Fujimoto Masashi, Shiba Masato, Kawakita Fumihiro, Shimojo Naoshi, Imanaka-Yoshida Kyoko, Yoshida Toshimichi, Kanamaru Kenji, Taki Waro, Suzuki Hidenori
Department of Neurosurgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan,
Acta Neurochir Suppl. 2015;120:99-103. doi: 10.1007/978-3-319-04981-6_17.
The authors have reported that tenascin-C (TNC), a matricellular protein, is induced after subarachnoid hemorrhage (SAH), associated with cerebral vasospasm. In this study, we examined whether TNC alone causes cerebral vasospasm-like constriction of the intracranial internal carotid arteries (ICAs) in rats, focusing on the p38 mitogen-activated protein kinase (MAPK)-mediated mechanisms.
First, we injected 10 μg of TNC into the cisterna magna of healthy rats and studied morphologically whether TNC caused constriction of the left ICA at 24-72 h after administration. Second, we examined the effect of SB203580 (a p38 MAPK inhibitor) on the vessel diameter of the left ICA in healthy rats at 24 h. Third, we evaluated the effect of SB203580 on TNC-induced constriction of the left ICA in healthy rats at 24 h.
TNC significantly induced cerebral vasospasm-like angiographic constriction of the left ICAs, which continued at least for 72 h. SB203580 itself had no effect on the diameter of normal ICAs, but abolished the TNC-induced vasoconstrictive effect on the left ICA.
These findings show that TNC causes left ICA constriction via activation of p38 MAPK, resembling post-SAH vasospasm, and suggest the possible involvement of TNC in the pathogenesis of cerebral vasospasm.
作者曾报道，细胞外基质蛋白腱生蛋白-C（TNC）在蛛网膜下腔出血（SAH）后被诱导产生，与脑血管痉挛相关。在本研究中，我们研究了单独的TNC是否会导致大鼠颅内颈内动脉（ICA）出现类似脑血管痉挛的收缩，重点关注p38丝裂原活化蛋白激酶（MAPK）介导的机制。
首先，我们将10μg TNC注入健康大鼠的脑池，并在给药后24 - 72小时从形态学上研究TNC是否会导致左侧ICA收缩。其次，我们在24小时时检测SB203580（一种p38 MAPK抑制剂）对健康大鼠左侧ICA血管直径的影响。第三，我们评估SB203580对健康大鼠在24小时时TNC诱导的左侧ICA收缩的影响。
TNC显著诱导左侧ICA出现类似脑血管痉挛的血管造影收缩，这种收缩至少持续72小时。SB203580本身对正常ICA的直径没有影响，但消除了TNC对左侧ICA的血管收缩作用。
这些发现表明，TNC通过激活p38 MAPK导致左侧ICA收缩，类似于SAH后的血管痉挛，并提示TNC可能参与了脑血管痉挛的发病机制。
