Nardai Sándor, Dobolyi Arpád, Pál Gabriella, Skopál Judit, Pintér Nándor, Lakatos Kinga, Merkely Béla, Nagy Zoltán
Department Section of Vascular Neurology, Heart and Vascular Center, Semmelweis University, Budapest, Hungary.
Laboratory of Neuromorphology and Human Brain Tissue Bank, Department of Anatomy, Histology and Embryology, Semmelweis University, Budapest, Hungary NAP Laboratory of Molecular and Systems Neurobiology, Institute of Biology, Hungarian Academy of Sciences and Eötvös Loránd University, Budapest, Hungary.
Restor Neurol Neurosci. 2015;33(1):1-14. doi: 10.3233/RNN-140420.
Our experiments aimed at exploring potential neurorestorative mechanisms of selegiline, a compound routinely used in the treatment of Parkinson's disease and previously shown to improve the functional recovery of stroke patients.
Selegiline was administered continuously via osmotic mini-pumps between 48 and 216 hours following middle cerebral artery occlusion (MCAO) in rats. Twenty-four hours before sacrifice, the animals underwent magnetic resonance imaging (MRI). After decapitation, the peri-infarct region was dissected to perform a TAQMAN array gene expression study, and brains were fixed for immunolabeling.
In addition to the previously known induction of anti-apoptosis genes, selegiline significantly increased the mRNA level of Notch 1 receptor and its ligand Jagged 1. Immunohistochemistry demonstrated elevated Notch 1 and Jagged 1 immunoreactivities in the peri-infarct region. Double labeling with glial markers revealed that both Notch 1 and Jagged 1 were expressed in astrocytes but not in microglia. MRI examination indicated significantly reduced edema in selegiline-treated rats compared to control MCAO rats, and increased capillary network density was found in the peri-infarct region of the selegiline-treated animals.
Our results suggest that selegiline treatment enhances Notch-Jagged signaling in astrocytes, reduces peri-lesional edema and potentially helps preserve the capillary network following focal ischemia.
我们的实验旨在探索司来吉兰的潜在神经修复机制，司来吉兰是一种常用于治疗帕金森病的化合物，此前已证明其可改善中风患者的功能恢复。
在大鼠大脑中动脉闭塞（MCAO）后48至216小时之间，通过渗透微型泵持续给予司来吉兰。在处死前24小时，对动物进行磁共振成像（MRI）检查。断头后，解剖梗死周边区域以进行TAQMAN阵列基因表达研究，并固定大脑进行免疫标记。
除了先前已知的抗凋亡基因诱导外，司来吉兰还显著提高了Notch 1受体及其配体Jagged 1的mRNA水平。免疫组织化学显示梗死周边区域Notch 1和Jagged 1免疫反应性升高。与胶质细胞标志物的双重标记显示，Notch 1和Jagged 1均在星形胶质细胞中表达，而在小胶质细胞中不表达。MRI检查表明，与对照MCAO大鼠相比，司来吉兰治疗的大鼠水肿明显减轻，并且在司来吉兰治疗动物的梗死周边区域发现毛细血管网络密度增加。
我们的结果表明，司来吉兰治疗可增强星形胶质细胞中的Notch-Jagged信号传导，减轻损伤周围水肿，并可能有助于在局灶性缺血后保留毛细血管网络。
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