Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran; Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Behav Brain Res. 2022 Sep 5;433:114001. doi: 10.1016/j.bbr.2022.114001. Epub 2022 Jul 7.
Stem cell-based treatments have been recommended as a feasible therapy for stroke victims due to their potential for angiogenesis, neurogenesis, and synaptic plasticity. The intracellular mechanisms of stem cells against cerebral hypoperfusion are not well recognized. In this study, by releasing the clips, the reperfusion period was extended to 96 h, and two hours after cerebral ischemia, animals received adipose-derived MSCs. MSCs were isolated from the inguinal fat pads of rats and injected into two-vessel occlusion (2VO) rats 1 h after ischemia induction. Ninety-six hours after 2VO induction, behavioral and molecular tests were assessed. Adipose-derived MSCs treatment improves neurological scores, passive avoidance memory, and novel object recognition tests in the 2VO model compared to 2VO rats (P < 0.001). MSCs treatment decreased TNF-α (P < 0.01) and IL-6 (P < 0.01) and apoptotic factors (Bax/Bcl-2 ratio and caspase-3 level (P < 0.01)) compared with ischemic rats. MSCs treatment of ischemic rats could enhance Klotho-α and AMPK-α compared with ischemic rats (P < 0.001). The study disclosed that adipose-derived MSCs could improve neurological damage and memory deficits by reducing neuronal death in cerebral ischemia. Data proposed that adipose-derived MSCs inhibit pro-inflammatory factors such as IL-6 and TNF-α, consequently decreasing apoptosis in the hippocampus of CCAO rats. Besides, the Klotho-α and AMPK-α measurements found that MSCs might induce intracellular neuroprotective pathways via activation of Klotho-α/AMPK-α signaling.
基于干细胞的治疗方法因其具有血管生成、神经发生和突触可塑性的潜力，被推荐为中风患者的可行治疗方法。干细胞对脑低灌注的细胞内机制尚未得到充分认识。在这项研究中，通过松开夹闭，将再灌注期延长至 96 小时，在脑缺血后两小时，动物接受脂肪来源的 MSC。MSC 从大鼠腹股沟脂肪垫中分离出来，并在缺血诱导后 1 小时注入两血管闭塞（2VO）大鼠。在 2VO 诱导后 96 小时，评估行为和分子测试。与 2VO 大鼠相比，脂肪来源的 MSC 治疗可改善 2VO 模型中的神经评分、被动回避记忆和新物体识别测试（P < 0.001）。与缺血大鼠相比，MSC 治疗可降低 TNF-α（P < 0.01）和 IL-6（P < 0.01）以及凋亡因子（Bax/Bcl-2 比值和 caspase-3 水平（P < 0.01））。与缺血大鼠相比，MSC 治疗缺血大鼠可增强 Klotho-α 和 AMPK-α（P < 0.001）。该研究表明，脂肪来源的 MSC 可通过减少脑缺血中的神经元死亡来改善神经损伤和记忆缺陷。数据表明，脂肪来源的 MSC 通过抑制促炎因子如 IL-6 和 TNF-α，从而减少 CCAO 大鼠海马中的细胞凋亡。此外，Klotho-α 和 AMPK-α 的测量结果表明，MSC 可能通过激活 Klotho-α/AMPK-α 信号通路诱导细胞内神经保护途径。
