Stem cell transplantation for treating stroke： status,trends and development

The developing approaches of thrombolytic therapy, endovascular treatment, neuroprotective therapy, and stem cell therapy have enabled breakthroughs in stroke treatment. In this study, we summarize and analyze trends and progress in stem cell transplantation for stroke treatment by retrieval of literature from Thomson Reuters Web of Science database, the NIH Clinical Trial Planning Grant Program, and Clinical Trials Registration Center in North America. In the last 10 years, there has been an increasing number of published articles on stem cell transplantation for stroke treatment. In particular, research from the USA and China has focused on stem cell transplantation. A total of 2,167 articles addressing stem cell transplantation for stroke treatment from 2004 to 2013 were retrieved from the Thomson Reuters Web of Science database. The ma- jority of these articles were from the USA （854, 39.4%）, with the journal Stroke publishing the most articles （145, 6.7%）. Of the published articles, 143 were funded by the National Institutes of Health （accounting for 6.6% of total publications）, and 91 by the National Natural Science Foundation of China. Between 2013 and 2014, the National Institutes of Health provided finan- cial support （$130 million subsidy） for 329 research projects on stroke therapy using stem cell transplantation. In 2014, 215 new projects were approved, receiving grants of up to $70,440,000. Ninety clinical trials focusing on stem cell transplantation for stroke were registered in the Clinical Trial Registration Center in North America, with 40 trials registered in the USA （ranked first place）. China had the maximum number of registered research or clinical trials （10 projects）.     

Visualization analysis of research frontiers and trends in nerve regeneration and osseoperception in the repair of tooth loss

This study analyzed 85 articles indexed by the Web of Science concerning nerve regeneration and osseoperception during tooth loss repair. Using the Web of Science database and Citespace Ⅲ software, a document co-citation network map was drawn by document co-citation analysis and word frequency analysis methods. Combined with emergent node secondary literature retrieval, subject headings with apparent changing word frequency trends were retrieved so as to identify research frontiers and development trends. Research frontiers and hotspots for neuronal calcium sensor protein were quantitatively explored to forecast future research developments in nerve regeneration and osseoperception during repair of tooth loss.     

Use of stem cell transplantation to treat epilepsy A Web of Science-based literature analysis

OBJECTIVE: To identify global research trends in the use of stem cell transplantation to treat epilepsy. DATA RETRIEVAL: We performed a bibliometric analysis of studies on the use of stem cell transplantation to treat epilepsy during 2002-2011, retrieved from Web of Science, using the key words epilepsy or epileptic or epilepticus or seizure and "stem cell". SELECTION CRITERIA: Inclusion criteria: (a) peer-reviewed published articles on the use of stem cell transplantation to treat epilepsy indexed in Web of Science; (b) original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material, and news items. MAIN OUTCOME MEASURES: (a) Annual publication output; (b) type of publication; (c) publication by research field; (d) publication by journal; (e) publication by author; (f) publication by country and institution; (g) publications by institution in China; (h) most-cited papers; and (i) papers published by Chinese authors or institutions. RESULTS: A total of 460 publications on the use of stem cell transplantation to treat epilepsy were retrieved from Web of Science, 2002-2011. The number of publications gradually increased over the 10-year study period. Articles and reviews constituted the major types of publications. More than half of the studies were in the field of neuroscience/neurology. The most prolific journals for this topic were Epilepsia, Bone Marrow Transplantation, and Journal of Neuroscience. Of the 460 publications, almost half came from American authors and institutions; relatively few papers were published by Chinese authors or institutions. CONCLUSION: Literature on stem cell transplantation for epilepsy includes many reports of basic research, but few of clinical trials or treatments. Exact effects are not yet evaluated. Epilepsy rehabilitation is a long-term, complex, and comprehensive system engineering. With advances in medical development, some effective medical, social and educational measures are needed to facilitate patient’s treatment and training and accelerate the recovery of life ability, learning ability and social adaptability to the largest extent to improve patient’s quality of life.     

Follicle and melanocyte stem cells, and their application in neuroscience A Web of Science-based literature analysis

OBJECTIVE: To identify global research trends of follicle and melanocyte stem cells, and their application in neuroscience. DATA RETRIEVAL: We performed a bibliometric analysis of studies from 2002 to 2011 on follicle and melanocyte stem cells, and their application in neuroscience, which were retrieved from the Web of Science, using the follicle stem cell or melanocyte stem cell, and neural, neuro or nerve. SELECTION CRITERIA: Inclusion criteria: (a) peer-reviewed published articles on follicle and melanocyte stem cells, and their application in neuroscience, which were indexed in the Web of Science; (b) original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material, and news items. Exclusion criteria: (a) articles that required manual searching or telephone access; (b) documents that were not published in the public domain; and (c) a number of corrected papers from the total number of articles. MAIN OUTCOME MEASURES: (1) Distribution of publications on follicle and melanocyte stem cells by years, journals, countries, institutions, institutions in China, and most cited papers. (2) Distribution of publications on the application of follicle and melanocyte stem cells in neuroscience by years, journals, countries, institutions, and most cited papers. RESULTS: Of the 348 publications from 2002 to 2011 on follicle and melanocyte stem cells, which were retrieved from the Web of Science, more than half were from American authors and institutes. The most prolific institutions in China for publication of papers on follicle and melanocyte stem cells were the Fourth Military Medical University and Third Military Medical University. The most prolific journals for publication of papers on follicle and melanocyte stem cells were the Journal of Investigative Dermatology, Pigment Cell & Melanoma Research. Of the 63 publications from 2002 to 2011 on the application of follicle and melanocyte stem cells in neuroscience, which were retrieved from the Web of Science, more than half were from American authors and institutes, and no papers were from Chinese authors and institutes. The most prolific journals for publication of papers on the application of follicle and melanocyte stem cells in neuroscience were the Journal of Investigative Dermatology, Pigment Cell & Melanoma Research. CONCLUSION: Based on our analysis of the literature and research trends, we found that follicle stem cells might offer further benefits in neural regenerative medicine.     

Acupuncture in stroke rehabilitation Literature retrieval based on international databases

OBJECTIVE: To identify global research trends of acupuncture in stroke rehabilitation using a bibliometric analysis of the Web of Science and the Clinical Trials registry database (ClinicalTrials.gov). DATA RETRIEVAL: We performed a bibliometric analysis of data retrievals for acupuncture in stroke rehabilitation from 1992 to 2011 using the Web of Science and ClinicalTrials.gov. SELECTION CRITERIA: Inclusion criteria: (1) Web of Science: (a) Peer-reviewed articles on acupuncture in stroke rehabilitation that were published and indexed in the Web of Science. (b) Type of articles: original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material and news items. (c) Year of publication: 1992-2011. (2) ClinicalTrials.gov: All clinical trials relating to acupuncture in stroke rehabilitation were searched in this database. Exclusion criteria: (1) Web of Science: (a) Articles that required manual searching or telephone access. (b) We excluded documents that were not published in the public domain. (c) We excluded a number of corrected papers from the total number of articles. (2) ClinicalTrials.gov: (a) We excluded clinical trials that were not in the ClinicalTrials.gov database. (b) We excluded clinical trials that dealt with magnetic stimulation other than acupuncture in stroke rehabilitation in the ClinicalTrials.gov database. MAIN OUTCOME MEASURES: (1) Type of literature; (2) annual publication output; (3) distribution according to journals; (4) distribution according to country; (5) distribution according to institution; (6) top cited articles over the last 20 years; and (7) clinical trials registered. RESULTS: (1) In all, 92 studies on acupuncture in stroke rehabilitation appeared in the Web of Science from 1992 to 2011, almost half of which derived from Chinese and American authors and institutes. The number of studies addressing acupuncture in stroke rehabilitation has gradually increased over the past 20 years. Most papers on acupuncture in stroke rehabilitation appeared in journals with a particular focus on rehabilitation research, such as Stroke, Archives of Physical Medicine, Cochrane Database of Systematic Reviews and Journal of Alternative and Complementary Medicine. (2) In the ClinicalTrials.gov, three studies can be searched on acupuncture and stroke, all of which were registered and sponsored by Chinese institutions since February 2009. CONCLUSION: From our analysis of the literature and research trends, we found that acupuncture in stroke rehabilitation may offer further benefits in regenerative medicine.     

Survey of spinal cord injury-induced neurogenic bladder studies using the Web of Science

OBJECTIVE:To identify global trends in research on spinal cord injury-induced neurogenic bladder, through a bibliometric analysis using the Web of Science. DATA RETRIEVAL:We performed a bibliometric analysis of studies on spinal cord injury-induced neurogenic bladder using the Web of Science.Data retrieval was performed using key words"spinal cord injury","spinal injury","neurogenic bladder","neuropathic bladder","neurogenic lower urinary tract dysfunction","neurogenic voiding dysfunction","neurogenic urination disorder"and "neurogenic vesicourethral dysfunction". SELECTION CRITERIA:Inclusion criteria:(a)published peer-reviewed articles on spinal cord injury-induced neurogenic bladder indexed in the Web of Science;(b)type of articles:original research articles and reviews;(c)year of publication:no limitation.Exclusion criteria:(a)articles that required manual searching or telephone access;(b)Corrected papers and book chapters. MAIN OUTCOME MEASURES:(1)Annual publication output;(2)distribution according to journals; (3)distribution according to subject areas;(4)distribution according to country;(5)distribution according to institution;and(6)top cited publications. RESULTS:There were 646 research articles addressing spinal cord injury-induced neurogenic bladder in the Web of Science.Research on spinal cord injury-induced neurogenic bladder was found in the Science Citation Index-Expanded as of 1946.The United States,Ireland and Switzerland were the three major countries contributing to studies in spinal cord injury-induced neurogenic bladder in the 1970s.However,in the 1990s,the United States,the United Kingdom,the Netherlands,Germany and Japan published more papers on spinal cord injury-induced neurogenic bladder than Switzerland,and Ireland fell off the top ten countries list.In this century,the United States ranks first in spinal cord injury-induced neurogenic bladder studies,followed by France,the United Kingdom,Germany,Switzerland and Japan.Subject categories including urology, nephrology and clinical neurology,as well as rehabilitation,are represented in spinal cord injury-induced neurogenic bladder studies. CONCLUSION:From our analysis of the literature and research trends,we conclude that spinal cord injury-induced neurogenic bladder is a hot topic that will continue to generate considerable research interest in the future.     

Research progress in rehabilitation treatment of stroke patients A bibliometric analysis

BACKGROUND: Stroke presents as a transient or chronic brain dysfunction and is associated with high morbidity and high mortality. The doctors and scientists would like to argue how to enhance the validity of the rehabilitation treatment and how to further improve the level of treatment on stroke. OBJECTIVE: The aim of this study was to quantitatively analyze the current worldwide progress in research on stroke rehabilitation treatment based on Web of Science database and ClinicalTrial.gov in the past 10 years. METHODS: We conducted a quantitative analysis of clinical trial articles regarding stroke rehabilitation published in English from 2003 to 2013 and indexed in the National Institutes of Health Clinical Trials registry and Web of Science databases. Data were downloaded on March 15, 2013. RESULTS: (1) From 2003 to 2013, 2 654 clinical trials investigating stroke were indexed in ClinicalTrials.gov. There were only 58 clinical trials registered in 2003, and there was a marked increase from 2005. A total of 605 clinical trials on the rehabilitation of stroke were conducted in the past 10 years. (2) The analysis showed that most of the trials in the field were registered by North American institutions. With respect to the Asian countries, China and Taiwan area of China also published a reasonable proportion of the trials, but comparatively speaking, the number of trials is really rare. Most of the interventions were drugs, followed by the devices, and behavioral interventions were ranked third. (3) In the past 10 years, there were 4 052 studies on stroke indexed by Web of Science database. CONCLUSION: From perspective of research progress, we found that the number of clinical trials and papers on stroke rehabilitation has increased significantly in the past 10 years, between them a remarkable positive correlation exists.     

Use of acupuncture to treat cerebral infarction in the last 10 years A Scopus-based literature analysis

OBJECTIVE: To identify global research trends in the use of acupuncture to treat cerebral infarction. DATA RETRIEVAL: We performed a bibliometric analysis of studies on the use of acupuncture to treat cerebral infarction published during 2002-2011, retrieved from Scopus, using the Key Words of acupuncture and cerebral infarction or ischemic stroke. SELECTION CRITERIA: Inclusion criteria: peer-reviewed articles on the use of acupuncture to treat cerebral infarction indexed in Scopus and published between 2002 and 2011; types of publications were original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material, and news items. Exclusion criteria: articles that required manual searching or telephone access; documents that were not published in the public domain; and corrected papers. MAIN OUTCOME MEASURES: (a) Annual publication output; (b) language of publication; (c) type of publication; (d) key words of publication; (e) publication by research field; (f) publication by journal; (g) publication by country and institution; (h) publication by author; (i) most-cited papers between 2002 and 2006; and (j) most-cited papers between 2007 and 2011. RESULTS: A total of 160 publications on the use of acupuncture to treat cerebral infarction from 2002-2011 were retrieved from Scopus. The number of publications increased gradually over the 10-year study period; most were written in Chinese or English. Articles and reviews constituted the major types. The most frequent key word used was acupuncture. The most prolific journals in this area were Zhongguo Zhen Jiu and the Chinese Journal of Clinical Rehabilitation. Of the 160 publications retrieved, half came from Chinese authors and institutions. Tianjin University of Traditional Chinese Medicine was the most prolific research institute. Two papers were cited 30 times; they were published in 2002 and 2009, respectively. CONCLUSION: In the field of neuroscience, there is little literature on acupuncture for cerebral infarction. The most-cited papers were cited 30 times in the past 3 years. We believe that, with advances in the study of mechanisms in neurobiology, research on acupuncture will also advance and will become the concern of more scholars.     

Transplantation of neural stem cells, Schwann cells and olfactory ensheathing cells for spinal cord injury A Web of Science-based literature analysis

OBJECTIVE: To identify global research trends in transplantation of neural stem cells, Schwann cells and olfactory ensheathing cells for spinal cord injury. DATA RETRIEVAL: We performed a bibliometric analysis of studies on transplantation of neural stem cells, Schwann cells and olfactory ensheathing cells for spinal cord injury published from 2002 to 2011 and retrieved from the Web of Science, using the key words spinal cord injury along with either neural stem cell, Schwann cell or olfactory ensheathing cell. SELECTION CRITERIA: Inclusion criteria: (a) peer-reviewed published articles on neural stem cells, Schwann cells or olfactory ensheathing cells for spinal cord injury indexed in the Web of Science; (b) original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial materials and news items; and (c) published between 2002 and 2011. Exclusion criteria: (a) articles that required manual searching or telephone access; (b) documents that were not published in the public domain; and (c) corrected papers. MAIN OUTCOME MEASURES: (1) Annual publication output, distribution by journal, distribution by institution and top-cited articles on neural stem cells; (2) annual publication output, distribution by journal, distribution by institution and top-cited articles on Schwann cells; (3) annual publication output, distribution by journal, distribution by institution and top-cited articles on olfactory ensheathing cells. RESULTS: This analysis, based on articles indexed in the Web of Science, identified several research trends among studies published over the past 10 years in transplantation of neural stem cells, Schwann cells and olfactory ensheathing cells for spinal cord injury. The number of publications increased over the 10-year period examined. Most papers appeared in journals with a focus on neurology, such as Journal of Neurotrauma, Experimental Neurology and Glia. Research institutes publishing on the use of neural stem cells to repair spinal cord injury were mostly in the USA and Canada. Those publishing on the use of Schwann cells were mostly in the USA and Canada as well. Those publishing on the use of olfactory ensheathing cells were mostly in the UK, the USA and Canada. CONCLUSION: On the basis of the large number of studies around the world, cell transplantation has proven to be the most promising therapeutic approach for spinal cord injury.     

Use of nerve conduits for peripheral nerve injury repair A Web of Science-based literature analysis

OBJECTIVE: To identify global research trends in the use of nerve conduits for peripheral nerve injury repair. DATA RETRIEVAL: Numerous basic and clinical studies on nerve conduits for peripheral nerve injury repair were performed between 2002-2011. We performed a bibliometric analysis of the institutions, authors, and hot topics in the field, from the Web of Science, using the key words peripheral nerve and conduit or tube. SELECTION CRITERIA: Inclusion criteria: peer-reviewed published articles on nerve conduits for peripheral nerve injury repair, indexed in the Web of Science; original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material, and news items. Exclusion criteria: articles requiring manual searching or telephone access; documents not published in the public domain; and several corrected papers. MAIN OUTCOME MEASURES: (a) Annual publication output; (b) publication type; (c) publication by research field; (d) publication by journal; (e) publication by funding agency; (f) publication by author; (g) publication by country and institution; (h) publications by institution in China; (i) most-cited papers. RESULTS: A total of 793 publications on the use of nerve conduits for peripheral nerve injury repair were retrieved from the Web of Science between 2002-2011. The number of publications gradually increased over the 10-year study period. Articles constituted the main type of publication. The most prolific journals were Biomaterials, Microsurgery, and Journal of Biomedical Materials Research Part A. The National Natural Science Foundation of China supported 27 papers, more than any other funding agency. Of the 793 publications, almost half came from American and Chinese authors and institutions. CONCLUSION: Nerve conduits have been studied extensively for peripheral nerve regeneration; however, many problems remain in this field, which are difficult for researchers to reach a consensus.     

基于CiteSpace的创伤性脑损伤研究文献计量学分析

目的通过对创伤性脑损伤（TBI）研究文献进行计量学分析,探索TBI领域的研究热点和研究趋势。 方法基于Web of Science核心数据库检索2016~2020年TBI研究的相关文献,通过CiteSpace.5.8.R3对发表文章年度分布、作者、机构、国家、期刊、被引情况和关键词等进行分析,并根据关键词的词频、中心性和聚类情况探讨TBI领域的研究热点和趋势。 结果（1）筛选后共纳入14 991篇文献,美国是发文量最多的国家,哈佛大学医学院是发文量最多的机构。（2）氧化应激、死亡率、儿童TBI、创伤后应激障碍、康复治疗是近5年TBI领域研究热点。（3）TBI的模型及损伤效应-生物学机制-诊断及治疗指南-个体治疗是TBI研究领域的研究趋势。 结论青少年人群TBI的损伤效应、分子机制、治疗方法的可靠性及有效性是TBI领域现在和未来研究的重点和方向。     

Bibliometric profile of neurogenic bladder in the literature: a 20-year bibliometric analysis

Neurogenic bladder is a dysfunction of the lower urinary tract caused by nervous system disorder. We investigated the trends in publication of articles under the topic “neurogenic bladder” using bibliometric analysis. Articles on neurogenic bladder, published between 1995 and 2014, were retrieved from the ISI Web of Science citation database. We analyzed the search results for authors, countries, institutions, journals, and top-cited papers. A total of 1,904 articles were retrieved. There was a small increase in the number of articles on neurogenic bladder from 1995 (n = 43) to 2014 (n = 117). The USA was the leading country in the total number of articles (n = 598). However, the number of publications from China has rapidly increased, and China was ranked second in 2014. Emmanuel Chartier-Kastler (n = 65) was the most productive author, and University of Paris VI (Paris 6) (n = 61) was the most productive institution. The Journal of Urology published the greatest number of articles on this topic (n = 285). Articles on neurogenic bladder were often published in a professional journal under the category Urology & Nephrology, Neurosciences & Neurology, or Rehabilitation. Visualization analysis based on co-citation networks was conducted using CiteSpace III. Visualization analysis revealed that the hot spots in neurogenic bladder were botulinum toxin-A, prazosin, bethanechol, and afferent pathways. These findings provide new insight into the publication trends and hot spots in neurogenic bladder.     

Stem cell transplantation for treating Duchenne muscular dystrophy A Web of Science-based literature analysis

OBJECTIVE: To identify global research trends in stem cell transplantation for treating Duchenne muscular dystrophy using a bibliometric analysis of Web of Science. DATA RETRIEVAL: We performed a bibliometric analysis of studies on stem cell transplantation for treating Duchenne muscular dystrophy from 2002 to 2011 retrieved from Web of Science. SELECTION CRITERIA: Inclusion criteria: (a) peer-reviewed published articles on stem cell transplantation for treating Duchenne muscular dystrophy indexed in Web of Science; (b) original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material, and news items; and (c) publication between 2002 and 2011. Exclusion criteria: (a) articles that required manual searching or telephone access; (b) documents that were not published in the public domain; and (c) corrected papers. MAIN OUTCOME MEASURES: (1) Annual publication output; (2) distribution according to subject areas; (3) distribution according to journals; (4) distribution according to country; (5) distribution according to institution; (6) distribution according to institution in China; (7) distribution according to institution that cooperated with Chinese institutions; (8) top-cited articles from 2002 to 2006; (9) top-cited articles from 2007 to 2011. RESULTS: A total of 318 publications on stem cell transplantation for treating Duchenne muscular dystrophy were retrieved from Web of Science from 2002 to 2011, of which almost half derived from American authors and institutes. The number of publications has gradually increased over the past 10 years. Most papers appeared in journals with a focus on gene and molecular research, such as Molecular Therapy, Neuromuscular Disorders, and PLoS One. The 10 most-cited papers from 2002 to 2006 were mostly about different kinds of stem cell transplantation for muscle regeneration, while the 10 most-cited papers from 2007 to 2011 were mostly about new techniques of stem cell transplantation for treating Duchenne muscular dystrophy. CONCLUSION: The publications on stem cell transplantation for treating Duchenne muscular dystrophy were relatively few. It also needs more research to confirm that stem cell therapy is a reliable treatment for Duchenne muscular dystrophy.     

国内外卒中患者照顾者领域研究热点与前沿可视化分析

目的 以文献计量学为基础，应用CiteSpace软件对国内外卒中患者照顾者领域研究现状及热点问题进行分析，为深入开展该领域的研究提供参考。方法 在中国知网和Web of Science数据库中检索从建库至2021年12月31日卒中患者照顾者领域的中英文文献，文献类型包括论著、综述、学位论文、会议论文。去除重复文献后，从发文量、作者、机构、国家、关键词等方面进行文献计量学分析。结果 共纳入1298篇中文文献（中国知网），1763篇英文文献（Web of Science）。对于卒中患者照顾者的研究，中英文文献发表均整体呈逐年上升趋势，中国知网数据库中，发文量从2002年的4篇增至2021年的164篇；郑州大学张振香是发文量最多（48篇）的作者，郑州大学护理与健康学院（50篇）是该领域发文量最多的机构；除主题词外，“影响因素”“照顾能力”“照顾负担”“抑郁”“焦虑”“自我感受负担”等为高频关键词。在Web of Science数据库中，发文量从2009年的103篇增至2021年的201篇；美国发文量最多（565篇），约翰霍普金斯医学院的Roth在作者中发文量最多，Univ Toronto（55篇）在发文机构中居首位；“quality of life”“rehabilitation”“support”“burden”“care”“depression symptom”“survivor”等为高频关键词。结论 国内外卒中患者照顾者领域的研究处于稳定发展阶段，发文作者、发文机构均呈现以高校和地域为中心的特点，但缺乏跨区域和跨单位合作；国内外研究热点不同，照顾负担及照顾能力的影响因素、卒中照顾者负性情绪为国内研究热点，照顾者生活质量的影响因素、照顾负担和抑郁症状、照顾者主导的康复对卒中患者的影响是国外研究热点。临床或科研工作者应加强各研究机构之间的合作，关注该领域的研究前沿和热点，提高研究深度和广度。     

Block of purinergic P2X(7) receptor is neuroprotective in an animal model of Alzheimer's disease

Pharmacological antagonism of the ionotropic purinergic P2X7R has been studied for effects on inflammatory reactivity and neuronal viability in amyloid-beta1-42-injected rat hippocampus. Amyloid-beta1-42-injected brains (7-day postinjection) demonstrated marked increases in P2X7R expression, gliosis, leakiness of blood-brain barrier and loss of hippocampal neurons. The P2X7R antagonist, brilliant blue G reduced levels of purinergic receptor expression, attenuated gliosis, diminished leakiness of blood-brain barrier and was neuroprotective in peptide-injected brain. Brilliant blue G also demonstrated neuroprotection and antagonism against inflammatory responses induced by the P2X7R agonist, 2',3'-(benzoyl-4-benzoyl)-ATP. The findings constitute the first report that pharmacological inhibition of P2X7R, possibly by acting to inhibit inflammatory reactivity, confers neuroprotection in an animal model of Alzheimer's disease brain.