Therapy Of Cerebrovascular Disease Research Articles

Ubiquitous regulation of cerebrovascular diseases by ubiquitin-modifying enzymes.

Cerebrovascular diseases (CVDs) are a major threat to global health. Elucidation of the molecular mechanisms underlying the pathology of CVDs is critical for the development of efficacious preventative and therapeutic approaches. Accumulating studies have highlighted the significance of ubiquitin-modifying enzymes (UMEs) in the regulation of CVDs. UMEs are a group of enzymes that orchestrate ubiquitination, a post-translational modification tightly involved in CVDs. Functionally, UMEs regulate multiple pathological processes in ischemic and hemorrhagic stroke, moyamoya disease, and atherosclerosis. Considering the important roles of UMEs in CVDs, they may become novel druggable targets for these diseases. Besides, techniques applying UMEs, such as proteolysis-targeting chimera and deubiquitinase-targeting chimera, may also revolutionize the therapy of CVDs in the future.

The choice of a modern neuroprotective drug as a basic strategy in the treatment of chronic cerebrovascular diseases

The topicality of the issues of effective treatment and prevention of cerebrovascular diseases (CVD) is not doubtful in view of their leadership in the top ranked causes of high mortality and disability in the general population almost all over the world, including Russia. The pathogenetic aspects of chronic CVD caused by hypoperfusion, which triggers a chain of successively developing metabolic disorders, represent a potential therapeutic target for the development of new dosage forms. The enormous clinical experience has been accumulated and evidence of therapeutic benefits in patients with various types of vascular and metabolic disorders accompanied by ischemia, including cerebrovascular disease, has been obtained over almost thirty years of active clinical use of ethylmethylhydroxypyridine succinate (6-methyl-2-ethylpyridin-3-ol butanedioate, EMHPS). It proved that EMHPS has such important effects as antioxidant, membrane-protective, antihypoxic, and anti-ischemic properties, as well as confirmed its hypoglycemic, hypolipidemic, antiplatelet and antithrombotic actions, which makes it an important component of the complex therapy of CVD. Progress in the development of innovative drugs is the result, on the one hand, of the availability of highly active pharmacological substances and, on the other hand, of the creation or selection of new dosage forms. The use of matrix tablets as a modern dosage form allowed us to efficiently optimize the pharmacokinetics of EMHPS, which led to the creation of a drug with a high predictive efficacy and safety. Thus, the developed new prolonged dosage form of EMHPS enables a constant-rate daily release of the active substance for 20 hours and reduces the likelihood of not only side effects, but also skipped intake during the day. The new dosage form of EMHPS is available at 375 and 750 mg doses, which makes it possible to take just 1 tablet per day and get all the therapeutic benefits while staying compliant.

Nanozyme-Enabled Treatment of Cardio- and Cerebrovascular Diseases.

Cardio- and cerebrovascular diseases are two major vascular-related diseases that lead to death worldwide. Reactive oxygen species (ROS) play a vital role in the occurrence and exacerbation of diseases. Excessive ROS induce cellular context damage and lead to tissue dysfunction. Nanozymes, as emerging enzyme mimics, offer a unique perspective for therapy through multifunctional activities, achieving essential results in the treatment of ROS-related cardio- and cerebrovascular diseases by directly scavenging excess ROS or regulating pathologically related molecules. This review first introduces nanozyme-enabled therapeutic mechanisms at the cellular level. Then, the therapies for several typical cardio- and cerebrovascular diseases with nanozymes are discussed, mainly including cardiovascular diseases, ischemia reperfusion injury, and neurological disorders. Finally, the challenges and outlooks for the application of nanozymes are also presented. This review will provide some instructive perspectives on nanozymes and promote the development of enzyme-mimicking strategies in cardio- and cerebrovascular disease therapy.

The Role of Concomitant Nrf2 Targeting and Stem Cell Therapy in Cerebrovascular Disease.

Despite the reality that a death from cerebrovascular accident occurs every 3.5 min in the United States, there are few therapeutic options which are typically limited to a narrow window of opportunity in time for damage mitigation and recovery. Novel therapies have targeted pathological processes secondary to the initial insult, such as oxidative damage and peripheral inflammation. One of the greatest challenges to therapy is the frequently permanent damage within the CNS, attributed to a lack of sufficient neurogenesis. Thus, recent use of cell-based therapies for stroke have shown promising results. Unfortunately, stroke-induced inflammatory and oxidative damage limit the therapeutic potential of these stem cells. Nuclear factor erythroid 2-related factor 2 (Nrf2) has been implicated in endogenous antioxidant and anti-inflammatory activity, thus presenting an attractive target for novel therapeutics to enhance stem cell therapy and promote neurogenesis. This review assesses the current literature on the concomitant use of stem cell therapy and Nrf2 targeting via pharmaceutical and natural agents, highlighting the need to elucidate both upstream and downstream pathways in optimizing Nrf2 treatments in the setting of cerebrovascular disease.

CHIP ameliorates cerebral ischemia-reperfusion injury by attenuating necroptosis and inflammation.

Blood reperfusion of ischemic cerebral tissue may cause cerebral ischemia-reperfusion (CIR) injury. Necroptosis and inflammation have been demonstrated to be involved in the disease-related process of CIR injury. The E3 ubiquitin ligase carboxyl terminus of Hsp70-interacting protein (CHIP) can modulate multiple cellular signaling processes, including necroptosis and inflammation. Numerous studies have demonstrated the neuroprotective effects of CHIP on multiple central nervous system (CNS) diseases. However, the effects of CHIP on CIR injury have not been fully explored. We hypothesize that CHIP can exert neuroprotective effects by attenuating necroptosis and inflammation during CIR injury. In the present study, adult wild-type (WT) C57BL/6 mice and CHIP knock-in (KI) mice with a C57BL/6 background and CHIP overexpression in neural tissue underwent middle cerebral artery occlusion (MCAO) surgery to simulate CIR onset. Our data indicated that CHIP expression in the peri-infarct tissue was markedly increased after MCAO surgery. Compared with WT mice, CHIP KI mice significantly improved neurological deficit scores, decreased cerebral infarct volume, and attenuated brain edema and neuronal damage. Meanwhile, CHIP overexpression attenuated necroptosis and inflammation induced by MCAO surgery. These findings indicated that overexpression of CHIP might exert neuroprotective effects by attenuating necroptosis and inflammation during CIR injury, and increasing CHIP levels may be a potential strategy in cerebrovascular disease therapy.

Cerebrovascular disease in senile patient (clinical case)

The article presents a clinical observation of a comorbid elderly patient with complaints typical for chronic cerebrovascular disease. A careful analysis of the clinical picture and a thorough assessment of the patient’s condition, including testing of cognitive and non-cognitive neuropsychiatric functions, made it possible to identify characteristic syndromes of cerebrovascular disease, which was additionally confirmed by the magnetic resonance imaging. The patient’s therapy regimen was optimized with an emphasis on clinically and pathogenetically justified methods taking into account the main clinical syndromes. Patient’s follow-up assessment has shown that the treatment was accompanied by significant positive dynamic, in both cognitive and emotional signs and symptoms. The article discusses the epidemiology of cerebrovascular diseases, their relationship with other geriatric syndromes in elderly and senile people. The main problems associated with the therapy of cerebrovascular diseases in elderly patients and the ways to eliminate them are discussed.

The practice of tracing nursing method in interventional therapy of cerebrovascular disease

Objective To explore the effect of tracing nursing method on postoperative nursing of patients with central cerebrovascular disease treated by interventional therapy. Methods From January 2012 to January 2017, a total of 90 patients who received interventional treatment for cerebrovascular diseases in the brain center were selected as the research subjects.Patients were randomly divided into the intervention group (using tracing nursing method postoperative nursing) and the control group (postoperative routine nursing) by the number table method, 45 cases of each group.The incidence of postoperative complications, nursing satisfaction, knowledge of cerebrovascular disease prevention and curative effect were analyzed and compared between the two groups. Results The incidence of complications in the intervention group was significantly lower than that in the control group.The nursing satisfaction, knowledge of cerebrovascular disease prevention, and treatment effect were significantly better than those in the control group, and the differences were statistically significant(P<0.05). Conclusion The traceability value is obtained by using the tracking nursing method, and the nursing quality system is constantly optimized, so as to improve the knowledge of the prevention and treatment of cerebrovascular disease among patients undergoing interventional treatment for cerebrovascular disease, reduce the incidence of complications, and improve the patients' satisfaction with the nursing work and the treatment effect. Key words: Tracking nursing; Cerebrovascular disease; Interventional therapy

Ask a neurologist: What primary care providers ask, and reducing referrals through eConsults.

Access to neurology consultation is limited by high demand and urgency of the presentation. Champlain BASETM (Building Access to Specialists through eConsultation) (eConsult service) aims to increase access through direct communication between primary care providers (PCPs) and specialists. Rapid responses to PCP questions can guide management and sometimes relieve the need for a formal consultation. We reviewed which topics were frequently addressed, the types of questions asked, and the effect on primary care for the patient. This is a retrospective review of 387 consecutive questions submitted to the Champlain BASETM service between May 2011 and January 2015 and the data generated from routine use and PCP exit surveys. Questions were categorized by topic and type and analyzed quantitatively. This included time required to answer each question and effect on plans for traditional referral and clinical course of action. The top 5 topics were headache (17%), incidental imaging findings (11%), numbness/tingling (11%), seizure (9%), and cerebrovascular disease (CVD) (9%). Fifty-one percent were related to diagnosis (choice of test, imaging interpretation, symptom interpretation), 23% to drug treatment (choice, adverse effects, prescribing instructions), and 17% to management (general, need for referral). Eighty-eight percent of questions took less than 10 minutes of specialist time to answer, and 80% were answered within 1 day. eConsults decreased face-to-face referrals by 50%. In 54% of cases, the PCP received information for a new course of action. We found that an eConsult service provides timely access to neurologists and can divert half of intended face-to-face consultations. The most common questions posed by PCPs regarded diagnosis and drug therapy for headaches, seizures, altered sensation, and CVD. eConsult services could provide guidance for continuing medical education planning in neurology.

Abstract 169: Neurovascular Disease is the Second Leading Cause of Death in the United States (US): A Modern Disease Burden Analysis

Introduction: The World Health Organization (WHO) in 2017 voted to return cerebrovascular disease from Circulatory Disorders to its historic home in Neurologic Disorders (forthcoming ICD-11), due to advances in cerebrovascular disease therapy and increased recognition of neurovascular contributions to dementia. Methods: Analyzing the WHO Global Burden of Disease Project 2015 data, we calculated the impact on attributable deaths and attributable disability (disability-adjusted life years lost - DALYs) of: 1) return of cerebrovascular diseases to the Neurologic Disorders category, and 2) use “neurovascular disease” state to include both “cerebrovascular diseases” and proportion of dementia due to neurovascular insults. Results: Reclassification of cerebrovascular disease as a Neurologic Disorder, in the US, increased the number of deaths attributable to Neurologic Disorders by 50.5%, from 326,000 to 490,000 per year, and increased DALYs lost by 37.3% (6.0 to 8.3 million). Worldwide, this reclassification increased the number of deaths attributable to Neurologic Disorders by 280% (2.3 to 8.6 million), and increased DALYs lost by 136%, (87.1 to 205.7 million). Systematic literature review shows vascular brain lesions contribute to 51% of clinically diagnosed Alzheimer disease and 65% of clinically diagnosed vascular dementia. Adding these cases to focal strokes, in the US, the number of deaths attributable to neurovascular disease increased by 90% (164,000 to 313,000), and DALYs lost increased by 37.3%, (2.3 to 3.7 million). Worldwide, the number of deaths attributable to neurovascular increased by 18% (6.3 to 7.5 million), and DALYs lost increased by 10.4% (119 to 131 million). Conclusions: When correctly classified according to modern pathophysiology, neurovascular disease moves from the 5 th to the 2 nd leading cause of death in the US; Neurologic Disorders moves from the 12 th to the 4 th leading cause of disability worldwide. This more accurate delineation of the national and global burden of neurovascular disease, should guide more informed allocation of resources for neurovascular research and clinical care.

Clinical neurophysiological methods in diagnosis and treatment of cerebrovascular diseases

Neurophysiological methods are gaining ground in the diagnosis and therapy of cerebrovascular disease. While the role of the EEG (electroencephalography) in the diagnosis of post-stroke epilepsy is constant, quantitative EEG para-meters, as new indicators of early efficiency after thrombolysis or in prognosis of patient's condition have proved their effectiveness in several clinical studies. In intensive care units, continuous EEG monitoring of critically ill patients became part of neurointenzive care protocols. SSEP (somatosesnsory evoked potencial) and EEG performed during carotid endarterectomy, are early indicative intraoperativ neuromonitoring methods of poor outcome. Neurorehabilitation is a newly discovered area of neurophysiology. Clinical studies have demonstrated the effectiveness of repetitive transcranial magnetic stimulation (rTMS) in the rehabilitation of stroke patients. Brain computer interface mark the onset of modern rehabi-litation, where the function deficit is replaced by robotic tehnology.

Алгоритм диагностики и терапии цереброваскулярных болезней в практике амбулаторного врача

Алгоритм диагностики и терапии цереброваскулярных болезней в практике амбулаторного врача

Synthesis, in silico and in vivo blood brain barrier permeability of ginkgolide B cinnamate

Ginkgolide B, one of the important components of Ginkgo biloba extracts, has been revealed to exhibit great potential in therapy of cerebrovascular diseases. However the lack of permeability greatly limited it from further clinical application. Based on the prediction model for blood brain barrier (BBB) permeation, herein a potential brain-targeting analog ginkgolide B cinnamate (GBC) was successfully synthesized and characterized. After intravenous administration of GBC or GB, liquid chromatography tandem mass spectrometry (LC–MS/MS) was conducted to determine the analog in rat plasma and brain. The results showed that GBC had a significant increase in BBB permeability. A significant 1.61-times increase in half-life was observed for GBC and the drug targeting index (DTI) value was calculated to be 9.91. The experiment results matched well with the predicted one, which revealed that BBB permeability prediction model combined with in vivo study could be used as a quick, feasible and efficient tool for brain-targeting drug design.

Evidence Base for Secondary Prevention - Antihypertensive Therapy in Cerebrovascular Disease

Abstract Antihypertensive therapy for preventing recurrence in survivors of stroke and transient ischemic attack patients requires much caution. Cutting the right balance between benefit and harm calls for the classical individual evidence based considerations. Current understanding to guide practices is briefly reviewed as stroke emerges as huge challenge with increasing longevity and chronic diseases.

Possibilities of using naftidrofuryl in the therapy of cerebrovascular diseases: Literature review and the authors’ observations

The efficacy of naftidrofuryl in treating cerebrovascular diseases is analyzed on the basis of a review of the Russian and foreign literature. Naftidrofuryl is a seroton 5-HT2 receptor antagonist and acts on brain energy metabolism mainly during hypoxia or ischemia. The results of preclinical studies proving the antispasmodic and neuroprotective properties of the drug and its capacity to normalize microcirculation in hypoxia are briefly considered. Experimental findings served as a basis for further studies of the efficacy of naftidrofuryl in patients with stroke, chronic cerebral ischemia, or vascular dementia. The use of naftidrofuryl (dusopharm) was demonstrated to statistically significantly enhance the efficiency of rehabilitation in post-stroke patients and to be followed by significant psychoemotional improvement. According to a Cochrane review, the naftidrofuryl-treated patients with vascular dementia showed a tendency towards better executive and cognitive functions, behavior, and mood. The drug was noted to have a positive effect on the health of patients with chronic cerebral ischemia. The authors provide the data of their trial of naftidrofuryl used in patients with dyscirculatory encephalopathy, which have confirmed its efficacy in this category of patients. The data available in the literature suggest that oral naftidrofuryl has a good tolerability and safety profile in patients with cerebrovascular diseases.

Macro- and microrheological parameters of blood in patients with cerebral and peripheral atherosclerosis: The molecular change mechanisms after pentoxifylline treatment

This study was designed to evaluate hemorheological changes in patients with cerebrovascular disease (CVD) and peripheral arterial disease (PAD) after 4 weeks of pentoxifylline therapy as well as to study red blood cell microrheological variables after the cell incubation with pentoxifylline and some phosphodiesterase (PDE) activity inhibitors. The patients with CVD (n = 50) and PAD (n = 33) were treated with pentoxifylline (400 mg, thrice a day) for 4 weeks. Before and after drug therapy the hemorheological measurements including plasma and whole blood viscosity, red blood cell aggregation (RBCA) and deformability (RBCD) were completed. In vitro study RBCs were incubated with: 1) Vinpocetine--inhibitor PDE-1, 10 μM; 2) Rolipram--PDE-4, 10 μM; 3) Isobutyl-methylxanthine (IBMX)--nonselective PDE inhibitor, 100 μM and with pentoxifylline, 10 μM The cell incubation was performed at 37 °C for 15 min. There were the positive changes of hemorheological profile after 4 weeks of the pentoxifylline therapy both in CVD and PAD patients. The marked RBCD changes were observed after the in vitro cell pentoxifylline treatment as well. Perhaps it is connected with the inhibition of the phosphodiesterase activity in RBCs. An application of drugs and chemicals that can inhibit the PDE activity resulted in RBCD rise and RBCA decrease. The experiments with the use of selective PDE inhibitors have revealed the similar red cell deformability changes. Vinpocetine increased RBCD significantly (p < 0.05). PDE-4 inhibitor--Rolipram stimulated RBCD by 15% (p < 0.05). Some more effective was IBMX. After cell incubation with it a significant rise of the deformability (by 27%; p < 0.05) was found. All drugs, having PDE activity decreased RBCA, but the most pronounced effect had Vinpocetine (50%; p < 0.05). Thus, administered pentoxifylline, daily (1200 mg), during four weeks improves hemorheological profile and especially its microrheological part as well as the blood transport capacity in subjects with cerebral and peripheral vascular disorders. It is most probably red cell microrheological control mechanisms may be associated with the phosphodiesterase activity alterations.

Blockage of the Renin-Angiotensin System in the Secondary Prevention of Stroke: Beneficial Effects Beyond Blood Pressure Reduction?

HomeStrokeVol. 40, No. 3Blockage of the Renin-Angiotensin System in the Secondary Prevention of Stroke: Beneficial Effects Beyond Blood Pressure Reduction? Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBBlockage of the Renin-Angiotensin System in the Secondary Prevention of Stroke: Beneficial Effects Beyond Blood Pressure Reduction? Luis Castilla-Guerra María del Carmen Fernández-Moreno Maria Dolores Jiménez-Hernandez Luis Castilla-GuerraLuis Castilla-Guerra Department of Internal Medicine, Hospital de Osuna, Seville, Spain Search for more papers by this author María del Carmen Fernández-MorenoMaría del Carmen Fernández-Moreno Department of Neurology, Hospital de Valme, Seville, Spain Search for more papers by this author Maria Dolores Jiménez-HernandezMaria Dolores Jiménez-Hernandez Department of Neurology, Hospital Virgen del Rocio, Seville, Spain Search for more papers by this author Originally published29 Jan 2009https://doi.org/10.1161/STROKEAHA.108.537639Stroke. 2009;40:e75Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: January 29, 2009: Previous Version 1 To the Editor:In the last few years, evidence from experimental and clinical studies have supported the hypothesis that angiotensin II might exert detrimental effects beyond the mechanical damage of high blood pressure (BP) and be a risk factor for ischemic stroke independent of its effect on BP. Thus, data from the HOPE and LIFE studies suggested that ACE inhibitors and angiotensin receptors blockers (ARB) may have protective effects for stroke that are independent of BP reduction.1 However, in view of recent published trials, data on the particular benefits of these specific antihypertensive agents for secondary stroke prevention are largely lacking. First, the Perindopril Protection against Recurrent Stroke Study (PROGRESS) trial provided no evidence of perindopril alone for preventing recurrent stroke. In fact, only the subgroup receiving both perindopril in combination with indapamide had reduced stroke recurrence.2 Furthermore, there is no evidence to date that using perindopril in combination with indapamide is more beneficial than using indapamide alone. Thus, the BP reduction with indapamide alone in the Poststroke Antihypertensive Treatment Study (PATS) trial was only 5/2 mm Hg, similar to the reduction seen with perindopril alone in the PROGRESS, and, on the contrary, significantly associated with stroke reduction.2,3 In addition, a systematic review on BP reduction in secondary prevention of stroke showed that calcium channel blockers were found to be better than ACE inhibitors in stroke prevention.4Recently, the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial, a multicenter trial involving more than 20 000 patients, has shown that termisaltan initiated soon after ischemic stroke and continued for 2.5 years did not significantly lower the rate of recurrent stroke or major cardiovascular events against placebo.5 This trial has important lessons for clinical practice and also illustrates that the extrapolation of the benefits of these drugs to the prevention of vascular recurrences after stroke may be inappropriate.Therefore, currently the question of whether agents that block the rennin–angiotensin system offer additional benefits independent of their effects on BP in patients with stroke seems to be a matter of faith.DisclosuresNone.1 Hankey GJ. Angiotensin-converting enzyme inhibitors for stroke prevention. Is there hope for progress after life? Stroke. 2003; 34: 354–356.LinkGoogle Scholar2 Wennberg R, Zimmermann C. The progress trial three years later: time for a balanced report of effectiveness. BMJ. 2004; 329: 968–970.CrossrefMedlineGoogle Scholar3 PATS Collaborating Group. Post-stroke antihypertensive treatment study. A preliminary result. Chin Med J. 1995; 108: 710–717.MedlineGoogle Scholar4 Zhang H, Thijs L, Staessen JA. Blood pressure lowering for primary and secondary prevention of stroke. Hypertension. 2006; 48: 187–195.LinkGoogle Scholar5 Yusuf S, Diener HC, Sacco RL, Cotton D, Ôunpuu S, Lawton WA, Palesch Y, Martin RH, Albers GW, Bath P, Bornstein N, Chan BPL, Chen ST, Cunha L, Dahlöf B, De Keyser J, Donnan GA, Estol C, Gorelick P, Gu V, Hermansson K, Hilbrich L, Markku Kaste M, Lu C, Machnig T, Pais P, Roberts R, Skvortsova V, Teal P, Toni D, VanderMaelen C, Voigt T, Weber M, Yoon BW, for the PRoFESS Study Group. Telmisartan to prevent recurrent stroke and cardiovascular events. N Engl J Med. 2008; 359.Google Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Pandit A (2015) Evidence base for secondary prevention – Antihypertensive therapy in cerebrovascular disease, Apollo Medicine, 10.1016/j.apme.2015.03.001, 12:2, (100-102), Online publication date: 1-Jun-2015. Castilla-Guerra L, Fernández-Moreno M, Romera-Tellado M and Álvarez-Suero J (2012) Prevención primaria del ictus en el anciano: evidencias actuales en el tratamiento de la hipertensión arterial, Revista Española de Geriatría y Gerontología, 10.1016/j.regg.2011.06.014, 47:3, (119-124), Online publication date: 1-May-2012. March 2009Vol 40, Issue 3 Advertisement Article InformationMetrics https://doi.org/10.1161/STROKEAHA.108.537639PMID: 19182077 Originally publishedJanuary 29, 2009 PDF download Advertisement

Antiplatelet therapy in cerebrovascular disease: implications of Management of Artherothrombosis with Clopidogrel in High-risk Patients and the Clopidogrel for High Artherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance studies' results for cardiologists.

Cardiovascular disease is prevalent among patients with stroke; thus, cardiologists frequently treat patients at high risk for stroke. Results from recent clinical trials of antiplatelet medications, given alone or in combination, may be of special interest to cardiologists. The MATCH study demonstrated no significant difference between clopidogrel alone and clopidogrel plus aspirin in reducing risk of vascular events after stroke or transient ischemic attack. A 1.3% increased risk of major bleeding was associated with clopidogrel plus aspirin. In CHARISMA, clopidogrel plus aspirin did not reach statistical significance vs. placebo plus aspirin in reducing incidence of myocardial infarction (MI), stroke, or death from cardiovascular causes in patients with stable atherothrombotic disease; clopidogrel was associated with an increase in moderate bleeding. These results suggest that clopidogrel plus aspirin may be inappropriate as first-line therapy for secondary stroke prevention. In patients with established cardiovascular disease at risk for MI or other vascular events, physicians must weigh the benefits and risks before choosing this therapy. Selection of an antiplatelet agent must be based on patient history, including previous MI and stroke, susceptibility to bleeding, and other high-risk factors (e.g. advanced age and diabetes). Aspirin plus extended-release dipyridamole may be more effective than clopidogrel for preventing stroke in high-risk patients. This article strives to put MATCH and CHARISMA results into context by providing an overview of antiplatelet therapy, including relevant clinical trial results, a review of current practice guidelines, and a summary of an ongoing study that will improve clinical decision making.

Development and question about interventional therapy for cerebrovascular disease

脑血管疾病严重危害人类健康.近年来,介入治疗以其微创、有效、安全和适应证较宽等特点逐渐受到医生与患者的肯定,成为治疗脑血管病的主要手段之一.随着神经影像学、导管技术和介入材料的迅速发展,血管内介入技术在治疗脑血管病方面日臻成熟,显示出广阔的前景,但也存在一些亟待解决的问题。

Efficacy of Dual Antiplatelet Therapy in Cerebrovascular Disease as Demonstrated by a Decline in Microembolic Signals

Background: The presence of microembolic signals (MES) may indicate an increased risk of recurrent ischemic events in patients with stroke. The optimal management of such patients is uncertain. We report the effect of clopidogrel in addition to aspirin on the number of MES in a series of patients with ischemic stroke and transient ischemic attack (TIA) due to large-vessel disease. Methods: 8 patients with either extracranial or intracranial artery stenosis were identified in 30-min MES studies by transcranial Doppler sonography as having MES. All patients were on antiplatelet therapy prior to baseline transcranial Doppler monitoring. The patients were subsequently treated with clopidogrel in addition to aspirin. Repeat MES studies were performed between day 3 and 7 with aspirin and clopidogrel. Results: All patients were Chinese. The median interval time from symptom onset to initial MES study was 7 days (range of 2–30). MES donor sites included 4 severely stenosed or occluded internal carotid arteries and 4 stenosed middle cerebral arteries. The median MES number at baseline was 8 (range 3–51). Repeat MES studies showed a significant decrease in MES (p = 0.012, Wilcoxon signed ranks test). 4 patients had complete cessation of MES and all patients showed a decline in MES. No patient had recurrent strokes or bleeding complications. Conclusion: The rapid and significant decline of MES in our stroke and TIA patients suggests the possible efficacy of dual antiplatelet therapy with aspirin and clopidogrel in patients with MES and symptomatic large-artery occlusive disease. Randomized controlled trials should be conducted to confirm this preliminary observation.

Estrogen and progestagens differentially modulate vascular proinflammatory factors

The potential benefit of ovarian hormone replacement therapy in cerebrovascular disease is well supported by experimental observations but not by recent large, randomized clinical trials. This discrepancy points out the need for better understanding of the vascular actions of ovarian hormones as well as medroxyprogesterone acetate (MPA), a synthetic analog of progesterone (P) widely prescribed in combination with estrogens. Therefore, we investigated whether in vivo exposure to 17beta-estradiol (E) and/or P or MPA modifies inflammation in the cerebral vasculature, a key process in the evolution of ischemic brain injury. Female rats were injected (ip) with LPS to induce inflammation, and 6 h later brains were taken for blood vessel isolation and Western blot analysis of the inflammatory enzymes inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2). In ovariectomized (O) females, LPS induced cerebrovascular iNOS and COX-2; however, this effect was significantly decreased when O animals were treated for 3 wk with E. In contrast, treatment of O females with either MPA or P exacerbated the cerebrovascular inflammatory response to LPS. In intact females, LPS induction of iNOS and COX-2 in cerebral vessels was found to vary with the stage of the estrous cycle: LPS had the greatest effect during estrus, when circulating estrogen is low and progesterone is high. Thus exposure to endogenous or exogenous ovarian hormones appears to modulate cerebrovascular inflammation. Anti-inflammatory effects of estrogen would attenuate ischemic brain injury; however, this vasoprotective benefit may be diminished in the presence of progestagens.