Farkas Orsolya, Tamás Andrea, Zsombok Andrea, Reglodi Dóra, Pál József, Büki Andras, Lengvári István, Povlishock John T, Dóczi Tamás
Department of Neurosurgery, University of Pécs, Medical Faculty, Hungary.
Regul Pept. 2004 Dec 15;123(1-3):69-75. doi: 10.1016/j.regpep.2004.05.014.
Pituitary adenylate cyclase activating polypeptide (PACAP) is a widely distributed neuropeptide that has numerous different actions. Recent studies have shown that PACAP exerts neuroprotective effects not only in vitro but also in vivo, in animal models of global and focal cerebral ischemia, Parkinson's disease and axonal injuries. Traumatic brain injury has an increasing mortality and morbidity and it evokes diffuse axonal injury which further contributes to its damaging effects. The aim of the present study was to examine the possible neuroprotective effect of PACAP in a rat model of diffuse axonal injury induced by impact acceleration. Axonal damage was assessed by immunohistochemistry using an antiserum against beta-amyloid precursor protein, a marker of altered axoplasmic transport considered as key feature in axonal injury. In these experiments, we have established the dose response curves for PACAP administration in traumatic axonal injury, demonstrating that a single post-injury intracerebroventricular injection of 100 microg PACAP significantly reduced the density of damaged, beta-amyloid precursor protein-immunoreactive axons in the corticospinal tract.
垂体腺苷酸环化酶激活多肽（PACAP）是一种广泛分布的神经肽，具有多种不同作用。最近的研究表明，PACAP不仅在体外，而且在体内，在全脑和局灶性脑缺血、帕金森病及轴突损伤的动物模型中均发挥神经保护作用。创伤性脑损伤的死亡率和发病率不断上升，它会引发弥漫性轴突损伤，进而加剧其损害作用。本研究的目的是在撞击加速诱导的弥漫性轴突损伤大鼠模型中检测PACAP可能的神经保护作用。通过使用抗β-淀粉样前体蛋白抗血清进行免疫组织化学评估轴突损伤，β-淀粉样前体蛋白是轴浆运输改变的标志物，被认为是轴突损伤的关键特征。在这些实验中，我们建立了创伤性轴突损伤中PACAP给药的剂量反应曲线，表明损伤后单次脑室内注射100μg PACAP可显著降低皮质脊髓束中受损的、β-淀粉样前体蛋白免疫反应性轴突的密度。
