Neural dysfunction and neuroinflammation in African brain disorders

非洲脑部疾病中的神经功能障碍和神经炎症

基本信息

批准号：
8069316
负责人：
Krister Sven Kristensson
金额：
$ 11.38万
依托单位：
KAROLINSKA INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-05-15 至 2012-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8069316
关键词：
AIDS neuropathy Acute Adult Affect Africa South of the Sahara African African Trypanosomiasis Arsenicals Awareness Biological Blood Blood - brain barrier anatomy Brain Brain Diseases Cameroon Cellular biology Central Africa Cerebral Malaria Cerebrospinal Fluid Cessation of life Child Clinical Collaborations Communicable Diseases Communities Country Developing Countries Diagnosis Diagnostic Disease Employee Strikes Encephalitis Epilepsy Europe European Functional disorder Future Goals Health Human Immune Income Infection Inflammation Inflammatory Institution International International Cooperation Laboratories Lead Left Liquid substance Medical Faculty Methods Molecular Biology Monitor Nervous system structure Neurocysticercosis Neurologic Neurologic Dysfunctions Neurosciences Parasites Patients Pattern Pharmaceutical Preparations Pilot Projects Plague Protocols documentation Rabies Recovery Research Research Personnel Research Project Grants Rest Rodent Rodent Model Science Sleep Sleep disturbances Staging Techniques Testing Therapeutic Therapeutic Intervention Toxoplasmosis Training Translations Trypanosoma brucei brucei Tsetse Flies Universities Wrist actigraphy base behavior change chemokine cytokine disability experience human disease meetings mortality neglect nervous system infection neuroinflammation novel relating to nervous system sleep epilepsy vector

项目摘要

DESCRIPTION (provided by applicant): "Neural dysfunction and neuroinflammation in African brain disorders". Infectious diseases of the brain are among the most devastating brain disorders that plague developing countries. In spite of this, research on these diseases is mostly neglected in the neuroscience community of the "North" of the world. It is therefore mandatory to strengthen the capacity for research in regions struck by these diseases, with a view to direct research to the needs in the field and increase the international awareness for collaborative research efforts. Several brain infections are lethal if left untreated, and treatments are often non-efficient, expensive or not readily available. Furthermore, such diseases cause neurological disabilities (epilepsy in cerebral malaria and neurocysticercosis, severe sleep disturbances in African trypanosomiasis and neuroAIDS and behavior changes in toxoplasmosis and rabies) and sequelae even after recovery from the acute illness. The aim of the R21 exploratory project is to plan for capacity building for research on brain dysfunctions in inflammatory diseases which are prevalent in sub-Saharan Africa. The activities will be centered around the Medical Faculty at the University of Yaounde 1 in Cameroon. This country is located at the cross-road between West and Central Africa and could therefore serve as a center for the world region in which inflammatory brain disease is most prevalent. Two European laboratories with extensive experience to conduct research on these diseases will co-operate with a Cameroonian partner in this capacity building endeavor. The research planned for the R21 project is focused on brain involvement in human African trypanosomiasis (HAT) caused by the parasites Trypanosoma brucei (Tb), spread tsetse flies in sub- Saharan Africa. The specific aim is to correlate Tb passage into the brain across the blood-brain barrier (BBB) with changes of inflammatory molecules (cytokines and chemokines) in the brain and functional changes (alterations of the sleep pattern and rest-activity rhythm during 24h). The latter could be revealed in patients by a non-invasive strategy, namely actigraph recordings with relatively inexpensive wrist-worn watches. Monitoring of brain invasion by Tb is mandatory for therapeutic interventions, because this encephalitic stage requires treatment with very toxic drugs. However, diagnostic criteria for this stage are still ill-defined, and better methods to diagnose and monitor the diseases are urgently needed. The needs will be assessed for research on other brain infections, prevalent in the region, which clinically present with neurological dysfunctions including epilepsy, sleep disruptions and behaviour changes .This platform for inflammatory brain disorder research projects will then have the potentials to be accessible to researchers in West and Central Africa countries PUBLIC HEALTH RELEVANCE: Infections of the nervous system affect large numbers of children and adults, especially in developing countries, causing inflammation of the brain and neurological disabilities or death. Most of these diseases are neglected because they affect the "South" of the world, but they also have an impact on countries of the "North", and research on these diseases can open new perspectives in brain sciences. This project proposes pilot studies on one of these neglected diseases, sleeping sickness, and a plan to strengthen research capacity in African countries in which infectious diseases are endemic.

描述（由申请人提供）：“非洲脑疾病中的神经功能障碍和神经炎症”。大脑的传染病是困扰发展中国家的最具破坏性的脑部疾病。尽管如此，关于这些疾病的研究主要在世界“北部”的神经科学界被忽略。因此，必须加强这些疾病击中的地区的研究能力，以期将研究直接研究，并提高国际对合作研究工作的认识。如果未经治疗，几种大脑感染是致命的，并且治疗通常是非效率，昂贵或不容易获得的。此外，这种疾病会引起神经疾病（脑疟疾的癫痫病和神经囊肿，非洲锥虫病和神经剂的严重睡眠障碍以及弓形虫病和狂犬病的行为变化）和次序伴随着急性疾病后的序列。 R21探索项目的目的是计划为炎症性疾病中脑功能障碍的研究能力建设，这些疾病在撒哈拉以南非洲普遍存在。这些活动将集中在喀麦隆Yaounde 1的医学院围绕。这个国家位于西部和中非之间的跨道路，因此可以成为炎症性脑疾病最普遍的世界地区中心。两家具有丰富经验的欧洲实验室，以对这些疾病进行研究，将与喀麦隆的合作伙伴合作。 R21项目计划的研究重点是由寄生虫Brucei（TB）引起的非洲非洲锥虫病（HAT），在撒哈拉以南非洲散布采摘蝇。具体的目的是将横跨血脑屏障（BBB）进入大脑的TB与大脑中炎症分子（细胞因子和趋化因子）的变化和功能变化（睡眠模式和24H期间的静止运动节奏的改变）相关联。后者可以通过一种非侵入性策略在患者中揭示，即用相对较便宜的腕部手表录音。对于治疗性干预，必须对结核病监测大脑侵袭，因为该脑阶段需要用非常有毒的药物进行治疗。但是，此阶段的诊断标准仍然不明显，并且迫切需要诊断和监测疾病的更好方法。将评估该地区的其他大脑感染的需求，该地区普遍存在，临床上出现神经系统功能障碍，包括癫痫，睡眠中断和行为改变。炎症性脑部疾病研究项目的平台将有可能可供西部和中部非洲国家的研究人员获得潜力公共卫生相关性：神经系统的感染会影响大量儿童和成人，尤其是在发展中国家，导致大脑炎症和神经障碍或死亡。这些疾病大多数被忽略了，因为它们会影响世界的“南方”，但它们也会影响“北方”的国家，对这些疾病的研究可以打开脑科学的新观点。该项目提出了有关这些被忽视的疾病之一，熟睡的疾病的试点研究，并计划在传染病是地方性疾病的非洲国家中加强研究能力的计划。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The Interplay Between Neuroinfections, the Immune System and Neurological Disorders: A Focus on Africa.

DOI：
10.3389/fimmu.2021.803475
发表时间：
2021
期刊：
Frontiers in immunology
影响因子：
7.3
作者：
Ngarka L;Siewe Fodjo JN;Aly E;Masocha W;Njamnshi AK
通讯作者：
Njamnshi AK

Mechanisms of CNS invasion and damage by parasites.

DOI：
10.1016/b978-0-444-53490-3.00002-9
发表时间：
2013
期刊：
Handbook of clinical neurology
影响因子：
0
作者：
K. Kristensson;W. Masocha;M. Bentivoglio
通讯作者：
K. Kristensson;W. Masocha;M. Bentivoglio

The Actigraphy Sleep Score: A New Biomarker for Diagnosis, Disease Staging, and Monitoring in Human African Trypanosomiasis.

体动记录睡眠评分：用于非洲人类锥虫病诊断、疾病分期和监测的新生物标志物。

DOI：
10.4269/ajtmh.20-0340
发表时间：
2020
期刊：
The American journal of tropical medicine and hygiene
影响因子：
0
作者：
Njamnshi,AlfredK;SekeEtet,PaulF;Ngarka,Leonard;Perrig,Stephen;Olivera,GabrielaC;Nfor,LeonardN;Njamnshi,WepnyuY;Acho,Alphonse;Muyembe,Jean-Jacques;Bentivoglio,Marina;Rottenberg,Martin;Kennedy,PeterGE
通讯作者：
Kennedy,PeterGE

Passage of parasites across the blood-brain barrier.