Yılmaz Muhammet Bahadır, Tönge Mehmet, Emmez Hakan, Kaymaz Figen, Kaymaz Memduh
Department of Neurosurgery, Ministry of Health, Training and Research Hospital, Kayseri, Turkey.
J Korean Neurosurg Soc. 2013 Jul;54(1):1-7. doi: 10.3340/jkns.2013.54.1.1. Epub 2013 Jul 31.
This study was undertaken in the belief that the atypical antipsychotic drug quetiapine could prevent apoptosis in the penumbra region following ischemia, taking into account findings that show 5-hydroxytryptamine-2 receptor blockers can prevent apoptosis.
We created 5 groups, each containing 6 animals. Nothing was done on the K-I group used for comparisons with the other groups to make sure adequate ischemia had been achieved. The K-II group was sacrificed on the 1st day after transient focal cerebral ischemia and the K-III group on the 3rd day. The D-I group was administered quetiapine following ischemia and sacrificed on the 1st day while the D-II group was administered quetiapine every day following the ischemia and sacrificed on the 3rd day. The samples were stained with the immunochemical TUNEL method and the number of apoptotic cells were counted.
There was a significant difference between the first and third day control groups (K-II/K-III : p=0.004) and this indicates that apoptotic cell death increases with time. This increase was not encountered in the drug groups (D-I/D-II : p=1.00). Statistical analysis of immunohistochemical data revealed that quetiapine decreased the apoptotic cell death that normally increased with time.
Quetiapine is already in clinical use and is a safe drug, in contrast to many substances that are used to prevent ischemia and are not normally used clinically. Our results and the literature data indicate that quetiapine could help both as a neuronal protector and to resolve neuropsychiatric problems caused by the ischemia in cerebral ischemia cases.
鉴于有研究表明5-羟色胺-2受体阻滞剂可预防细胞凋亡,本研究基于非典型抗精神病药物喹硫平能够预防缺血后半暗带区域细胞凋亡这一信念而开展。
我们创建了5组,每组包含6只动物。对用于与其他组进行比较的K-I组未做任何处理,以确保实现了充分的缺血。K-II组在短暂性局灶性脑缺血后第1天处死,K-III组在第3天处死。D-I组在缺血后给予喹硫平并于第1天处死,而D-II组在缺血后每天给予喹硫平并于第3天处死。样本采用免疫化学TUNEL法染色,并对凋亡细胞数量进行计数。
第1天和第3天的对照组之间存在显著差异(K-II/K-III:p = 0.004),这表明凋亡性细胞死亡随时间增加。在药物组中未出现这种增加(D-I/D-II:p = 1.00)。免疫组化数据的统计分析显示,喹硫平减少了通常随时间增加的凋亡性细胞死亡。
与许多用于预防缺血但通常不用于临床的物质不同,喹硫平已在临床使用且是一种安全的药物。我们的结果和文献数据表明,喹硫平在脑缺血病例中既可以作为神经元保护剂,又有助于解决由缺血引起的神经精神问题。