone and suggests that autologous cord blood transplantation may be an additional and causative treatment of pediatric cerebral palsy after brain damage. PMID:23762741

  15. Essential role of adenosine, adenosine A1 receptors, and ATP-sensitive K+ channels in cerebral ischemic preconditioning.

    PubMed Central

    Heurteaux, C; Lauritzen, I; Widmann, C; Lazdunski, M

    1995-01-01

    Preconditioning with sublethal ischemia protects against neuronal damage after subsequent lethal ischemic insults in hippocampal neurons. A pharmacological approach using agonists and antagonists at the adenosine A1 receptor as well as openers and blockers of ATP-sensitive K+ channels has been combined with an analysis of neuronal death and gene expression of subunits of glutamate and gamma-aminobutyric acid receptors, HSP70, c-fos, c-jun, and growth factors. It indicates that the mechanism of ischemic tolerance involves a cascade of events including liberation of adenosine, stimulation of adenosine A1 receptors, and, via these receptors, opening of sulfonylurea-sensitive ATP-sensitive K+ channels. Images Fig. 2 Fig. 3 PMID:7753861

  16. 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

  17. The effect of intravenous insulin on accumulation of excitotoxic and other amino acids in the ischemic rat cerebral cortex.

    PubMed

    Guyot, L L; Diaz, F G; O'Regan, M H; Ren, J; Phillis, J W

    2000-07-01

    Insulin has been reported to be neuroprotective during cerebral ischemia/reperfusion. However, it may also increase the sensitivity of cultured cortical neurons to glutamate toxicity. The experiments described here utilized a rat four-vessel occlusion model with cerebral cortical windows to determine the effects of intravenous insulin, alone (I) or combined with glucose (IG) to maintain physiologic blood glucose levels, on the extracellular accumulation of amino acids in superfusates of the cerebral cortex. Aspartate, phosphoethanolamine, taurine and gamma-aminobutyric acid were increased in the I and IG groups and glutamate was increased in the IG group compared to controls during ischemia/reperfusion. Insulin treatment attenuated the rebound in cortical superfusate glucose levels in both groups of animals during reperfusion. The increases in amino acid release during reperfusion may be due to a lack of glycolytically derived energy available for amino acid uptake systems and ionic pumps. PMID:10869816

  18. Crohns disease with central nervous system vasculitis causing subarachnoid hemorrhage due to aneurysm and cerebral ischemic stroke.

    PubMed

    Garge, Shaileshkumar S; Vyas, Pooja D; Modi, Pranav D; Ghatge, Sharad

    2014-10-01

    Cerebral vasculitis secondary to Crohn's disease (CD) seems to be a very rare phenomenon. We report a 39-year-old male who presented with headache, vomiting, and left-sided weakness in the known case of CD. Cross-sectional imaging (computed tomography and magnetic resonance imaging,) showed right gangliocapsular acute infarct with supraclinoid cistern subarachnoid hemorrhage (SAH). Cerebral digital substraction angiography (DSA) showed dilatation and narrowing of right distal internal carotid artery (ICA). Left ICA was chronically occluded. His inflammatory markers were significantly raised. Imaging features are suggestive of cerebral vasculitis. Arterial and venous infarcts due to thrombosis are known in CD. Our case presented with acute subarachnoid hemorrhage in supraclinoid cistern due to rupture of tiny aneurysm of perforator arteries causing SAH and infarction in right basal ganglia. Patient was treated conservatively with immunosuppression along with medical management of SAH. PMID:25506170

  19. 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

  20. Relationship between deep medullary veins in susceptibility-weighted imaging and ipsilateral cerebrovascular reactivity of middle cerebral artery in patients with ischemic stroke

    PubMed Central

    HAN, XIANJUN; OUYANG, LINHUI; ZHANG, CHUNNING; MA, HAILING; QIN, JINGCUI

    2016-01-01

    Deep cerebral veins have been recently associated with the severity of hemodynamic impairment in moyamoya disease. The aim of the current study was to determine the correlation of deep medullary veins (DMVs) in susceptibility-weighted imaging (SWI) with ipsilateral cerebrovascular reactivity (CVR) of and anterior cecebrocervical artery stenosis in patients with ischemic stroke. Patients with unilateral TIA or infarction who underwent 3.0 T magnetic resonance imaging SWI, digital subtraction angiography and transcranial Doppler with CO2 stimulation within the first 7 days of hospitalization were retrospectively selected. CVR and stenosis of anterior cerebrocervical arteries were compared between different DMVs stages in symptomatic hemispheres (SHs) and asymptomatic hemispheres (AHs). A total of 61 patients were subsequently included in the present study. A univariate analysis was conducted and results for age (PAHs=0.004, PSHs=0.006), hypertension (PAHs=0.008, PSHs=0.020), current smoking (PAHs=0.006, PSHs=0.021), CVR (PAHs=0.000, PSHs=0.000), and artery stenosis (PAHs=0.000, PSHs=0.000) were obtained. The results suggested statistically significant differences between DMVs grades in SHs and AHs. A subsequent multivariate analysis revealed that CVR (ORAHs=0.925, 95% CIAHs: 0.873–0.981; ORSHs=0.945, 95% CISHs: 0.896–0.996), and artery stenosis (ORAH=3.147, 95% CIAH: 1.010–9.806; ORSHs=2.882, 95% CISHs: 1.017–8.166) were independent risk factors of DMVs. In conclusion, 3.0 T SWI was useful in detecting the DMVs around the lateral ventricle in patients with atherosclerotic ischemic stroke. CVR and stenosis of anterior cerebrocervical arteries were independent risk factors for ipsilateral DMVs in SHs and AHs. PMID:27284303

  1. 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

  2. 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

  3. 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

  4. 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

  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

    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

  6. Ischemic preconditioning maintains the immunoreactivities of glucokinase and glucokinase regulatory protein in neurons of the gerbil hippocampal CA1 region following transient cerebral ischemia.

    PubMed

    Cho, Young Shin; Cho, Jun Hwi; Shin, Bich-Na; Cho, Geum-Sil; Kim, In Hye; Park, Joon Ha; Ahn, Ji Hyeon; Ohk, Taek Geun; Cho, Byung-Ryul; Kim, Young-Myeong; Hong, Seongkweon; Won, Moo-Ho; Lee, Jae-Chul

    2015-10-01

    Glucokinase (GK) is involved in the control of blood glucose homeostasis. In the present study, the effect of ischemic preconditioning (IPC) on the immunoreactivities of GK and its regulatory protein (GKRP) following 5 min of transient cerebral ischemia was investigated in gerbils. The gerbils were randomly assigned to four groups (sham‑operated group, ischemia‑operated group, IPC + sham‑operated group and IPC + ischemia‑operated group). IPC was induced by subjecting the 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) at 5 days post‑ischemia; however, in the IPC+ischemia‑operated group, the neurons in the SP were well protected. Following immunohistochemical investigation, the immunoreactivities of GK and GKRP in the neurons of the SP were markedly decreased in the CA1, but not the CA2/3, from 2 days post‑ischemia, and were almost undetectable in the SP 5 days post‑ischemia. In the IPC + ischemia‑operated group, the immunoreactivities of GK and GKRP in the SP of the CA1 were similar to those in the sham‑group. In brief, the findings of the present study demonstrated that IPC notably maintained the immunoreactivities of GK and GKRP in the neurons of the SP of CA1 following ischemia‑reperfusion. This indicated that GK and GKRP may be necessary for neuron survival against transient cerebral ischemia. PMID:26134272

  7. Ischemic preconditioning maintains the immunoreactivities of glucokinase and glucokinase regulatory protein in neurons of the gerbil hippocampal CA1 region following transient cerebral ischemia

    PubMed Central

    CHO, YOUNG SHIN; CHO, JUN HWI; SHIN, BICH-NA; CHO, GEUM-SIL; KIM, IN HYE; PARK, JOON HA; AHN, JI HYEON; OHK, TAEK GEUN; CHO, BYUNG-RYUL; KIM, YOUNG-MYEONG; HONG, SEONGKWEON; WON, MOO-HO; LEE, JAE-CHUL

    2015-01-01

    Glucokinase (GK) is involved in the control of blood glucose homeostasis. In the present study, the effect of ischemic preconditioning (IPC) on the immunoreactivities of GK and its regulatory protein (GKRP) following 5 min of transient cerebral ischemia was investigated in gerbils. The gerbils were randomly assigned to four groups (sham-operated group, ischemia-operated group, IPC + sham-operated group and IPC + ischemia-operated group). IPC was induced by subjecting the 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) at 5 days post-ischemia; however, in the IPC+ischemia-operated group, the neurons in the SP were well protected. Following immunohistochemical investigation, the immunoreactivities of GK and GKRP in the neurons of the SP were markedly decreased in the CA1, but not the CA2/3, from 2 days post-ischemia, and were almost undetectable in the SP 5 days post-ischemia. In the IPC + ischemia-operated group, the immunoreactivities of GK and GKRP in the SP of the CA1 were similar to those in the sham-group. In brief, the findings of the present study demonstrated that IPC notably maintained the immunoreactivities of GK and GKRP in the neurons of the SP of CA1 following ischemia-reperfusion. This indicated that GK and GKRP may be necessary for neuron survival against transient cerebral ischemia. PMID:26134272

  8. [The dynamics of lipid peroxidation in patients with acute disorders of the cerebral circulation of an ischemic nature].

    PubMed

    Suslina, Z A; Fedorova, T N; Kistenev, B A; Khrapova, E V; Maksimova, M Iu

    1999-01-01

    Lipid peroxidation (LP) was analysed in the blood and atherogenic lipoproteins of 36 patients with ischemic stroke in the internal carotid arteries at the acute stage (1, 7 and 21 days). During 1-7 days 22 patients (group 1) were treated with haemocorrecting drugs (rheopolyglucin, euphyllin, aspirin, curantyl, trental) and 14 patients (group 2) were treated with vasoactive and metabolic drugs (cavinton, complamin, actovegin). On days 8-21 all the patients received the same treatment: pyracetam and essential. Before the treatment both activation of LP and exhaustion of endogenic antioxidant background were observed in blood samples of all the patients. Significant changes of LP parameters were observed in group 1 up to day 7, but they reached the basic level on the 21 day. No significant changes were observed in group 2. Thus, haemocorrecting drugs had some antioxidant effects, but to provide a steady antioxidant effect it is necessary to use special antioxidants. PMID:10441849

  9. Induction of the HSP110/105 family in the rat hippocampus in cerebral ischemia and ischemic tolerance.

    PubMed

    Yagita, Y; Kitagawa, K; Ohtsuki, T; Tanaka, S; Hori, M; Matsumoto, M

    2001-07-01

    Recently, the authors isolated a novel gene of the HSP110 family, ischemia responsive protein 94 kDa (irp94), and demonstrated the expression of this gene after transient forebrain ischemia. In the current study, the authors investigated the expression profiles of all HSP110 family members including hsp110/105 and osp94/apg-1, after transient forebrain ischemia using rat four-vessel occlusion model. Among three members of the HSP110 family, induction of hsp110/105 was the most prominent after ischemia. hsp110/105 mRNA expression was clearly enhanced from 4 to 24 hours after a 6-minute or longer ischemic period. First, hsp110/105 mRNA expression was induced in the dentate gyrus, and later in the pyramidal layer. HSP110/105 protein expression also was enhanced by a 6-minute or longer period of ischemia. Profiles of HSP110/105 expression after ischemia were similar to those of inducible HSP70. After transient forebrain ischemia for 10 minutes, HSP110/105 protein was induced in the dentate gyrus and the CA3 pyramidal layer, but not in the CA1 pyramidal neurons. However, 6 minutes of ischemia induced the HSP110/105 protein, as well as the HSP70 protein, in the CA1 region. CA1 pyramidal neurons expressing HSP110/105 acquired tolerance against subsequent severe ischemia. In conclusion, HSP110/105 showed the most prominent induction after ischemia among the three HSP110 gene family members. Colocalization of HSP110/105 and HSP70 in the CA1 neurons that acquired tolerance suggested that induced HSP110/105 might contribute to ischemic tolerance together with HSP70. PMID:11435793

  10. Neuroprotective effects of compound FLZ in an ischemic model mediated by improving cerebral blood flow and enhancing Hsp27 expression.

    PubMed

    Ma, Bo; Li, Min; Ma, Tao; Liu, Geng-Tao; Zhang, Jianjun

    2016-08-01

    Compound FLZ is a synthetic novel derivate of natural squamosamide, which has potent neuroprotective effects based on our previous study. We are now aiming to investigate the effects of FLZ on cerebral blood flow (CBF), infarct volume, neurological function, heat shock protein 70 (Hsp70), and Hsp27 expression in transient focal ischemia. For this goal, an animal model of middle cerebral artery occlusion (MCAO) for 2h followed by reperfusion was used, and animals received low or high doses of FLZ (150 or 300mg/kg), orally 10min after MCAO onset. The results show that the infarct volume was 32.7% for the vehicle control group, and reduced to 17.6 and 12.8% for the low and high dose FLZ-treated groups, respectively. FLZ treatment also significantly improved the neurobehavioral score from 2.6 in the vehicle control group to 1.0 and 0.9 in the low and high dose groups, respectively. Further, FLZ significantly induced Hsp27 over-expression and reduced over-expression of HSP70, a sensitive marker of acute ischemia, in ipsilateral cortex by a dose-dependent manner. In addition, CBF was quantified using laser-Doppler flowmetry. During ischemia, regional CBF (rCBF) was improved from approximately 30% to over 50% of the baseline and the reperfusion-induced hyperemia was reduced in both FLZ dosage groups. Particularly, high dose FLZ reduced rCBF during hyperemia by 30%. In conclusion, FLZ (150 and 300mg/kg) can significantly reduce the infarct volume and improve neurobehavioral deficits in a rat MCAO model, most likely through improving CBF in the penumbra and enhancing Hsp27 expression. PMID:24675028

  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. Long-Term Population-Based Cerebral Ischemic Event and Cognitive Outcomes of Direct Oral Anticoagulants Compared With Warfarin Among Long-term Anticoagulated Patients for Atrial Fibrillation.

    PubMed

    Jacobs, Victoria; May, Heidi T; Bair, Tami L; Crandall, Brian G; Cutler, Michael J; Day, John D; Mallender, Charles; Osborn, Jeffrey S; Stevens, Scott M; Weiss, J Peter; Woller, Scott C; Bunch, T Jared

    2016-07-15

    Direct oral anticoagulants (DOACs) have been used in clinical practice in the United States for the last 4 to 6 years. Although DOACs may be an attractive alternative to warfarin in many patients, long-term outcomes of use of these medications are unknown. We performed a propensity-matched analysis to report patient important outcomes of death, stroke/transient ischemic attack (TIA), bleeding, major bleeding, and dementia in patients taking a DOAC or warfarin. Patients receiving long-term anticoagulation from June 2010 to December 2014 for thromboembolism prevention with either warfarin or a DOAC were matched 1:1 by index date and propensity score. Multivariable Cox hazard regression was performed to determine the risk of death, stroke/TIA, major bleed, and dementia by the anticoagulant therapy received. A total of 5,254 patients were studied (2,627 per group). Average age was 72.4 ± 10.9 years, and 59.0% were men. Most patients were receiving long-term anticoagulation for AF management (warfarin: 96.5% vs DOAC: 92.7%, p <0.0001). Rivaroxaban (55.3%) was the most commonly used DOAC, followed by apixaban (22.5%) and dabigatran (22.2%). The use of DOACs compared with warfarin was associated with a reduced risk of long-term adverse outcomes: death (p = 0.09), stroke/TIA (p <0.0001), major bleed (p <0.0001), and bleed (p = 0.14). No significant outcome variance was noted in DOAC-type comparison. In the AF multivariable model patients taking DOAC were 43% less likely to develop stroke/TIA/dementia (hazard ratio 0.57 [CI 0.17, 1.97], p = 0.38) than those taking warfarin. Our community-based results suggest better long-term efficacy and safety of DOACs compared with warfarin. DOAC use was associated with a lower risk of cerebral ischemic events and new-onset dementia. PMID:27236255

  13. Association of MTHFR C677T Genotype With Ischemic Stroke Is Confined to Cerebral Small Vessel Disease Subtype

    PubMed Central

    Traylor, Matthew; Adib-Samii, Poneh; Thijs, Vincent; Sudlow, Cathie; Rothwell, Peter M.; Boncoraglio, Giorgio; Dichgans, Martin; Meschia, James; Maguire, Jane; Levi, Christopher; Rost, Natalia S.; Rosand, Jonathan; Hassan, Ahamad; Bevan, Steve; Markus, Hugh S.

    2016-01-01

    Background and Purpose— Elevated plasma homocysteine levels are associated with stroke. However, this might be a reflection of bias or confounding because trials have failed to demonstrate an effect from homocysteine lowering in stroke patients, although a possible benefit has been suggested in lacunar stroke. Genetic studies could potentially overcome these issues because genetic variants are inherited randomly and are fixed at conception. Therefore, we tested the homocysteine levels–associated genetic variant MTHFR C677T for association with magnetic resonance imaging–confirmed lacunar stroke and compared this with associations with large artery and cardioembolic stroke subtypes. Methods— We included 1359 magnetic resonance imaging–confirmed lacunar stroke cases, 1824 large artery stroke cases, 1970 cardioembolic stroke cases, and 14 448 controls, all of European ancestry. Furthermore, we studied 3670 ischemic stroke patients in whom white matter hyperintensities volume was measured. We tested MTHFR C677T for association with stroke subtypes and white matter hyperintensities volume. Because of the established association of homocysteine with hypertension, we additionally stratified for hypertension status. Results— MTHFR C677T was associated with lacunar stroke (P=0.0003) and white matter hyperintensity volume (P=0.04), but not with the other stroke subtypes. Stratifying the lacunar stroke cases for hypertension status confirmed this association in hypertensive individuals (P=0.0002), but not in normotensive individuals (P=0.30). Conclusions— MTHFR C677T was associated with magnetic resonance imaging–confirmed lacunar stroke, but not large artery or cardioembolic stroke. The association may act through increased susceptibility to, or interaction with, high blood pressure. This heterogeneity of association might explain the lack of effect of lowering homocysteine in secondary prevention trials which included all strokes. PMID:26839351

  14. Dynamic changes of cerebral-specific proteins in full-term newborns with hypoxic-ischemic encephalopathy.

    PubMed

    Liu, Fang; Yang, Suyan; Du, Zhifang; Guo, Zhimei

    2013-06-01

    The aim of this study was to observe the dynamic changes of serum brain-derived neurotrophic factor (BDNF), S-100B, and Tau proteins levels in full-term newborns with hypoxic-ischemic encephalopathy (HIE) and to discuss their significance in brain damage. Serum samples of 28 full-term newborns diagnosed with HIE and 20 controls were obtained in the first 24 h of life. Another serum samples were also taken, respectively, at 3 and 7 days of life in HIE group. The concentrations of BDNF, S-100B, and Tau proteins were measured by the enzyme-linked immunosorbent assay method. Mean concentrations of BDNF, S-100B, and Tau proteins among different time period and in different grades of HIE group were calculated and compared. Compared with the control group, serum BDNF and proteins S-100B levels in HIE group were significantly elevated in 24 h after birth (P < 0.05) and their concentrations were also significantly higher among patients with mod-severe HIE compared to those with mild HIE at 24 h and 7 days after asphyxia (P < 0.05). Regardless of whether mod-severe HIE or mild HIE, there were no significant difference of serum BDNF and proteins S-100B among the three different time periods. There was no difference in Tau protein levels between HIE group and control group, also no difference between mod-severe HIE group and mild HIE group. BDNF and proteins S-100B are up-regulated early in asphyxia neonates with HIE; and the released amount of BDNF and proteins S-100B from nerve center system correlate with the extent of encephalopathy. PMID:23203841

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

    PubMed

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

    2016-07-01

    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

  16. Electroacupuncture Pretreatment Attenuates Cerebral Ischemic Injury via Notch Pathway-Mediated Up-Regulation of Hypoxia Inducible Factor-1α in Rats.

    PubMed

    Zhao, Yu; Deng, Bin; Li, Yichong; Zhou, Lihua; Yang, Lei; Gou, Xingchun; Wang, Qiang; Chen, Guozhong; Xu, Hao; Xu, Lixian

    2015-11-01

    We have reported electroacupuncture (EA) pretreatment induced the tolerance against focal cerebral ischemia through activation of canonical Notch pathway. However, the underlying mechanisms have not been fully understood. Evidences suggest that up-regulation of hypoxia inducible factor-1α (HIF-1α) contributes to neuroprotection against ischemia which could interact with Notch signaling pathway in this process. Therefore, the current study is to test that up-regulation of HIF-1α associated with Notch pathway contributes to the neuroprotection of EA pretreatment. Sprague-Dawley rats were treated with EA at the acupoint "Baihui (GV 20)" 30 min per day for successive 5 days before MCAO. HIF-1α levels were measured before and after reperfusion. Then, HIF-1α antagonist 2ME2 and γ-secretase inhibitor MW167 were used. Neurologic deficit scores, infarction volumes, neuronal apoptosis, and Bcl2/Bax were evaluated. HIF-1α and Notch1 intracellular domain (NICD) were assessed. The results showed EA pretreatment enhanced the neuronal expression of HIF-1α, reduced infarct volume, improved neurological outcome, inhibited neuronal apoptosis, up-regulated expression of Bcl-2, and down-regulated expression of Bax after reperfusion in the penumbra, while the beneficial effects were attenuated by 2ME2. Furthermore, intraventricular injection with MW167 efficiently suppressed both up-regulation of NICD and HIF-1α after reperfusion. However, administration with 2ME2 could only decrease the expression of HIF-1α in the penumbra. In conclusion, EA pretreatment exerts neuroprotection against ischemic injury through Notch pathway-mediated up-regulation of HIF-1α. PMID:25976178

  17. 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

  18. 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.

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

    PubMed

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

    2016-04-01

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

  20. 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

  1. 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

  2. In Acute Stroke, Can CT Perfusion-Derived Cerebral Blood Volume Maps Substitute for Diffusion-Weighted Imaging in Identifying the Ischemic Core?

    PubMed Central

    Copen, William A.; Morais, Livia T.; Wu, Ona; Schwamm, Lee H.; Schaefer, Pamela W.; González, R. Gilberto; Yoo, Albert J.

    2015-01-01

    Background and Purpose In the treatment of patients with suspected acute ischemic stroke, increasing evidence suggests the importance of measuring the volume of the irreversibly injured “ischemic core.” The gold standard method for doing this in the clinical setting is diffusion-weighted magnetic resonance imaging (DWI), but many authors suggest that maps of regional cerebral blood volume (CBV) derived from computed tomography perfusion imaging (CTP) can substitute for DWI. We sought to determine whether DWI and CTP-derived CBV maps are equivalent in measuring core volume. Methods 58 patients with suspected stroke underwent CTP and DWI within 6 hours of symptom onset. We measured low-CBV lesion volumes using three methods: “objective absolute,” i.e. the volume of tissue with CBV below each of six published absolute thresholds (0.9–2.5 mL/100 g), “objective relative,” whose six thresholds (51%-60%) were fractions of mean contralateral CBV, and “subjective,” in which two radiologists (R1, R2) outlined lesions subjectively. We assessed the sensitivity and specificity of each method, threshold, and radiologist in detecting infarction, and the degree to which each over- or underestimated the DWI core volume. Additionally, in the subset of 32 patients for whom follow-up CT or MRI was available, we measured the proportion of CBV- or DWI-defined core lesions that exceeded the follow-up infarct volume, and the maximum amount by which this occurred. Results DWI was positive in 72% (42/58) of patients. CBV maps’ sensitivity/specificity in identifying DWI-positive patients were 100%/0% for both objective methods with all thresholds, 43%/94% for R1, and 83%/44% for R2. Mean core overestimation was 156–699 mL for objective absolute thresholds, and 127–200 mL for objective relative thresholds. For R1 and R2, respectively, mean±SD subjective overestimation were -11±26 mL and -11±23 mL, but subjective volumes differed from DWI volumes by up to 117 and 124

  3. Age-dependent acceleration of ischemic injury in endothelial nitric oxide synthase-deficient mice: potential role of impaired VEGF receptor 2 expression.

    PubMed

    Qian, Hu Sheng; de Resende, Micheline Monterio; Beausejour, Christian; Huw, Ling-Yuh; Liu, Perry; Rubanyi, Gabor M; Kauser, Katalin

    2006-04-01

    Morbidity and mortality of peripheral arterial occlusive disease significantly increases with age, often exhibiting more severe disease pathology and decreased treatment effectiveness. Therapeutic angiogenesis with angiogenic growth factors may represent a valuable treatment option for the severely ill, older adult patient population. Aging is considered an independent cardiovascular risk factor, but pathomechanistically it is not well understood. Diminished endothelial nitric oxide (EDNO) production has been considered as a major contributor to the aging process. To investigate the effect of age on postischemic revascularization independent of changes in EDNO, we used endothelial nitric oxide synthase-deficient (ecNOS-KO) mice. We found an age-dependent acceleration in ischemic injury following unilateral femoral artery ligation in these animals compared to C57BL/J6 mice. Postischemic revascularization, quantified by measuring von Willebrand factor expression, was significantly impaired, suggesting that factors other than progressive EDNO deterioration are also involved in the age-dependent severe disease phenotype. Ischemia led to an increase in the expression of vascular endothelial growth factor receptor-2, KDR, in younger ecNOS-KO; however, this increase in KDR expression was absent in the older animals. Lack of increased KDR expression may provide a mechanistic explanation for the severe ischemic injury and perhaps can be used as a clinical marker to identify severe, vascular endothelial growth factor refractory patient population. PMID:16680073

  4. 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 ...

  5. 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

  6. 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

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

    PubMed Central

    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

  8. 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

  9. Pre-ischemic treadmill training for prevention of ischemic brain injury via regulation of glutamate and its transporter GLT-1.

    PubMed

    Yang, Xiaojiao; He, Zhijie; Zhang, Qi; Wu, Yi; Hu, Yongshan; Wang, Xiaolou; Li, Mingfen; Wu, Zhiyuan; Guo, Zhenzhen; Guo, Jingchun; Jia, Jie

    2012-01-01

    Pre-ischemic treadmill training exerts cerebral protection in the prevention of cerebral ischemia by alleviating neurotoxicity induced by excessive glutamate release following ischemic stroke. However, the underlying mechanism of this process remains unclear. Cerebral ischemia-reperfusion injury was observed in a rat model after 2 weeks of pre-ischemic treadmill training. Cerebrospinal fluid was collected using the microdialysis sampling method, and the concentration of glutamate was determined every 40 min from the beginning of ischemia to 4 h after reperfusion with high-performance liquid chromatography (HPLC)-fluorescence detection. At 3, 12, 24, and 48 h after ischemia, the expression of the glutamate transporter-1 (GLT-1) protein in brain tissues was determined by Western blot respectively. The effect of pre-ischemic treadmill training on glutamate concentration and GLT-1 expression after cerebral ischemia in rats along with changes in neurobehavioral score and cerebral infarct volume after 24 h ischemia yields critical information necessary to understand the protection mechanism exhibited by pre-ischemic treadmill training. The results demonstrated that pre-ischemic treadmill training up-regulates GLT-1 expression, decreases extracellular glutamate concentration, reduces cerebral infarct volume, and improves neurobehavioral score. Pre-ischemic treadmill training is likely to induce neuroprotection after cerebral ischemia by regulating GLT-1 expression, which results in re-uptake of excessive glutamate. PMID:22949807

  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. Chronic lead treatment accelerates photochemically induced platelet aggregation in cerebral microvessels of mice, in vivo

    SciTech Connect

    Al Dhaheri, A.H.; El-Sabban, F.; Fahim, M.A.

    1995-04-01

    Effects of two chronic treatment levels with lead on platelet aggregation in cerebral (pial) microcirculation of the mouse were investigated. Exposure to lead was made by subcutaneous injections for 7 days of lead acetate dissolved in 5% glucose solution, vehicle. Two doses of lead were used, a low dose of 0.1 mg/kg and a high dose of 1.0 mg/kg. Adult male mice were divided into three groups, 10 each; one group was injected with vehicle (control), another was injected with the low dose, and the third was injected with the high dose. Additional mice were used for the determination of hematological parameters and for the lead level in serum of the three groups. On the eighth day, platelet aggregation in pial microvessels of these groups of mice was carried out in vivo. Animals were anesthetized (urethane, 1-2 mg/g, ip), the trachea was intubated, and a craniotomy was performed. Platelet aggregation in pial microvessels was induced photochemically, by activation of circulating sodium fluorescein (0.1 mg/25 g, iv) with an intense mercury light. The time required for the first platelet aggregate to appear in pial arterioles was significantly shorter in the lead-treated mice than in control. This effect was in a dose-dependent manner; 113 {+-} 44 sec for low dose and 71 {+-} 18 sec for high dose vs 155 {+-} 25 sec for control, P < 0.02 and P < 0.001, respectively. Between the two lead-treated groups, the high dose significantly (P < 0.05) shortened the time to first aggregate. These data evidenced an increased susceptibility to cerebrovascular thrombosis as a result of exposure to lead. 26 refs., 4 figs., 2 tabs.

  13. 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%).

  14. Ischemic Conditioning: Implications for Emergency Medicine.

    PubMed

    Frumkin, Kenneth; Bloom, Adam S

    2016-09-01

    Ischemic conditioning refers to the ability of brief episodes of controlled hypoperfusion around the time of an acute ischemic event to protect the target organ from reperfusion injury. A considerable body of literature suggests that interventions as simple and safe as repetitively inflating a blood pressure cuff could reduce the size and long-term morbidity of myocardial and cerebral infarction. This review introduces and summarizes the body of evidence contributing to these impressions. PMID:26973174

  15. Therapeutic hypothermia for acute ischemic stroke.

    PubMed

    Froehler, Michael T; Ovbiagele, Bruce

    2010-04-01

    Intravenous recombinant tissue plasminogen activator remains the only US FDA-approved treatment for acute ischemic stroke. However, the very limited time window for its administration restricts its usefulness. Furthermore, it is becoming increasingly clear that, given the numerous pathways via which cerebral ischemia causes cell death, the capacity to inhibit multiple mechanisms simultaneously may provide additive or synergistic beneficial clinical effects for stroke patients. Although no clinical trials have yet investigated the efficacy of therapeutic hypothermia in focal cerebral ischemia, its pleiotropic neuroprotective actions, positive results in preclinical studies, as well as proven enhancement of neurologic outcomes in survivors of cardiac arrest and newborns with hypoxic-ischemic encephalopathy, make this neuroprotective strategy highly promising. This review presents an overview of the potential role of hypothermia in the treatment of acute ischemic stroke and discusses ischemic cell death pathophysiology, neuroprotective mechanisms of hypothermia, methodologies employed for the induction of hypothermia, results from animal models of cerebral ischemia, and finally, currently available clinical trial data. Two valuable lessons learned thus far are that first, rapid induction of hypothermia is key and is best accomplished with a combination of ice-cold saline infusion and the use of endovascular cooling devices, and second, that shivering can be overcome with aggressive anti-shivering protocols including meperidine, buspirone and surface warming. We await the results of clinical trials to determine the utility of therapeutic hypothermia in acute ischemic stroke. If proven efficacious, hypothermia would be a welcome complement to established reperfusion therapies for ischemic stroke patients. PMID:20397832

  16. SEA0400, a novel and selective inhibitor of the Na+-Ca2+ exchanger, attenuates reperfusion injury in the in vitro and in vivo cerebral ischemic models.

    PubMed

    Matsuda, T; Arakawa, N; Takuma, K; Kishida, Y; Kawasaki, Y; Sakaue, M; Takahashi, K; Takahashi, T; Suzuki, T; Ota, T; Hamano-Takahashi, A; Onishi, M; Tanaka, Y; Kameo, K; Baba, A

    2001-07-01

    The effect of the newly synthesized compound 2-[4-[(2,5-difluorophenyl)methoxy]phenoxy]-5-ethoxyaniline (SEA0400) on the Na+-Ca2+ exchanger (NCX) was investigated and compared against that of 2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea (KB-R7943). In addition, the effects of SEA0400 on reperfusion injury in vitro and in vivo were examined. SEA0400 was extremely more potent than KB-R7943 in inhibiting Na+-dependent Ca2+ uptake in cultured neurons, astrocytes, and microglia: IC50s of SEA0400 and KB-R7943 were 5 to 33 nM and 2 to 4 microM, respectively. SEA0400 at the concentration range that inhibited NCX exhibited negligible affinities for the Ca2+ channels, Na+ channels, K+ channels, norepinephrine transporter, and 14 receptors, and did not affect the activities of the Na+/H+ exchanger, Na+,K+-ATPase, Ca2+-ATPase, and five enzymes. SEA0400, unlike KB-R7943, did not inhibit the store-operated Ca2+ entry in cultured astrocytes. SEA0400 attenuated dose- dependently paradoxical Ca2+ challenge-induced production of reactive oxygen species, DNA ladder formation, and nuclear condensation in cultured astrocytes, whereas it did not affect thapsigargin-induced cell injury. Furthermore, administration of SEA0400 reduced infarct volumes after a transient middle cerebral artery occlusion in rat cerebral cortex and striatum. These results indicate that SEA0400 is the most potent and selective inhibitor of NCX, and suggest that the compound may exert protective effects on postischemic brain damage. PMID:11408549

  17. Notoginsenoside R1 Protects against Neonatal Cerebral Hypoxic-Ischemic Injury through Estrogen Receptor-Dependent Activation of Endoplasmic Reticulum Stress Pathways.

    PubMed

    Wang, Yan; Tu, Liu; Li, Yingbo; Chen, Di; Wang, Shali

    2016-06-01

    Notoginsenoside R1 (NGR1) is a phytoestrogen that is isolated from Panax notoginseng It is used in China to treat many diseases, including hypoxic-ischemic encephalopathy (HIE), and it has been shown to target estrogen receptors. Endoplasmic reticulum (ER) stress plays an important role in the development of cell apoptosis during ischemia, and ER stress is known to be regulated by estrogen; however, the neuroprotective mechanisms of NGR1 in neonatal HIE is unclear. In this study, oxygen-glucose deprivation/reoxygenation (OGD/R) in primary cortical neurons and unilateral ligation of the common carotid artery (CCL), followed by exposure to a hypoxic environment in 7-day-old postnatal Sprague-Dawley rats were used to mimic HIE episodes. Potential neuroprotective effects of NGR1 against neonatal HIE and its mechanisms were examined. After HIE conditions in vitro and in vivo, we administered NGR1 or the estrogen receptor inhibitor ICI-182780 and measured cell apoptosis, brain injury by MTT assay, TTC stain, and so forth. Expression of estrogen receptors α (ERα) and β (ERβ), ER stress-associated proteins was detected by Western blot upon stimulation with HIE, NGR1, or ICI-182780. Results showed that after HIE, ER chaperone GRP78 was activated, ER stress-associated proapoptotic proteins (CHOP, PERK, ERO1-α, and IRE1α) were increased, caspase-12 was increased, and BCL-2 was decreased. The ER stress response and neuronal apoptosis were attenuated by NGR1 treatment. However, neuroprotective properties of NGR1 against HIE-induced apoptosis and ER stress were attenuated by ICI-182780. These results suggest that NGR1 may be an effective treatment of HIE by reducing ER stress-induced neuronal apoptosis and brain injury via estrogen receptors. PMID:26892460

  18. Cerebrovascular ischemic events in wind instrument players.

    PubMed

    Evers, S; Altenmüller, E; Ringelstein, E B

    2000-09-26

    Two cases of ischemic stroke due to carotid artery dissection occurring during wind instrument playing, probably caused by increased intrathoracic and subsequent intrapharyngeal pressure, are presented. A review of the literature revealed three similar patients with other types of cerebrovascular events, such as paradoxical cerebral embolism due to a patent foramen ovale and spinal epidural hematoma during trumpet playing. PMID:10994010

  19. 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

  20. Microglia in ischemic brain injury

    PubMed Central

    Weinstein, Jonathan R; Koerner, Ines P; Möller, Thomas

    2010-01-01

    Microglia are resident CNS immune cells that are active sensors in healthy brain and versatile effectors under pathological conditions. Cerebral ischemia induces a robust neuroinflammatory response that includes marked changes in the gene-expression profile and phenotype of a variety of endogenous CNS cell types (astrocytes, neurons and microglia), as well as an influx of leukocytic cells (neutrophils, macrophages and T-cells) from the periphery. Many molecules and conditions can trigger a transformation of surveying microglia to microglia of an alerted or reactive state. Here we review recent developments in the literature that relate to microglial activation in the experimental setting of in vitro and in vivo ischemia. We also present new data from our own laboratory demonstrating the direct effects of in vitro ischemic conditions on the microglial phenotype and genomic profile. In particular, we focus on the role of specific molecular signaling systems, such as hypoxia inducible factor-1 and Toll-like receptor-4, in regulating the microglial response in this setting. We then review histological and novel radiological data that confirm a key role for microglial activation in the setting of ischemic stroke in humans. We also discuss recent progress in the pharmacologic and molecular targeting of microglia in acute ischemic stroke. Finally, we explore how recent studies on ischemic preconditioning have increased interest in pre-emptively targeting microglial activation in order to reduce stroke severity. PMID:20401171

  1. 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

  2. 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. PMID:26254165

  3. Flow Augmentation in Acute Ischemic Stroke.

    PubMed

    Yadollahikhales, Golnaz; Borhani-Haghighi, Afshin; Torabi-Nami, Mohammad; Edgell, Randall; Cruz-Flores, Salvador

    2016-01-01

    There is an urgent need for additional therapeutic options for acute ischemic stroke considering the major pitfalls of the options available. Herein, we briefly review the role of cerebral blood flow, collaterals, vasoreactivity, and reperfusion injury in acute ischemic stroke. Then, we reviewed pharmacological and interventional measures such as volume expansion and induced hypertension, intra-aortic balloon counterpulsation, partial aortic occlusion, extracranial-intracranial carotid bypass surgery, sphenopalatine ganglion stimulation, and transcranial laser therapy with regard to their effects on flow augmentation and neuroprotection. PMID:25475112

  4. [Development of Researches on Scalp Acupuncture for Ischemic Stroke].

    PubMed

    Tian, Liang; Wang, Jin-hai; Sun, Run-jie; Zhang, Xing-hua; Yuan, Bo; Du, Xiao-zheng

    2016-02-01

    Ischemic stroke is one of the commonly met diseases in clinical practice nowadays. Acupuncture therapy is widly used in the treatment of sequela of ischemic stroke in China and its mechanisms have been extensively studied in recen years. In the present paper, the authors focus on the development of studies on the mechanism of scalp acupuncture therapy in the treatment of ischemic stroke. Results indicate that scalp acupuncture intervention can 1) improve cerebral blood circulation to promote regional energy metabolism, 2) up-regulate expression of glial cell-line derived neurotrophic factor (GDNF), etc., possibly promoting proliferation and differentiation of neural stem cells in the focal cerebral cortex and hippocampus, 3) reduce contents of excitatory amino acid and increase level of gamma-aminobutyric acid (GABA) to lower neurogenic toxicity, and relieve cerebral injury, 4) ease cerebral vascular immunoinflammatory reactions, 5) regulate blood lipid metabolism to resist cerebral free radical damage, and 6) inhibit cerebral cortical apoptosis. However, these results only revealed very limited intrinsic mechanisms of scalp acupuncture in improving ischemic stroke. Further studies using comprehensive techniques of multi-disciplines as molecular biology, electrophysiology, etc. are definitely needed. PMID:27141629

  5. Ischemic preconditioning protects against ischemic brain injury.

    PubMed

    Ma, Xiao-Meng; Liu, Mei; Liu, Ying-Ying; Ma, Li-Li; Jiang, Ying; Chen, Xiao-Hong

    2016-05-01

    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

  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. 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 ...

  8. 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

  9. 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

  10. Pre-ischemic exercise alleviates oxidative damage following ischemic stroke in rats.

    PubMed

    Feng, Rui; Zhang, Min; Wang, Xiao; Li, Wen-Bin; Ren, Shi-Qing; Zhang, Feng

    2014-10-01

    Physical exercise has been proved to be neuroprotective in clinical trials and animal experiments. However, the exact mechanism underlying this neuroprotective effect remains unclear. The aim of the present study was to explore whether pre-ischemic treadmill training could act as a form of ischemic preconditioning in a rat following ischemic stroke by reducing oxidative damage. Fifty-four rats were randomly divided into three groups (n=18 per group): Sham surgery, middle cerebral artery occlusion (MCAO) without exercise and MCAO with exercise. Subsequent to treadmill training, ischemic stroke was induced by occluding the MCA for 1.5 h, followed by reperfusion. Six rats in each group were evaluated for neurological deficits and then sacrificed by decapitation to calculate the infarct volume. The remaining rats in each group were sacrificed to detect the level of superoxide dismutase (SOD) activity (n=6) and malondialdehyde (MDA) concentration (n=6). The results indicated that pre-ischemic exercise training reduced brain infarct volume and neurological deficits, increased SOD activity and decreased the concentration of MDA following ischemic stroke. In conclusion, treadmill exercise training prior to MCAO/reperfusion increased the antioxidant ability and decreased the oxidative damage in the brain subsequent to ischemic stroke. PMID:25187848

  11. Progressive "vascular" corticobasal syndrome due to bilateral ischemic hemispheric lesions.

    PubMed

    Kim, Young-Do; Kim, Joong-Seok; Lee, Eek-Sung; Yang, Dong-Won; Lee, Kwang-Soo; Kim, Yeong-In

    2009-01-01

    We report a patient that presented with the corticobasal syndrome (CBS), including progressive dementia, asymmetric parkinsonism associated with constructional and ideomotor apraxia, action myoclonus and focal hand dystonia. Magnetic resonance imaging of the brain revealed extensive ischemic lesions in both fronto-temporo-parieto-occipital lobes and steno-occlusion of the middle cerebral arteries, bilaterally. This case illustrates that extensive cortical vascular-ischemic lesions may present with symptoms mimicking the corticobasal syndrome. PMID:19755778

  12. Ketogenic Diet Provides Neuroprotective Effects against Ischemic Stroke Neuronal Damages

    PubMed Central

    Shaafi, Sheyda; Mahmoudi, Javad; Pashapour, Ali; Farhoudi, Mehdi; Sadigh-eteghad, Saeed; Akbari, Hossein

    2014-01-01

    Ischemic stroke is a leading cause of death and disability in the world. Many mechanisms contribute in cell death in ischemic stroke. Ketogenic diet which has been successfully used in the drug-resistant epilepsy has been shown to be effective in many other neurologic disorders. The mechanisms underlying of its effects are not well studied, but it seems that its neuroprotective ability is mediated at least through alleviation of excitotoxicity, oxidative stress and apoptosis events. On the basis of these mechanisms, it is postulated that ketogenic diet could provide benefits to treatment of cerebral ischemic injuries. PMID:25671178

  13. Ischemic Strokes (Clots)

    MedlinePlus

    ... Quiz 5 Things to Know About Stroke Ischemic Strokes (Clots) Updated:Jul 12,2016 Ischemic stroke accounts ... strokes. Read more about silent strokes . TIA and Stroke: Medical Emergencies When someone has shown symptoms of ...

  14. Resveratrol and ischemic preconditioning in the brain.

    PubMed

    Raval, Ami P; Lin, Hung Wen; Dave, Kunjan R; Defazio, R Anthony; Della Morte, David; Kim, Eun Joo; Perez-Pinzon, Miguel A

    2008-01-01

    Cardiovascular pathologies in the French are not prevalent despite high dietary saturated fat consumption. This is commonly referred to as the "French Paradox" attributing its anti-lipidemic effects to moderate consumption of red wine. Resveratrol, a phytoalexin found in red wine, is currently the focus of intense research both in the cardiovascular system and the brain. Current research suggests resveratrol may enhance prognosis of neurological disorders such as, Parkinson's, Huntington's, Alzheimer's diseases and stroke. The beneficial effects of resveratrol include: antioxidation, free radical scavenger, and modulation of neuronal energy homeostasis and glutamatergic receptors/ion channels. Resveratrol directly increases sirtuin 1 (SIRT1) activity, a NAD(+) (oxidized form of nicotinamide adenine dinucleotide)-dependent histone deacetylase related to increased lifespan in various species similar to calorie restriction. We recently demonstrated that brief resveratrol pretreatment conferred neuroprotection against cerebral ischemia via SIRT1 activation. This neuroprotective effect produced by resveratrol was similar to ischemic preconditioning-induced neuroprotection, which protects against lethal ischemic insults in the brain and other organ systems. Inhibition of SIRT1 abolished ischemic preconditioning-induced neuroprotection in CA1 region of the hippocampus. Since resveratrol and ischemic preconditioning-induced neuroprotection require activation of SIRT1, this common signaling pathway may provide targeted therapeutic treatment modalities as it relates to stroke and other brain pathologies. In this review, we will examine common signaling pathways, cellular targets of resveratrol, and ischemic preconditioning-induced neuroprotection as it relates to the brain. PMID:18537630

  15. [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

  16. Doppler-derived acceleration rate of right ventricular early filling as a measurement of right atrial pressure in chronic heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

    PubMed

    Scapellato, F; Eleuteri, E; Temporelli, P L; Imparato, A; Corrà, U; Giannuzzi, P

    1998-02-15

    This study demonstrates that a Doppler-derived tricuspid flow velocity pattern provides an accurate, feasible, and noninvasive method of estimating and monitoring mean right atrial pressure in patients with heart failure due to left ventricular systolic dysfunction, and who are both in sinus rhythm and atrial fibrillation. In particular, the acceleration rate of early right ventricular filling is a powerful and independent predictor of mean right atrial pressure. PMID:9485149

  17. 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

  18. Vasospasm in Cerebral Inflammation

    PubMed Central

    Eisenhut, Michael

    2014-01-01

    All forms of cerebral inflammation as found in bacterial meningitis, cerebral malaria, brain injury, and subarachnoid haemorrhage have been associated with vasospasm of cerebral arteries and arterioles. Vasospasm has been associated with permanent neurological deficits and death in subarachnoid haemorrhage and bacterial meningitis. Increased levels of interleukin-1 may be involved in vasospasm through calcium dependent and independent activation of the myosin light chain kinase and release of the vasoconstrictor endothelin-1. Another key factor in the pathogenesis of cerebral arterial vasospasm may be the reduced bioavailability of the vasodilator nitric oxide. Therapeutic trials in vasospasm related to inflammation in subarachnoid haemorrhage in humans showed a reduction of vasospasm through calcium antagonists, endothelin receptor antagonists, statins, and plasminogen activators. Combination of therapeutic modalities addressing calcium dependent and independent vasospasm, the underlying inflammation, and depletion of nitric oxide simultaneously merit further study in all conditions with cerebral inflammation in double blind randomised placebo controlled trials. Auxiliary treatment with these agents may be able to reduce ischemic brain injury associated with neurological deficits and increased mortality. PMID:25610703

  19. 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 ...

  20. 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

  1. Clinical and morphological correlations in acute ischemic stroke.

    PubMed

    Slujitoru, Anca Stefania; Enache, Andreea Lorena; Pintea, Irina Lavinia; Rolea, Elisabeta; Stocheci, Cristina Mariana; Pop, O T; Predescu, Anca

    2012-01-01

    We studied the clinical and histopathological changes in twenty-seven cases of acute ischemic stroke, aged between 65 and 75 years. All deaths occurred within 30 days after stroke. The aim of our study was to establish the clinical and histological correlations in acute ischemic stroke to detect prognostic factors. Brain lesions after acute stroke were observed in all regions. Our study describes the heterogeneity of brain injury after acute ischemic stroke with the participation of all brain components and the chronology in which these lesions develop and evolve. By histological and immunohistochemical studies, we identified neuronal, glial and vascular damage. The neurons had undergone in the area of lesion a process of necrosis, ballooning or condensation process. In the ischemic penumbra, we observed the presence of red neurons. Vascular lesions were represented by the discontinuity of capillaries, always associated with a marked perivascular edema. The following clinical and morphological correlations were established: liquefactive necrosis, astrocyte gliosis, phagocytosis phenomena are the more intense the later the death of the patient; apoptosis phenomena are the more intense the faster the death of the patient; the entire cerebral microcirculation presented microscopic modifications following the ischemic strokes, regardless of the time since the lesion occurred and the histological examination was made; the major neurological complications of the ischemic stroke - the hemorrhagic transformation phenomena, cerebral edema, were microscopically objectified, regardless of the time since the lesion occurred and the histological examination was made. PMID:23303014

  2. Oligodendrogenesis after cerebral ischemia

    PubMed Central

    Zhang, Ruilan; Chopp, Michael; Zhang, Zheng Gang

    2013-01-01

    Neural stem cells in the subventricular zone (SVZ) of the lateral ventricle of adult rodent brain generate oligodendrocyte progenitor cells (OPCs) that disperse throughout the corpus callosum and striatum where some of OPCs differentiate into mature oligodendrocytes. Studies in animal models of stroke demonstrate that cerebral ischemia induces oligodendrogenesis during brain repair processes. This article will review evidence of stroke-induced proliferation and differentiation of OPCs that are either resident in white matter or are derived from SVZ neural progenitor cells and of therapies that amplify endogenous oligodendrogenesis in ischemic brain. PMID:24194700

  3. 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

  4. 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

  5. A more consistent intraluminal rhesus monkey model of ischemic stroke

    PubMed Central

    Zhao, Bo; Shang, Guowei; Chen, Jian; Geng, Xiaokun; Ye, Xin; Xu, Guoxun; Wang, Ju; Zheng, Jiasheng; Li, Hongjun; Akbary, Fauzia; Li, Shengli; Lu, Jing; Ling, Feng; Ji, Xunming

    2014-01-01

    Endovascular surgery is advantageous in experimentally induced ischemic stroke because it causes fewer cranial traumatic lesions than invasive surgery and can closely mimic the pathophysiology in stroke patients. However, the outcomes are highly variable, which limits the accuracy of evaluations of ischemic stroke studies. In this study, eight healthy adult rhesus monkeys were randomized into two groups with four monkeys in each group: middle cerebral artery occlusion at origin segment (M1) and middle cerebral artery occlusion at M2 segment. The blood flow in the middle cerebral artery was blocked completely for 2 hours using the endovascular microcoil placement technique (1 mm × 10 cm) (undetachable), to establish a model of cerebral ischemia. The microcoil was withdrawn and the middle cerebral artery blood flow was restored. A reversible middle cerebral artery occlusion model was identified by hematoxylin-eosin staining, digital subtraction angiography, magnetic resonance angiography, magnetic resonance imaging, and neurological evaluation. The results showed that the middle cerebral artery occlusion model was successfully established in eight adult healthy rhesus monkeys, and ischemic lesions were apparent in the brain tissue of rhesus monkeys at 24 hours after occlusion. The rhesus monkeys had symptoms of neurological deficits. Compared with the M1 occlusion group, the M2 occlusion group had lower infarction volume and higher neurological scores. These experimental findings indicate that reversible middle cerebral artery occlusion can be produced with the endovascular microcoil technique in rhesus monkeys. The M2 occluded model had less infarction and less neurological impairment, which offers the potential for application in the field of brain injury research. PMID:25657726

  6. Ischemic Stroke during Pregnancy and Puerperium

    PubMed Central

    Del Zotto, Elisabetta; Giossi, Alessia; Volonghi, Irene; Costa, Paolo; Padovani, Alessandro; Pezzini, Alessandro

    2011-01-01

    Ischemic stroke during pregnancy and puerperium represents a rare occurrence but it could be a serious and stressful event for mothers, infants, and also families. Whenever it does occur, many concerns arise about the safety of the mother and the fetus in relation to common diagnostic tests and therapies leading to a more conservative approach. The physiological adaptations in the cardiovascular system and in the coagulability that accompany the pregnant state, which are more significant around delivery and in the postpartum period, likely contribute to increasing the risk of an ischemic stroke. Most of the causes of an ischemic stroke in the young may also occur in pregnant patients. Despite this, there are specific conditions related to pregnancy which may be considered when assessing this particular group of patients such as pre-eclampsia-eclampsia, choriocarcinoma, peripartum cardiomiopathy, amniotic fluid embolization, and postpartum cerebral angiopathy. This article will consider several questions related to pregnancy-associated ischemic stroke, dwelling on epidemiological and specific etiological aspects, diagnostic issue concerning the use of neuroimaging, and the related potential risks to the embryo and fetus. Therapeutic issues surrounding the use of anticoagulant and antiplatelets agents will be discussed along with the few available reports regarding the use of thrombolytic therapy during pregnancy. PMID:21331336

  7. [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

  8. Hypoxic Ischemic Encephalopathy: Pathophysiology and Experimental Treatments

    PubMed Central

    Allen, Kimberly A.; Brandon, Debra H.

    2011-01-01

    Hypoxic ischemic encephalopathy (HIE) is a serious birth complication affecting full term infants: 40–60% of affected infants die by 2 years of age or have severe disabilities. The majority of the underlying pathologic events of HIE are a result of impaired cerebral blood flow and oxygen delivery to the brain with resulting primary and secondary energy failure. In the past, treatment options were limited to supportive medical therapy. Currently, several experimental treatments are being explored in neonates and animal models to ameliorate the effects of secondary energy failure. This review discusses the underlying pathophysiologic effects of a hypoxic-ischemic event and experimental treatment modalities being explored to manage infants with HIE. Further research is needed to better understand if the long-term impact of the experimental treatments and whether the combinations of experimental treatments can improve outcomes in infants with HIE. PMID:21927583

  9. Evolving Treatments for Acute Ischemic Stroke.

    PubMed

    Zerna, Charlotte; Hegedus, Janka; Hill, Michael D

    2016-04-29

    The purpose of this article is to review advances in stroke treatment in the hyperacute period. With recent evolutions of technology in the fields of imaging, thrombectomy devices, and emergency room workflow management, as well as improvement in statistical methods and study design, there have been ground breaking changes in the treatment of acute ischemic stroke. We describe how stroke presents as a clinical syndrome and how imaging as the most important biomarker will help differentiate between stroke subtypes and treatment eligibility. The evolution of hyperacute treatment has led to the current standard of care: intravenous thrombolysis with tissue-type plasminogen activator and endovascular treatment for proximal vessel occlusion in the anterior cerebral circulation. All patients with acute ischemic stroke are in need of hyperacute secondary prevention because the risk of recurrence is highest closest to the index event. The dominant themes of modern stroke care are the use of neurovascular imaging and speed of diagnosis and treatment. PMID:27126651

  10. 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

  11. Sustained linear acceleration

    NASA Technical Reports Server (NTRS)

    Fraser, T. M.

    1973-01-01

    The subjective effects of sustained acceleration are discussed, including positive, negative, forward, backward, and lateral acceleration effects. Physiological effects, such as retinal and visual response, unconsciousness and cerebral function, pulmonary response, and renal output, are studied. Human tolerance and performance under sustained acceleration are ascertained.

  12. Effects of Semelil (ANGIPARS™) on focal cerebral ischemia in male rats

    PubMed Central

    Asadi-Shekaari, M; Eftekhar Vaghefi, H; Talakoub, A; Khorram Khorshid, HR

    2010-01-01

    Background and the purpose of the study Cerebral ischemia is one of the main causes of long term disability and death in aged populations. Many herbal drugs and extracts have been used for the treatment of cerebral ischemia induced insults. This study was designed to investigate the protective effect of Semelil (ANGIPARS™), a new herbal drug, on focal cerebral ischemia in male rats. Material and methods Male rats were divided into five groups: sham-operated, ischemic animals treated with distilled water as vehicle, ischemic animals treated with 1, 10 and 100 mg/kg of Semilil respectively. Middle cerebral artery occlusion (MCAO) model was used in NMRI rats and neuronal injury analyzed in hippocampal CA1 sector after 48 hrs of Middle Cerebral Artery (MCAO). Results Results of this study showed that treatment with semelil attenuated ischemic damages and has positive effects on focal cerebral ischemia. PMID:22615626

  13. Factoring in Factor VIII With Acute Ischemic Stroke

    PubMed Central

    Siegler, James E.; Samai, Alyana; Albright, Karen C.; Boehme, Amelia K.; Martin-Schild, Sheryl

    2016-01-01

    There is growing research interest into the etiologies of cryptogenic stroke, in particular as it relates to hypercoagulable states. An elevation in serum levels of the procoagulant factor VIII is recognized as one such culprit of occult cerebral infarctions. It is the objective of the present review to summarize the molecular role of factor VIII in thrombogenesis and its clinical use in the diagnosis and prognosis of acute ischemic stroke. We also discuss the utility of screening for serum factor VIII levels among patients at risk for, or those who have experienced, ischemic stroke. PMID:25669199

  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. Cerebral palsy

    MedlinePlus

    Cerebral palsy is a group of disorders that can involve brain and nervous system functions, such as movement, ... and thinking. There are several different types of cerebral palsy, including spastic, dyskinetic, ataxic, hypotonic, and mixed.

  18. 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

  19. Brain protection therapy in acute cerebral infarction.

    PubMed

    Katsura, Ken-ichiro; Suda, Satoshi; Abe, Arata; Kanamaru, Takuya; Toda, Yusuke; Katayama, Yasuo

    2012-01-01

    Many drugs for cerebral infarction that were shown to be effective in animal experiments have shown negative results in human clinical trials. For this reason, a completely new approach is needed to develop brain protection therapies against cerebral infarction. Brain protection therapies can be categorized into 3 types: 1) lengthening the therapeutic time window for thrombolytic therapy, 2) reducing the side effects of thrombolytic therapy, and 3) brain protection drug therapy for patients with contraindications for thrombolytic therapy (including combination therapy). Here, we show our recent results of brain protection therapy. First, combination therapy with 2 effective drugs was tried, and time-lag administration was performed. Combination therapy was effective and lengthened the therapeutic time window. Next, a completely new approach to improve cerebral ischemic damage, namely, H2 gas inhalation therapy, was tried. This therapy was also effective, even in the ischemic core. PMID:22687352

  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. Lubiprostone induced ischemic colitis.

    PubMed

    Sherid, Muhammed; Sifuentes, Humberto; Samo, Salih; Deepak, Parakkal; Sridhar, Subbaramiah

    2013-01-14

    Ischemic colitis accounts for 6%-18% of the causes of acute lower gastrointestinal bleeding. It is often multifactorial and more commonly encountered in the elderly. Several medications have been implicated in the development of colonic ischemia. We report a case of a 54-year old woman who presented with a two-hour history of nausea, vomiting, abdominal pain, and bloody stool. The patient had recently used lubiprostone with close temporal relationship between the increase in the dose and her symptoms of rectal bleeding. The radiologic, colonoscopic and histopathologic findings were all consistent with ischemic colitis. Her condition improved without any serious complications after the cessation of lubiprostone. This is the first reported case of ischemic colitis with a clear relationship with lubiprostone (Naranjo score of 10). Clinical vigilance for ischemic colitis is recommended for patients receiving lubiprostone who are presenting with abdominal pain and rectal bleeding. PMID:23345954

  3. Inflammatory response and neuronal necrosis in rats with cerebral ischemia

    PubMed Central

    Wu, Lingfeng; Zhang, Kunnan; Hu, Guozhu; Yan, Haiyu; Xie, Chen; Wu, Xiaomu

    2014-01-01

    In the middle cerebral artery occlusion model of ischemic injury, inflammation primarily occurs in the infarct and peripheral zones. In the ischemic zone, neurons undergo necrosis and apoptosis, and a large number of reactive microglia are present. In the present study, we investigated the pathological changes in a rat model of middle cerebral artery occlusion. Neuronal necrosis appeared 12 hours after middle cerebral artery occlusion, and the peak of neuronal apoptosis appeared 4 to 6 days after middle cerebral artery occlusion. Inflammatory cytokines and microglia play a role in damage and repair after middle cerebral artery occlusion. Serum intercellular cell adhesion molecule-1 levels were positively correlated with the permeability of the blood-brain barrier. These findings indicate that intercellular cell adhesion molecule-1 may be involved in blood-brain barrier injury, microglial activation, and neuronal apoptosis. Inhibiting blood-brain barrier leakage may alleviate neuronal injury following ischemia. PMID:25422636

  4. [Pathology and strategies for the treatment of ischemic brain injury].

    PubMed

    Takagi, Norio

    2009-10-01

    Cerebral ischemia, a pathological condition in which brain tissue experiences a shortage or lack of glucose and oxygen, provokes an irreversible neurodegenerative disorder that may lead clinically to a progressive dementia and global cognitive deterioration. Accumulating evidence indicates many biochemical cascades that lead ultimately to ischemia-induced cell death. However, the cellular and molecular aspects of cerebral ischemia are not yet fully understood. Since the pattern of pathophysiological alterations is not the same for all cells in the ischemic brain, a good understanding of the cellular and molecular alterations induced by cerebral ischemia is needed to develop strategies for the treatment of stroke. This review summarizes recent advances concerning the pathophysiological alterations caused by cerebral ischemia, focusing on the modification of properties of glutamate receptors, which modification may be linked to the development of cerebral infarction. Furthermore, the effects of hepatocyte growth factor on learning dysfunction and cerebral vessel injury after cerebral ischemia are also summarized. Finally, this review describes a possible ameliorative effect of the injection of exogenous neural progenitor cells on cerebral ischemia-induced learning and memory dysfunction. PMID:19797876

  5. 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

  6. Multiparametric, Longitudinal Optical Coherence Tomography Imaging Reveals Acute Injury and Chronic Recovery in Experimental Ischemic Stroke

    PubMed Central

    Srinivasan, Vivek J.; Mandeville, Emiri T.; Can, Anil; Blasi, Francesco; Climov, Mihail; Daneshmand, Ali; Lee, Jeong Hyun; Yu, Esther; Radhakrishnan, Harsha; Lo, Eng H.; Sakadžić, Sava; Eikermann-Haerter, Katharina; Ayata, Cenk

    2013-01-01

    Progress in experimental stroke and translational medicine could be accelerated by high-resolution in vivo imaging of disease progression in the mouse cortex. Here, we introduce optical microscopic methods that monitor brain injury progression using intrinsic optical scattering properties of cortical tissue. A multi-parametric Optical Coherence Tomography (OCT) platform for longitudinal imaging of ischemic stroke in mice, through thinned-skull, reinforced cranial window surgical preparations, is described. In the acute stages, the spatiotemporal interplay between hemodynamics and cell viability, a key determinant of pathogenesis, was imaged. In acute stroke, microscopic biomarkers for eventual infarction, including capillary non-perfusion, cerebral blood flow deficiency, altered cellular scattering, and impaired autoregulation of cerebral blood flow, were quantified and correlated with histology. Additionally, longitudinal microscopy revealed remodeling and flow recovery after one week of chronic stroke. Intrinsic scattering properties serve as reporters of acute cellular and vascular injury and recovery in experimental stroke. Multi-parametric OCT represents a robust in vivo imaging platform to comprehensively investigate these properties. PMID:23940761

  7. 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

  8. Gene expression profiling in the human middle cerebral artery after cerebral ischemia.

    PubMed

    Vikman, P; Edvinsson, L

    2006-12-01

    We have investigated the gene expression in human middle cerebral artery (MCA) after ischemia. Ischemic stroke affects the perfusion in the affected area and experimental cerebral ischemia results in upregulation of vasopressor receptors in the MCA leading to the ischemic area. We obtained human MCA samples distributing to the ischemic area, 7-10 days post-stroke. The gene expression was examined with real-time polymerase chain reaction (PCR) and microarray, proteins were studied with immunohistochemistry. We investigated genes previously shown to be upregulated in animal models of cerebral ischemia (e.g. ET(A), ET(B), AT1, AT2, and 5-HT(2A/1B/1D)). Their mRNA expression was increased compared with controls, consistent with findings in experimental stroke. Immunohistochemistry showed upregulation of the receptors localized on the smooth muscle cells. The gene expression was profiled with microarray and seven genes chosen for further investigation with real-time PCR; ELK3, LY64, Metallothionin IG, POU3F4, Actin alpha2, RhoA and smoothelin. Six of these were regulated the same way when confirming array expression with real-time PCR. Gene expression studies in the human MCA leading to the ischemic region is similar to that seen after MCA occlusion in rats. We found new genes that support the dynamic changes that occur in the MCA distributing to the ischemic region. PMID:17116215

  9. Azithromycin protects mice against ischemic stroke injury by promoting macrophage transition towards M2 phenotype.

    PubMed

    Amantea, Diana; Certo, Michelangelo; Petrelli, Francesco; Tassorelli, Cristina; Micieli, Giuseppe; Corasaniti, Maria Tiziana; Puccetti, Paolo; Fallarino, Francesca; Bagetta, Giacinto

    2016-01-01

    To develop novel and effective treatments for ischemic stroke, we investigated the neuroprotective effects of the macrolide antibiotic azithromycin in a mouse model system of transient middle cerebral artery occlusion. Intraperitoneal administration of azithromycin significantly reduced blood-brain barrier damage and cerebral infiltration of myeloid cells, including neutrophils and inflammatory macrophages. These effects resulted in a dose-dependent reduction of cerebral ischemic damage, and in a remarkable amelioration of neurological deficits up to 7 days after the insult. Neuroprotection was associated with increased arginase activity in peritoneal exudate cells, which was followed by the detection of Ym1- and arginase I-immunopositive M2 macrophages in the ischemic area at 24-48 h of reperfusion. Pharmacological inhibition of peritoneal arginase activity counteracted azithromycin-induced neuroprotection, pointing to a major role for drug-induced polarization of migratory macrophages towards a protective, non-inflammatory M2 phenotype. PMID:26518285

  10. Diffuse Cerebral Vasculopathy in a HIV-Positive Patient with Recurrent Strokes.

    PubMed

    Kao, Hung-Wen; Chen, Cheng-Yu; Hsueh, Chun-Jen; Lo, Chung-Ping; Juan, Chun-Jung; Chang, Wei-Chou; Huang, Guo-Shu

    2008-02-18

    The causes of ischemic stroke in the young adult are diverse. Human immunodeficiency virus (HIV) infection-related vasculopathy is usually not included in the list of differential diagnoses. HIV-positive patients may present with acute neurologic dysfunction of different causes, among which cerebral infarction is an uncommon one. Herein, we report a HIV-infected young man who suffered from recurrent ischemic strokes with evidence of cerebral vasculopathy on serial magnetic resonance images. PMID:24256749

  11. 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.

  12. Astaxanthin reduces ischemic brain injury in adult rats

    PubMed Central

    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.

    2009-01-01

    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.—Shen, H., Kuo, C.-C., Chou, J., Delvolve, A., Jackson, S. N., Post, J., Woods, A. S., Hoffer, B. J., Wang, Y., Harvey, B. K. Astaxanthin reduces ischemic brain injury in adult rats. PMID:19218497

  13. Pre-ischemic treadmill training alleviates brain damage via GLT-1-mediated signal pathway after ischemic stroke in rats.

    PubMed

    Wang, X; Zhang, M; Yang, S-D; Li, W-B; Ren, S-Q; Zhang, J; Zhang, F

    2014-08-22

    Physical exercise could play a neuroprotective role in both human and animals. However, the involved signal pathways underlying the neuroprotective effect are still not well established. This study was to investigate the possible signal pathways involved in the neuroprotection of pre-ischemic treadmill training after ischemic stroke. Seventy-two SD rats were randomly assigned into three groups (n=24/group): sham surgery group, middle cerebral artery occlusion (MCAO) group and MCAO with exercise group. Following three weeks of treadmill training exercise, ischemic stroke was induced by occluding the middle cerebral artery (MCA) in rat for 2 h, followed by reperfusion. Twenty-four hours after MCAO/reperfusion, 12 rats in each group were evaluated for neurological deficit scores and then sacrificed to measure the infarct volume (n=6) and cerebral edema (n=6). Six rats in each group were sacrificed to measure the expression level of glutamate transporter-1 (GLT-1), protein kinase C-α (PKC-α), Akt, and phosphatidylinositol 3 kinase (PI3K) (n=6). Two hundred and eighty minutes (4.67 h) after occlusion, six rats in each group were decapitated to detect the mRNA expression level of metabotropic glutamate receptor 5 (mGluR5) and N-methyl-D-aspartate receptor subunit type 2B (NR2B) (n=6).The results demonstrated that pre-ischemic treadmill training exercise reduced brain infarct volume, cerebral edema and neurological deficits, also decreased the over expression of PKC-α and increased the expression level of GLT-1, Akt and PI3K after ischemic stroke (p<0.05). The over-expression of mGluR5 and NR2B mRNA was also inhibited by pre-ischemic exercise (p<0.05). In summary, exercise preconditioning ameliorated brain damage after ischemic stroke, which might be involved in two signal pathways: PKC-α-GLT-1-Glutamate and PI3K/Akt-GLT-1-Glutamate. PMID:24907601

  14. Angiogenesis-regulating microRNAs and ischemic stroke

    PubMed Central

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

    2014-01-01

    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 post-stroke 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. PMID:26156265

  15. Effects of rapamycin on cerebral oxygen supply and consumption during reperfusion after cerebral ischemia.

    PubMed

    Chi, O Z; Barsoum, S; Vega-Cotto, N M; Jacinto, E; Liu, X; Mellender, S J; Weiss, H R

    2016-03-01

    Activation of the mammalian target of rapamycin (mTOR) leads to cell growth and survival. We tested the hypothesis that inhibition of mTOR would increase infarct size and decrease microregional O2 supply/consumption balance after cerebral ischemia-reperfusion. This was tested in isoflurane-anesthetized rats with middle cerebral artery blockade for 1h and reperfusion for 2h with and without rapamycin (20mg/kg once daily for two days prior to ischemia). Regional cerebral blood flow was determined using a C(14)-iodoantipyrine autoradiographic technique. Regional small-vessel arterial and venous oxygen saturations were determined microspectrophotometrically. The control ischemic-reperfused cortex had a similar blood flow and O2 consumption to the contralateral cortex. However, microregional O2 supply/consumption balance was significantly reduced in the ischemic-reperfused cortex. Rapamycin significantly increased cerebral O2 consumption and further reduced O2 supply/consumption balance in the reperfused area. This was associated with an increased cortical infarct size (13.5±0.8% control vs. 21.5±0.9% rapamycin). We also found that ischemia-reperfusion increased AKT and S6K1 phosphorylation, while rapamycin decreased this phosphorylation in both the control and ischemic-reperfused cortex. This suggests that mTOR is important for not only cell survival, but also for the control of oxygen balance after cerebral ischemia-reperfusion. PMID:26742793

  16. EFFECTS OF RAPAMYCIN ON CEREBRAL OXYGEN SUPPLY AND CONSUMPTION DURING REPERFUSION AFTER CEREBRAL ISCHEMIA

    PubMed Central

    CHI, O. Z.; BARSOUM, S.; VEGA-COTTO, N. M.; JACINTO, E.; LIU, X.; MELLENDER, S. J.; WEISS, H. R.

    2016-01-01

    Abstract—Activation of the mammalian target of rapamycin (mTOR) leads to cell growth and survival. We tested the hypothesis that inhibition of mTOR would increase infarct size and decrease microregional O2 supply/consumption balance after cerebral ischemia–reperfusion. This was tested in isoflurane-anesthetized rats with middle cerebral artery blockade for 1 h and reperfusion for 2 h with and without rapamycin (20 mg/kg once daily for two days prior to ischemia). Regional cerebral blood flow was determined using a C14-iodoantipyrine autoradiographic technique. Regional small-vessel arterial and venous oxygen saturations were determined microspectrophotometrically. The control ischemic-reperfused cortex had a similar blood flow and O2 consumption to the contralateral cortex. However, microregional O2 supply/consumption balance was significantly reduced in the ischemic-reperfused cortex. Rapamycin significantly increased cerebral O2 consumption and further reduced O2 supply/consumption balance in the reperfused area. This was associated with an increased cortical infarct size (13.5 ± 0.8% control vs. 21.5 ± 0.9% rapamycin). We also found that ischemia–reperfusion increased AKT and S6K1 phosphorylation, while rapamycin decreased this phosphorylation in both the control and ischemic-reperfused cortex. This suggests that mTOR is important for not only cell survival, but also for the control of oxygen balance after cerebral ischemia–reperfusion. PMID:26742793

  17. [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

  18. 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

  19. Dual targeted nanocarrier for brain ischemic stroke treatment.

    PubMed

    Zhao, Yue; Jiang, Yan; Lv, Wei; Wang, Zhongyuan; Lv, Lingyan; Wang, Baoyan; Liu, Xin; Liu, Yang; Hu, Quanyin; Sun, Wujin; Xu, Qunwei; Xin, Hongliang; Gu, Zhen

    2016-07-10

    Focal cerebral ischemia, known as stroke, causes serious long-term disabilities globally. Effective therapy for cerebral ischemia demands a carrier that can penetrate the blood-brain barrier (BBB) and subsequently target the ischemia area in brain. Here, we designed a novel neuroprotectant (ZL006) loaded dual targeted nanocarrier based on liposome (T7&SHp-P-LPs/ZL006) conjugated with T7 peptide (T7) and stroke homing peptide (SHp) for penetrating BBB and targeting ischemia area, respectively. Compared with non-targeting liposomes, T7&SHp-P-LPs/ZL006 could transport across BCEC cells and significantly enhance cellular uptake and reduce cells apoptosis of excitatory amino acid stimulated PC-12 cells. However, there was no significant difference in cellular uptake between SHp-modified and plain liposomes when PC-12 cells were incubated without excitatory amino acid. Besides, ex vivo fluorescent images indicated that DiR labeled T7&SHp-P-LPs could efficiently transport across BBB and mostly accumulated in ischemic region rather than normal cerebral hemisphere of MCAO rats. Furthermore, T7&SHp-P-LPs/ZL006 could enhance the ability of in vivo anti-ischemic stroke of MCAO rats. These results demonstrated that T7&SHp-P-LPs could be used as a safe and effective dual targeted nanocarrier for ischemic stroke treatment. PMID:27142584

  20. 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

  1. Cerebral oximetry and cardiac arrest.

    PubMed

    Skhirtladze-Dworschak, Keso; Dworschak, Martin

    2013-12-01

    Cerebral oximetry is a Food and Drug Administration-approved technology that allows monitoring of brain oxygen saturation in accessible superficial brain cortex regions, which are amongst the most vulnerable in regard to ischemic or hypoxic injury. Since most oxygen in the area of interest is located in the venous compartment, the determined regional brain oxygen saturation approximately reflects the local balance between oxygen delivery and oxygen consumption. Major systemic alterations in blood oxygen content and oxygen delivery will be accompanied by corresponding changes in regional brain saturation. This systematic review, which is based on a Medline search, focuses on the characteristic changes in regional cerebral oxygen saturation that occur, when global oxygen supply to the brain ceases. It further highlights the potential application of cerebral oximetry in the management of cardiac arrest victims, the predictability of clinical outcome after global cerebral ischemia, and it also indicates possible potentials for the management of cerebral reperfusion after having instituted return of spontaneous circulation. PMID:23782549

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

    PubMed

    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

  3. 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

  4. Rodent models of cerebral ischemia

    SciTech Connect

    Ginsberg, M.D.; Busto, R. )

    1989-12-01

    The use of physiologically regulated, reproducible animal models is crucial to the study of ischemic brain injury--both the mechanisms governing its occurrence and potential therapeutic strategies. Several laboratory rodent species (notably rats and gerbils), which are readily available at relatively low cost, are highly suitable for the investigation of cerebral ischemia and have been widely employed for this purpose. We critically examine and summarize several rodent models of transient global ischemia, resulting in selective neuronal injury within vulnerable brain regions, and focal ischemia, typically giving rise to localized brain infarction. We explore the utility of individual models and emphasize the necessity for meticulous experimental control of those variables that modulate the severity of ischemic brain injury.169 references.

  5. Ischemic Colitis Revealing Polyarteritis Nodosa

    PubMed Central

    Hamzaoui, Amira; Litaiem, Noureddine; Smiti Khanfir, M.; Ayadi, Sofiene; Nfoussi, Haifa; Houman, M. H.

    2013-01-01

    Ischemic colitis is one of the most common intestinal ischemic injuries. It results from impaired perfusion of blood to the bowel and is rarely caused by vasculitis. We report a case of ischemic colitis revealing polyarteritis nodosa (PAN) in a 55-year-old man. Histological examination of the resected colon led to the diagnosis of PAN. PMID:24382967

  6. 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…

  7. 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. PMID:26837375

  8. Sensitivity of the neuroimaging techniques in ischemic stroke.

    PubMed

    Smajlović, Dzevdet; Sinanović, Osman

    2004-01-01

    The aim of this study was to investigate and compare the sensitivity and effectiveness of neuroimaging techniques in 190 patients with acute ischemic stroke. The first computed tomography (CT) scan for all patients was performed within the first 12 hours of the stroke symptoms onset. For each patient, between the third and fifth day of the hospitalization, at least one more neuroimaging procedure (CT and/or magnetic resonance imaging--MRI, and/or diffusion weighted imaging--DWI) was done. The CT scan in the first 12 hours of the stroke onset was positive in 32% of the patients; the highest number of the positive findings was in the patients with total anterior circulation infarct (52%). After 48 hours of the stroke onset second CT was positive in 85% (75/89), MRI in 93.5% (115/123), and DWI in 98.8% (79/80) patients. MRI was significantly more sensitive than CT in detection of ischemic lesion (88% vs. 72%, P=0.01), particularly in the patients with lacunar infarcts (75% vs. 50%, P=0.005). In detection of ischemic stroke 48 hours of the stroke onset the slightly higher number of strokes were detected on DWI in comparison with MRI (98.6% vs. 88.7%). According to our results, within the first 12 hours after the stroke onset, CT is reliable only for detection of considerable number of cortical ischemic strokes of the anterior cerebral circulation. After 48 hours from the stroke onset CT, MRI and DWI show high sensitivity in the detection of ischemic lesion of all clinical stroke subtypes. MRI is more sensitive in comparison with CT in detection of ischemic lesion, while DWI does not show dominance in comparison with MRI in identification of ischemic stroke after 48 hours of the symptoms onset. PMID:15628251

  9. Defining the Ischemic Penumbra using Magnetic Resonance Oxygen Metabolic Index

    PubMed Central

    An, Hongyu; Ford, Andria L.; Chen, Yasheng; Zhu, Hongtu; Ponisio, Rosana; Kumar, Gyanendra; Shanechi, Amirali Modir; Khoury, Naim; Vo, Katie D.; Williams, Jennifer; Derdeyn, Colin P.; Diringer, Michael N.; Panagos, Peter; Powers, William J.; Lee, Jin-Moo; Lin, Weili

    2015-01-01

    Background and Purpose Penumbral biomarkers promise to individualize treatment windows in acute ischemic stroke. We used a novel MRI approach which measures oxygen metabolic index (OMI), a parameter closely related to PET-derived cerebral metabolic rate of oxygen utilization, to derive a pair of ischemic thresholds: (1) an irreversible-injury threshold which differentiates ischemic core from penumbra and (2) a reversible-injury threshold which differentiates penumbra from tissue not-at-risk for infarction. Methods Forty acute ischemic stroke patients underwent MRI at three time-points after stroke onset: < 4.5 hours (for OMI threshold derivation), 6 hours (to determine reperfusion status), and 1 month (for infarct probability determination). A dynamic susceptibility contrast method measured CBF, and an asymmetric spin echo sequence measured OEF, to derive OMI (OMI=CBF*OEF). Putative ischemic threshold pairs were iteratively tested using a computation-intensive method to derive infarct probabilities in three tissue groups defined by the thresholds (core, penumbra, and not-at-risk tissue). An optimal threshold pair was chosen based on its ability to predict: infarction in the core, reperfusion-dependent survival in the penumbra, and survival in not-at-risk tissue. The predictive abilities of the thresholds were then tested within the same cohort using a 10-fold cross-validation method. Results The optimal OMI ischemic thresholds were found to be 0.28 and 0.42 of normal values in the contralateral hemisphere. Using the 10-fold cross-validation method, median infarct probabilities were 90.6% for core, 89.7% for non-reperfused penumbra, 9.95% for reperfused penumbra, and 6.28% for not-at-risk tissue. Conclusions OMI thresholds, derived using voxel-based, reperfusion-dependent infarct probabilities, delineated the ischemic penumbra with high predictive ability. These thresholds will require confirmation in an independent patient sample. PMID:25721017

  10. Cerebral ischemia in rabbit: a new experimental model with immunohistochemical investigation.

    PubMed

    Yamamoto, K; Yoshimine, T; Yanagihara, T

    1985-12-01

    Regional cerebral ischemia was produced in the rabbit by unilateral transorbital occlusion of the middle cerebral artery (procedure I); the middle cerebral and azygos anterior cerebral or anterior communicating artery (procedure II); or the middle cerebral, azygos anterior cerebral or anterior communicating, and internal carotid artery (procedure III). Evolution of ischemic lesions was examined with the immunohistochemical reaction for tubulin. With procedure I, ischemic lesions did not become constantly visible for 6 h in the basal ganglia and for 8 h in the frontoparietal region of the cerebral cortex. With procedure II, it was shortened to 3 h in the basal ganglia and to 6 h in the cerebral cortex. With procedure III, the ischemic lesions were observed in 1 h both in the basal ganglia and in the cerebral cortex as loss of the reaction for tubulin in the neuropil, nerve cell bodies, and dendrites. The evidence of neuronal damage became apparent in the same areas later by staining with hematoxylin-eosin. The experimental model presented here may be suitable for investigation of the mechanism that shifts reversible ischemia to cerebral infarction and for evaluation of the effectiveness of pharmacological intervention. PMID:3932374

  11. Cerebral Air Embolism from Angioinvasive Cavitary Aspergillosis

    PubMed Central

    Lin, Chen; Barrio, George A.; Hurwitz, Lynne M.; Kranz, Peter G.

    2014-01-01

    Background. Nontraumatic cerebral air embolism cases are rare. We report a case of an air embolism resulting in cerebral infarction related to angioinvasive cavitary aspergillosis. To our knowledge, there have been no previous reports associating these two conditions together. Case Presentation. A 32-year-old female was admitted for treatment of acute lymphoblastic leukemia (ALL). Her hospital course was complicated by pulmonary aspergillosis. On hospital day 55, she acutely developed severe global aphasia with right hemiplegia. A CT and CT-angiogram of her head and neck were obtained demonstrating intravascular air emboli within the left middle cerebral artery (MCA) branches. She was emergently taken for hyperbaric oxygen therapy (HBOT). Evaluation for origin of the air embolus revealed an air focus along the left lower pulmonary vein. Over the course of 48 hours, her symptoms significantly improved. Conclusion. This unique case details an immunocompromised patient with pulmonary aspergillosis cavitary lesions that invaded into a pulmonary vein and caused a cerebral air embolism. With cerebral air embolisms, the acute treatment option differs from the typical ischemic stroke pathway and the provider should consider emergent HBOT. This case highlights the importance of considering atypical causes of acute ischemic stroke. PMID:25197589

  12. 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

  13. 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.

  14. Imaging of cerebral venous thrombosis.

    PubMed

    Bonneville, F

    2014-12-01

    Cerebral venous thrombosis (CVT) is a potentially life-threatening emergency. The wide ranging of clinical symptoms makes the use of imaging in "slices" even more important for diagnosis. Both CT and MRI are used to diagnose the occlusion of a venous sinus, but MRI is superior to CT for detecting a clot in the cortical or deep veins. CT can show the hyperintense clot spontaneously and CT angiography the intraluminal defect. MRI also detects this thrombus, whose signal varies over time: in the acute phase, it is hypointense in T2*, whilst T1 and T2 can appear falsely reassuring; in the subacute phase, it is hyperintense on all sequences (T1, T2, FLAIR, T2*, diffusion). MRI easily shows the ischemic damage, even hemorrhagic, in the cerebral parenchyma in cases of CVT. Finally, imaging may reveal pathology at the origin of the CVT, such as a fracture of the skull, infection, tumor, dural fistula, or intracranial hypotension. PMID:25465119

  15. 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

  16. Omega-3 fatty acids protect the brain against ischemic injury by activating Nrf2 and upregulating heme oxygenase 1.

    PubMed

    Zhang, Meijuan; Wang, Suping; Mao, Leilei; Leak, Rehana K; Shi, Yejie; Zhang, Wenting; Hu, Xiaoming; Sun, Baoliang; Cao, Guodong; Gao, Yanqin; Xu, Yun; Chen, Jun; Zhang, Feng

    2014-01-29

    Ischemic stroke is a debilitating clinical disorder that affects millions of people, yet lacks effective neuroprotective treatments. Fish oil is known to exert beneficial effects against cerebral ischemia. However, the underlying protective mechanisms are not fully understood. The present study tests the hypothesis that omega-3 polyunsaturated fatty acids (n-3 PUFAs) attenuate ischemic neuronal injury by activating nuclear factor E2-related factor 2 (Nrf2) and upregulating heme oxygenase-1 (HO-1) in both in vitro and in vivo models. We observed that pretreatment of rat primary neurons with docosahexaenoic acid (DHA) significantly reduced neuronal death following oxygen-glucose deprivation. This protection was associated with increased Nrf2 activation and HO-1 upregulation. Inhibition of HO-1 activity with tin protoporphyrin IX attenuated the protective effects of DHA. Further studies showed that 4-hydroxy-2E-hexenal (4-HHE), an end-product of peroxidation of n-3 PUFAs, was a more potent Nrf2 inducer than 4-hydroxy-2E-nonenal derived from n-6 PUFAs. In an in vivo setting, transgenic mice overexpressing fatty acid metabolism-1, an enzyme that converts n-6 PUFAs to n-3 PUFAs, were remarkably resistant to focal cerebral ischemia compared with their wild-type littermates. Regular mice fed with a fish oil-enhanced diet also demonstrated significant resistance to ischemia compared with mice fed with a regular diet. As expected, the protection was associated with HO-1 upregulation, Nrf2 activation, and 4-HHE generation. Together, our data demonstrate that n-3 PUFAs are highly effective in protecting the brain, and that the protective mechanisms involve Nrf2 activation and HO-1 upregulation by 4-HHE. Further investigation of n-3 PUFA neuroprotective mechanisms may accelerate the development of stroke therapies. PMID:24478369

  17. Is longer sevoflurane preconditioning neuroprotective in permanent focal cerebral ischemia?

    PubMed

    Qiu, Caiwei; Sheng, Bo; Wang, Shurong; Liu, Jin

    2013-08-15

    Sevoflurane preconditioning has neuroprotective effects in the cerebral ischemia/reperfusion model. However, its influence on permanent cerebral ischemia remains unclear. In the present study, the rats were exposed to sevoflurane for 15, 30, 60, and 120 minutes, followed by induction of permanent cerebral ischemia. Results demonstrated that 30- and 60-minute sevoflurane preconditioning significantly reduced the infarct volume at 24 hours after cerebral ischemia, and 60-minute lurane preconditioning additionally reduced the number of TUNEL- and caspase-3-positive cells in the ischemic penumbra. However, 120-minute sevoflurane preconditioning did not show evident neuroprotective effects. Moreover, 60-minute sevoflurane preconditioning significantly attenuated neurological deficits and infarct volume in rats at 4 days after cerebral ischemia. These findings indicated that 60-minute sevoflurane preconditioning can induce the best neuroprotective effects in rats with permanent cerebral ischemia through the inhibition of apoptosis. PMID:25206521

  18. Inflammation, Cerebral Vasospasm, and Evolving Theories of Delayed Cerebral Ischemia

    PubMed Central

    Carr, Kevin R.; Zuckerman, Scott L.; Mocco, J

    2013-01-01

    Cerebral vasospasm (CVS) is a potentially lethal complication of aneurysmal subarachnoid hemorrhage (aSAH). Recently, the symptomatic presentation of CVS has been termed delayed cerebral ischemia (DCI), occurring as early as 3-4 days after the sentinel bleed. For the past 5-6 decades, scientific research has promulgated the theory that cerebral vasospasm plays a primary role in the pathology of DCI and subsequently delayed ischemic neurological decline (DIND). Approximately 70% of patients develop CVS after aSAH with 50% long-term morbidity rates. The exact etiology of CVS is unknown; however, a well-described theory involves an antecedent inflammatory cascade with alterations of intracellular calcium dynamics and nitric oxide fluxes, though the intricacies of this inflammatory theory are currently unknown. Consequently, there have been few advances in the clinical treatment of this patient cohort, and morbidity remains high. Identification of intermediaries in the inflammatory cascade can provide insight into newer clinical interventions in the prevention and management of cerebral vasospasm and will hopefully prevent neurological decline. In this review, we discuss current theories implicating the inflammatory cascade in the development of CVS and potential treatment targets. PMID:24058736

  19. Adenosine and Ischemic Preconditioning

    PubMed Central

    Liang, Bruce T.; Swierkosz, Tomasz A.; Herrmann, Howard C.; Kimmel, Stephen; Jacobson, Kenneth A.

    2012-01-01

    Adenosine is released in large amounts during myocardial ischemia and is capable of exerting potent cardioprotective effects in the heart. Although these observations on adenosine have been known for a long time, how adenosine acts to achieve its anti-ischemic effect remains incompletely understood. However, recent advances on the chemistry and pharmacology of adenosine receptor ligands have provided important and novel information on the function of adenosine receptor subtypes in the cardiovascular system. The development of model systems for the cardiac actions of adenosine has yielded important insights into its mechanism of action and have begun to elucidate the sequence of signalling events from receptor activation to the actual exertion of its cardioprotective effect. The present review will focus on the adenosine receptors that mediate the potent anti-ischemic effect of adenosine, new ligands at the receptors, potential molecular signalling mechanisms downstream of the receptor, mediators for cardioprotection, and possible clinical applications in cardiovascular disorders. PMID:10607860

  20. 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. ...

  1. Cerebral angiography

    MedlinePlus

    ... Cerebral angiography is done in the hospital or radiology center. You lie on an x-ray table. ... be done in preparation for medical treatment (interventional radiology procedures) by way of certain blood vessels. What ...

  2. [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

  3. Ischemic tissue injury.

    PubMed Central

    Jennings, R. B.; Ganote, C. E.; Reimer, K. A.

    1975-01-01

    The subendocardial to subepicardial gradient in the severity of ischemia following acute coronary occlusion is described. The effects of mild, moderate, and severe ischemia on cell structure and function are compared in summary form, and special attention is given to the effects of severe ischemia on myocardial cells. The characteristics of reversible and irreversible ischemic injury are defined in biologic terms. The failure of cell volume regulation in cells which have entered an irreversible state of ischemic injury is demonstrated by the use of free-hand slices in vitro. Irreversibility is associated with structural defects in the plasma membrane and is reflected in an increased slice inulin-diffusible space, increased slice H2O and Na+ content, and failure of the tissue to maintain the high K+ and Mg2+ levels characteristic of normal left ventricular myocardium. Defective cell membrane function is an early feature of irreversible ischemic injury and may be a primary event in the genesis of the irreversible state. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:1180331

  4. 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

  5. The transcriptome of cerebral ischemia

    PubMed Central

    VanGilder, Reyna L.; Huber, Jason D.; Rosen, Charles L.; Barr, Taura L.

    2015-01-01

    The molecular causality and response to stroke is complex. Yet, much of the literature examining the molecular response to stroke has focused on targeted pathways that have been well-characterized. Consequently, our understanding of stroke pathophysiology has made little progress by way of clinical therapeutics since tissue plasminogen activator was approved for treatment nearly a decade ago. The lack of clinical translation is in part due to neuron-focused studies, preclinical models of cerebral ischemia and the paradoxical nature of neuro-inflammation. With the evolution of the Stroke Therapy Academic Industry Roundtable criteria streamlining research efforts and broad availability of genomic technologies, the ability to decipher the molecular fingerprint of ischemic stroke is on the horizon. This review highlights preclinical microarray findings of the ischemic brain, discusses the transcriptome of cerebral preconditioning and emphasizes the importance of further characterizing the role of the neurovascular unit and peripheral white blood cells in mediating stroke damage and repair within the penumbra. PMID:22381515

  6. Protein methionine oxidation augments reperfusion injury in acute ischemic stroke

    PubMed Central

    Gu, Sean X.; Blokhin, Ilya O.; Wilson, Katina M.; Dhanesha, Nirav; Doddapattar, Prakash; Grumbach, Isabella M.; Chauhan, Anil K.; Lentz, Steven R.

    2016-01-01

    Reperfusion injury can exacerbate tissue damage in ischemic stroke, but little is known about the mechanisms linking ROS to stroke severity. Here, we tested the hypothesis that protein methionine oxidation potentiates NF-κB activation and contributes to cerebral ischemia/reperfusion injury. We found that overexpression of methionine sulfoxide reductase A (MsrA), an antioxidant enzyme that reverses protein methionine oxidation, attenuated ROS-augmented NF-κB activation in endothelial cells, in part, by protecting against the oxidation of methionine residues in the regulatory domain of calcium/calmodulin-dependent protein kinase II (CaMKII). In a murine model, MsrA deficiency resulted in increased NF-κB activation and neutrophil infiltration, larger infarct volumes, and more severe neurological impairment after transient cerebral ischemia/reperfusion injury. This phenotype was prevented by inhibition of NF-κB or CaMKII. MsrA-deficient mice also exhibited enhanced leukocyte rolling and upregulation of E-selectin, an endothelial NF-κB–dependent adhesion molecule known to contribute to neurovascular inflammation in ischemic stroke. Finally, bone marrow transplantation experiments demonstrated that the neuroprotective effect was mediated by MsrA expressed in nonhematopoietic cells. These findings suggest that protein methionine oxidation in nonmyeloid cells is a key mechanism of postischemic oxidative injury mediated by NF-κB activation, leading to neutrophil recruitment and neurovascular inflammation in acute ischemic stroke. PMID:27294204

  7. Early embolic events complicating intravenous thrombolysis for acute ischemic stroke.

    PubMed

    Chou, Ping Song; Lin, Chien Hung; Chao, Hai Lun; Chao, A Ching

    2012-11-01

    Intravenous recombinant tissue plasminogen activator (IV rt-PA) is the only established thrombolytic therapy for acute ischemic stroke. However, secondary embolism after IV rt-PA for acute ischemic stroke is recognized as an uncommon complication, and the pathophysiology is unclear. We describe a 72-year-old man with acute infarction in the territory of left anterior cerebral artery who developed new infarction in the territory of right middle cerebral artery and acute peripheral arterial occlusion after IV rt-PA therapy. It suggested a central embolic source. Because the patient has paroxysmal atrial fibrillation (Af), the possible embolic sources may come from fragmentation of pre-existing intra-atrial clot. Although Af and the presence of cardiac thrombus are not contraindication for IV rt-PA in acute ischemic stroke, our case and review suggested that the administration of IV rt-PA to patients with known Af and intracardiac thrombus could represent a particular risk situation and should be carefully evaluated. PMID:22205004

  8. Evidence for Cerebral Hemodynamic Measurement-based Therapy in Symptomatic Major Cerebral Artery Disease

    PubMed Central

    YAMAUCHI, Hiroshi

    In patients with atherosclerotic internal carotid artery or middle cerebral artery occlusive disease, chronic reduction in cerebral perfusion pressure (chronic hemodynamic compromise) increases the risk of ischemic stroke and can be detected by directly measuring hemodynamic parameters. However, strategies for selecting treatments based on hemodynamic measurements have not been clearly established. Bypass surgery has been proven to improve hemodynamic compromise. However, the benefit of bypass surgery for reducing the stroke risk in patients with hemodynamic compromise is controversial. The results of the two randomized controlled trials were inconsistent. Hypertension is a major risk factor for stroke, and antihypertensive therapy provides general benefit to patients with symptomatic atherosclerotic major cerebral artery disease. However, the benefit of strict control of blood pressure for reducing the stroke risk in patients with hemodynamic compromise is a matter of debate. The results of the two observational studies were different. We must establish strategies for selecting treatments based on hemodynamic measurements in atherosclerotic major cerebral artery disease. PMID:26041631

  9. 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

  10. 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

  11. 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

  12. 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 ...

  13. 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. ...

  14. Developing drug strategies for the neuroprotective treatment of acute ischemic stroke.

    PubMed

    Tuttolomondo, Antonino; Pecoraro, Rosaria; Arnao, Valentina; Maugeri, Rosario; Iacopino, Domenico Gerardo; Pinto, Antonio

    2015-01-01

    Developing new treatment strategies for acute ischemic stroke in the last twenty years has offered some important successes, but also several failures. Most trials of neuroprotective therapies have been uniformly negative to date. Recent research has reported how excitatory amino acids act as the major excitatory neurotransmitters in the cerebral cortex and hippocampus. Furthermore, other therapeutic targets such as free radical scavenger strategies and the anti-inflammatory neuroprotective strategy have been evaluated with conflicting data in animal models and human subjects with acute ischemic stroke. Whereas promising combinations of neuroprotection and neurorecovery, such as citicoline, albumin and cerebrolysin have been tested with findings worthy of further evaluation in larger randomized clinical trials. Understanding the complexities of the ischemic cascade is essential to developing pharmacological targets for acute ischemic stroke in neuroprotective or flow restoration therapeutic strategies. PMID:26469760

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

    PubMed

    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

  16. 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

  17. Perfusion Angiography in Acute Ischemic Stroke.

    PubMed

    Scalzo, Fabien; 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 T max, 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

  18. 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

  19. Glibenclamide for the treatment of ischemic and hemorrhagic stroke.

    PubMed

    Caffes, Nicholas; Kurland, David B; Gerzanich, Volodymyr; Simard, J Marc

    2015-01-01

    Ischemic and hemorrhagic strokes are associated with severe functional disability and high mortality. Except for recombinant tissue plasminogen activator, therapies targeting the underlying pathophysiology of central nervous system (CNS) ischemia and hemorrhage are strikingly lacking. Sur1-regulated channels play essential roles in necrotic cell death and cerebral edema following ischemic insults, and in neuroinflammation after hemorrhagic injuries. Inhibiting endothelial, neuronal, astrocytic and oligodendroglial sulfonylurea receptor 1-transient receptor potential melastatin 4 (Sur1-Trpm4) channels and, in some cases, microglial KATP (Sur1-Kir6.2) channels, with glibenclamide is protective in a variety of contexts. Robust preclinical studies have shown that glibenclamide and other sulfonylurea agents reduce infarct volumes, edema and hemorrhagic conversion, and improve outcomes in rodent models of ischemic stroke. Retrospective studies suggest that diabetic patients on sulfonylurea drugs at stroke presentation fare better if they continue on drug. Additional laboratory investigations have implicated Sur1 in the pathophysiology of hemorrhagic CNS insults. In clinically relevant models of subarachnoid hemorrhage, glibenclamide reduces adverse neuroinflammatory and behavioral outcomes. Here, we provide an overview of the preclinical studies of glibenclamide therapy for CNS ischemia and hemorrhage, discuss the available data from clinical investigations, and conclude with promising preclinical results that suggest glibenclamide may be an effective therapeutic option for ischemic and hemorrhagic stroke. PMID:25749474

  20. Cerebral perfusion reserve indexes determined by fluoromethane positron emission scanning

    SciTech Connect

    Levine, R.L.; Sunderland, J.J.; Lagreze, H.L.; Nickles, R.J.; Rowe, B.R.; Turski, P.A.

    1988-01-01

    An index of cerebral perfusion reserve (RES%), defined as the percent change of regional cerebral blood flow over baseline per mm Hg of end-tidal CO/sub 2/ tension, was determined for each middle cerebral artery (MCA) territory in patients with unilateral carotid distribution transient ischemic attacks or minor cerebrovascular accidents and was compared with that of age-matched, neurologically normal volunteers. Vasodilator responses to induced hypercapnia were tested during inhalation of 5% CO/sub 2/ in 95% O/sub 2/ while regional cerebral blood flow was measured by fluoromethane inhalation positron emission tomography. Mean RES% for 24 normal MCA territories was 5.2 +/- 0.8%. Mean RES% for 15 patient nonischemic MCA territories was 3.8 +/- 1.3% and for 15 ischemic MCA territories was 2.8 +/- 1.9% (both p less than 0.001). Individual RES% values and symmetry ratios between ischemic and nonischemic regions were also determined and compared with angiographic data. Areas of diminished, asymmetric, or paradoxical (two patients) CO/sub 2/ reactivity appear to correspond to areas of compensatory vasodilation. We found this technique to be a safe and reproducible method for defining and recording localized areas of cerebral tissue at apparent risk for hemodynamically related damage.

  1. [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

  2. Hepatitis C and recurrent treatment-resistant acute ischemic stroke

    PubMed Central

    Tarsia, Joseph; Dunn, Casey; Aysenne, Aimee; Shah, Basil; Moore, David F.

    2013-01-01

    Since the introduction of recombinant tissue plasminogen activator and thrombolysis, acute ischemic stroke has become a treatable disorder if the patient presents within the 4.5-hour time window. Typically, sporadic stroke is caused by atherosclerotic disease involving large or small cerebral arteries or secondary to a cardioembolic source often associated with atrial fibrillation. In the over-65-year age group, more rare causes of stroke, such as antiphospholipid syndromes, are unusual; such stroke etiologies are mostly seen in a younger age group (<55 years). Here we describe acute ischemic stroke in three patients >65 years with hepatitis C–associated antiphospholipid antibodies. We suggest that screening for antiphospholipid disorders in the older patient might be warranted, with potential implications for therapeutic management and secondary stroke prevention. PMID:23543984

  3. Brain-derived neurotrophic factor inhibits glucose intolerance after cerebral ischemia

    PubMed Central

    Shu, Xiaoliang; Zhang, Yongsheng; Xu, Han; Kang, Kai; Cai, Donglian

    2013-01-01

    Brain-derived neurotrophic factor is associated with the insulin signaling pathway and glucose tabolism. We hypothesized that expression of brain-derived neurotrophic factor and its receptor may be involved in glucose intolerance following ischemic stress. To verify this hypothesis, this study aimed to observe the changes in brain-derived neurotrophic factor and tyrosine kinase B receptor expression in glucose metabolism-associated regions following cerebral ischemic stress in mice. At day 1 after middle cerebral artery occlusion, the expression levels of brain-derived neurotrophic factor were significantly decreased in the ischemic cortex, hypothalamus, liver, skeletal muscle, and pancreas. The expression levels of tyrosine kinase B receptor were decreased in the hypothalamus and liver, and increased in the skeletal muscle and pancreas, but remained unchanged in the cortex. Intrahypothalamic administration of brain-derived neurotrophic factor (40 ng) suppressed the decrease in insulin receptor and tyrosine-phosphorylated insulin receptor expression in the liver and skeletal muscle, and inhibited the overexpression of gluconeogenesis-associated phosphoenolpyruvate carboxykinase and glucose-6-phosphatase in the liver of cerebral ischemic mice. However, serum insulin levels remained unchanged. Our experimental findings indicate that brain-derived neurotrophic factor can promote glucose metabolism, reduce gluconeogenesis, and decrease blood glucose levels after cerebral ischemic stress. The low expression of brain-derived neurotrophic factor following cerebral ischemia may be involved in the development of glucose intolerance. PMID:25206547

  4. [Platelets, atherothrombosis, antiplatelet drugs and cerebral ischemia].

    PubMed

    Bousser, Marie-Germaine

    2013-02-01

    Platelets play a much more important role in myocardial ischemia than in cerebral ischemia, because atherothrombosis - the underlying cause of the vast majority of myocardial infarcts - is responsible for only 25-30% of cerebral infarcts. Aspirin is the only effective antiplatelet drug for primary prevention of ischemic events, especially those affecting the heart. For secondary prevention of cerebral infarction, clopidogrel and the combination of aspirin with extended-release dipyridamole are both marginally better than aspirin alone, but aspirin remains the gold standard worldwide because of its remarkable cost/benefit/tolerability ratio. The clopidogrel-aspirin combination is to be avoided because of the risk of hemorrhage, particularly in the brain and gastrointestinal tract. Revascularization strategies and the choice of antiplatelet drugs for the acute phase of myocardial and cerebral ischemia are very different, consisting of endovascular treatment and aggressive platelet inhibition for coronary infarcts, versus intravenous thrombolysis and / or aspirin for cerebral infarcts. None of the new antiplatelet drugs used in acute coronary syndromes has so far been studied in acute cerebral ischemia. PMID:24919368

  5. 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

  6. Neuroprotective profile of novel SRC kinase inhibitors in rodent models of cerebral ischemia.

    PubMed

    Liang, Shi; Pong, Kevin; Gonzales, Cathleen; Chen, Yi; Ling, Huai-Ping; Mark, Robert J; Boschelli, Frank; Boschelli, Diane H; Ye, Fei; Barrios Sosa, Ana Carolina; Mansour, Tarek S; Frost, Philip; Wood, Andrew; Pangalos, Menelas N; Zaleska, Margaret M

    2009-12-01

    Src kinase signaling has been implicated in multiple mechanisms of ischemic injury, including vascular endothelial growth factor (VEGF)-mediated vascular permeability that leads to vasogenic edema, a major clinical complication in stroke and brain trauma. Here we report the effects of two novel Src kinase inhibitors, 4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(4-methyl-1-piperazinyl)propoxy]-3-quinolinecarbonitrile (SKI-606) and 4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[4-(4-methypiperazin-1-yl)but-1-ynyl]-3-quinolinecarbonitrile (SKS-927), on ischemia-induced brain infarction and short- and long-term neurological deficits. Two well established transient [transient middle cerebral artery occlusion (tMCAO)] and permanent [permanent middle cerebral artery occlusion (pMCAO)] focal ischemia models in the rat were used with drug treatments initiated up to 6 h after onset of stroke to mimic the clinical scenario. Brain penetration of Src inhibitors, their effect on blood-brain barrier integrity and VEGF signaling in human endothelial cells were also evaluated. Our results demonstrate that both agents potently block VEGF-mediated signaling in human endothelial cells, penetrate rat brain upon systemic administration, and inhibit postischemic Src activation and vascular leakage. Treatment with SKI-606 or SKS-927 (at the doses of 3-30 mg/kg i.v.) resulted in a dose-dependent reduction in infarct volume and robust protection from neurological impairments even when the therapy was initiated up to 4- to 6-h after tMCAO. Src blockade after pMCAO resulted in accelerated improvement in recovery from motor, sensory, and reflex deficits during a long-term (3 weeks) testing period poststroke. These data demonstrate that the novel Src kinase inhibitors provide effective treatment against ischemic conditions within a clinically relevant therapeutic window and may constitute a viable therapy for acute stroke. PMID:19741150

  7. Treatment with Evasin-3 reduces atherosclerotic vulnerability for ischemic stroke, but not brain injury in mice

    PubMed Central

    Copin, Jean-Christophe; da Silva, Rafaela F; Fraga-Silva, Rodrigo A; Capettini, Luciano; Quintao, Silvia; Lenglet, Sébastien; Pelli, Graziano; Galan, Katia; Burger, Fabienne; Braunersreuther, Vincent; Schaller, Karl; Deruaz, Maud; Proudfoot, Amanda E; Dallegri, Franco; Stergiopulos, Nikolaos; Santos, Robson A S; Gasche, Yvan; Mach, François; Montecucco, Fabrizio

    2013-01-01

    Neutrophilic inflammation might have a pathophysiological role in both carotid plaque rupture and ischemic stroke injury. Here, we investigated the potential benefits of the CXC chemokine-binding protein Evasin-3, which potently inhibits chemokine bioactivity and related neutrophilic inflammation in two mouse models of carotid atherosclerosis and ischemic stroke, respectively. In the first model, the chronic treatment with Evasin-3 as compared with Vehicle (phosphate-buffered saline (PBS)) was investigated in apolipoprotein E-deficient mice implanted of a ‘cast' carotid device. In the second model, acute Evasin-3 treatment (5 minutes after cerebral ischemia onset) was assessed in mice subjected to transient left middle cerebral artery occlusion. Although CXCL1 and CXCL2 were upregulated in both atherosclerotic plaques and infarcted brain, only CXCL1 was detectable in serum. In carotid atherosclerosis, treatment with Evasin-3 was associated with reduction in intraplaque neutrophil and matrix metalloproteinase-9 content and weak increase in collagen as compared with Vehicle. In ischemic stroke, treatment with Evasin-3 was associated with reduction in ischemic brain neutrophil infiltration and protective oxidants. No other effects in clinical and histological outcomes were observed. We concluded that Evasin-3 treatment was associated with reduction in neutrophilic inflammation in both mouse models. However, Evasin-3 administration after cerebral ischemia onset failed to improve poststroke outcomes. PMID:23250107

  8. 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. PMID:24323655

  9. 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

  10. A fast multiparameter MRI approach for acute stroke assessment on a 3T clinical scanner: preliminary results in a non-human primate model with transient ischemic occlusion

    PubMed Central

    Tong, Frank; Li, Chun-Xia; Yan, Yumei; Nair, Govind; Nagaoka, Tsukasa; Tanaka, Yoji; Zola, Stuart; Howell, Leonard

    2014-01-01

    Many MRI parameters have been explored and demonstrated the capability or potential to evaluate acute stroke injury, providing anatomical, microstructural, functional, or neurochemical information for diagnostic purposes and therapeutic development. However, the application of multiparameter MRI approach is hindered in clinic due to the very limited time window after stroke insult. Parallel imaging technique can accelerate MRI data acquisition dramatically and has been incorporated in modern clinical scanners and increasingly applied for various diagnostic purposes. In the present study, a fast multiparameter MRI approach including structural T1-weighted imaging (T1W), T2-weighted imaging (T2W), diffusion tensor imaging (DTI), T2-mapping, proton magnetic resonance spectroscopy, cerebral blood flow (CBF), and magnetization transfer (MT) imaging, was implemented and optimized for assessing acute stroke injury on a 3T clinical scanner. A macaque model of transient ischemic stroke induced by a minimal interventional approach was utilized for evaluating the multiparameter MRI approach. The preliminary results indicate the surgical procedure successfully induced ischemic occlusion in the cortex and/or subcortex in adult macaque monkeys (n=4). Application of parallel imaging technique substantially reduced the scanning duration of most MRI data acquisitions, allowing for fast and repeated evaluation of acute stroke injury. Hence, the use of the multiparameter MRI approach with up to five quantitative measures can provide significant advantages in preclinical or clinical studies of stroke disease. PMID:24834423

  11. Angiotensin II type-2 receptor stimulation induces neuronal VEGF synthesis after cerebral ischemia.

    PubMed

    Mateos, Laura; Perez-Alvarez, Maria Jose; Wandosell, Francisco

    2016-07-01

    Intense efforts are being undertaken to understand the pathobiology of ischemia and to develop novel and effective treatments. Angiotensin II type 2 receptor (AT2R) is related with a beneficial role in neurodegenerative disorders, including ischemia. However, the underlying molecular mechanism remains elusive. In this study, we have established that AT2R stimulation by C21 compound, a specific AT2R agonist, caused a VEGF upregulation. Using mouse primary cortical neurons exposed to oxygen-glucose deprivation (OGD), we established that this effect was mediated by a mechanism dependent of mTORC1 signaling since mTOR inhibition abolished the C21-induced VEGF upregulation. Also, we have temporally characterized the changes on VEGF levels after ischemia induction in rats using two different approaches: transient and permanent middle cerebral artery occlusion (tMCAO and pMCAO). VEGF levels were permanently augmented after reperfusion (tMCAO) whereas lower levels of VEGF were found after pMCAO, remarkably at 21days. Therefore, C21 compound accelerated the recovery of the neurological status of pMCAO rats, reduced the ischemic damage area and abolished pMCAO-induced VEGF downregulation at 21days. This effect of C21 compound was mainly observed in neurons of the peri-infarct area. Our results suggest that a C21-induced VEGF upregulation may be crucial after an ischemic neuronal insult in both of our experimental approaches. This upregulation was mediated by a mechanism dependent of Akt/mTOR signaling pathway, since mTOR inhibition abolished the VEGF upregulation induced by C21. Considering that VEGF is involved in regenerative processes, we propose that AT2R activation could be used as a potential pharmacological strategy after ischemic stroke. PMID:27045356

  12. 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

  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. Contributing Mechanisms of Aortic Atheroma in Ischemic Cerebrovascular Disease.

    PubMed

    Kong, Qi; Ma, Xin

    2015-12-01

    In recent years, the correlation between aortic atheroma (AA) and the occurrence and recurrence of ischemic cerebrovascular disease (ICVD) has attracted much attention, but the contributory mechanisms remain controversial. This review analyzes related research on the roles of AA in ICVD, and demonstrates the correlation between the formation and development of AA and abnormal metabolism, inflammation, hemodynamic changes, and other contributory factors. The presence of complex aortic plaque (CAP) in the ascending aorta and aortic arch increases the risk of cerebral embolism and degree of injury, while the association between CAP in the descending aorta and cerebral embolism remains ambiguous. AA also functions as an indicator of atherosclerosis burden as well as hypercoagulability, which may further increase the risk of ICVD. Further study on the relationship of AA to ICVD will improve diagnosis and treatment in clinical practice. PMID:26522269

  15. Physical exercise training and neurovascular unit in ischemic stroke.

    PubMed

    Wang, X; Zhang, M; Feng, R; Li, W B; Ren, S Q; Zhang, J; Zhang, F

    2014-06-20

    Physical exercise could exert a neuroprotective effect in both clinical studies and animal experiments. A series of related studies have indicated that physical exercise could reduce infarct volume, alleviate neurological deficits, decrease blood-brain barrier dysfunction, promote angiogenesis in cerebral vascular system and increase the survival rate after ischemic stroke. In this review, we summarized the protective effects of physical exercise on neurovascular unit (NVU), including neurons, astrocytes, pericytes and the extracellular matrix. Furthermore, it was demonstrated that exercise training could decrease the blood-brain barrier dysfunction and promote angiogenesis in cerebral vascular system. An awareness of the exercise intervention benefits pre- and post stroke may lead more stroke patients and people with high-risk factors to accept exercise therapy for the prevention and treatment of stroke. PMID:24780769

  16. [Cerebral manifestations of thromboangiitis obliterans. Case report].

    PubMed

    Aszalos, Csongor; Dongó, Eleni; Farkas, Zsuzsanna; Kollár, Attila; Magyar, Péter; Várallyay, György; Bereczki, Dániel; Vastagh, Ildikó

    2016-07-01

    Thromboangiits obliterans (Buerger's disease) is a non-atherosclerotic, segmental inflammatory and obliterative disease affecting small and medium sized arteries and veins. The etiology is still unknown, but it is in close relationship with tobacco use. Symptoms begin under the age of 45 years and the undulating course is typical. Patients usually present with acute and chronic ischemic or infectious acral lesions. Diagnosis is usually based on clinical and angiographic criteria and it is important to exclude autoimmune disease, thrombophilia, diabetes, and proximal embolic sources. Even though Buerger's disease most commonly involves the arteries of the extremities, the pathologic findings sometimes affect the cerebral, coronary and internal thoracic, renal and mesenteric arteries as well. The authors present the history of a patient with known Buerger's disease and acute ischemic stroke. Brain imaging detected acute and chronic ischemic lesions caused by middle cerebral non-atherosclerotic arteriopathy on the symptomatic side. Other etiology was excluded by detailed investigations. Orv. Hetil., 2016, 157(30), 1207-1211. PMID:27452071

  17. 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

  18. Acute Ischemic Stroke Intervention.

    PubMed

    Khandelwal, Priyank; Yavagal, Dileep R; Sacco, Ralph L

    2016-06-01

    Acute ischemic stroke (AIS) is the leading cause of disability worldwide and among the leading causes of mortality. Although intravenous tissue plasminogen activator (IV-rtPA) was approved nearly 2 decades ago for treatment of AIS, only a minority of patients receive it due to a narrow time window for administration and several contraindications to its use. Endovascular approaches to recanalization in AIS developed in the 1980s, and recently, 5 major randomized trials showed an overwhelming superior benefit of combining endovascular mechanical thrombectomy with IV-rtPA over IV-rtPA alone. In this paper, we discuss the evolution of catheter-based treatment from first-generation thrombectomy devices to the game-changing stent retrievers, results from recent trials, and the evolving stroke systems of care to provide timely access to acute stroke intervention to patients in the United States. PMID:27256835

  19. 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

  20. [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. PMID:23805635

  1. Concurrent Ruptured Pseudoaneurysm of the Internal Carotid Artery and Cerebral Infarction as an Initial Manifestation of Polycythemia Vera

    PubMed Central

    Choi, Kyu-Sun; Ryu, Je-Il; Oh, Young-Ha

    2015-01-01

    The most common neurologic manifestations of polycythemia vera (PV) are cerebral infarction and transient ischemic attacks, while cerebral hemorrhage or intracranial dissection has been rarely associated with PV. Here we report the first case of a 59-year-old patient with intracranial supraclinoid internal carotid artery (ICA) dissection causing cerebral infarction and concomitant subarachnoid hemorrhage due to pseudoaneurysm rupture as clinical onset of PV. This case report discusses the possible mechanism and treatment of this extremely rare condition. PMID:26361530

  2. 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

  3. 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

  4. Ischemic ulcers - self-care

    MedlinePlus

    ... restrict blood flow. Certain lifestyle changes can help prevent ischemic ulcers. If you have a wound, taking these steps can improve blood flow and aid healing. Quit smoking. Smoking can lead to clogged arteries. ...

  5. Can postmortem computed tomography detect antemortem hypoxic-ischemic encephalopathy?

    PubMed

    Shirota, Go; Ishida, Masanori; Shintani, Yukako; Abe, Hiroyuki; Ikemura, Masako; Fukayama, Masashi; Gonoi, Wataru

    2016-09-01

    The purpose of this study was to evaluate the usefulness of brain postmortem computed tomography (PMCT) findings for the detection of global hypoxia or hypoperfusion leading to hypoxic-ischemic encephalopathy (HIE) prior to death. Cadavers of individuals who died from non-traumatic causes were subjected to PMCT and pathological autopsy. Cases with an episode of cardiopulmonary arrest, hypoxia, or hypoperfusion that required intensive respiratory management at least 24 h before death and exhibited findings of HIE in conventional autopsy (HIE group, n = 6) were compared with those without such episodes prior to death (control group; overall, n = 37; age-matched, n = 8) with regard to four parameters: (1) width of the central sulcus (CS), (2) attenuation difference at the basal ganglia (BG) level, (3) attenuation difference between cerebral gray matter (GM) and cerebral white matter (WM), and (4) attenuation difference between cerebellar GM and cerebral GM. The results revealed significant differences in the width of the CS (P < 0.001), attenuation difference at the BG level (P < 0.001), and attenuation difference between cerebral GM and cerebral WM (P = 0.009) between the HIE group and the overall control group. When the age-matched control group and the HIE group were compared, there was a significant difference in the width of the CS (P = 0.026) and attenuation difference at the BG level (P < 0.001). Our results suggest that effacement of the sulcus of the cerebral hemisphere and the loss of contrast at the BG level on brain PMCT indicate the existence of HIE prior to death. PMID:27342771

  6. [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. PMID:26103818

  7. 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 ...

  8. 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 ...

  9. 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

  10. Cerebral Amyloid Angiopathy: Emerging Concepts

    PubMed Central

    2015-01-01

    Cerebral amyloid angiopathy (CAA) involves cerebrovascular amyloid deposition and is classified into several types according to the amyloid protein involved. Of these, sporadic amyloid β-protein (Aβ)-type CAA is most commonly found in older individuals and in patients with Alzheimer's disease (AD). Cerebrovascular Aβ deposits accompany functional and pathological changes in cerebral blood vessels (CAA-associated vasculopathies). CAA-associated vasculopathies lead to development of hemorrhagic lesions [lobar intracerebral macrohemorrhage, cortical microhemorrhage, and cortical superficial siderosis (cSS)/focal convexity subarachnoid hemorrhage (SAH)], ischemic lesions (cortical infarction and ischemic changes of the white matter), and encephalopathies that include subacute leukoencephalopathy caused by CAA-associated inflammation/angiitis. Thus, CAA is related to dementia, stroke, and encephalopathies. Recent advances in diagnostic procedures, particularly neuroimaging, have enabled us to establish a clinical diagnosis of CAA without brain biopsies. Sensitive magnetic resonance imaging (MRI) methods, such as gradient-echo T2* imaging and susceptibility-weighted imaging, are useful for detecting cortical microhemorrhages and cSS. Amyloid imaging with amyloid-binding positron emission tomography (PET) ligands, such as Pittsburgh Compound B, can detect CAA, although they cannot discriminate vascular from parenchymal amyloid deposits. In addition, cerebrospinal fluid markers may be useful, including levels of Aβ40 for CAA and anti-Aβ antibody for CAA-related inflammation. Moreover, cSS is closely associated with transient focal neurological episodes (TFNE). CAA-related inflammation/angiitis shares pathophysiology with amyloid-related imaging abnormalities (ARIA) induced by Aβ immunotherapies in AD patients. This article reviews CAA and CAA-related disorders with respect to their epidemiology, pathology, pathophysiology, clinical features, biomarkers, diagnosis

  11. 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

  12. 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

  13. [Ischemic myocardial metabolism and antianginal drugs].

    PubMed

    Ichihara, K

    1986-12-01

    The effect of several kinds of antianginal drugs: nitrates, coronary vasodilators, beta-adrenergic blocking agents and calcium entry blocking agents on the myocardial metabolism and myocardial acidosis during ischemia was studied in the dog heart in vivo. Ischemia was induced by ligating the left anterior descending coronary artery. Ischemia accelerated anaerobic metabolism in the myocardium, in which glycogen breakdown, accumulation of glycolytic intermediates, loss of high energy phosphate and tissue acidosis occurred. Nitroglycerin, beta-adrenergic blocking agents such as propranolol, and some calcium entry blocking agents such as diltiazem and flunarizine prevented the myocardial metabolism from shifting to an anaerobic metabolism in spite of ischemia. However, coronary vasodilators and the dihydropyridine type of calcium entry blocking agents were not capable of reducing changes in the myocardial metabolism and myocardial acidosis during ischemia. The author makes a point in the present review that all the drugs which dilate coronary artery are not always effective on the ischemic myocardium. PMID:3549484

  14. Insulin-regulated aminopeptidase deficiency provides protection against ischemic stroke in mice.

    PubMed

    Pham, Vi; Albiston, Anthony L; Downes, Catherine E; Wong, Connie H Y; Diwakarla, Shanti; Ng, Leelee; Lee, Seyoung; Crack, Peter J; Chai, Siew Yeen

    2012-04-10

    Recent studies have demonstrated that angiotensin IV (Ang IV) provides protection against brain injury caused by cerebral ischemia. Ang IV is a potent inhibitor of insulin-regulated aminopeptidase (IRAP). Therefore, we examined the effect of IRAP gene inactivation on neuroprotection following transient middle cerebral artery occlusion (MCAo) in mice. IRAP knockout mice and wild-type controls were subjected to 2 h of transient MCAo using the intraluminal filament technique. Twenty-four hours after reperfusion, neurological deficits of the stroke-induced mice were assessed and infarct volumes were measured by TTC staining. The cerebral infarct volume was significantly reduced in the IRAP knockout mice compared to wild-type littermates with corresponding improvement in neurological performance at 24 h post-ischemia. An increase in compensatory cerebral blood flow during MCAo was observed in the IRAP knockout animals with no differences in cerebral vascular anatomy detected. The current study demonstrates that deletion of the IRAP gene protects the brain from ischemic damage analogous to the effect of the IRAP inhibitor, Ang IV. This study indicates that IRAP is potentially a new therapeutic target for the development of treatment for ischemic stroke. PMID:21895534

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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

  2. [Intervention effect of Tibetan patent medicine Ruyi Zhenbao pills in acute ischemic stroke in rats].

    PubMed

    Liu, Rui-ying; Wu, Wei-jie; Tan, Rui; Xie, Bin; Zhong, Zhen-dong; He, Jing-ping; Chen, Yao; Kang, Xin-li

    2015-02-01

    Ischemic stroke is a primary cause of death and long-term disability all over the world. This disease is resulted from ischemia and hypoxia in brain tissues because of insufficient blood supply and causes a series of physiochemical metabolism disorders and physiological dysfunction. Its high disability ratio has bright huge burdens to society, governments and families. However, there is not efficacious medicine to treat it. In this study, a right middle cerebral artery occlusion was established in rats to observe the multi-path and multi-aspect intervention effects of Tibetan patent medicine Ruyi Zhenbao pills in reducing injuries to Nissl bodies, cerebral edema and inflammatory reactions and preventing cellular apoptosis, in order to lay a foundation for defining its therapeutic mechanism in acute ischemic stroke. PMID:26084187

  3. 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

  4. 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

  5. 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

  6. 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.

  7. Chronic oleoylethanolamide treatment improves spatial cognitive deficits through enhancing hippocampal neurogenesis after transient focal cerebral ischemia.

    PubMed

    Yang, Li-Chao; Guo, Han; Zhou, Hao; Suo, Da-Qin; Li, Wen-Jun; Zhou, Yu; Zhao, Yun; Yang, Wu-Shuang; Jin, Xin

    2015-04-15

    Oleoylethanolamide (OEA) has been shown to have neuroprotective effects after acute cerebral ischemic injury. The aim of this study was to investigate the effects of chronic OEA treatment on ischemia-induced spatial cognitive impairments, electrophysiology behavior and hippocampal neurogenesis. Daily treatments of 30 mg/kg OEA significantly ameliorated spatial cognitive deficits and attenuated the inhibition of long-term potentiation (LTP) in the middle cerebral artery occlusion (MCAO) rat model. Moreover, OEA administration improved cognitive function in a manner associated with enhanced neurogenesis in the hippocampus. Further study demonstrated that treatment with OEA markedly increased the expressions of brain-derived neurotrophic factor (BDNF) and peroxisome proliferator-activated receptors α (PPARα). Our data suggest that chronic OEA treatment can exert functional recovery of cognitive impairments and neuroprotective effects against cerebral ischemic insult in rats via triggering of neurogenesis in the hippocampus, which supports the therapeutic use of OEA for cerebral ischemia. PMID:25748831

  8. 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

    2016-03-01

    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

  9. 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.

  10. Ischemic Stroke after Heart Transplantation.

    PubMed

    Acampa, Maurizio; Lazzerini, Pietro Enea; Guideri, Francesca; Tassi, Rossana; Martini, Giuseppe

    2016-05-01

    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

  11. 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

  12. 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

  13. CD28 superagonist-mediated boost of regulatory T cells increases thrombo-inflammation and ischemic neurodegeneration during the acute phase of experimental stroke.

    PubMed

    Schuhmann, Michael K; Kraft, Peter; Stoll, Guido; Lorenz, Kristina; Meuth, Sven G; Wiendl, Heinz; Nieswandt, Bernhard; Sparwasser, Tim; Beyersdorf, Niklas; Kerkau, Thomas; Kleinschnitz, Christoph

    2015-01-01

    While the detrimental role of non-regulatory T cells in ischemic stroke is meanwhile unequivocally recognized, there are controversies about the properties of regulatory T cells (Treg). The aim of this study was to elucidate the role of Treg by applying superagonistic anti-CD28 antibody expansion of Treg. Stroke outcome, thrombus formation, and brain-infiltrating cells were determined on day 1 after transient middle cerebral artery occlusion. Antibody-mediated expansion of Treg enhanced stroke size and worsened functional outcome. Mechanistically, Treg increased thrombus formation in the cerebral microvasculature. These findings confirm that Treg promote thrombo-inflammatory lesion growth during the acute stage of ischemic stroke. PMID:25315859

  14. 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

  15. Diverse functions of pericytes in cerebral blood flow regulation and ischemia

    PubMed Central

    Fernández-Klett, Francisco; Priller, Josef

    2015-01-01

    Pericytes are mural cells with contractile properties. Here, we provide evidence that microvascular pericytes modulate cerebral blood flow in response to neuronal activity (‘functional hyperemia'). Besides their role in neurovascular coupling, pericytes are responsive to brain damage. Cerebral ischemia is associated with constrictions and death of capillary pericytes, followed by fibrotic reorganization of the ischemic tissue. The data suggest that precapillary arterioles and capillaries are major sites of hemodynamic regulation in the brain. PMID:25853910

  16. 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

  17. 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

  18. 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

  19. 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

  20. Tocotrienol vitamin E protects against preclinical canine ischemic stroke by inducing arteriogenesis.

    PubMed

    Rink, Cameron; Christoforidis, Greg; Khanna, Savita; Peterson, Laura; Patel, Yojan; Khanna, Suchin; Abduljalil, Amir; Irfanoglu, Okan; Machiraju, Raghu; Bergdall, Valerie K; Sen, Chandan K

    2011-11-01

    Vitamin E consists of tocopherols and tocotrienols, in which α-tocotrienol is the most potent neuroprotective form that is also effective in protecting against stroke in rodents. As neuroprotective agents alone are insufficient to protect against stroke, we sought to test the effects of tocotrienol on the cerebrovascular circulation during ischemic stroke using a preclinical model that enables fluoroscopy-guided angiography. Mongrel canines (mean weight=26.3±3.2 kg) were supplemented with tocotrienol-enriched (TE) supplement (200 mg b.i.d, n=11) or vehicle placebo (n=9) for 10 weeks before inducing transient middle cerebral artery (MCA) occlusion. Magnetic resonance imaging was performed 1 hour and 24 hours post reperfusion to assess stroke-induced lesion volume. Tocotrienol-enriched supplementation significantly attenuated ischemic stroke-induced lesion volume (P<0.005). Furthermore, TE prevented loss of white matter fiber tract connectivity after stroke as evident by probabilistic tractography. Post hoc analysis of cerebral angiograms during MCA occlusion revealed that TE-supplemented canines had improved cerebrovascular collateral circulation to the ischemic MCA territory (P<0.05). Tocotrienol-enriched supplementation induced arteriogenic tissue inhibitor of metalloprotease 1 and subsequently attenuated the activity of matrix metalloproteinase-2. Outcomes of the current preclinical trial set the stage for a clinical trial testing the effects of TE in patients who have suffered from transient ischemic attack and are therefore at a high risk for stroke. PMID:21673716

  1. 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

  2. Hypoxic and ischemic hypoxia exacerbate brain injury associated with metabolic encephalopathy in laboratory animals.

    PubMed Central

    Vexler, Z S; Ayus, J C; Roberts, T P; Fraser, C L; Kucharczyk, J; Arieff, A I

    1994-01-01

    Hypoxemia is a major comorbid factor for permanent brain damage in several metabolic encephalopathies. To determine whether hypoxia impairs brain adaptation to hyponatremia, worsening brain edema, we performed in vitro and in vivo studies in cats and rats with hyponatremia plus either ischemic or hypoxic hypoxia. Mortality with hypoxic hypoxia was 0%; with hyponatremia, 22%; and with hyponatremia+hypoxia, 100%. Hyponatremia in cats produced brain edema, with a compensatory decrease of brain sodium. Ischemic hypoxia also resulted in brain edema, but with elevation of brain sodium. However, when ischemic hypoxia was superimposed upon hyponatremia, there was elevation of brain sodium with further elevation of water. Outward sodium transport in cat cerebral cortex synaptosomes was measured via three major pathways through which brain osmolality can be decreased. After hyponatremia, sodium transport was significantly altered such that brain cell osmolality would decrease: 44% increase in Na(+)-K(+)-ATPase transport activity (ouabain inhibitable); 26% decrease in amiloride-sensitive sodium uptake. The change in veratridine-stimulated sodium uptake was not significant (P > 0.05). When ischemic hypoxia was superimposed upon hyponatremia, all of the cerebral adaptive changes induced by hyponatremia alone were eliminated. Thus, hypoxia combined with hyponatremia produces a major increase in brain edema and mortality, probably by eliminating the compensatory mechanisms of sodium transport initiated by hyponatremia that tend to minimize brain swelling. Images PMID:8282795

  3. The role of autophagic and lysosomal pathways in ischemic brain injury

    PubMed Central

    Gu, Zhaohua; Sun, Yinyi; Liu, Kangyong; Wang, Fen; Zhang, Ting; Li, Qiang; Shen, Liwei; Zhou, Ling; Dong, Liang; Shi, Nan; Zhang, Qian; Zhang, Wei; Zhao, Meizhen; Sun, Xiaojiang

    2013-01-01

    Autophagy is involved in neural cell death after cerebral ischemia. Our previous studies showed that rapamycin-induced autophagy decreased the rate of apoptosis, but the rate of apoptosis was creased after the autophagy inhibitor, 3-methyladenine, was used. In this study, a suture-occluded method was performed to generate a rat model of brain ischemia. Under a transmission electron microscope, autophagic bodies and autophagy lysosomes were markedly accumulated in neurons at 4 hours post brain ischemic injury, with their numbers gradually reducing over time. Western blotting demonstrated that protein levels of light chain 3-II and cathepsin B were significantly increased within 4 hours of ischemic injury, but these levels were not persistently upregulated over time. Confocal microscopy showed that autophagy was mainly found in neurons with positive light chain 3 signal. Injection of rapamycin via tail vein promoted the occurrence of autophagy in rat brain tissue after cerebral ischemia and elevated light chain 3 and cathepsin B expression. However, injection of 3-methyladenine significantly diminished light chain 3-II and cathepsin B expression. Results verified that autophagic and lysosomal activity is increased in ischemic neurons. Abnormal components in cells can be eliminated through upregulating cell autophagy or inhibiting autophagy after ischemic brain injury, resulting in a dynamic balance of substances in cells. Moreover, drugs that interfere with autophagy may be potential therapies for the treatment of brain injury. PMID:25206520

  4. 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

  5. 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

  6. Delayed Postconditioning Protects against Focal Ischemic Brain Injury in Rats

    PubMed Central

    Ren, Chuancheng; Gao, Xuwen; Niu, Gang; Yan, Zhimin; Chen, Xiaoyuan; Zhao, Heng

    2008-01-01

    Background We and others have reported that rapid ischemic postconditioning, interrupting early reperfusion after stroke, reduces infarction in rats. However, its extremely short therapeutic time windows, from a few seconds to minutes after reperfusion, may hinder its clinical translation. Thus, in this study we explored if delayed postconditioning, which is conducted a few hours after reperfusion, offers protection against stroke. Methods and Results Focal ischemia was generated by 30 min occlusion of bilateral common carotid artery (CCA) combined with permanent occlusion of middle cerebral artery (MCA); delayed postconditioning was performed by repetitive, brief occlusion and release of the bilateral CCAs, or of the ipsilateral CCA alone. As a result, delayed postconditioning performed at 3h and 6h after stroke robustly reduced infarct size, with the strongest protection achieved by delayed postconditioning with 6 cycles of 15 min occlusion/15 min release of the ipsilateral CCA executed from 6h. We found that this delayed postconditioning provided long-term protection for up to two months by reducing infarction and improving outcomes of the behavioral tests; it also attenuated reduction in 2-[18F]-fluoro-2-deoxy-D-glucose (FDG)-uptake therefore improving metabolism, and reduced edema and blood brain barrier leakage. Reperfusion in ischemic stroke patients is usually achieved by tissue plasminogen activator (tPA) application, however, t-PA's side effect may worsen ischemic injury. Thus, we tested whether delayed postconditioning counteracts the exacerbating effect of t-PA. The results showed that delayed postconditioning mitigated the worsening effect of t-PA on infarction. Conclusion Delayed postconditioning reduced ischemic injury after focal ischemia, which opens a new research avenue for stroke therapy and its underlying protective mechanisms. PMID:19066627

  7. 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.

  8. [Ischemic Stroke, Excitatory Amino Acids Toxicity and the Adjustment of Acupuncture Intervention].

    PubMed

    Li, Xiao-xiao; Lu, Sheng-feng; Zhu, Bing-mei; Fu, Shu-ping

    2016-04-01

    Excitatory amino acids toxicity is an onset causation of cerebral ischemia injury cascade reaction, and eventually leading to brain cell necrosis and apoptosis. Acupuncture is reported to be effective for ischemic stroke in clinical practice and animal experiments, but its mechanism is still under exploring. In this paper the authors introduce the research status of antiexcitatory amino acids toxicity effect of acupuncture in ischemic stroke animals by summarizing its effects on subunits of ionotropic glutamate receptor (NMDA/AMPA) and metabotropic glutamate receptors (mGluRs), and on astrocyte activities. Results indicated that acupuncture intervention may down-regulate the expression levels of cerebral multi-types (NR 1, NR 2 B) of glutamate NMDA receptors, up-regulate expression of glutamate transporter-1, NR 2 A, cannabinoid receptor (CBR) type 1 and 2, and suppress activities of cerebral astrocytes, reduce the content of extracellular glutamate to lower its toxicity and to improve stroke at last. The present paper may provide a reference for acupuncture research on ischemic brain injury. PMID:27323449

  9. Tissue-Type Plasminogen Activator Regulates the Neuronal Uptake of Glucose in the Ischemic Brain

    PubMed Central

    Wu, Fang; Wu, Jialing; Nicholson, Andrew D.; Echeverry, Ramiro; Haile, Woldeab B.; Catano, Marcela; An, Jie; Lee, Andrew K.; Duong, Duc; Dammer, Eric B.; Seyfried, Nicholas T.; Tong, Frank C.; Votaw, John R.; Medcalf, Robert; Yepes, Manuel

    2012-01-01

    The ability to sense and adapt to hypoxic conditions plays a pivotal role in neuronal survival. Hypoxia induces the release of tissue-type plasminogen activator (tPA) from cerebral cortical neurons. We found that the release of neuronal tPA or treatment with recombinant tPA (rtPA) promotes cell survival in cerebral cortical neurons previously exposed to hypoxic conditions in vitro or experimental cerebral ischemia in vivo. Our studies using liquid chromatography and tandem mass spectrometry revealed that tPA activates the mammalian target of rapamycin (mTOR) pathway which adapts cellular processes to the availability of energy and metabolic resources. We found that mTOR activation leads to accumulation of the hypoxia-inducible factor-1α (HIF-1α) and induction and recruitment to the cell membrane of the HIF-1α-regulated neuronal transporter of glucose GLUT3. Accordingly, in vivo positron emission tomography studies with 18-fluorodeoxyglucose in mice overexpressing tPA in neurons show that neuronal tPA induces the uptake of glucose in the ischemic brain and that this effect is associated with decrease in the volume of the ischemic lesion and improved neurological outcome following the induction of ischemic stroke. Our data indicate that tPA activates a cell signaling pathway that allows neurons to sense and adapt to oxygen and glucose deprivation. PMID:22815500

  10. Cerebral perturbations during exercise in hypoxia.

    PubMed

    Verges, Samuel; Rupp, Thomas; Jubeau, Marc; Wuyam, Bernard; Esteve, François; Levy, Patrick; Perrey, Stéphane; Millet, Guillaume Y

    2012-04-15

    Reduction of aerobic exercise performance observed under hypoxic conditions is mainly attributed to altered muscle metabolism due to impaired O(2) delivery. It has been recently proposed that hypoxia-induced cerebral perturbations may also contribute to exercise performance limitation. A significant reduction in cerebral oxygenation during whole body exercise has been reported in hypoxia compared with normoxia, while changes in cerebral perfusion may depend on the brain region, the level of arterial oxygenation and hyperventilation induced alterations in arterial CO(2). With the use of transcranial magnetic stimulation, inconsistent changes in cortical excitability have been reported in hypoxia, whereas a greater impairment in maximal voluntary activation following a fatiguing exercise has been suggested when arterial O(2) content is reduced. Electromyographic recordings during exercise showed an accelerated rise in central motor drive in hypoxia, probably to compensate for greater muscle contractile fatigue. This accelerated development of muscle fatigue in moderate hypoxia may be responsible for increased inhibitory afferent signals to the central nervous system leading to impaired central drive. In severe hypoxia (arterial O(2) saturation <70-75%), cerebral hypoxia per se may become an important contributor to impaired performance and reduced motor drive during prolonged exercise. This review examines the effects of acute and chronic reduction in arterial O(2) (and CO(2)) on cerebral blood flow and cerebral oxygenation, neuronal function, and central drive to the muscles. Direct and indirect influences of arterial deoxygenation on central command are separated. Methodological concerns as well as future research avenues are also considered. PMID:22319046

  11. 3-N-butylphthalide improves neuronal morphology after chronic cerebral ischemia.

    PubMed

    Zhao, Wanhong; Luo, Chao; Wang, Jue; Gong, Jian; Li, Bin; Gong, Yingxia; Wang, Jun; Wang, Hanqin

    2014-04-01

    3-N-butylphthalide is an effective drug for acute ischemic stroke. However, its effects on chronic cerebral ischemia-induced neuronal injury remain poorly understood. Therefore, this study ligated bilateral carotid arteries in 15-month-old rats to simulate chronic cerebral ischemia in aged humans. Aged rats were then intragastrically administered 3-n-butylphthalide. 3-N-butylphthalide administration improved the neuronal morphology in the cerebral cortex and hippocampus of rats with chronic cerebral ischemia, increased choline acetyltransferase activity, and decreased malondialdehyde and amyloid beta levels, and greatly improved cognitive function. These findings suggest that 3-n-butylphthalide alleviates oxidative stress caused by chronic cerebral ischemia, improves cholinergic function, and inhibits amyloid beta accumulation, thereby improving cerebral neuronal injury and cognitive deficits. PMID:25206879

  12. 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.

  13. HYPERTENSIVE-ISCHEMIC LEG ULCERS

    PubMed Central

    Farber, Eugene M.; Schmidt, Otto E. L.

    1950-01-01

    Ischemic ulcers of the leg having characteristics different from those of ordinary leg ulcers have been observed in a small number of hypertensive patients, mostly women, during the past few years. Such ulcers are usually located above the ankle. They begin with a small area of purplish discoloration at the site of slight trauma, and progress to acutely tender ulceration. In studies of tissue removed from the margin and the base of an ulcer of this kind, obliterative arteriolar sclerotic changes, ischemic-appearing connective tissue and inflammatory changes were noted. Two additional cases are reported. ImagesFigure 1.Figure 2.Figure 3.Figure 4. PMID:15398887

  14. 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

  15. 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

  16. [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

  17. 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

  18. Combination of early and delayed ischemic postconditioning enhances brain-derived neurotrophic factor production by upregulating the ERK-CREB pathway in rats with focal ischemia

    PubMed Central

    WU, HUI; YANG, SHAO-FENG; DAI, JIONG; QIU, YONG-MING; MIAO, YI-FENG; ZHANG, XIAO-HUA

    2015-01-01

    Ischemic postconditioning, including early and delayed ischemic postconditioning, has been recognized as a simple and promising strategy in the treatment of stroke. However, the effects of the combination of early and delayed ischemic postconditioning, and the mechanisms underlying these effects, remain unclear. The aim of the present study was to determine whether the combination of early and delayed ischemic postconditioning offers greater protection against stroke, and enhances the production of brain-derived neurotrophic factor (BDNF). A combination of early and delayed ischemic postconditioning was established by repeated, transient occlusion and reperfusion of the ipsilateral common carotid artery in a rat model of middle cerebral artery occlusion. Infarct size, motor function, cerebral blood flow and brain edema were then evaluated, in order to confirm the effects of combinative ischemic postconditioning. TUNEL staining was used to analyze the rate of apoptosis of cells in the penumbral area. BDNF, extracellular signal-regulated kinases 1/2 (ERK1/2) and cAMP response element-binding protein (CREB) expression was detected using immunofluorescence staining and western blot analysis. The results of the present study indicated that the combination of early and delayed ischemic postconditioning further reduced the infarct volume, stabilized cerebral blood disturbance and attenuated neuronal apoptosis, compared with either alone. However, combinative postconditioning exerted the same effect on neurological function and brain edema, compared with early or delayed ischemic postconditioning alone. Further investigation indicated that combinative ischemic postconditioning increased the expression of BDNF, and a significantly higher number of BDNF-positive cells was observed in neurons and astrocytes from the combined group than in the early or delayed groups. Combinative ischemic postconditioning also induced the phosphorylation of ERK1/2 and CREB in the cortex

  19. Critical Care for Patients with Massive Ischemic Stroke

    PubMed Central

    Koh, Younsuck; Choi, H. Alex; Lee, Kiwon

    2014-01-01

    Malignant cerebral edema following ischemic stroke is life threatening, as it can cause inadequate blood flow and perfusion leading to irreversible tissue hypoxia and metabolic crisis. Increased intracranial pressure and brain shift can cause herniation syndrome and finally brain death. Multiple randomized clinical trials have shown that preemptive decompressive hemicraniectomy effectively reduces mortality and morbidity in patients with malignant middle cerebral artery infarction. Another life-saving decompressive surgery is suboccipital craniectomy for patients with brainstem compression by edematous cerebellar infarction. In addition to decompressive surgery, cerebrospinal fluid drainage by ventriculostomy should be considered for patients with acute hydrocephalus following stroke. Medical treatment begins with sedation, analgesia, and general measures including ventilatory support, head elevation, maintaining a neutral neck position, and avoiding conditions associated with intracranial hypertension. Optimization of cerebral perfusion pressure and reduction of intracranial pressure should always be pursued simultaneously. Osmotherapy with mannitol is the standard treatment for intracranial hypertension, but hypertonic saline is also an effective alternative. Therapeutic hypothermia may also be considered for treatment of brain edema and intracranial hypertension, but its neuroprotective effects have not been demonstrated in stroke. Barbiturate coma therapy has been used to reduce metabolic demand, but has become less popular because of its systemic adverse effects. Furthermore, general medical care is critical because of the complex interactions between the brain and other organ systems. Some challenging aspects of critical care, including ventilator support, sedation and analgesia, and performing neurological examinations in the setting of a minimal stimulation protocol, are addressed in this review. PMID:25328873

  20. Acute Chagas Disease Induces Cerebral Microvasculopathy in Mice

    PubMed Central

    Nisimura, Lindice Mitie; Estato, Vanessa; de Souza, Elen Mello; Reis, Patricia A.; Lessa, Marcos Adriano; Castro-Faria-Neto, Hugo Caire; Pereira, Mirian Claudia de Souza; Tibiriçá, Eduardo; Garzoni, Luciana Ribeiro

    2014-01-01

    Cardiomyopathy is the main clinical form of Chagas disease (CD); however, cerebral manifestations, such as meningoencephalitis, ischemic stroke and cognitive impairment, can also occur. The aim of the present study was to investigate functional microvascular alterations and oxidative stress in the brain of mice in acute CD. Acute CD was induced in Swiss Webster mice (SWM) with the Y strain of Trypanosoma cruzi (T. cruzi). Cerebral functional capillary density (the number of spontaneously perfused capillaries), leukocyte rolling and adhesion and the microvascular endothelial-dependent response were analyzed over a period of fifteen days using intravital video-microscopy. We also evaluated cerebral oxidative stress with the thiobarbituric acid reactive species TBARS method. Compared with the non-infected group, acute CD significantly induced cerebral functional microvascular alterations, including (i) functional capillary rarefaction, (ii) increased leukocyte rolling and adhesion, (iii) the formation of microvascular platelet-leukocyte aggregates, and (iv) alteration of the endothelial response to acetylcholine. Moreover, cerebral oxidative stress increased in infected animals. We concluded that acute CD in mice induced cerebral microvasculopathy, characterized by a reduced incidence of perfused capillaries, a high number of microvascular platelet-leukocyte aggregates, a marked increase in leukocyte-endothelium interactions and brain arteriolar endothelial dysfunction associated with oxidative stress. These results suggest the involvement of cerebral microcirculation alterations in the neurological manifestations of CD. PMID:25010691

  1. 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.

  2. Transient Aortic Occlusion Augments Collateral Blood Flow and Reduces Mortality During Severe Ischemia due to Proximal Middle Cerebral Artery Occlusion.

    PubMed

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

    2016-04-01

    Cerebral collateral circulation provides alternative vascular routes for blood to reach ischemic tissues during stroke. Collateral therapeutics attempt to augment flow through these collateral channels to reduce ischemia and brain damage during acute ischemic stroke. Transient aortic occlusion (TAO) has pre-clinical data suggesting that it can augment collateral blood flow and clinical data suggesting a benefit for patients with moderate cortical strokes. By diverting blood from the periphery towards the cerebral circulation, TAO has the potential to augment primary collateral flow at the circle of Willis and thereby improve outcome even during large, hemispheric strokes. Using proximal middle and anterior cerebral artery occlusion in rats, we demonstrate that TAO reduces mortality and improves collateral blood flow in severely ischemic animals. As such, TAO may be an effective therapy to reduce early mortality during severe ischemia associated with proximal occlusions. PMID:26706246

  3. 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

  4. Evaluation of mean diffusion and kurtosis MRI mismatch in subacute ischemic stroke: Comparison with NIHSS score.

    PubMed

    Guo, Yue-Lin; Zhang, Zhong-Ping; Zhang, Gui-Shan; Kong, Ling-Mei; Rao, Hai-Bing; Chen, Wei; Wang, Guang-Wen; Shen, Zhi-Wei; Zheng, Wen-Bin; Wu, Ren-Hua

    2016-08-01

    Neurological deterioration (ND) is a devastating complication following ischemic stroke. This study aimed to identify the differences in lesion characteristics in subacute ischemic stroke patients with and without ND using diffusional kurtosis imaging (DKI), as well as to confirm the responsible lesions that may lead to ND, as assessed by the National Institutes of Health Stroke Scale (NIHSS) score. Seventy-nine patients with subacute cerebral infarction were allocated to the ND (-) and ND (+) groups according to the NIHSS score and lesion number. The mean diffusion (MD) lesions were significantly larger than the mean kurtosis (MK) deficits in the ND (+) group (P<0.05); however, there was no significant difference in the ND (-) group (P>0.05). The MD and MK in the lesion recovered to normal levels over time; however, the recovery trends in the ND (+) group were substantially slower than the ND (-) group. The differences between the two groups were only significant regarding the MK (p<0.05). Furthermore, multiple infarction lesions exhibited good consistency in the ND (-) group, but were non-homogeneous in the ND (+) group. To the best of our knowledge, this is the first study to demonstrate that a significant MD/MK mismatch and heterogeneity of multiple ischemic lesions on MK in subacute ischemic stroke may represent a new expansion of an ischemic lesion or acute reinfarction, which is closely related to ND. PMID:27208488

  5. 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

  6. 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. PMID:27275837

  7. Treatment of stroke with liposomal neuroprotective agents under cerebral ischemia conditions.

    PubMed

    Fukuta, Tatsuya; Ishii, Takayuki; Asai, Tomohiro; Sato, Akihiko; Kikuchi, Takashi; Shimizu, Kosuke; Minamino, Tetsuo; Oku, Naoto

    2015-11-01

    Since the proportion of patients given thrombolytic therapy with tissue plasminogen activator (t-PA) is very limited because of the narrow therapeutic window, the development of new therapies for ischemic stroke has been desired. We previously reported that liposomes injected intravenously accumulate in the ischemic region of the brain via disruption of the blood-brain barrier that occurs under cerebral ischemia. In the present study, we investigated the efficacy of a liposomal neuroprotective agent in middle cerebral artery occlusion (MCAO) rats to develop ischemic stroke therapy prior to the recovery of cerebral blood flow. For this purpose, PEGylated liposomes encapsulating FK506 (FK506-liposomes) were prepared and injected intravenously into MCAO rats after a 1-h occlusion. This treatment significantly suppressed the expansion of oxidative stress and brain cell damage. In addition, administration of FK506-liposomes before reperfusion significantly ameliorated motor function deficits of the rats caused by ischemia/reperfusion injury. These findings suggest that FK506-liposomes effectively exerted a neuroprotective effect during ischemic conditions, and that combination therapy with a liposomal neuroprotectant plus t-PA could be a promising therapeutic strategy for ischemic stroke. PMID:26455340

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

    PubMed Central

    Zhang, Chao; Wen, Yan; Fan, Xiaonong; Yang, Sha; Tian, Guang; Zhou, Xueyi; Chen, Yaqiong; Meng, Zhihong

    2015-01-01

    Microarray analysis was used to investigate the changes of gene expression of ischemic stroke and acupuncture intervention in middle cerebral artery occlusion (MCAo) rat brain. Results showed that acupuncture intervention had a remarkable improvement in neural deficit score, cerebral blood flow, and cerebral infarction volume of MCAo rats. Microarray analysis showed that a total of 627 different expression genes were regulated in ischemic stroke. 417 genes were upregulated and 210 genes were downregulated. A total of 361 different expression genes were regulated after acupuncture intervention. Three genes were upregulated and 358 genes were downregulated. The expression of novel genes after acupuncture intervention, including Tph1 and Olr883, was further analyzed by Real-Time Quantitative Polymerase Chain Reaction (RT-PCR). Upregulation of Tph1 and downregulation of Olr883 indicated that the therapeutic effect of acupuncture for ischemic stroke may be closely related to the suppression of poststroke depression and regulation of olfactory transduction. In conclusion, the present study may enrich our understanding of the multiple pathological process of ischemic brain injury and indicate possible mechanisms of acupuncture on ischemic stroke. PMID:25861363

  9. [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

  10. 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

  11. 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

  12. 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.

  13. Targeting caspase-6 and caspase-8 to promote neuronal survival following ischemic stroke

    PubMed Central

    Shabanzadeh, A P; D'Onofrio, P M; Monnier, P P; Koeberle, P D

    2015-01-01

    Previous studies show that caspase-6 and caspase-8 are involved in neuronal apoptosis and regenerative failure after trauma of the adult central nervous system (CNS). In this study, we evaluated whether caspase-6 or -8 inhibitors can reduce cerebral or retinal injury after ischemia. Cerebral infarct volume, relative to appropriate controls, was significantly reduced in groups treated with caspase-6 or -8 inhibitors. Concomitantly, these treatments also reduced neurological deficits, reduced edema, increased cell proliferation, and increased neurofilament levels in the injured cerebrum. Caspase-6 and -8 inhibitors, or siRNAs, also increased retinal ganglion cell survival at 14 days after ischemic injury. Caspase-6 or -8 inhibition also decreased caspase-3, -6, and caspase-8 cleavage when assayed by western blot and reduced caspase-3 and -6 activities in colorimetric assays. We have shown that caspase-6 or caspase-8 inhibition decreases the neuropathological consequences of cerebral or retinal infarction, thereby emphasizing their importance in ischemic neuronal degeneration. As such, caspase-6 and -8 are potential targets for future therapies aimed at attenuating the devastating functional losses that result from retinal or cerebral stroke. PMID:26539914

  14. 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, ...

  15. Cerebral Infarction Caused by a Tortuous Subclavian Artery: a Case Report

    PubMed Central

    Jeong, Eun Hye; Yu, Hyun-Jeung; Choi, Soung Sil; Rhim, Jong Kook; Kwon, Kye Won; Roh, Sook Young

    2014-01-01

    Tortuous arteries are common clinical observation. Although mild tortuosity is asymptomatic, severe tortuosity can lead to ischemic attack in several organs. With advances in imaging technology, an increasing number of tortuous vessels have been detected. The purpose of this report is to describe a case of acute cerebral infarction due to tortuous subclavian artery and to review the literature. PMID:24644532

  16. [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

  17. 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

  18. 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.

  19. [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

  20. H₂S attenuates cognitive deficits through Akt1/JNK3 signaling pathway in ischemic stroke.

    PubMed

    Wen, Xiangru; Qi, Dashi; Sun, Ying; Huang, Xiaojing; Zhang, Fang; Wu, Jian; Fu, Yanyan; Ma, Kai; Du, Yang; Dong, Hongyan; Liu, YongHai; Liu, Hongzhi; Song, Yuanjian

    2014-08-01

    Neuronal damage in the hippocampal formation which is more sensitive to ischemic stimulation and easily injured will cause severe learning and memory impairment. Therefore, inhibiting hippocampal neuron injuries is the main contributor for learning and memory impairment during cerebral ischemia. Hydrogen sulfide (H2S) is a new type of neurotransmitter that regulates the nervous, circulatory and immune systems as well as various adverse factors that can reduce cerebral vascular or brain parenchyma injury. During an ischemic stroke, H2S inhibits hippocampal neuronal damage, reducing learning and memory impairment. However, this molecular mechanism has not been elucidated clearly. In this study, we established four-vessel occlusion model in rats with cerebral ischemia. We found that NaHS (28 mmol/kg, intraperitoneally, for 7 days before ischemia), donor of H2S, significantly shortened the distance and time of loading onto the hidden platform in the positioning navigation process, decreased the latency in the space exploration process when cognitive testing with Morris water maze was performed during ischemic stroke in rats. NaHS also significantly shortened latency and reduced the number of errors in the platform diving experiment. The survival rate of neurons in the CA1 area of the hippocampus and the phosphorylation of Akt in the neurons were increased, the phosphorylation ASK1 and JNK3 were inhibited by NaHS. After an intracerebroventricular injection of LY294002 (inhibitor of PI3K/Akt, 10 μL, 100 nmol in 25% DMSO in PBS), the above effects of NaHS were attenuated. These findings suggest that H2S may improve the survival rate of hippocampal neurons and reduce the impairment of learning and memory by increasing the phosphorylation of Akt, inhibiting the phosphorylation of ASK1 and JNK3 in rats with induced ischemic stroke. PMID:24768640

  1. 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

  2. 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

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

    PubMed

    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

  4. 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

  5. Extracellular Spermine Exacerbates Ischemic Neuronal Injury through Sensitization of ASIC1a Channels to Extracellular Acidosis

    PubMed Central

    Duan, Bo; Wang, Yi-Zhi; Yang, Tao; Chu, Xiang-Ping; Yu, Ye; Huang, Yu; Cao, Hui; Hansen, Jillian; Simon, Roger P.; Zhu, Michael X.; Xiong, Zhi-Gang; Xu, Tian-Le

    2011-01-01

    Ischemic brain injury is a major problem associated with stroke. It has been increasingly recognized that acid-sensing ion channels (ASICs) contribute significantly to ischemic neuronal damage, but the underlying mechanism has remained elusive. Here, we show that extracellular spermine, one of the endogenous polyamines, exacerbates ischemic neuronal injury through sensitization of ASIC1a channels to extracellular acidosis. Pharmacological blockade of ASIC1a or deletion of the ASIC1 gene greatly reduces the enhancing effect of spermine in ischemic neuronal damage both in cultures of dissociated neurons and in a mouse model of focal ischemia. Mechanistically, spermine profoundly reduces desensitization of ASIC1a by slowing down desensitization in the open state, shifting steady-state desensitization to more acidic pH, and accelerating recovery between repeated periods of acid stimulation. Spermine-mediated potentiation of ASIC1a activity is occluded by PcTX1 (psalmotoxin 1), a specific ASIC1a inhibitor binding to its extracellular domain. Functionally, the enhanced channel activity is accompanied by increased acid-induced neuronal membrane depolarization and cytoplasmic Ca2+ overload, which may partially explain the exacerbated neuronal damage caused by spermine. More importantly, blocking endogenous spermine synthesis significantly attenuates ischemic brain injury mediated by ASIC1a but not that by NMDA receptors. Thus, extracellular spermine contributes significantly to ischemic neuronal injury through enhancing ASIC1a activity. Our data suggest new neuroprotective strategies for stroke patients via inhibition of polyamine synthesis and subsequent spermine–ASIC interaction. PMID:21307247

  6. United Cerebral Palsy

    MedlinePlus

    ... of UCP blog for the latest updates. 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 ...

  7. Cerebral amyloid angiopathy

    MedlinePlus

    Cerebral amyloid angiopathy is a neurological condition in which proteins called amyloid build up on the walls of the arteries ... The cause of cerebral amyloid angiopathy is unknown. Sometimes, it ... Persons with this condition have deposits of amyloid protein ...

  8. 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 ...

  9. 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

  10. Remote ischemic conditioning for acute ischemic stroke: dawn in the darkness.

    PubMed

    Pan, Jingrui; Li, Xiangpen; Peng, Ying

    2016-07-01

    Stroke is a leading cause of disability with high morbidity and mortality worldwide. Of all strokes, 87% are ischemic. The only approved treatments for acute ischemic stroke are intravenous thrombolysis with alteplase within 4.5 h and thrombectomy within 8 h after symptom onset, which can be applied to just a few patients. During the past decades, ischemic preconditioning has been widely studied to confirm its neuroprotection against subsequent ischemia/reperfusion injury in the brain, including preconditioning in situ or in a remote organ (such as a limb) before onset of brain ischemia, the latter of which is termed as remote ischemic preconditioning. Because acute stroke is unpredicted, ischemic preconditioning is actually not suitable for clinical application. So remote ischemic conditioning performed during or after the ischemic duration of the brain was then designed to study its neuroprotection alone or in combination with alteplase in animals and patients, which is named as remote ischemic perconditioning or remote ischemic postconditioning. As expected, animal experiments and clinical trials both showed exciting results, indicating that an evolution in the treatment for acute ischemic stroke may not be far away. However, some problems or disputes still exist. This review summarizes the research progress and unresolved issues of remote ischemic conditioning (pre-, per-, and post-conditioning) in treating acute ischemic stroke, with the hope of advancing our understanding of this promising neuroprotective strategy for ischemic stroke in the near future. PMID:26812782

  11. [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

  12. Imaging of occlusive thrombi in acute ischemic stroke

    PubMed Central

    Gasparian, GG; Sanossian, N; Shiroishi, MS; Liebeskind, DS

    2015-01-01

    Thrombi, or clots, often occlude proximal segments of the cerebral arterial circulation in acute ischemic stroke. Thromboembolic occlusion or thrombi superimposed on atherosclerotic plaque are the principal focus of acute stroke therapies such as thrombolysis or thrombectomy. We review the imaging characteristics of thrombi on multimodal CT and MRI, angiography and ultrasonography, summarizing recent studies that facilitate therapeutic decision-making from these noninvasive studies. Information about the location, size and imaging characteristics can be ascertained using these techniques. Imaging findings in relation to occlusive thrombus have been correlated with clot pathology, response to therapeutic interventions, and clinical outcome. Diagnostic evaluation of occlusive thrombi on noninvasive studies now constitutes an integral component of acute stroke management. PMID:25545291

  13. Mutant Erythropoietin without Erythropoietic Activity is Neuroprotective against Ischemic Brain Injury

    PubMed Central

    Gan, Yu; Xing, Juan; Jing, Zheng; Stetler, R. Anne; Zhang, Feng; Luo, Yumin; Ji, Xunmin; Gao, Yanqin; Cao, Guodong

    2012-01-01

    Background and Purpose Erythropoietin (EPO) confers potent neuroprotection against ischemic injury. However, treatment for stroke requires high doses and multiple administrations of EPO, which may cause deleterious side effects due to its erythropoietic activity. This study identifies a novel non-erythropoietic mutant EPO (MEPO) and investigates its potential neuroprotective effects and underlying mechanism in animal model of cerebral ischemia. Methods We constructed a series of MEPOs, each containing a single amino acid mutation within the erythropoietic motif, and tested their erythropoietic activity. Using cortical neuronal cultures exposed to NMDA neurotoxicity and a murine model of transient middle cerebral artery occlusion (MCAO), neuroprotection and neurofunctional outcomes were assessed as well as activation of intracellular signaling pathways. Results The serine to isoleucine mutation at position 104 (S104I-EPO) completely abolished the erythropoietic and platelet-stimulating activity of EPO. Administration of S104I-EPO significantly inhibited NMDA-induced neuronal death in primary cultures, and protected against cerebral infarction and neurological deficits with an efficacy similar to that of wild-type EPO. Both S104I-EPO and wild-type EPO activated similar pro-survival signaling pathways, such as PI3K/AKT, MAPK/ERK1/2 and STAT5. Inhibition of PI3K/AKT or MAPK/ERK1/2 signaling pathways significantly attenuated the neuroprotective effects of S104I-EPO, indicating that activation of these pathways underlies the neuroprotective mechanism of MEPO against cerebral ischemia. Conclusions S104I-EPO confers neuroprotective effects comparable to those of wild-type EPO against ischemic brain injury, with the added benefit of lacking erythropoietic and platelet-stimulating side effects. Our novel findings suggest that the non-erythropoietic mutant EPO is a legitimate candidate for ischemic stroke intervention. PMID:22984011

  14. 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

  15. 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…

  16. Advanced cerebral monitoring in neurocritical care.

    PubMed

    Barazangi, Nobl; Hemphill, J Claude

    2008-01-01

    New cerebral monitoring techniques allow direct measurement of brain oxygenation and metabolism. Investigation using these new tools has provided additional insight into the understanding of the pathophysiology of acute brain injury and suggested new ways to guide management of secondary brain injury. Studies of focal brain tissue oxygen monitoring have suggested ischemic thresholds in focal regions of brain injury and demonstrated the interrelationship between brain tissue oxygen tension (P bt O 2 ) and other cerebral physiologic and metabolic parameters. Jugular venous oxygen saturation (SjVO 2 ) monitoring may evaluate global brain oxygen delivery and consumption, providing thresholds for detecting brain hypoperfusion and hyperperfusion. Furthermore, critically low values of P bt O 2 and SjVO 2 have also been predictive of mortality and worsened functional outcome, especially after head trauma. Cerebral microdialysis measures the concentrations of extracellular metabolites which may be relevant to cerebral metabolism or ischemia in focal areas of injury. Cerebral blood flow may be measured in the neurointensive care unit using continuous methods such as thermal diffusion and laser Doppler flowmetry. Initial studies have also attempted to correlate findings from advanced neuromonitoring with neuroimaging using dynamic perfusion computed tomography, positron emission tomography, and Xenon computed tomography. Additionally, new methods of data acquisition, storage, and analysis are being developed to address the increasing burden of patient data from neuromonitoring. Advanced informatics techniques such as hierarchical data clustering, generalized linear models, and heat map dendrograms are now being applied to multivariable patient data in order to better develop physiologic patient profiles to improve diagnosis and treatment. PMID:19127034

  17. 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

  18. Neuroprotective effects of rutaecarpine on cerebral ischemia reperfusion injury

    PubMed Central

    Yan, Chunlin; Zhang, Ji; Wang, Shu; Xue, Guiping; Hou, Yong

    2013-01-01

    Rutaecarpine, an active component of the traditional Chinese medicine Tetradium ruticarpum, has been shown to improve myocardial ischemia reperfusion injury. Because both cardiovascular and cerebrovascular diseases are forms of ischemic vascular disease, they are closely related. We hypothesized that rutaecarpine also has neuroprotective effects on cerebral ischemia reperfusion injury. A cerebral ischemia reperfusion model was established after 84, 252 and 504 μg/kg carpine were given to mice via intraperitoneal injection, daily for 7 days. Results of the step through test, 2,3,5-triphenyl tetrazolium chloride dyeing and oxidative stress indicators showed that rutaecarpine could improve learning and memory ability, neurological symptoms and reduce infarction volume and cerebral water content in mice with cerebral ischemia reperfusion injury. Rutaecarpine could significantly decrease the malondialdehyde content and increase the activities of superoxide dismutase and glutathione peroxidase in mouse brain. Therefore, rutaecarpine could improve neurological function following injury induced by cerebral ischemia reperfusion, and the mechanism of this improvement may be associated with oxidative stress. These results verify that rutaecarpine has neuroprotective effects on cerebral ischemia reperfusion in mice. PMID:25206511

  19. [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

  20. Intravenous thrombolytics for ischemic stroke.

    PubMed

    Barreto, Andrew D

    2011-07-01

    For many decades, intravenous (IV) thrombolytics have been delivered to treat acute thrombosis. Although these medications were originally effective for coronary thrombosis, their mechanisms have proven beneficial for many other disease processes, including ischemic stroke. Treatment paradigms for acute ischemic stroke have largely followed those of cardiology. Specifically, the aim has been to recanalize the occluded artery and to restore perfusion to the brain that remains salvageable. To that end, rapid clot lysis was sought using thrombolytic medicines already proven effective in the coronary arteries. IV-thrombolysis for ischemic stroke began its widespread adoption in the late 1990s after the publication of the National Institute of Neurological Disorders and Stroke study. Since that time, other promising IV-thrombolytics have been developed and tested in human trials, but as of yet, none have been proven better than a placebo. Adjunctive treatments are also being evaluated. The challenge remains balancing reperfusion and salvaging brain tissue with the potential risks of brain hemorrhage. PMID:21638138

  1. 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

  2. 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

  3. [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

  4. 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

  5. Hyperbaric Oxygen Therapy in Acute Ischemic Stroke: A Review

    PubMed Central

    Ding, Zheng; Tong, Wesley C.; Lu, Xiao-Xin; Peng, Hui-Ping

    2014-01-01

    Stroke, also known as cerebrovascular disease, is a common and serious neurological disease, which is also the fourth leading cause of death in the United States so far. Hyperbaric medicine, as an emerging interdisciplinary subject, has been applied in the treatment of cerebral vascular diseases since the 1960s. Now it is widely used to treat a variety of clinical disorders, especially hypoxia-induced disorders. However, owing to the complex mechanisms of hyperbaric oxygen (HBO) treatment, the therapeutic time window and the undefined dose as well as some common clinical side effects (such as middle ear barotrauma), the widespread promotion and application of HBO was hindered, slowing down the hyperbaric medicine development. In August 2013, the US Food and Drug Administration declared artery occlusion as one of the 13 specific indications for HBO therapy. This provides opportunities, to some extent, for the further development of hyperbaric medicine. Currently, the mechanisms of HBO therapy for ischemic stroke are still not very clear. This review focuses on the potential mechanisms of HBO therapy in acute ischemic stroke as well as the time window. PMID:25337089

  6. 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

  7. Cerebral ischemia as an apparent complication of anterior cervical discectomy in a patient with an incomplete circle of Willis.

    PubMed

    Drummond, John C; Englander, Raymond N; Gallo, Catherine J

    2006-03-01

    A 58-yr-old patient sustained a cerebral ischemic injury in the distribution of the carotid artery ipsilateral to retraction during an anterior cervical discectomy. Relative hypotension was permitted during the anesthetic. Angiography revealed an anatomic variant of the circle of Willis that resulted in minimal collateralizaton of the left internal carotid artery territory. The combination of that vascular variant with relative hypotension and some degree of carotid compression appears to have resulted in clinically significant cerebral ischemia. PMID:16492847

  8. [Comparative evaluation of the neuroprotective activity of phenibut and piracetam under experimental cerebral ischemia conditions in rats].

    PubMed

    Tiurenkov, I N; Bagmetov, M N; Epishina, V V; Borodkina, L E; Voronkov, A V

    2006-01-01

    The neuroprotective properties of phenibut and piracetam were studied in rats with cerebral ischemia caused by bilateral irreversible simultaneous occlusion of carotid arteries and gravitational overload in craniocaudal vector. In addition, the effects of both drugs on microcirculation in brain cortex under ischemic injury conditions were studied. Phenibut and (to a lower extent) piracetam reduced a neuralgic deficiency, amnesia, and the degree of cerebral circulation drop, and improved the spontaneous movement and research activity deteriorated by brain ischemia. PMID:16878492

  9. Elevated high-mobility group box 1 levels in patients with cerebral and myocardial ischemia.

    PubMed

    Goldstein, Richard S; Gallowitsch-Puerta, Margot; Yang, Lihong; Rosas-Ballina, Mauricio; Huston, Jared M; Czura, Christopher J; Lee, David C; Ward, Mae F; Bruchfeld, Annette N; Wang, Haichao; Lesser, Martin L; Church, Adam L; Litroff, Adam H; Sama, Andrew E; Tracey, Kevin J

    2006-06-01

    Cerebral and myocardial ischemia, two of the leading causes of morbidity and mortality worldwide, are associated with inflammation that can lead to multiple organ failure and death. High-mobility group box 1(HMGB1), a recently described mediator of lethal systemic inflammation, has been detected in individuals with severe sepsis and hemorrhagic shock, but its role during ischemic injury in humans is unknown. To determine whether systemic HMGB1 levels are elevated after ischemic injury, a prospective observational study was performed in subjects with a diagnosis of either Acute Coronary Syndrome (ACS) or cerebral vascular ischemia (transient ischemic attack or cerebral vascular accident). Subjects (n, 16; age [mean], 67+/-16.3 years) were enrolled in the North Shore-LIJ emergency department within 24 h of symptom onset. Blood samples were collected, and HMGB1 levels analyzed by Western blot analysis using previously described methods (Wang et al. Science. 1999). Control samples were obtained from healthy age- and sex-matched volunteers (n, 16; age [mean], 68+/-15.8 years). Here, we report that serum HMGB1 levels were significantly elevated in both myocardial ischemia subjects (myocardial control serum HMGB1, 1.94+/-2.05 ng/mL, vs. myocardial ischemia serum HMGB1, 159+/-54.3 ng/mL; P<0.001); and in cerebral ischemia subjects (cerebral control serum HMGB1, 16.8+/-10.9 ng/mL, vs. cerebral ischemia serum HMGB1, 218+/-18.8 ng/mL; P<0.001). These results suggest that systemic HMGB1 levels are elevated in human ischemic disease. PMID:16721263

  10. 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

  11. Early identification of potentially salvageable tissue with MRI-based predictive algorithms after experimental ischemic stroke

    PubMed Central

    Bouts, Mark J R J; Tiebosch, Ivo A C W; van der Toorn, Annette; Viergever, Max A; Wu, Ona; Dijkhuizen, Rick M

    2013-01-01

    Individualized stroke treatment decisions can be improved by accurate identification of the extent of salvageable tissue. Magnetic resonance imaging (MRI)-based approaches, including measurement of a ‘perfusion-diffusion mismatch' and calculation of infarction probability, allow assessment of tissue-at-risk; however, the ability to explicitly depict potentially salvageable tissue remains uncertain. In this study, five predictive algorithms (generalized linear model (GLM), generalized additive model, support vector machine, adaptive boosting, and random forest) were tested in their potency to depict acute cerebral ischemic tissue that can recover after reperfusion. Acute T2-, diffusion-, and perfusion-weighted MRI, and follow-up T2 maps were collected from rats subjected to right-sided middle cerebral artery occlusion without subsequent reperfusion, for training of algorithms (Group I), and with spontaneous (Group II) or thrombolysis-induced reperfusion (Group III), to determine infarction probability-based viability thresholds and prediction accuracies. The infarction probability difference between irreversible—i.e., infarcted after reperfusion—and salvageable tissue injury—i.e., noninfarcted after reperfusion—was largest for GLM (20±7%) with highest accuracy of risk-based identification of acutely ischemic tissue that could recover on subsequent reperfusion (Dice's similarity index=0.79±0.14). Our study shows that assessment of the heterogeneity of infarction probability with MRI-based algorithms enables estimation of the extent of potentially salvageable tissue after acute ischemic stroke. PMID:23571283

  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. PMID:26222355

  13. 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

  14. Deficiency in Serine Protease Inhibitor Neuroserpin Exacerbates Ischemic Brain Injury by Increased Postischemic Inflammation

    PubMed Central

    Ludewig, Peter; Bernreuther, Christian; Krasemann, Susanne; Arunachalam, Priyadharshini; Gerloff, Christian; Glatzel, Markus; Magnus, Tim

    2013-01-01

    The only approved pharmacological treatment for ischemic stroke is intravenous administration of plasminogen activator (tPA) to re-canalize the occluded cerebral vessel. Not only reperfusion but also tPA itself can induce an inflammatory response. Microglia are the innate immune cells of the central nervous system and the first immune cells to become activated in stroke. Neuroserpin, an endogenous inhibitor of tPA, is up-regulated following cerebral ischemia. To examine neuroserpin-dependent mechanisms of neuroprotection in stroke, we studied neuroserpin deficient (Ns−/−) mice in an animal model of temporal focal ischemic stroke. Infarct size and neurological outcome were worse in neuroserpin deficient mice even though the fibrinolytic activity in the ischemic brain was increased. The increased infarct size was paralleled by a selective increase in proinflammatory microglia activation in Ns−/− mice. Our results show excessive microglial activation in Ns−/− mice mediated by an increased activity of tPA. This activation results in a worse outcome further underscoring the potential detrimental proinflammatory effects of tPA. PMID:23658802

  15. 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

  16. 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

  17. 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

  18. 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

  19. [Effect of cerebrum compositum preparation on functional state of the central nervous system in elderly patients with ischemic stroke].

    PubMed

    Kuznetsova, S M; Lukach, O I

    2004-01-01

    The article presents the results obtained after having treated patients with ischemic stroke during a rehabilitation period with cerebrum compositum. It has been also studied its influence on psychoemotional condition, bioelectrical activity of brain and cerebral hemodynamics. The results of the conducted trial prove cerebrum compositum remedy to have a harmonious influence on bioelectrical activity of brain and cerebral hemodynamics as well as it improves psychological state, alleviates anxiety and enhances initiative and physical activity of the treated patients. Positive complex influence on functional state of central nervous system of the medication ensure us to recommend cerebrum compositum during rehabilitation of patients having stroke positive anamnesis. PMID:15605833

  20. Selective ROCK2 inhibition in focal cerebral ischemia

    PubMed Central

    Hyun Lee, Jeong; Zheng, Yi; von Bornstadt, Daniel; Wei, Ying; Balcioglu, Aygul; Daneshmand, Ali; Yalcin, Nilufer; Yu, Esther; Herisson, Fanny; Atalay, Yahya B; Kim, Maya H; Ahn, Yong-Joo; Balkaya, Mustafa; Sweetnam, Paul; Schueller, Olivier; Poyurovsky, Masha V; Kim, Hyung-Hwan; Lo, Eng H; Furie, Karen L; Ayata, Cenk

    2014-01-01

    Objective Rho-associated kinase (ROCK) is a key regulator of numerous processes in multiple cell types relevant in stroke pathophysiology. ROCK inhibitors have improved outcome in experimental models of acute ischemic or hemorrhagic stroke. However, the relevant ROCK isoform (ROCK1 or ROCK2) in acute stroke is not known. Methods We characterized the pharmacodynamic and pharmacokinetic profile, and tested the efficacy and safety of a novel selective ROCK2 inhibitor KD025 (formerly SLx-2119) in focal cerebral ischemia models in mice. Results KD025 dose-dependently reduced infarct volume after transient middle cerebral artery occlusion. The therapeutic window was at least 3 h from stroke onset, and the efficacy was sustained for at least 4 weeks. KD025 was at least as efficacious in aged, diabetic or female mice, as in normal adult males. Concurrent treatment with atorvastatin was safe, but not additive or synergistic. KD025 was also safe in a permanent ischemia model, albeit with diminished efficacy. As one mechanism of protection, KD025 improved cortical perfusion in a distal middle cerebral artery occlusion model, implicating enhanced collateral flow. Unlike isoform-nonselective ROCK inhibitors, KD025 did not cause significant hypotension, a dose-limiting side effect in acute ischemic stroke. Interpretation Altogether, these data show that KD025 is efficacious and safe in acute focal cerebral ischemia in mice, implicating ROCK2 as the relevant isoform in acute ischemic stroke. Data suggest that selective ROCK2 inhibition has a favorable safety profile to facilitate clinical translation. PMID:24466563

  1. 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

  2. A Smoothened receptor agonist is neuroprotective and promotes regeneration after ischemic brain injury

    PubMed Central

    Chechneva, O V; Mayrhofer, F; Daugherty, D J; Krishnamurty, R G; Bannerman, P; Pleasure, D E; Deng, W

    2014-01-01

    Ischemic stroke occurs as a result of blood supply interruption to the brain causing tissue degeneration, patient disabilities or death. Currently, treatment of ischemic stroke is limited to thrombolytic therapy with a narrow time window of administration. The sonic hedgehog (Shh) signaling pathway has a fundamental role in the central nervous system development, but its impact on neural cell survival and tissue regeneration/repair after ischemic stroke has not been well investigated. Here we report the neuroprotective properties of a small-molecule agonist of the Shh co-receptor Smoothened, purmorphamine (PUR), in the middle cerebral artery occlusion model of ischemic stroke. We found that intravenous administration of PUR at 6 h after injury was neuroprotective and restored neurological deficit after stroke. PUR promoted a transient upregulation of tissue-type plasminogen activator in injured neurons, which was associated with a reduction of apoptotic cell death in the ischemic cortex. We also observed a decrease in blood–brain barrier permeability after PUR treatment. At 14 d postinjury, attenuation of inflammation and reactive astrogliosis was found in PUR-treated animals. PUR increased the number of newly generated neurons in the peri-infarct and infarct area and promoted neovascularization in the ischemic zone. Notably, PUR treatment did not significantly alter the ischemia-induced level of Gli1, a Shh target gene of tumorigenic potential. Thus our study reports a novel pharmacological approach for postischemic treatment using a small-molecule Shh agonist, providing new insights into hedgehog signaling-mediated mechanisms of neuroprotection and regeneration after stroke. PMID:25341035

  3. 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.

  4. 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

  5. Cellular prion protein promotes post-ischemic neuronal survival, angioneurogenesis and enhances neural progenitor cell homing via proteasome inhibition

    PubMed Central

    Doeppner, T R; Kaltwasser, B; Schlechter, J; Jaschke, J; Kilic, E; Bähr, M; Hermann, D M; Weise, J

    2015-01-01

    Although cellular prion protein (PrPc) has been suggested to have physiological roles in neurogenesis and angiogenesis, the pathophysiological relevance of both processes remain unknown. To elucidate the role of PrPc in post-ischemic brain remodeling, we herein exposed PrPc wild type (WT), PrPc knockout (PrP−/−) and PrPc overexpressing (PrP+/+) mice to focal cerebral ischemia followed by up to 28 days reperfusion. Improved neurological recovery and sustained neuroprotection lasting over the observation period of 4 weeks were observed in ischemic PrP+/+ mice compared with WT mice. This observation was associated with increased neurogenesis and angiogenesis, whereas increased neurological deficits and brain injury were noted in ischemic PrP−/− mice. Proteasome activity and oxidative stress were increased in ischemic brain tissue of PrP−/− mice. Pharmacological proteasome inhibition reversed the exacerbation of brain injury induced by PrP−/−, indicating that proteasome inhibition mediates the neuroprotective effects of PrPc. Notably, reduced proteasome activity and oxidative stress in ischemic brain tissue of PrP+/+ mice were associated with an increased abundance of hypoxia-inducible factor 1α and PACAP-38, which are known stimulants of neural progenitor cell (NPC) migration and trafficking. To elucidate effects of PrPc on intracerebral NPC homing, we intravenously infused GFP+ NPCs in ischemic WT, PrP−/− and PrP+/+ mice, showing that brain accumulation of GFP+ NPCs was greatly reduced in PrP−/− mice, but increased in PrP+/+ animals. Our results suggest that PrPc induces post-ischemic long-term neuroprotection, neurogenesis and angiogenesis in the ischemic brain by inhibiting proteasome activity. PMID:26673668

  6. What's new in cerebral palsy.

    PubMed

    JONES, M H

    1953-11-01

    Among new researches bearing on cerebral palsy are the growth of brain cells in tissue cultures for experimentation; the use of polysaccharides to prevent the formation of a glial barrier to nerve growth after injury; observation of changes in reactions of neurons at various stages of development; the finding of hypernatremia and hyperchloremia in lesions of the frontal lobe and the thalamus; stimulation of cerebral blood flow by injection of sodium bicarbonate and retardation with ammonium chloride; and studies of serial sections of brains of palsied children who died. Study of development in the early months of life has made possible the detection of significant abnormalities in behavior early in life. Loss of hearing may be tested in very young children by measuring minute variations in electrical resistance of the skin upon auditory stimulation of the sympathetic nervous system. Conditions which have been described as having been confused with cerebral palsy are dislocation of a cervical vertebra, hereditary spastic paraplegia, transverse myelopathy, injury to the spinal cord or cauda equina by anomalous growths of the spine, and also encephalitis and meningitis. Sedation has proved a valuable adjunct to electroencephalographic study of cerebral palsy. Better criteria for abnormality in the young child should be determined and the application of them more clearly standardized. Simple exercises are useful for early training of palsied children to stimulate development. "Crossed laterality"-the dominant eye being contralateral to the preferred hand-has been counteracted by special training with great success in eliminating emotional and behavior problems and accelerating development.Recent studies indicate that only 50 per cent of cerebral palsy patients have normal or better intelligence. Subluxation of the hip joint, a common deformity associated with cerebral palsy, can sometimes be corrected by operation if detected at an early stage. Radical ablation of

  7. Linear Accelerators

    NASA Astrophysics Data System (ADS)

    Sidorin, Anatoly

    2010-01-01

    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.

  8. 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.

  9. Experimental models of perinatal hypoxic-ischemic brain damage.

    PubMed

    Vannucci, R C

    1993-01-01

    Animal research has provided important information on the pathogenesis of and neuropathologic responses to perinatal cerebral hypoxia-ischemia. In experimental animals, structural brain damage from hypoxia-ischemia has been produced in immature rats, rabbits, guinea pigs, sheep and monkeys (18, 20, 24, 25, 38). Of the several available animal models, the fetal and newborn rhesus monkey and immature rat have been studied most extensively because of their similarities to humans in respect to the physiology of reproduction and their neuroanatomy at or shortly following birth. Given the frequency of occurrence of human perinatal hypoxic-ischemic brain damage and the multiple, often severe neurologic handicaps which ensue in infants and children, it is not surprising that the above described animal models have been developed. These models have provided the basis for investigations to clarify not only physiologic and biochemical mechanisms of tissue injury but also the efficacy of specific management strategies. Hopefully, such animal research will continue to provide important information regarding how best to prevent or minimize the devastating consequences of perinatal cerebral hypoxia-ischemia. PMID:8311995

  10. 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.

  11. Houshiheisan compound prescription protects neurovascular units after cerebral ischemia.

    PubMed

    Wang, Haizheng; Wang, Lei; Zhang, Nan; Zhang, Qi; Zhao, Hui; Zhang, Qiuxia

    2014-04-01

    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

  12. Association of reduced folate carrier-1 (RFC-1) polymorphisms with ischemic stroke and silent brain infarction.

    PubMed

    Cho, Yunkyung; Kim, Jung O; Lee, Jeong Han; Park, Hye Mi; Jeon, Young Joo; Oh, Seung Hun; Bae, Jinkun; Park, Young Seok; Kim, Ok Joon; Kim, Nam Keun

    2015-01-01

    Stroke is the second leading cause of death in the world and in South Korea. Ischemic stroke and silent brain infarction (SBI) are complex, multifactorial diseases influenced by multiple genetic and environmental factors. Moderately elevated plasma homocysteine levels are a major risk factor for vascular diseases, including stroke and SBI. Folate and vitamin B12 are important regulators of homocysteine metabolism. Reduced folate carrier (RFC), a bidirectional anion exchanger, mediates folate delivery to a variety of cells. We selected three known RFC-1 polymorphisms (-43C>T, 80A>G, 696T>C) and investigated their relationship to cerebral infarction in the Korean population. We used the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to analyze associations between the three RFC-1 polymorphisms, disease status, and folate and homocysteine levels in 584 ischemic stroke patients, 353 SBI patients, and 505 control subjects. The frequencies of the RFC-1 -43TT, 80GG, and 696CC genotypes differed significantly between the stroke and control groups. The RFC-1 80A>G substitution was also associated with small artery occlusion and SBI. In a gene-environment analysis, the RFC-1 -43C>T, 80A>G, and 696T>C polymorphisms in the ischemic stroke group had combined effects with all environmental factors. In summary, we found that the RFC-1 -43C>T, 80A>G, and 696T>C polymorphisms may be risk factors for ischemic stroke. PMID:25659099

  13. 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

  14. 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

  15. Vagus Nerve Stimulation in Ischemic Stroke: Old Wine in a New Bottle

    PubMed Central

    Cai, Peter Y.; Bodhit, Aakash; Derequito, Roselle; Ansari, Saeed; Abukhalil, Fawzi; Thenkabail, Spandana; Ganji, Sarah; Saravanapavan, Pradeepan; Shekar, Chandana C.; Bidari, Sharatchandra; Waters, Michael F.; Hedna, Vishnumurthy Shushrutha

    2014-01-01

    Vagus nerve stimulation (VNS) is currently Food and Drug Administration-approved for treatment of both medically refractory partial-onset seizures and severe, recurrent refractory depression, which has failed to respond to medical interventions. Because of its ability to regulate mechanisms well-studied in neuroscience, such as norepinephrine and serotonin release, the vagus nerve may play an important role in regulating cerebral blood flow, edema, inflammation, glutamate excitotoxicity, and neurotrophic processes. There is strong evidence that these same processes are important in stroke pathophysiology. We reviewed the literature for the role of VNS in improving ischemic stroke outcomes by performing a systematic search for publications in Medline (1966–2014) with keywords “VNS AND stroke” in subject headings and key words with no language restrictions. Of the 73 publications retrieved, we identified 7 studies from 3 different research groups that met our final inclusion criteria of research studies addressing the role of VNS in ischemic stroke. Results from these studies suggest that VNS has promising efficacy in reducing stroke volume and attenuating neurological deficits in ischemic stroke models. Given the lack of success in Phase III trials for stroke neuroprotection, it is important to develop new therapies targeting different neuroprotective pathways. Further studies of the possible role of VNS, through normally physiologically active mechanisms, in ischemic stroke therapeutics should be conducted in both animal models and clinical studies. In addition, recent advent of a non-invasive, transcutaneous VNS could provide the potential for easier clinical translation. PMID:25009531

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

    PubMed Central

    Förster, Alex; Wenz, Holger; Groden, Christoph

    2016-01-01

    The hyperintense acute reperfusion marker (HARM) has initially been described in acute ischemic stroke. The phenomenon is caused by blood-brain barrier disruption following acute reperfusion and consecutive delayed gadolinium enhancement in the subarachnoid space on fluid attenuated inversion recovery (FLAIR) images. Here we report the case of an 80-year-old man who presented with transient paresis and sensory loss in the right arm. Initial routine stroke MRI including diffusion- and perfusion-weighted imaging demonstrated no acute pathology. Follow-up MRI after three hours demonstrated subarachnoid gadolinium enhancement in the left middle cerebral artery territory consistent with HARM that completely resolved on follow-up MRI three days later. This case illustrates that even in transient ischemic attack patients disturbances of the blood-brain barrier may be present which significantly exceed the extent of acute ischemic lesions on diffusion-weighted imaging. Inclusion of FLAIR images with delayed acquisition after intravenous contrast agent application in MRI stroke protocols might facilitate the diagnosis of a recent acute ischemic stroke. PMID:27127673

  17. 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

  18. 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

  19. 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

  20. Neuroprotective effects of a glutathione depletor in rat post-ischemic reperfusion brain damage.

    PubMed

    Giacomo, Claudia Di; Santangelo, Rosa; Sorrenti, Valeria; Volti, Giovanni L; Acquaviva, Rosaria

    2015-01-01

    The induction of heme oxygenase (HO), the rate-limiting enzyme in heme degradation, occurs as an adaptative response to oxidative stress and is consequent to decrease in cellular glutathione levels. Our previous studies demonstrated significant increase in survival rates of rats treated with glutathione depletors and submitted to transient cerebral ischemia. The aim of the present research was to test the effects of L-Buthionine sulfoximine (BSO), a glutathione depletor, during cerebral post-ischemic reperfusion. Cerebral ischemia was induced by bilateral clamping of common carotid arteries for 20 min. Each sample was used for glutathione ad lipid peroxidation level dosage and for evaluating the expression of heme oxygenase both after a single subcutaneous administration of BSO and without treatment. In the same experimental conditions, endothelial, inducible and neuronal Nitric Oxide Synthase (eNOS, iNOS and nNOS) and Dimethylarginine Dimethyl amine Hydrolases (DDAH-1 and DDAH-2) were also evaluated. Results obtained in the present study suggested that HO-1 over-expression may be implicated in the protective effect of BSO in post-ischemic reperfusion brain damage, although the involvement of other important stress mediators cannot be ruled out. PMID:25613502

  1. Melatonin Ameliorates Injury and Specific Responses of Ischemic Striatal Neurons in Rats

    PubMed Central

    Ma, Yuxin; Feng, Qiqi; Ma, Jing; Feng, Zhibo; Zhan, Mali; OuYang, Lisi; Mu, Shuhua; Liu, Bingbing; Jiang, Zhuyi; Jia, Yu; Li, Youlan

    2013-01-01

    Studies have confirmed that middle cerebral artery occlusion (MCAO) causes striatal injury in which oxidative stress is involved in the pathological mechanism. Increasing evidence suggests that melatonin may have a neuroprotective effect on cerebral ischemic damage. This study aimed to examine the morphological changes of different striatal neuron types and the effect of melatonin on striatal injury by MCAO. The results showed that MCAO induced striatum-related dysfunctions of locomotion, coordination, and cognition, which were remarkably relieved with melatonin treatment. MCAO induced severe striatal neuronal apoptosis and loss, which was significantly decreased with melatonin treatment. Within the outer zone of the infarct, the number of Darpp-32+ projection neurons and the densities of dopamine-receptor-1 (D1)+ and dopamine-receptor-2 (D2)+ fibers were reduced; however, both parvalbumin (Parv)+ and choline acetyltransferase (ChAT)+ interneurons were not significantly decreased in number, and neuropeptide Y (NPY)+ and calretinin (Cr)+ interneurons were even increased. With melatonin treatment, the loss of projection neurons and characteristic responses of interneurons were notably attenuated. The present study demonstrates that the projection neurons are rather vulnerable to ischemic damage, whereas the interneurons display resistance and even hyperplasia against injury. In addition, melatonin alleviates striatal dysfunction, neuronal loss, and morphological transformation of interneurons resulting from cerebral ischemia. PMID:23686363

  2. 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

  3. 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

  4. Cerebral thrombosis and myeloproliferative neoplasms.

    PubMed

    Artoni, Andrea; Bucciarelli, Paolo; Martinelli, Ida

    2014-11-01

    Myeloproliferative neoplasms (MPN) are acquired clonal disorders characterized by the proliferation of bone marrow myeloid cells. Different somatic mutations have been recently associated with MPN, the most common being JAK-2 V617F. Among MPN, polycythemia vera and essential thrombocythemia are particularly associated with an increased risk to develop thrombotic complications, either arterial or venous. Cerebrovascular events (stroke and transient ischemic attacks) are prevalent, accounting for approximately two-thirds of all events. Also cerebral vein thrombosis can complicate MPN and can be the first manifestation of the disease. Risk factors for thrombosis in patients with MPN are related or unrelated to the disease. Among the former there are cellular risk factors, such as increased white blood cell counts, vascular cell activation, endothelial dysfunction, and plasmatic risk factors, such as increased plasma viscosity, reduced levels of protein S, increased thrombin generation. The latter include increased age and previous thrombotic events. In addition, common cardiovascular risk factors (smoking, hypertension, diabetes, dyslipidemia, obesity) contribute to the pathogenesis of arterial events, whereas circumstantial risk factors (particularly oral contraceptive use and pregnancy/puerperium) to that of venous events. Primary prevention of arterial thrombosis with antiplatelet therapy is warranted in the majority of patients with MPN, whereas primary prevention of venous thrombosis is limited to anticoagulant prophylaxis during high-risk situations. Secondary prevention includes long-term antiplatelet therapy for arterial and short- or long-term anticoagulant therapy for venous thrombosis, depending on the risk factors present at the first event. PMID:25217248

  5. Radix Ilicis Pubescentis total flavonoids ameliorates neuronal damage and reduces lesion extent in a mouse model of transient ischemic attack

    PubMed Central

    Miao, Ming-san; Guo, Lin; Li, Rui-qi; Zhang, Xiao-lei

    2016-01-01

    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. PMID:27127483

  6. [Etiology of cerebral palsy].

    PubMed

    Jaisle, F

    1996-01-01

    The "perinatal asphyxia" is regarded to be one of the causes of cerebral palsy, though in the very most of the children with cerebral palsy there is found no hypoxia during labour. It should be mentioned, that the definition of "perinatal" and "asphyxia" neither are unic nor concret. And also there is no correlation between nonreassuring fetal heart rate patterns and acidosis in fetal blood with the incidence of cerebral palsy. Numerous studies in pregnant animals failed in proving an acute intrapartal hypoxia to be the origin of the cerebral palsy. Myers (1975) describes four patterns of anatomic brain damage after different injuries. Only his so called oligo-acidotic hypoxia, which is protracted and lasts over a longer time is leading to brain injury, which can be regarded in analogy to the injury of children with cerebral palsy. Summarising the update publications about the causes of cerebral palsy and the studies in pregnant animals there is no evidence that hypoxia during labour may be the cause of cerebral palsy. There is a great probability of a pre(and post-)natal origin of brain injury (for instance a periventricular leucomalacia found after birth) which leads to cerebral palsy. Short after labour signs of a so called "asphyxia" may occur in addition to this preexisting injury and misrepresent the cause of cerebral palsy. Finally the prepartal injury may cause both: Cerebral palsy and hypoxia. PMID:9035826

  7. Management of ischemic optic neuropathies

    PubMed Central

    Hayreh, Sohan Singh

    2011-01-01

    Ischemic optic neuropathies (IONs) consist primarily of two types: anterior ischemic optic neuropathy (AION) and posterior ischemic optic neuropathy (PION). AION comprises arteritic AION (A-AION: due to giant cell arteritis) and non-arteritic AION (NA-AION: due to other causes). PION consists of arteritic PION (A-PION: due to giant cell arteritis), non-arteritic PION (NA-PION: due to other causes), and surgical PION (a complication of several systemic surgical procedures). These five types of ION are distinct clinical entities etiologically, pathogenetically, clinically and from the management point of view. In the management of AION, the first crucial step with patients aged 50 and over is to identify immediately whether it is arteritic or not because A-AION is an ophthalmic emergency and requires urgent treatment with high-dose steroid therapy to prevent any further visual loss in one or both eyes. Patients with NA-AION, when treated with systemic corticosteroid therapy within first 2 weeks of onset, had significantly better visual outcome than untreated ones. Systemic risk factors, particularly nocturnal arterial hypotension, play major roles in the development of NA-AION; management of them is essential in its prevention and management. NA-PION patients, when treated with high-dose systemic steroid therapy during the very early stages of the disease, showed significant improvement in visual acuity and visual fields, compared to untreated eyes. A-PION, like A-AION, requires urgent treatment with high-dose steroid therapy to prevent any further visual loss in one or both eyes. There is no satisfactory treatment for surgical PION, except to take prophylactic measures to prevent its development. PMID:21350282

  8. Protection mechanism of early hyperbaric oxygen therapy in rats with permanent cerebral ischemia

    PubMed Central

    Yu, Min; Xue, Yixue; Liang, Weidi; Zhang, Yupeng; Zhang, Zhiqiang

    2015-01-01

    [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. PMID:26644690

  9. Neuroprotection and reduced gliosis by atomoxetine pretreatment in a gerbil model of transient cerebral ischemia.

    PubMed

    Park, Joon Ha; Shin, Bich Na; Chen, Bai Hui; Kim, In Hye; Ahn, Ji Hyeon; Cho, Jeong-Hwi; Tae, Hyun-Jin; Lee, Jae-Chul; Lee, Choong-Hyun; Kim, Young-Myeong; Lee, Yun Lyul; Kim, Sung Koo; Won, Moo-Ho

    2015-12-15

    Atomoxetine (ATX) is a non-stimulant selective norepinephrine reuptake inhibitor that is widely used for the treatment of attention-deficit/hyperactivity disorder (ADHD). In this study, we firstly examined neuroprotective effects of pre- or post-treatment with 15 and 30 mg/kg ATX against ischemic damage in the gerbil hippocampal cornus ammonis 1 (CA1) region subjected to 5 min of transient cerebral ischemia using cresyl violet staining, neuronal nuclei immunohistochemistry and Fluoro-J B histofluorescence staining. We found that only pre-treatment with 30 mg/kg ATX protected CA1 pyramidal neurons from ischemic insult. In addition, pre-treatment with 30 mg/kg ATX, which had neuroprotective effect against ischemic damage, distinctly attenuated the activation of astrocytes and microglia in the ischemic CA1 region compared with the vehicle-treated ischemia group by glial fibrillary acidic protein (for astrocytes) and ionized calcium-binding adapter molecule 1 (for microglia) immunohistochemistry. In brief, our present results indicate that ATX has neuroprotective effect against