Andrey Belayev

Carolina Neurosurgery and Spine Associates

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Weizhao Zhao

University of Miami

Myron D. Ginsberg

University of Miami

Raul Busto

University of Miami

Ludmila Belayev

Louisiana State University Health Sciences Center New Orleans

Larissa Khoutorova

Louisiana State University Health Sciences Center New Orleans

Adam S Arthur

Semmes Murphey Foundation

Daniel Hoit

University of Tennessee Health Science Center

Tomotaka Ohshima

Aichi Medical University

Christopher J. Moran

Mallinckrodt (United States)

Yongbo Zhang

Henan Provincial Chest Hospital

Cooperative Institutions

University of Miami

University of Tennessee Health Science Center

Neurological Surgery

Amgen (United States)

Centre National de la Recherche Scientifique

Semmes Murphey Foundation

University of Tennessee at Knoxville

Université Paris Cité

National and Kapodistrian University of Athens

Kariya Toyota General Hospital

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Neuroprotective Effect of Darbepoetin Alfa, a Novel Recombinant Erythropoietic Protein, in Focal Cerebral Ischemia in Rats

Stroke (2005)

Ludmila Belayev Larissa Khoutorova Weizhao Zhao Alexey Vigdorchik Andrey Belayev

Background and Purpose— Darbepoetin alfa is a novel erythropoiesis-stimulating protein developed for treating anemia. In animal models, exogenous recombinant human erythropoietin has been reported to be beneficial in treating experimental cerebral ischemia. In this study, we determined whether darbepoetin alfa would protect in a rat model of transient focal cerebral ischemia. Methods— Rats received 2-hour middle cerebral artery suture-occlusion. The drug (darbepoetin alfa, 10 μg/kg) or vehicle was administered intraperitoneally 2 hours after onset of middle cerebral artery occlusion. Animals were allowed to survive for 3 or 14 days. Behavioral tests were performed sequentially. Infarct volumes and brain swelling were determined. Results— Darbepoetin alfa-treated rats showed improved neuroscores relative to vehicle-treated animals beginning within 1 hour of treatment and persisting throughout the 14-day survival period. Darbepoetin alfa significantly reduced corrected total (cortical + subcortical) infarct volume (56.3±20.6 and 110.8±6.8 mm 3 , respectively) and total infarct areas at multiple levels compared with vehicle in the 14-day survival group. Brain swelling was not affected by treatment. Conclusion— Darbepoetin alfa confers behavioral and histological neuroprotection after focal ischemia in rats.

Darbepoetin alfa

10.1161/01.str.0000160753.36093.da

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The first North American use of the Pipeline Flex flow diverter

BMJ Case Reports (2015)

Edward Duckworth Christopher Nickele Daniel Hoit Andrey Belayev Christopher J. Moran

Flow diversion for the management of intracranial aneurysms represents a paradigm shift in how aneurysms are managed. The Pipeline embolization device (PED) is, to date, the only flow diverter approved for use in the USA by the Food and Drug Administration. Limitations and complications with new treatment strategies are inevitable, and with the PED there have been reports of complications, most commonly with challenging deployments. Once deployment has been initiated, the device is ‘one-way’; it can only be deployed further or removed. Yet, situations arise in which the ability to recapture or reposition the device would be advantageous. A second-generation Pipeline has been developed that addresses these concerns. We report the first use in North America of this second-generation Pipeline device: the Pipeline Flex. We discuss our rationale for using the device, our impressions of its operation, and the relevant literature concerning the current state of flow diversion.

Flow diverter

FLEX

First generation

10.1136/bcr-2014-011548

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Citations (14)

Republished: The first North American use of the Pipeline Flex flow diverter

Journal of NeuroInterventional Surgery (2015)

Edward Duckworth Christopher Nickele Daniel Hoit Andrey Belayev Christopher J. Moran

Flow diverter

FLEX

First generation

10.1136/neurintsurg-2014-011548.rep

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Citations (8)

8-F balloon guide catheter for embolization of anterior circulation aneurysms: an institutional experience in 152 patients.

PubMed (2017)

Tomotaka Ohshima Chinmaya Dash Andrey Belayev Taiki Yamamoto Shunsaku Goto

The use of 8-F balloon guide catheter (BGC) for proximal flow control was previously shown to prevent distal embolic complications during mechanical clot retrieval in patients with acute ischemic stroke. In this retrospective study, the utility of 8-F BGCs for proximal flow control during endovascular coiling of anterior circulation aneurysms was investigated. Patients who underwent endovascular coiling for anterior circulation aneurysms between August 2013 and December 2016 were retrospectively analyzed. Among a total of 152 patients included in this series, 64 patients presented with aneurysmal rupture, whereas the aneurysms were detected incidentally or due to mass effects in the remaining patients. 8-F BGCs were successfully navigated in all patients. The balloon was inflated during navigation in 19 patients. Inflation of the catheter balloon during coil embolization was required in 34 patients; this was performed as an emergency maneuver in six of these patients. Thromboembolic complications occurred in one patient. 8-F BGC can be effectively used for proximal flow control during endovascular treatment of anterior circulation aneurysms. The other advantages included improved navigation of tortuous arterial anatomy, coil stabilization during aneurysmal coiling, and freedom to utilize aneurysmal neck-remodeling balloons for additional adjunctive techniques or to deploy rescue stents. This novel approach might be safely and effectively used in patients undergoing endovascular treatment for anterior circulation aneurysms.

10.18999/nagjms.79.4.435

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Citations (8)

Spinal cord herniation or intradural arachnoid cyst?

The Spine Journal (2014)

Viktor Bartanusz Jennifer Gentry Savage Andrey Belayev

Arachnoid cyst

Spinal Cord Diseases

10.1016/j.spinee.2013.05.045

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Experimental Intracerebral Hemorrhage in the Mouse

Stroke (2003)

Ludmila Belayev Isabel Saul Karell Curbelo Raul Busto Andrey Belayev

Background and Purpose— A major limitation of intracerebral hemorrhage (ICH) research is the lack of reproducible animal models. The present study was conducted to validate in the mouse the double-injection method of ICH initially developed in the rat. We investigated the effect of intrastriatal injection of blood or cerebrospinal fluid (CSF) on cerebral blood flow (CBF), neurological score, hematoma volume, and brain swelling. Methods— Male C57BL/6 mice were anesthetized with halothane/nitrous oxide delivered by face mask. Rectal and cranial temperatures were regulated at 37°C to 37.5°C. Mice were placed in a stereotactic frame, and a 30-gauge stainless steel cannula was introduced through a burr hole into the left striatum. Each mouse received a 5-μL injection of either whole blood or CSF (over 3 minutes), followed 7 minutes later by 10 μL injected over 5 minutes. The injection cannula was slowly withdrawn 10 minutes after the second injection. Control mice had only cannula insertion. CBF was studied by laser Doppler perfusion imaging. Neurological status was evaluated on days 1 and 2. After 2 days, hematoma volume and brain swelling were calculated. Results— Physiological values were stable. Mice with ICH but not those with CSF or cannula alone had a marked, persistent neurological deficit and a highly reproducible hematoma, whose mean±SEM volume was 2.0±0.2 mm 3 compared with a lesion size of 0.2±0.1 mm 3 in mice with CSF. Residual swelling of the ipsilateral hemisphere at 48 hours was 5.7% in the hematoma and 1.5% in the CSF groups. Relative CBF in the neocortex ipsilateral to the injection site declined by ∼45% to 60% during the first 20 minutes after cannula insertion/injection in all groups but began to renormalize at ∼25 to 30 minutes in the CSF and cannula-only groups; in the hematoma group, cortical hypoperfusion of ∼35% to 50% persisted during the 90-minute measurement period. Conclusions— The present ICH model in mice produces a consistent neurological deficit, hypoperfusion, hematoma volume, and brain swelling. This model closely mimics human hypertensive basal ganglionic ICH and should be useful for the evaluation of pharmaceutical therapies. Laser Doppler perfusion imaging is a useful new technique to quantify relative CBF changes and can be used for studies of dynamic changes of CBF in this in vivo model of ICH in mice.

Stroke

10.1161/01.str.0000088061.06656.1e

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Citations (115)

Stilbazulenyl nitrone, a novel antioxidant, is highly neuroprotective in focal ischemia

Annals of Neurology (2003)

Myron D. Ginsberg Dávid Becker Raul Busto Andrey Belayev Yongbo Zhang

Abstract Azulenyl nitrones are novel chain‐breaking antioxidants with low oxidation potentials and high lipophilicity—properties favoring their efficacy as neuroprotectants. We tested the second‐generation azulenyl nitrone, stilbazunenlyl nitrone (STAZN), in focal ischemic stroke. Physiologically monitored rats received 2 hours of middle cerebral artery occlusion by intraluminal suture, resulting in substantial cortical and striatal infarcation. Neurobehavior was quantified on a standard battery, and brains were perfusion‐fixed for quantitative histopathology at 3 days. In 3 independent series, rats were treated at either 2h + 4h, or 2h + 4h + 24h + 48h, after onset of ischemia; vehicle‐treated rats received dimethylsulfoxide or saline. All animals (n = 52) developed high‐grade neurological deficits (score 11 of 12) during ischemia, which improved, in STAZN‐treated rats, within 1–1.5 h of the initial dose and fell to a median score of 3 at 72 h, compared to 8 in vehicle rats. STAZN treatment reduced mean cortical infarct volume by 64–97%, and total infarct volume by 42–72%. In over one‐half of STAZN‐treated animals, cortical infarction was virtually abolished. Regression analysis predicted that STAZN would confer ∼50% cortical neuroprotection even in the most severely affected cases. The potency of STAZN was orders‐of‐magnitude greater than other nitrones such as NXY‐059. These results suggest that STAZN has great promise for ischemic stroke. Ann Neurol 2003

Stroke

Nitrone

10.1002/ana.10659

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Citations (71)

Enriched environment delays the onset of hippocampal damage after global cerebral ischemia in rats

Brain Research (2003)

Andrey Belayev Isabel Saul Yitao Liu Weizhao Zhao Myron D. Ginsberg

Histopathology

Brain ischemia

10.1016/s0006-8993(02)04089-1

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Citations (36)

Neuroprotective Effect of SolCD39, a Novel Platelet Aggregation Inhibitor, on Transient Middle Cerebral Artery Occlusion in Rats

Stroke (2003)

Ludmila Belayev Larissa Khoutorova Theresa Deisher Andrey Belayev Raul Busto

Background and Purpose— SolCD39 is a soluble form of recombinant human ecto-ATP/ADPase (NTPDase1) and represents a new class of antithrombotic agents. SolCD39 blocks and reverses platelet activation, preventing recruitment of additional platelets into a growing thrombus. The purpose of this study was to examine the effect of solCD39 on neurological deficit, infarct size, and extent of edema after transient middle cerebral artery occlusion (MCAO) in rats. Methods— Physiologically controlled Sprague-Dawley rats underwent 2-hour MCAO by retrograde insertion of an intraluminal suture coated with poly- l -lysine. The agent (solCD39) was administered intravenously before MCAO or at 1-hour or 3-hour recirculation. Other groups received vehicle (Tris-buffered saline) or human albumin (as a “positive” neuroprotective control; 25%, 0.5% of body weight) at 1-hour recirculation. Neurological status was evaluated during occlusion (at 60 minutes) and daily for 3 days after MCAO. Brains were perfusion-fixed at 72 hours, and infarct volumes and brain swelling were determined. Results— Pretreatment with solCD39 significantly improved the neurological score at 72 hours compared with the vehicle group (4.4±0.6 versus 7.6±0.6, respectively; P =0.008). Cortical infarct areas were significantly reduced at multiple levels by pretreatment with solCD39. Total striatal infarct area was also significantly reduced compared with vehicle by both solCD39 pretreatment (48% mean reduction) and solCD39 treatment at 3-hour recirculation (51% mean reduction). Treatment with SolCD39 significantly reduced total infarct volume (corrected for brain swelling) by an average of 71% to 72% when administered either before ischemia or at 3 hours of recirculation compared with vehicle. Treatment with albumin significantly reduced neurological score and total, cortical, and subcortical infarction at multiple levels, as expected. Conclusions— Treatment with SolCD39, administered either before or at 3 hours after MCAO, improves neurological score and reduces infarct size compared with vehicle. A pharmacological agent of this type appears to have potential for the treatment of focal ischemic stroke.

10.1161/01.str.0000056169.45365.15

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Citations (75)

Caffeinol confers cortical but not subcortical neuroprotection after transient focal cerebral ischemia in rats

Brain Research (2004)

Ludmila Belayev Larissa Khoutorova Yongbo Zhang Andrey Belayev Weizhao Zhao

Histopathology

10.1016/j.brainres.2004.02.039

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Citations (25)