IONIC HOMEOSTASIS AND SEIZURE REGULATION

离子稳态和癫痫调节

基本信息

  • 批准号:
    6363964
  • 负责人:
  • 金额:
    $ 18.69万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2000
  • 资助国家:
    美国
  • 起止时间:
    2000-04-01 至 2004-02-28
  • 项目状态:
    已结题

项目摘要

Although epilepsy is a common neurological problem, the mechanisms involved in the initiation and termination of seizure discharges are poorly understood. The long-term goal of this research is to understand how neurons become synchronized into seizure discharges and to understand how the brain terminates the synchronization allowing the seizure to end. In this grant period the focus will be on the role of the ionic environment in neuronal synchronization. First, the role of the neuronal Na+/K+ ATPase as an uptake mechanism in the recovery of the [K+]0 from elevated levels during and after neuronal activity will be tested by measuring the ceiling level and rate of recovery of the [K+]0 in vivo in normal adult rats and in rats treated with astrocyte inhibitors during and after seizures induced by electrical stimulation, administration of chemical convulsants and during and after spreading depression. This hypothesis will be further tested in vitro in the dentate gyrus during non-synaptic field bursts and during spreading depression in control conditions and after treatments designed to alter glial and neuronal uptake mechanisms. To determine whether the abnormal regulation of the [K+]0 in the immature brain is due to developmental immaturity of the neuronal Na+/K+ ATPase, the ceiling level and rate of recovery of the [K+]0 in vivo and in vitro in adult and juvenile rats (PN 10-25) will be compared. Finally, a quantitative interpretation of activity-dependent changes in [K+]0 that have been measured to date and that are to be gathered during this grant period will be developed. A second hypothesis to be tested is that alterations of the intracellular pH of the granule cells are critical for the termination of seizure discharges in the dentate gyrus. First, the intracellular pH fluctuations in vitro and extracellular fluctuations in pH in vivo and in vitro and their correspondence with the seizure discharges and dependence on normal glial function will be determined in normal rats and in rats treated with astrocyte inhibitors. Finally, to determine whether alterations in intracellular pH underlies the termination of the seizure discharges, manipulations that alter the seizure duration and the ability of the tissue to pump hydrogen ions will be carried out in vitro while measuring intracellular pH.
虽然癫痫是一种常见的神经系统疾病,但癫痫发作放电的启动和终止机制尚不清楚。这项研究的长期目标是了解神经元是如何同步进入癫痫发作放电的,以及大脑是如何终止同步使癫痫发作结束的。在此拨款期间,重点将放在离子环境在神经元同步中的作用。首先,神经元Na+/K+ atp酶作为一种摄取机制,在神经元活动期间和之后从升高的水平中恢复[K+]0的作用将通过测量正常成年大鼠和接受星形细胞抑制剂治疗的大鼠体内[K+]0的上限水平和恢复速率进行测试,这些大鼠在电刺激引起的癫痫发作期间和之后,施用化学惊厥剂,以及在扩散性抑郁症期间和之后。这一假设将在体外的齿状回实验中得到进一步的验证,在非突触场爆发和控制组条件下的扩散性抑郁期间,以及在旨在改变胶质和神经元摄取机制的治疗之后。为了确定未成熟脑中[K+]0的异常调节是否由于神经元Na+/K+ atp酶发育不成熟,我们将比较成年和幼年大鼠(PN 10-25)体内和体外[K+]0的上限水平和恢复率。最后,将对迄今已测得的并将在本赠款期间收集的[K+]0中与活动相关的变化进行定量解释。第二个有待验证的假设是,颗粒细胞内pH值的改变对于终止齿状回癫痫发作放电至关重要。首先,将在正常大鼠和星形胶质细胞抑制剂治疗的大鼠中确定体外细胞内pH波动和体内和体外细胞外pH波动及其与癫痫发作放电的对应关系和对正常胶质细胞功能的依赖。最后,为了确定细胞内pH值的改变是否导致癫痫发作放电的终止,将在体外测量细胞内pH值的同时进行改变癫痫发作持续时间和组织泵氢离子能力的操作。

项目成果

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Janet Lynn Stringer其他文献

Janet Lynn Stringer的其他文献

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{{ truncateString('Janet Lynn Stringer', 18)}}的其他基金

IONIC HOMEOSTASIS AND SEIZURE REGULATION
离子稳态和癫痫调节
  • 批准号:
    6531118
  • 财政年份:
    2000
  • 资助金额:
    $ 18.69万
  • 项目类别:
IONIC HOMEOSTASIS AND SEIZURE REGULATION
离子稳态和癫痫调节
  • 批准号:
    6637696
  • 财政年份:
    2000
  • 资助金额:
    $ 18.69万
  • 项目类别:
Ionic Homeostasis and Seizure Regulation
离子稳态和癫痫发作调节
  • 批准号:
    6970065
  • 财政年份:
    2000
  • 资助金额:
    $ 18.69万
  • 项目类别:
Ionic Homeostasis and Seizure Regulation
离子稳态和癫痫发作调节
  • 批准号:
    7082163
  • 财政年份:
    2000
  • 资助金额:
    $ 18.69万
  • 项目类别:
IONIC HOMEOSTASIS AND SEIZURE REGULATION
离子稳态和癫痫调节
  • 批准号:
    6088151
  • 财政年份:
    2000
  • 资助金额:
    $ 18.69万
  • 项目类别:
MECHANISMS OF SEIZURE CONTROL IN LIMBIC CIRCUITS
边缘系统的癫痫发作控制机制
  • 批准号:
    2259968
  • 财政年份:
    1994
  • 资助金额:
    $ 18.69万
  • 项目类别:
MECHANISMS OF SEIZURE CONTROL IN LIMBIC CIRCUITS
边缘系统的癫痫发作控制机制
  • 批准号:
    2796976
  • 财政年份:
    1994
  • 资助金额:
    $ 18.69万
  • 项目类别:
MECHANISMS OF SEIZURE CONTROL IN LIMBIC CIRCUITS
边缘系统的癫痫发作控制机制
  • 批准号:
    2546407
  • 财政年份:
    1994
  • 资助金额:
    $ 18.69万
  • 项目类别:
MECHANISMS OF SEIZURE CONTROL IN LIMBIC CIRCUITS
边缘系统的癫痫发作控制机制
  • 批准号:
    2259967
  • 财政年份:
    1994
  • 资助金额:
    $ 18.69万
  • 项目类别:
MECHANISMS OF SEIZURE CONTROL IN LIMBIC CIRCUITS
边缘系统的癫痫发作控制机制
  • 批准号:
    2259969
  • 财政年份:
    1994
  • 资助金额:
    $ 18.69万
  • 项目类别:
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