Inhibition of pre-ischeamic conditioning in the mouse caudate brain slice by NMDA- or adenosine A1 receptor antagonists.

Inhibition of pre-ischeamic conditioning in the mouse caudate brain slice by NMDA- or adenosine A1 receptor antagonists.
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DOI:
10.1016/j.ejphar.2012.10.021
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发表时间:
2013-01-05
影响因子:
5
通讯作者:
Davidson, Colin
Davidson, Colin
中科院分区:
医学2区
文献类型:
--
作者:
Chauhan, Nikky K.;Young, Andrew M. J.;Gibson, Claire L.;Davidson, Colin

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有证据表明,缺血预处理(PIC)对后续的缺血事件具有保护作用。尽管海马等一些脑区受到了广泛关注,但PIC在其他脑区的受体机制尚不清楚。我们先前已表明,10分钟的氧糖剥夺(OGD)可引发尾状核对第二次OGD事件的耐受。在此我们进一步研究预处理事件时长对第二次OGD事件的影响。将小鼠尾状脑片用充有95%O₂/5%CO₂的人工脑脊液(aCSF)进行灌流。通过降低aCSF葡萄糖浓度并充以95%N₂/5%CO₂来实现OGD。在大约5分钟的OGD后,观察到大量多巴胺外流,推测是由缺氧去极化引起的。在60分钟后施加第二次OGD事件时,多巴胺外流延迟且减少。我们首先研究了将预处理事件时长从5分钟改变到40分钟的影响,发现对PIC的耐受性随着预处理时长的增加而增加。然后我们研究了PIC的潜在受体机制。我们发现,用MK - 801或8 - 环戊基 - 1,3 - 二丙基黄嘌呤(DPCPX)预孵育会降低对第二次OGD事件的耐受性。这些数据表明,N - 甲基 - D - 天冬氨酸(NMDA)或腺苷A₁受体的激活可引发小鼠尾状核的PIC。
Evidence suggests that pre-ischeamic conditioning (PIC) offers protection against a subsequent ischeamic event. Although some brain areas such as the hippocampus have received much attention, the receptor mechanisms of PIC in other brain regions are unknown. We have previously shown that 10 min oxygen and glucose deprivation (OGD) evokes tolerance to a second OGD event in the caudate. Here we further examine the effect of length of conditioning event on the second OGD event. Caudate mouse brain slices were superfused with artificial cerebro-spinal fluid (aCSF) bubbled with 95%O2/5%CO2. OGD was achieved by reducing the aCSF glucose concentration and by bubbling with 95%N2/5%CO2. After approximately 5 min OGD a large dopamine efflux was observed, presumably caused by anoxic depolarisation. On applying a second OGD event, 60 min later, dopamine efflux was delayed and reduced. We first examined the effect of varying the length of the conditioning event from 5 to 40 min and found tolerance to PIC increased with increasing duration of conditioning. We then examined the receptor mechanism(s) underlying PIC. We found that pre-incubation with either MK-801 or 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) reduced tolerance to the second OGD event. These data suggest that either N-methyl-d-aspartate (NMDA) or adenosine A1 receptor activation evokes PIC in the mouse caudate.
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