Department of Neurosurgery, The General Hospital of Western Theater Command, Chengdu, China; Department of Geriatrics, The General Hospital of Western Theater Command, Chengdu, China.
Department of Geriatrics, The General Hospital of Western Theater Command, Chengdu, China.
Behav Brain Res. 2019 Jul 23;367:194-200. doi: 10.1016/j.bbr.2019.04.004. Epub 2019 Apr 3.
Subarachnoid hemorrhage (SAH) may lead to brain atrophy and cognitive dysfunction. This study aimed to compare the efficacy of nimodipine and deferoxamine on these sequelae of SAH. A rat model of SAH was established by the double-hemorrhage method. These rats were injected with saline (intraperitoneal, IP), nimodipine (IP), or deferoxamine (IP and intranasal) every 12 h for 5 days after SAH. The MRI scanning, including magnetic resonance angiography, diffusion tensor imaging, Tweighted imaging, was performed to detect the brain structure. The levels of iron metabolism-related proteins were examined by Western blot analysis. The Morris water maze (MWM) test was used to assess the cognitive function. Then, then neurons in the cortex and hippocampus were counted on hematoxylin and eosin-stained brain sections. Significant cerebral vasospasm (CVS) was found in the saline and deferoxamine groups, but not in the nimodipine group. Cerebral peduncle injury was detected in the saline and nimodipine groups, but not significantly in the deferoxamine group. Compared with nimodipine, deferoxamine reduced transferrin (Tf), Tf receptor, and ferritin levels after SAH. The MWM performances were significantly worse in the saline and nimodipine groups than that in the deferoxamine group. Brain atrophy and neuronal losses were more significant in the saline and nimodipine groups than in the deferoxamine group. Nimodipine significantly ameliorated CVS, but it did not improve the late changes in brain structure and cognitive function. Deferoxamine effectively reduced neuronal cell death and ameliorated cognitive function after SAH.
蛛网膜下腔出血（SAH）可导致脑萎缩和认知功能障碍。本研究旨在比较尼莫地平与去铁胺对 SAH 这些后遗症的疗效。通过双出血法建立大鼠 SAH 模型。这些大鼠在 SAH 后每天腹腔注射（IP）生理盐水（IP）、尼莫地平（IP）或去铁胺（IP 和鼻内），每 12 小时一次，共 5 天。磁共振成像（MRI）扫描，包括磁共振血管造影、弥散张量成像、T 加权成像，用于检测脑结构。Western blot 分析检测铁代谢相关蛋白水平。Morris 水迷宫（MWM）测试用于评估认知功能。然后，在苏木精和伊红染色的脑切片上计数皮质和海马中的神经元。在生理盐水和去铁胺组中发现明显的脑血管痉挛（CVS），但在尼莫地平组中未发现。在生理盐水和尼莫地平组中检测到脑桥损伤，但在去铁胺组中不明显。与尼莫地平相比，去铁胺降低了 SAH 后的转铁蛋白（Tf）、Tf 受体和铁蛋白水平。与去铁胺组相比，生理盐水和尼莫地平组的 MWM 表现明显更差。与去铁胺组相比，生理盐水和尼莫地平组的脑萎缩和神经元丢失更明显。尼莫地平显著改善 CVS，但不能改善脑结构和认知功能的晚期变化。去铁胺可有效减少神经元细胞死亡并改善 SAH 后的认知功能。
