scholarly journals Cerebrovascular and Neuroprotective Effects of Adamantane Derivative

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Ruben S. Mirzoyan ◽  
Tamara S. Gan’shina ◽  
Denis V. Maslennikov ◽  
Georgy I. Kovalev ◽  
Ivan A. Zimin ◽  
...  
Keyword(s):  
Blood Flow ◽  
Nmda Receptors ◽  
Middle Cerebral Artery ◽  
Brain Tissue ◽  
Cerebral Artery ◽  
Brain Ischemia ◽  
Adamantane Derivative ◽  
Neuroprotective Activity ◽  
Neuroprotective Effects ◽  
The Brain

Objectives. The influence of 5-hydroxyadamantane-2-on was studied on the rats’ brain blood flow and on morphological state of brain tissue under the condition of brain ischemia. The interaction of the substance with NMDA receptors was also studied.Methods. Study has been implemented using the methods of local blood flow registration by laser flowmeter, [3H]-MK-801binding, and morphological examination of the brain tissue. We used the models of global transient ischemia of the brain, occlusion of middle cerebral artery, and hypergravity ischemia of the brain.Results. Unlike memantine, antagonist of glutamatergic receptors, the 5-hydroxyadamantane-2-on does not block NMDA receptors but enhances the cerebral blood flow of rats with brain ischemia. This effect is eliminated by bicuculline. Under conditions of permanent occlusion of middle cerebral artery, 5-hydroxyadamantane-2-on has recovered compensatory regeneration in neural cells, axons, and glial cells, and the number of microcirculatory vessels was increased. 5-Hydroxyadamantane-2-on was increasing the survival rate of animals with hypergravity ischemia.Conclusions. 5-Hydroxyadamantane-2-on, an adamantane derivative, which is not NMDA receptors antagonist, demonstrates significant cerebrovascular and neuroprotective activity in conditions of brain ischemia. Presumably, the GABA-ergic system of brain vessels is involved in mechanisms of cerebrovascular and neuroprotective activity of 5-hydroxyadamantane-2-on.

scholarly journals Brain Tissue Concentrations of ATP, Phosphocreatine, Lactate, and Tissue pH in Relation to Reduced Cerebral Blood Flow following Experimental Acute Middle Cerebral Artery Occlusion

1988 ◽  
Vol 8 (6) ◽  
pp. 866-874 ◽  
Author(s):  
T. P. Obrenovitch ◽  
O. Garofalo ◽  
R. J. Harris ◽  
L. Bordi ◽  
M. Ono ◽  
...  
Keyword(s):  
Blood Flow ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Brain Tissue ◽  
Cerebral Artery ◽  
Artery Occlusion ◽  
Tissue Samples ◽  
Tissue Ph ◽  
Focal Ischaemia ◽  
Cerebral Artery Occlusion

Local CBF (LCBF) was compared with the corresponding local tissue concentration of ATP, phosphocreatine (PCr), and lactate in anaesthetized baboons subjected to focal ischaemia produced by middle cerebral artery occlusion (MCAO). LCBF hydrogen electrodes were implanted in cortical regions where MCAO had been previously shown to produce severe and penumbral ischaemia and in posterior regions where blood flow is not altered. Metabolites were assayed in small tissue samples collected either by cryoprobe biopsy in the regions where LCBFs were measured (series 1) or by sampling appropriate regions of the rapidly frozen brain (series 2). Subsequent topographical study of brain tissue pH with umbelliferone was performed in this latter series. The results from these two series are compared and discussed in terms of the more appropriate way to perform simultaneous electrode measurements and analysis of tissue samples for studying focal ischaemia in the primate brain. They confirm that the concentrations of ATP and PCr decrease, and that lactate level increases, with decreasing blood flow. These metabolites tended to change more rapidly below a blood flow threshold, rather than showing a steady decrease as the blood flow was reduced, although the variability of the data precluded us from establishing this with confidence. Topographical study of tissue pH often showed sharp boundaries between zones of very low pH and regions with normal pH.

scholarly journals Brain permeability of bilobalide as probed by microdialysis before and after middle cerebral artery occlusion in mice

2010 ◽  
Vol 13 (4) ◽  
pp. 607 ◽  
Author(s):  
Dorothee Lang ◽  
Christian Ude ◽  
Mario Wurglics ◽  
Manfred Schubert-Zsilavecz ◽  
Jochen Klein
Keyword(s):  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Artery Occlusion ◽  
Maximum Plasma ◽  
Active Constituent ◽  
Neuroprotective Effects ◽  
Before And After ◽  
Cerebral Artery Occlusion ◽  
The Brain

ABSTRACT. Purpose. Bilobalide is an active constituent of Ginkgo biloba and has shown neuroprotective effects in mice with cerebral ischemia. In the present study, we investigated brain permeability of bilobalide (i) in healthy mice and (ii) in mice before or after stroke. Methods. We have used in vivo microdialysis and LC-MS to estimate extracellular levels of bilobalide. 10 mg/kg of bilobalide was given by i.p. injection to control mice, and 60 minutes before and after middle cerebral artery occlusion (MCAO). Results. Bilobalide was already detectable in brain striatal microdialysates 10 min after i.p. administration and reached maximum levels (19 ng/mL, corresponding to 0.92 µM) after 40 min. Maximum plasma bilobalide levels were 5.9 µM. After an ischemic insult, the drug could be dialysed with similar efficiency as in control mice indicating slow elimination from the ischemic brain. When the drug was given after MCAO, availability in the brain was low, but measurable, at approx. 10% of control values. Conclusions. Our data demonstrate that bilobalide easily crosses the blood brain barrier and reaches extracellular concentrations in the brain that allow efficient interaction with target molecules such as neurotransmitter receptors. Availability of the drug in ischemic tissue is high when given before ischemia, but severely limited after MCAO.

scholarly journals Neuroprotective and cerebrovascular effects of endogenous N-Arachidonoyl-GABA and its putative Cox-2 metabolite – GABA conjugate with Prostaglandin E2

2021 ◽  
Vol 7 (3) ◽  
pp. 49-61
Author(s):  
Narine R. Mirzoyan ◽  
Nelly G. Khostikyan ◽  
Vahe S. Meliksetyan ◽  
Arpine A. Hakobyan ◽  
Tamara S. Gan’shina ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Ischemia ◽  
Prostaglandin E2 ◽  
Brain Tissue ◽  
Brain Ischemia ◽  
Cerebral Circulation ◽  
Transient Ischemia ◽  
Cox 2 ◽  
The Brain ◽  
Rat Brain Tissue

Introduction: The aim of the study was to compare the neuroprotective and cerebrovascular effects of bioactive, endogenous lipid – N-arachidonoyl-GABA (AA-GABA) and GABA conjugate with prostaglandin E2 (PGE2-GABA) by evaluation of a morphological state of rat brain tissue and lipofuscin levels under the condition of permanent focal brain ischemia, as well as cerebral circulation under the condition of global transient ischemia. Materials and methods: The study has been implemented using the models of the left middle cerebral artery occlusion (MCAO) and global transient ischemia of the brain. A morphological examination of the brain tissue, a registration of local blood flow by laser flowmeter, and quantitative measurement of lipofuscin by fluorescence spectroscopy were used. Results and discussion: AA-GABA and the putative COX-2 metabolite PGE2-GABA showed significant neuroprotective and cerebrovascular effects in rat models of global and focal cerebral ischemia. In the MCAO model, AA-GABA and PGE2-GABA at a dose of 2 mg/kg/day administered i.p. for 6 or 12 days led to: 1) significant restoration of neurons and glial cells with intracellular regeneration of cytoplasmic and nuclear structures, 2) decrease in brain tissue edema; 3) attenuated thrombosis and stasis, and 4) absence of large necrotic foci in rat brain tissue. AA-GABA and PGE2-GABA at the same dose prevented excessive accumulation of lipofuscin in both brain hemispheres in rats with MCAO. All the studied compounds increase cerebral blood circulation in rats subjected to global transient ischemia. However, the cerebrovascular effect of PGE2-GABA was superior to the activity of AA-GABA and all other tested compounds. AA-GABA and PGE2-GABA, unlike PGE2 and nimodipine, increase the cerebral blood flow in rats with global transient brain ischemia and have no influence on the intact animals. Apparently, the GABAergic vascular system of the brain is involved in the mechanisms of the neuroprotective action of AA-GABA and PGE2-GABA. Conclusion: For the first time, we demonstrated the ability of AA-GABA and its putative metabolite COX-2 PGE2-GABA to improve cerebral circulation, attenuate structural damage and lipofuscin accumulation during cerebral ischemia. The natural origin of AA-GABA, which possesses neuroprotective and cerebrovascular activity, as well as anti-aggregatory activity, allows considering AA-GABA as one of the endogenous protective factors in ischemic brain lesions. Graphical abstract:

scholarly journals Eyeballing stroke: Blood flow alterations in the eye and visual impairments following transient middle cerebral artery occlusion in adult rats

2020 ◽  
Vol 29 ◽  
pp. 096368972090580
Author(s):  
Jea-young Lee ◽  
Vanessa Castelli ◽  
Brooke Bonsack ◽  
Julián García-Sánchez ◽  
Chase Kingsbury ◽  
...  
Keyword(s):  
Blood Flow ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Artery Occlusion ◽  
Laser Doppler ◽  
Adult Rats ◽  
Visual Deficits ◽  
Cerebral Artery Occlusion ◽  
The Brain

Middle cerebral artery occlusion in rodents remains a widely used model of ischemic stroke. Recently, we reported the occurrence of retinal ischemia in animals subjected to middle cerebral artery occlusion, owing in part to the circulatory juxtaposition of the ophthalmic artery to the middle cerebral artery. In this study, we examined the eye hemodynamics and visual deficits in middle cerebral artery occlusion-induced stroke rats. The brain and eye were evaluated by laser Doppler at baseline (prior to middle cerebral artery occlusion), during and after middle cerebral artery occlusion. Retinal function-relevant behavioral and histological outcomes were performed at 3 and 14 days post-middle cerebral artery occlusion. Laser Doppler revealed a typical reduction of at least 80% in the ipsilateral frontoparietal cortical area of the brain during middle cerebral artery occlusion compared to baseline, which returned to near-baseline levels during reperfusion. Retinal perfusion defects closely paralleled the timing of cerebral blood flow alterations in the acute stages of middle cerebral artery occlusion in adult rats, characterized by a significant blood flow defect in the ipsilateral eye with at least 90% reduction during middle cerebral artery occlusion compared to baseline, which was restored to near-baseline levels during reperfusion. Moreover, retinal ganglion cell density and optic nerve depth were significantly decreased in the ipsilateral eye. In addition, the stroke rats displayed eye closure. Behavioral performance in a light stimulus-mediated avoidance test was significantly impaired in middle cerebral artery occlusion rats compared to control animals. In view of visual deficits in stroke patients, closely monitoring of brain and retinal perfusion via laser Doppler measurements and examination of visual impairments may facilitate the diagnosis and the treatment of stroke, including retinal ischemia.

Abstract W P209: Development of a Useful Brain Ischemic Stroke Model via a Transient Occlusion of Middle Cerebral Artery in the Nonhuman Primate

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Eiketsu Sho ◽  
Zhenghua Zhu ◽  
Yuchao Zhao ◽  
Jiqiao Chen ◽  
Daomei He ◽  
...  
Keyword(s):  
Blood Flow ◽  
Ischemic Stroke ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Nonhuman Primate ◽  
Stroke Model ◽  
Cynomolgus Monkeys ◽  
Stroke Research ◽  
Reperfusion Period ◽  
The Brain

Objectives: Most experimental stroke research is carried out in rodents, but given differences between rodents and human, the nonhuman primate (NHP) models may provide a valuable tool to study the clinical therapy. We developed a surgical method for transient occlusion of the middle cerebral artery (MCA-M1) in the Cynomolgus monkeys to evaluate the MCA territory blood flow, the model stability, animal clinical neurological behavior, morphology changes under magnetic resonance imaging (MRI) and histopathology. Methods: The left brain sylvian fissure was exposed by a small fronto-temporal craniotomy. The MCA-M1 was exposed by microsurgical dissection and clipped for 4 hours. The brain blood flow was measured in the MCA territory during the ischemia period and early phase of reperfusion period. The clinical neurological examinations and MRI were carried out at regular post-operative course till 4 weeks of stroke. Results: During MCA occlusion, the MCA territory blood flow was decreased significantly in 80%. This territory was reflowed right after reperfusion and showed an overload in about 20% over pre ischemia flow within 1hr after reperfusion and gradually returned to previous flow (Fig 1). Animal neurological behavior changed significantly within 1 week and became a steady status of neurological impairment. MRI demonstrated extensive MCA territory infarction. Histologically, at the end of 4 week stroke the brain showed a clear board of glia proliferation between infarct and normal brain tissue. Conclusion: These results indicate a stable ischemic stroke model in cynomolgus monkeys after complete MCA-M1 occlusion, which will be a useful NHP stroke model for stroke research and the clinical therapeutic studies. Fig 1 Changes in MCA territory blood flow during ischemia-reperfusion period

scholarly journals Neuroprotective mechanisms of the ubiquinol action in experimental focal ischemia

2020 ◽  
Vol 66 (2) ◽  
pp. 145-150
Author(s):  
T.N. Fedorova ◽  
V.S. Gusakov ◽  
A.A. Devyatov ◽  
O.A. Muzichuk ◽  
A.V. Lopachev ◽  
...  
Keyword(s):  
Cell Death ◽  
Cerebral Ischemia ◽  
Brain Tissue ◽  
Focal Cerebral Ischemia ◽  
Neuroprotective Effect ◽  
Lipid Hydroperoxide ◽  
New Drugs ◽  
Neuroprotective Activity ◽  
Neuroprotective Effects ◽  
The Brain

Ischemic stroke is one of the most socially important diseases characterized by impaired cerebral circulation with focal damage of the brain tissue and decreased functionality. Despite the successes of modern pharmacology, possibilities of pharmacotherapy for stroke remain limited, and the research for new drugs with neuroprotective effects that can prevent brain cell death is still relevant. In this study we have investigated the neuroprotective activity of ubiquinol as a part of an innovative form on a rat model of irreversible 24 h-cerebral ischemia with evaluation of the mechanisms of its neuroprotective effect. Ubiquinol (30 mg/kg), administered intravenously in the acute period of irreversible 24 h focal cerebral ischemia, had a direct neuroprotective effect, characterized by a decrease in the volume of brain tissue necrosis. The protective effect of ubiquinol is due to its ability to inhibit the development of oxidative stress by the direct anti-radical action, preventing the increase in the lipid hydroperoxide content in the brain tissue adjacent to the focus of necrosis, lowering the lipid oxidation rate in plasma against under conditions of increased total antioxidant activity in the brain and blood of experimental animals. In vitro experiments have shown the ability of ubiquinol to prevent cell death in primary culture of cerebral neurons of rat brain under 4 h oxygen/glucose deprivation followed by 20 h reoxygenation.

Abstract WP168: Association of Stenosis, Proximal Flow and Distal Perfusion in Subjects With Middle Cerebral Artery Stenosis

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Xiaowei Song ◽  
Wenwen Chen ◽  
Yunduo Li ◽  
David S Liebeskind ◽  
Rui Li ◽  
...  
Keyword(s):  
Blood Flow ◽  
Middle Cerebral Artery ◽  
Brain Tissue ◽  
Cerebral Artery ◽  
Tissue Perfusion ◽  
Artery Stenosis ◽  
Compensatory Mechanism ◽  
4D Flow ◽  
Distal Perfusion ◽  
Relative Flow

Introduction: Hemodynamic compromise caused by intracranial artery stenosis is one of the critical factors contributing to ischemic stroke. However, the association between flow and stenosis has not been well determined quantitatively, nor its correlation with distal perfusion. The purpose of this study was to investigate the association of blood flow in different grades of stenosis, as well as its association with distal brain tissue perfusion. Methods: Intracranial 4D flow and perfusion were obtained in 33 patients (mean 56 years old) with different grades of unilateral middle cerebral artery (MCA) stenosis. GTFlow was used to measure the flow at the proximal of stenosis and the symmetrical location of contralateral side (Fig 1a). Olea was accessed to calculate the perfusion parameters in MCA area. The average net flow at the proximal of stenosis was compared in patients with different grades(<30%,30-49%,50-69%, and ≥70%) of stenosis. Correlation between relative flow(stenosis/contralateral) and perfusion parameters were also compared in different pial collateral status. Results: Blood flow at the proximal of stenosis changes with the grades of stenosis increasing (Fig 1b, p =0.01). Subjects with <50% and ≥50% stenosis differ in MCA flow, rCBF and rTTP, but not in rCBV (Fig 1c).Spearman correlation analysis indicated that the relative flow was also associated with rTTP shown in distal brain tissue in subjects with poor collateral (Fig 1d, r=-0.69, p =0.02), but not in patients with good collateral. No association between relative flow and rCBF was detected in this group of population. Conclusion: In conclusion, decreased flow at the proximal of stenosis could result in the delay of perfusion in distal brain tissue in patients with poor collateral. Association of flow and stenosis, as well as its relationship with distal perfusion need further study, collateral status and potential compensatory mechanism should be considered in future study.

SIGNIFICANTLY LOWER RIGHT MIDDLE CEREBRAL ARTERY BLOOD FLOW VELOCITY IN THE FIRST EPISODE OF PSYCHOSIS DURING NEUROCOGNITIVE TESTING

2018 ◽  
Vol 30 (2) ◽  
pp. 172-182 ◽  
Author(s):  
Ivana Kekin ◽  
◽  
Dina Bosnjak ◽  
Porin Makaric ◽  
Zarko Bajic ◽  
...  
Keyword(s):  
Blood Flow ◽  
Middle Cerebral Artery ◽  
Flow Velocity ◽  
Cerebral Artery ◽  
Blood Flow Velocity ◽  
First Episode ◽  
Artery Blood Flow ◽  
Neurocognitive Testing

scholarly journals Doppler ultrasound in pregnancy – quality requirements of DEGUM and clinical application (part 2)

2021 ◽  
Author(s):  
Renaldo Faber ◽  
Kai-Sven Heling ◽  
Horst Steiner ◽  
Ulrich Gembruch
Keyword(s):  
Blood Flow ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Umbilical Artery ◽  
Prophylactic Treatment ◽  
Doppler Sonography ◽  
First Trimester ◽  
Ductus Venosus ◽  
Fetal Diagnosis

AbstractThis second part on Doppler sonography in prenatal medicine and obstetrics reviews its clinical applications. While this has not become the initially anticipated screening tool, it is used for the diagnosis and surveillance of a variety of fetal pathologies. For example, the sonography-based determination of uterine artery blood flow indices is an important parameter for the first trimester multimodal preeclampsia risk assessment, increasing accuracy and providing indication for the prophylactic treatment with aspirin. It also has significant implications for the diagnosis and surveillance of growth-restricted fetuses in the second and third trimesters through Doppler-sonographic analysis of umbilical artery, middle cerebral artery and ductus venosus. Here, especially the hemodynamics of the ductus venosus provides a critical criterium for birth management of severe, early-onset FGR before 34 + 0 weeks of gestation. Further, determination of maximum blood flow velocity of the middle cerebral artery is a central parameter in fetal diagnosis of anemia which has been significantly improved by this analysis. However, it is important to note that the mentioned improvements can only be achieved through highest methodological quality. Importantly, all these analyses are also applied to twins and higher order multiples. Here, for the differential diagnosis of specific complications such as TTTS, TAPS and TRAP, the application of Doppler sonography has become indispensable. To conclude, the successful application of Doppler sonography requires both exact methodology and precise pathophysiological interpretation of the data.

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