Alleviation of ischemia-induced brain edema by activation of the central histaminergic system in rats
Alleviation of ischemia-induced brain edema by activation of the central histaminergic system in rats
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DOI：
10.1254/jphs.08114fp
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发表时间：
2008-09-01
影响因子：
3.5
通讯作者：
Nagaro, Takumi
中科院分区：
文献类型：
--
作者：
Irisawa, Yumi;Adachi, Naoto;Nagaro, Takumi
我们已经报道，中枢组胺能活动的易化可以防止缺血性脑损伤的发展。鉴于脑水肿是脑损伤的主要原因，我们研究了组胺前体L组氨酸和硫代巴比妥钠对脑缺血后脑水肿的影响。组胺H-3受体拮抗剂，这两种药物都能增强中枢组胺能活性。大鼠大脑中动脉一过性闭塞造成局灶性脑缺血2 h，再灌流24 h后测定脑含水量和脑梗塞面积。用微透析法检测纹状体细胞外组胺浓度的变化，并评价这些化合物的作用。再灌流后即刻和6h重复给予L-组氨酸(1000 mg/kg×2，ip)可减少缺血区含水量的增加。同时给予硫代巴比妥钠(5 mg/kg，S.C.)L-组氨酸(1000 mg/kg，i.p.)完全防止脑水肿的形成和减轻脑梗塞，尽管单剂量的L组氨酸在再灌流后立即没有显示任何益处。纹状体组织胺水平在再灌流后逐渐升高，在缺血时也逐渐升高。同时给予硫代巴比妥钠和L-组氨酸可显著增加脑组织中组胺浓度，再灌流后5~6h组胺浓度较生理盐水组增加230%。L-组氨酸单独作用不影响缺血后组胺输出的增加。这些发现表明，在脑缺血开始后，中枢组胺能系统的进一步激活可以防止脑缺血所致脑水肿的发展。
We have reported that facilitation of central histaminergic activity prevents the development of ischemia-induced brain injury. Since cerebral edema is a major cause of brain damage, we studied effects on brain edema of postischemic administration Of L-histidine, a precursor of histamine, and thioperamide.. a histamine H-3-receptor antagonist, both of which enhance central histaminergic activity. Focal cerebral ischemia for 2 h was provoked by transient occlusion of the right middle cerebral artery in rats, and the water content and infarct size were determined 24 h after reperfusion. Changes in the extracellular concentration of histamine were examined in the striatum by a microdialysis procedure, and effects of these compounds were evaluated. Repeated administration of L-histidine (1000 mg/kg x 2, i.p.), immediately and 6 h after reperfusion, reduced the increase in the water contents in ischemic regions. Simultaneous administration of thioperamide (5 mg/kg, s.c.) with L-histidine (1000 mg/kg, i.p.) completely prevented edema formation and alleviated brain infarction, although a single dose of L-histidine, immediately after reperfusion, showed no benefits. The striatal histamine level was gradually increased after reperfusion as well as during ischemia. Simultaneous administration of thioperamide with L-histidine markedly increased the brain histamine concentration, and the value increased up to 230% of that in the saline group 5 - 6 h after reperfusion. L-Histidine alone did not affect the increase in the histamine output after ischemia. These findings suggest that further activation of the central histaminergic system after initiation of cerebral ischemia prevents development of ischemia-induced brain edema.