HYPOTHERMIA PROTECTS AGAINST ORGANOPHOSPHATE TOXICITY

低温可防止有机磷酸盐中毒

基本信息

  • 批准号:
    8337698
  • 负责人:
  • 金额:
    $ 37.38万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2011
  • 资助国家:
    美国
  • 起止时间:
    2011-09-30 至 2014-08-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): The goal of this project is to develop safe and effective treatments against the damage to the brain caused by organophosphate (OP) induced status epilepticus (SE). Exposure to organophosphates has been identified as a major chemical threat for terrorist attacks against civilians or for exposure by an accident or natural disaster. Advances have been made to stop SE, but at present there are no therapies available to prevent the long term morbidity associated with SE. Our research laboratory has made a major advance in understanding how SE causes neuronal damage and the development of acquired epilepsy. We discovered that following OP SE there is a prolonged elevation in hippocampal neuronal calcium (Ca2+) that lasts for over a week. Furthermore, the Ca2+ plateau plays a major role in causing SE induced neuronal damage and the development of acquired epilepsy. We made a breakthrough in our preliminary research and discovered that hypothermia treatment following OP SE can prevent the Ca2+ plateau following SE. This study will develop this novel finding and test the Central Hypothesis that hypothermia applied after SE can rapidly reverse the long lasting Ca2+ plateau and thus decrease or prevent the SE induced neuronal loss and development of acquired epilepsy. This study will use the organophosphate, diisopropylfluorophosphate (DFP) to induce OP SE in rats. Our laboratory is ideally suited to conduct these studies and has developed the necessary skills to carry out the following specific aims: Aim 1: Determine whether hypothermia can prevent the development of the Ca2+ plateau after SE when administered after DFP SE. Hypothesis: The Ca2+ plateau from SE can be prevented or reversed by treatment after DFP SE with hypothermia. Aim 2: Determine whether hypothermia prevents neuronal loss and the development of AE when administered after DFP SE. Hypothesis: Hypothermia can decrease or prevent neuronal loss and AE from SE when administered after DFP SE. Hypothermia is widely used in hospitals and ambulances to treat cardiac arrest and anoxic brain injury. The preliminary results demonstrate the feasibility of these studies and underscore the potential significance of conducting this exploratory study. If these preliminary findings are documented, this study may provide the first insight for the use of hypothermia as an effective CounterACT measure to protect the brain against organophosphate toxicity.
描述(由申请人提供):本项目的目标是开发安全有效的治疗方法,以对抗由有机磷(OP)引起的癫痫持续状态(SE)对大脑的损害。接触有机磷已被确定为针对平民的恐怖袭击或因事故或自然灾害而接触有机磷的主要化学威胁。在阻止SE方面已经取得了进展,但目前还没有有效的治疗方法来预防与SE相关的长期发病率。我们的研究实验室在了解SE如何引起神经元损伤和获得性癫痫的发展方面取得了重大进展。我们发现,在OP SE之后,海马神经元钙(Ca2+)的升高持续了一个多星期。此外,Ca2+平台在引起SE诱导的神经元损伤和获得性癫痫的发展中起主要作用。我们在前期研究中取得了突破,发现OP SE后的低温治疗可以预防SE后的Ca2+平台。本研究将发展这一新发现,并验证中心假设,即在SE后应用低温可以迅速逆转长期持续的Ca2+平台,从而减少或防止SE诱导的神经元丢失和获得性癫痫的发展。本研究将采用有机磷酸盐二异丙基氟磷酸(DFP)诱导大鼠OP SE。我们的实验室非常适合进行这些研究,并开发了必要的技能,以实现以下具体目标:目标1:确定在DFP SE后给予低温是否可以防止SE后Ca2+平台的发展。假设:低体温DFP SE后的Ca2+平台可以预防或逆转。目的2:确定低温是否能预防DFP SE后神经元丢失和AE的发生。假设:在DFP SE后给予低温可以减少或防止神经元丢失和SE引起的AE。低温疗法在医院和救护车上广泛应用于治疗心脏骤停和缺氧脑损伤。初步结果证明了这些研究的可行性,并强调了开展本探索性研究的潜在意义。如果这些初步发现被记录下来,这项研究可能为使用低温作为一种有效的对抗措施来保护大脑免受有机磷中毒提供了第一个见解。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

ROBERT John DELORENZO其他文献

ROBERT John DELORENZO的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('ROBERT John DELORENZO', 18)}}的其他基金

Novel Counteract Agents To Reduce Mortality And Morbidity Following Organophosphate Status Epilepticus
新型对抗剂可降低有机磷癫痫持续状态后的死亡率和发病率
  • 批准号:
    9349995
  • 财政年份:
    2017
  • 资助金额:
    $ 37.38万
  • 项目类别:
HYPOTHERMIA REDUCES MORTALITY AND MORBIDITY FROM STATUS EPILEPTICUS
低温可降低癫痫持续状态的死亡率和发病率
  • 批准号:
    9084757
  • 财政年份:
    2015
  • 资助金额:
    $ 37.38万
  • 项目类别:
HYPOTHERMIA PROTECTS AGAINST ORGANOPHOSPHATE TOXICITY
低温可防止有机磷酸盐中毒
  • 批准号:
    8215143
  • 财政年份:
    2011
  • 资助金额:
    $ 37.38万
  • 项目类别:
MECHANISM OF CANNABINOID ANTI-CONVULSANT EFFECTS
大麻素抗惊厥作用机制
  • 批准号:
    7318589
  • 财政年份:
    2007
  • 资助金额:
    $ 37.38万
  • 项目类别:
STATUS EPILEPTICUS REORGANIZES CANNABINOID RECEPTORS
癫痫持续状态重组大麻素受体
  • 批准号:
    7994399
  • 财政年份:
    2007
  • 资助金额:
    $ 37.38万
  • 项目类别:
STATUS EPILEPTICUS REORGANIZES CANNABINOID RECEPTORS
癫痫持续状态重组大麻素受体
  • 批准号:
    7342830
  • 财政年份:
    2007
  • 资助金额:
    $ 37.38万
  • 项目类别:
STATUS EPILEPTICUS REORGANIZES CANNABINOID RECEPTORS
癫痫持续状态重组大麻素受体
  • 批准号:
    7540372
  • 财政年份:
    2007
  • 资助金额:
    $ 37.38万
  • 项目类别:
STATUS EPILEPTICUS REORGANIZES CANNABINOID RECEPTORS
癫痫持续状态重组大麻素受体
  • 批准号:
    7196351
  • 财政年份:
    2007
  • 资助金额:
    $ 37.38万
  • 项目类别:
Counter Measures Against Acetylcholine Receptor Activated Status Epilepticus
乙酰胆碱受体激活性癫痫持续状态的对策
  • 批准号:
    7224545
  • 财政年份:
    2006
  • 资助金额:
    $ 37.38万
  • 项目类别:
Counter Measures Against Acetylcholine Receptor Activated Status Epilepticus
乙酰胆碱受体激活性癫痫持续状态的对策
  • 批准号:
    7906817
  • 财政年份:
    2006
  • 资助金额:
    $ 37.38万
  • 项目类别:

相似海外基金

Transcriptional assessment of haematopoietic differentiation to risk-stratify acute lymphoblastic leukaemia
造血分化的转录评估对急性淋巴细胞白血病的风险分层
  • 批准号:
    MR/Y009568/1
  • 财政年份:
    2024
  • 资助金额:
    $ 37.38万
  • 项目类别:
    Fellowship
Combining two unique AI platforms for the discovery of novel genetic therapeutic targets & preclinical validation of synthetic biomolecules to treat Acute myeloid leukaemia (AML).
结合两个独特的人工智能平台来发现新的基因治疗靶点
  • 批准号:
    10090332
  • 财政年份:
    2024
  • 资助金额:
    $ 37.38万
  • 项目类别:
    Collaborative R&D
Acute senescence: a novel host defence counteracting typhoidal Salmonella
急性衰老:对抗伤寒沙门氏菌的新型宿主防御
  • 批准号:
    MR/X02329X/1
  • 财政年份:
    2024
  • 资助金额:
    $ 37.38万
  • 项目类别:
    Fellowship
Cellular Neuroinflammation in Acute Brain Injury
急性脑损伤中的细胞神经炎症
  • 批准号:
    MR/X021882/1
  • 财政年份:
    2024
  • 资助金额:
    $ 37.38万
  • 项目类别:
    Research Grant
KAT2A PROTACs targetting the differentiation of blasts and leukemic stem cells for the treatment of Acute Myeloid Leukaemia
KAT2A PROTAC 靶向原始细胞和白血病干细胞的分化,用于治疗急性髓系白血病
  • 批准号:
    MR/X029557/1
  • 财政年份:
    2024
  • 资助金额:
    $ 37.38万
  • 项目类别:
    Research Grant
Combining Mechanistic Modelling with Machine Learning for Diagnosis of Acute Respiratory Distress Syndrome
机械建模与机器学习相结合诊断急性呼吸窘迫综合征
  • 批准号:
    EP/Y003527/1
  • 财政年份:
    2024
  • 资助金额:
    $ 37.38万
  • 项目类别:
    Research Grant
FITEAML: Functional Interrogation of Transposable Elements in Acute Myeloid Leukaemia
FITEAML:急性髓系白血病转座元件的功能研究
  • 批准号:
    EP/Y030338/1
  • 财政年份:
    2024
  • 资助金额:
    $ 37.38万
  • 项目类别:
    Research Grant
STTR Phase I: Non-invasive focused ultrasound treatment to modulate the immune system for acute and chronic kidney rejection
STTR 第一期:非侵入性聚焦超声治疗调节免疫系统以治疗急性和慢性肾排斥
  • 批准号:
    2312694
  • 财政年份:
    2024
  • 资助金额:
    $ 37.38万
  • 项目类别:
    Standard Grant
ロボット支援肝切除術は真に低侵襲なのか?acute phaseに着目して
机器人辅助肝切除术真的是微创吗?
  • 批准号:
    24K19395
  • 财政年份:
    2024
  • 资助金额:
    $ 37.38万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
Acute human gingivitis systems biology
人类急性牙龈炎系统生物学
  • 批准号:
    484000
  • 财政年份:
    2023
  • 资助金额:
    $ 37.38万
  • 项目类别:
    Operating Grants
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了