Lee T H, Abe K, Aoki M, Nakamura M, Kogure K, Itoyama Y
Department of Neurology, Tohoku University School of Medicine, Sendai, Japan.
Stroke. 1994 Jul;25(7):1425-31; discussion 1432. doi: 10.1161/01.str.25.7.1425.
L-Threo-3,4-dihydroxyphenylserine (DOPS) is reported to increase the nerve growth factor (NGF) synthesis in cultured mouse L-M fibroblast and astroglial cells, and this effect is not blocked by treatment with decarboxylase inhibitor. NGF is suggested to play an important role in neuronal survival and regeneration under pathological conditions. We evaluated the possible protective effect of DOPS against hippocampal CA1 cell death after transient forebrain ischemia in gerbils.
Male mongolian gerbils were treated with DOPS (30, 100, or 300 mg/kg IP) plus benserazide (10 mg/kg IP) (n = 28) or vehicle (n = 7) before 3.5 minutes of forebrain ischemia. For histopathologic study, the animals were decapitated 7 days after recirculation, and neuronal density of the hippocampal CA1 area was counted after cresyl violet staining. For immunohistochemical study, another group of gerbils (n = 34) was recovered for 1, 3, and 8 hours and 1, 2, and 7 days, when they were decapitated. The brain sections were stained against NGF, NGF receptor, and HSP70 using the avidin-biotin-peroxidase method.
Preservation of the hippocampal CA1 cells was found in the brains treated with 300 mg/kg DOPS plus benserazide (neuronal density, 125 +/- 24 cells per millimeter) compared with the vehicle-treated ones (49 +/- 11 cells per millimeter) (P < .01). The immunoreactive NGF was greatly reduced from 3 hours after recirculation in the vehicle group, but it was much less reduced in the 300-mg/kg-DOPS-plus-benserazide group as compared with the vehicle group. The immunoreactivity for NGF receptor was gradually induced from 1 hour after recirculation with the peak at 1 day in the vehicle group, but it was only slightly induced at 8 hours in the 300-mg/kg-DOPS-plus-benserazide group. HSP70 immunoreactivity was also induced from 3 hours with the peak at 1 day in the vehicle group. However, in the 300-mg/kg-DOPS-plus-benserazide group, the induction of HSP70 was found from 8 hours and was much less intensive.
Treatment with DOPS is protective to the ischemic hippocampal CA1 cells, and the NGF-receptor system may play a role in this protective effect of DOPS.
据报道，L-苏式-3,4-二羟基苯丝氨酸（DOPS）可增加培养的小鼠L-M成纤维细胞和星形胶质细胞中神经生长因子（NGF）的合成，且脱羧酶抑制剂处理不能阻断这种作用。提示NGF在病理条件下的神经元存活和再生中起重要作用。我们评估了DOPS对沙土鼠短暂性前脑缺血后海马CA1区细胞死亡的可能保护作用。
雄性蒙古沙土鼠在3.5分钟前脑缺血前接受DOPS（30、100或300mg/kg腹腔注射）加苄丝肼（10mg/kg腹腔注射）（n = 28）或溶剂（n = 7）处理。用于组织病理学研究的动物在再灌注7天后断头，经甲酚紫染色后计数海马CA1区的神经元密度。用于免疫组织化学研究的另一组沙土鼠（n = 34）在再灌注1、3和8小时以及1、2和7天后断头。脑切片采用抗生物素蛋白-生物素-过氧化物酶法进行NGF、NGF受体和HSP70染色。
与溶剂处理组（每毫米49±11个细胞）相比，300mg/kg DOPS加苄丝肼处理组（每毫米125±24个细胞）的大脑中发现海马CA1细胞得到保留（P <.01）。溶剂组再灌注3小时后免疫反应性NGF大幅降低，但与溶剂组相比，300mg/kg DOPS加苄丝肼组的降低程度要小得多。溶剂组再灌注1小时后NGF受体的免疫反应性逐渐诱导，在1天时达到峰值，但300mg/kg DOPS加苄丝肼组在8小时时仅轻微诱导。溶剂组HSP70免疫反应性也从3小时开始诱导，在1天时达到峰值。然而，在300mg/kg DOPS加苄丝肼组中，HSP70的诱导从8小时开始，且强度要小得多。
DOPS处理对缺血性海马CA1细胞具有保护作用，NGF受体系统可能在DOPS的这种保护作用中发挥作用。
