Spreading depression and delayed neuronal death

抑郁症的蔓延和迟发性神经元死亡

• 批准号: 09671584
• 负责人: IIJIMA Takehiko
• 金额: $ 2.11万
• 依托单位: Kyorin University Department of Anesthesiology
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671584/
• 关键词: spreading depression; glutamate; amino acids; ischemia; hypoperfusion; delayed neuronal death; microdialysis; high performance liquid chromatography; brain ischemia; hippocampus

Spreading depression (SD) in a flow-restricted area of the brain may be prolonged and may become potentially harmful by releasing glutamate. We induced SD in an oligemia model and examined the subsequent glutamate release. In 18 anesthetized male Fischer rats, a laser Doppler flowmeter, an electroenzymatic electrode and microdialysis probe for continuous measurement of glutamate and amino acid assay respectively. And a calomel electrode for measuring DC potential were placed through a cranial window positioned 3 mm away from a second window where KCl-soaked cotton was placed to initiate SD.The left carotid artery or both the common carotid arteries were ligated to suppress reactive hyperemia of SD.SD produced an increase in glutamate from 24.8*13.8 to 33.5*25.3 muM (peak value)(P<0.0001). After ligation of both carotid arteries, the duration of SD increased from 1.5*0.6 mm (before ligation) to 6.4*5.1 mm (P<0.05). Glutamate reached a peak level of 63.9*72.3 muM, then quickly returned to the control value. The dialysate glutamate concentrations were 0.55*0.09, 0.25*0.19, 0.49*0.28 and 0.74*0.48 muM under the control, SD, SD induced after bilateral carotid ligation and reperfusion conditions, respectively. The dialysate glutamate concentrations of the 4 animals that developed AD increased significantly to 2.7*2.4 muM (P<O.05 compared with the control value) and continued to increase after reperfusion to 3.7*1.6 muM (p<O.O5 compared with the control value). The glutamate concentrations did not differ even after SD induction with hypoperfusion (all p>O.O5 cf control), whereas anoxic depolarization caused significantly high glutamate release. It is concluded that prolonged SD is not accompanied by a progressive increase in glutamate. Therefore, glutamate release induced by SD may not exert harmful effects on neurons.

大脑血流受限区域的抑郁症（SD）传播可能会持续很长时间，并且可能会因释放谷氨酸而变得潜在有害。我们在低血症模型中诱导了 SD，并检查了随后的谷氨酸释放。在 18 只麻醉的雄性 Fischer 大鼠中，使用激光多普勒流量计、电酶电极和微透析探针分别连续测量谷氨酸和氨基酸含量。将用于测量直流电势的甘汞电极放置在距第二个窗口 3 mm 处的颅骨窗口，其中放置 KCl 浸泡的棉花以启动 SD。结扎左颈动脉或两条总颈动脉以抑制 SD 的反应性充血。SD 使谷氨酸从 24.8*13.8 增加到 33.5*25.3 muM（峰值） 值）（P<0.0001）。双侧颈动脉结扎后，SD持续时间由结扎前的1.5*0.6 mm增加至6.4*5.1 mm（P<0.05）。谷氨酸达到峰值水平63.9*72.3μM，然后很快回到对照值。在对照、SD、双侧颈动脉结扎和再灌注条件下诱导的SD下，透析液谷氨酸浓度分别为0.55*0.09、0.25*0.19、0.49*0.28和0.74*0.48μM。发生AD的4只动物的透析液谷氨酸浓度显着升高至2.7*2.4μM(与对照值相比P<0.05)，并且在再灌注后继续升高至3.7*1.6μM(与对照值相比P<0.05)。即使在灌注不足的 SD 诱导后，谷氨酸浓度也没有差异（所有 p>0.05 cf 对照），而缺氧去极化导致显着高的谷氨酸释放。结论是，延长的 SD 并不伴随着谷氨酸的逐渐增加。因此，SD诱导的谷氨酸释放可能不会对神经元产生有害影响。

项目成果

Iijima T: "Pathophysiology of Spreading depression" Jpn J Anesthesiology. 47 (6). 662-677 (1998)

Iijima T：“抑郁症扩散的病理生理学”Jpn J Anesthesiology。

飯島 毅彦: "Spreading depressionと虚血性神経細胞死" 脳と神経. 50(1). 18-25 (1998)

Takehiko Iijima：“扩散性抑郁症和缺血性神经元死亡”《大脑与神经》50(1) (1998)。

Iijima T., Shimase C., Sankawa H: "Amino acid release during spreading depression in a flow-compromised cortical area" Brain Research. 818 (2). 553-555 (1999)

Iijima T.、Shimase C.、Sankawa H：“血流受损皮质区域扩散抑郁期间的氨基酸释放”大脑研究。

Iijima T.: "Amino acid release during spreading depression in a flow-compromised cortical area" Brain Research. 818(2). 553-555 (1999)

Iijima T.：“在血流受损的皮质区域扩散抑郁期间氨基酸的释放”大脑研究。

Iijima T.: "Relationship between glutamate release,bloodflow and spreading depression real-time monitaring using an electroenzymatic dialysis electracte" Neuro Science Research. 32. 201-207 (1998)

Iijima T.：“使用电酶透析电解液实时监测谷氨酸释放、血流和扩散抑郁之间的关系”神经科学研究。