Long term assessment of neurological effects after red tide exposure

摘要： Karenia brevis（K. brevis），负责赤潮有害藻华的微藻，定期释放一种 佛罗里达西南部一组强效神经毒性短尾藻毒素，间歇性地导致大量海洋生物 终身发病率和死亡率。虽然自16日以来，墨西哥湾就有记录显示这些水华 世纪以来，有证据表明，近几十年来，这种现象的频率和强度一直在增加， 可能是由佛罗里达的人类发展和较高的海湾水温驱动的。虽然急性 赤潮暴露对人类肺部健康的负面影响是相对有据可查的， 最近对赤潮期间急诊室入院的研究也表明， 神经系统疾病重复暴露于短尾蛇毒素对人体中枢神经系统的影响 目前尚不清楚，但经常接触密切相关的雪卡毒素可导致慢性神经系统疾病 包括类似于慢性疲劳综合症的病症。此外，其他长期接触的哺乳动物，如 海牛和海豚，显示出各种各样的神经系统症状，最有可能是由于已知的机制， 在外周和中枢神经系统的电压门控离子通道的短毒素的行动。之一 有记录以来最长的赤潮，2017年11月至2019年2月，暴露在佛罗里达西南部 居民长期和强烈的烟雾状短尾丝虫毒素水平。 我们已经开始招募来自Manatee和Sarasota两个县地区的志愿者居民（统称为 “Manasota”），由于他们的家庭或工作地点，他们在这次水华期间受到不同程度的暴露。这些 受试者提供了人口统计学、健康史和区域/活动信息以及生物学信息， 样品这些受试者将成为我们希望在18个月内随访的队列的一部分， 没有或存在随后的开花。队列招募将在以下志愿者中完成： 在沿海地区，以及那些住在内陆的人，他们将经历更低的，或没有， 短尾丝虫毒素气溶胶暴露我们会将他们暴露在烟雾中的短尾蛇毒素 诊断。此外，我们将检查与相同的短尾孢毒素暴露相关的生物标志物， 神经系统后遗症本研究的目的是确定暴露如何与神经系统 诊断，并开始表征那些发展神经学诊断和 那些没有。例如，暴露剂量、持续时间或免疫反应的标志物可以预测 神经学结果。这项工作将是第一个提供纵向数据的神经 重复暴露于短尾孢毒素的后果，产生一个队列，用于检查长期结果 并将建立一个生物储藏库，用于研究短尾丝虫毒素接触和人类健康。

Abstract: Karenia brevis (K. brevis), the microalgae responsible for Red Tide harmful algal blooms, regularly releases a suite of potent neurotoxic brevetoxins in southwest Florida and is intermittently responsible for massive marine life morbidity and mortality. While these blooms have been documented in the Gulf of Mexico since the 16th century, evidence suggests that their frequency and intensity have been increasing in recent decades, most likely driven by human development in Florida and higher Gulf water temperatures. Although the acute negative consequences of Red Tide exposure on pulmonary health in humans are relatively well-documented, recent studies of ER admissions during Red Tide blooms also demonstrate increased diagnoses of neurological conditions. The impact on the central nervous system of repeat exposure of brevetoxin in humans is not known, but frequent exposure to the closely-related ciguatoxin can result in chronic neurological illness including conditions similar to chronic fatigue syndrome. Furthermore, other chronically exposed mammals, like manatees and dolphins, display a wide variety of neurological signs most likely due to the known mechanism of action of brevetoxins on voltage-gated ion channels in the peripheral and central nervous systems. One of the longest Red Tide blooms on record, November 2017 to February 2019, exposed southwest Florida residents to prolonged and intense aerosolized brevetoxin levels. We have begun enrolling volunteer residents from the two-county region of Manatee and Sarasota (collectively “Manasota”) who were differentially exposed during this bloom by virtue of their home or work locations. These subjects have provided demographic, health history, and zone/activity information as well as biological samples. These subjects will be part of the cohort that we would like to follow over 18 months during periods of absence or presence of subsequent blooms. The cohort recruitment will be completed with volunteers who live in coastal regions as well as those who live further inland and who will have experienced much lower, or no, brevetoxin aerosol exposure. We will correlate their exposure to aerosolized brevetoxins with neurological diagnoses. Furthermore, we will examine biomarkers of brevetoxin exposure in relation to the same neurological sequelae. The purpose of this study is to determine how exposure relates to neurological diagnoses and to begin to characterize differences between those that develop neurological diagnoses and those that do not. For instance, exposure dose, duration, or markers of immune response may predict neurological outcomes. This work will be the first to provide longitudinal data on the neurological consequences of repeat brevetoxin exposure, generate a cohort for the examination of long-term outcomes and will establish a biorepository for studies of brevetoxin exposure and human health.