Department of Physiology, Armed Forces Medical College, Pune, India.
Department of Biophysics, Panjab University, Chandigarh, India.
Mol Biol Rep. 2019 Dec;46(6):6215-6230. doi: 10.1007/s11033-019-05060-7. Epub 2019 Sep 7.
Several mechanisms are involved in the loss of cellular integrity and tissue destructions in various brain regions during ischemic insult. The affected brain employs various self-repair mechanisms during the poststroke recovery. Therefore, the current study involves time course changes in different brain regions following ischemia in terms of inflammation, oxidative stress and apoptosis for which a bilateral common carotid arteries occlusion model was chosen. The development of oxidative stress was seen with a marked increase in ROS and NO levels with concomitant decrease in GSH levels and also the activities of anti-oxidant enzymes. These alterations were accompanied with decreased levels of neurotransmitters and motor and cognitive deficits at various time points. Increased expressions of various pro-inflammatory cytokines and a decline in BDNF levels in hippocampal regions on 7th day post ischemia, suggesting their role in its pathogenesis. The restoration of BDNF and neurotransmitter levels along with significant decline in inflammatory cytokine levels 14th day onwards following ischemia in hippocampus suggested poststroke recovery. The extent of neuronal damage was found to be increased significantly on 7th day post ischemia as indicated by TUNEL assay and hematoxylin and eosin staining depicting enhanced number of pyknotic neurons in cortical and hippocampal regions. Cortical regions of the ischemic brains were severely affected while hippocampal regions showed significant poststroke recovery, which might attributed to the normalization of BDNF and pro-inflammatory cytokine levels. In conclusion, the present study established the central role of BDNF and pro-inflammatory cytokines in the poststroke recovery. Also, the cortical and hippocampal regions were found to be more susceptible for ischemic injury. As our results indicated, full recovery after ischemic injury in different brain regions was not achieved, therefore further studies with long-term recovery time are required to be conducted.
在缺血性损伤过程中，几种机制涉及到细胞完整性的丧失和各种大脑区域的组织破坏。受影响的大脑在中风后恢复期间采用各种自我修复机制。因此，目前的研究涉及到缺血后不同大脑区域在炎症、氧化应激和细胞凋亡方面的时间进程变化，为此选择了双侧颈总动脉闭塞模型。氧化应激的发展表现为 ROS 和 NO 水平的显著增加，同时 GSH 水平和抗氧化酶的活性降低。这些变化伴随着各种时间点神经递质和运动及认知功能障碍的降低。在缺血后第 7 天，海马区各种促炎细胞因子的表达增加和 BDNF 水平的降低，表明它们在发病机制中的作用。缺血后第 14 天，海马区 BDNF 和神经递质水平的恢复以及炎症细胞因子水平的显著下降，提示中风后恢复。缺血后第 7 天，TUNEL 检测和苏木精-伊红染色显示皮质和海马区的神经元损伤明显增加，表明神经元损伤程度显著增加。缺血大脑的皮质区域受到严重影响，而海马区域显示出显著的中风后恢复，这可能归因于 BDNF 和促炎细胞因子水平的正常化。总之，本研究确立了 BDNF 和促炎细胞因子在中风后恢复中的核心作用。此外，皮质和海马区更容易受到缺血性损伤。正如我们的结果所表明的，不同大脑区域的缺血性损伤后并未完全恢复，因此需要进行更长时间恢复时间的进一步研究。
