Department of Neurosurgery, The 904th Hospital of PLA, Medical School of Anhui Medical University, Wuxi, Jiangsu, 214044, China.
Department of Neurosurgery, The 904th Hospital of PLA, Medical School of Anhui Medical University, Wuxi, Jiangsu, 214044, China.
Neurochem Int. 2022 Feb;153:105257. doi: 10.1016/j.neuint.2021.105257. Epub 2021 Dec 22.
Intracranial hypertension (IH) remains a common symptom of neurological diseases, and requires stepwise treatments to release intracranial pressure (ICP). In the present study, we built a rat model of epidural extreme intracranial hypertension (EEIH) and verified the effectiveness of a surgery method called controlled decompression on attenuating brain injury induced by EEIH. For the model part, we determined the level of EEIH of rats via recording ICP and cerebral perfusion pressure (CPP) and the variation tendency of survival rates, mean blood artery pressure and mean velocity (Vm) of left middle cerebral artery (LMCA) as ICP ascending. SD rats were assigned into 4 groups: Sham group, Controlled decompression group (Con group), Rapid decompression group (Rap group) and Rapid decompression + Necrostatin-1 (Nec-1) group (Rap+Nec-1 group). The results suggested that controlled decompression lowered cerebral water content, improved neurological function, and attenuated EEIH-induced inflammation response and ROS generation to a greater extent than rapid decompression. Meanwhile, controlled decompression functioned to preserve more Nissl bodies, indicating alleviated neuron injury after EEIH. Additionally, the permeability of blood brain barrier (BBB) was also safeguarded in the Con group. Western blotting (WB) and Real-time Polymerase Chain Reaction (rt-PCR) assays consistently determined lower protein and mRNA levels of necroptosis-related molecules receptor interacting protein kinase 1 (RIPK1), interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like protein (MLKL) (WB only) in the Con and Rap+Nec-1 group. Double immunofluorescent staining found weaker fluorescence intensity of RIPK3 in the compressed cortex of the Con and Rap+Nec-1 group.
颅内高压（IH）仍然是神经系统疾病的常见症状，需要逐步治疗以释放颅内压（ICP）。在本研究中，我们构建了硬膜外极端颅内高压（EEIH）大鼠模型，并验证了一种称为控制减压的手术方法对减轻 EEIH 引起的脑损伤的有效性。在模型部分，我们通过记录 ICP 和脑灌注压（CPP）以及存活率、左大脑中动脉（LMCA）平均动脉压和平均速度（Vm）的变化趋势来确定大鼠的 EEIH 水平，随着 ICP 的升高。SD 大鼠被分为 4 组：假手术组、控制减压组（Con 组）、快速减压组（Rap 组）和快速减压+坏死酶-1（Nec-1）组（Rap+Nec-1 组）。结果表明，与快速减压相比，控制减压可降低脑含水量，改善神经功能，减轻 EEIH 诱导的炎症反应和 ROS 生成。同时，控制减压在 EEIH 后可保留更多的尼氏体，表明神经元损伤减轻。此外，Con 组还可保护血脑屏障（BBB）的通透性。Western blot（WB）和实时聚合酶链反应（rt-PCR）检测结果一致表明，Con 组和 Rap+Nec-1 组中与坏死性凋亡相关的分子受体相互作用蛋白激酶 1（RIPK1）、相互作用蛋白激酶 3（RIPK3）和混合谱系激酶结构域样蛋白（MLKL）的蛋白和 mRNA 水平较低（仅 WB）。双免疫荧光染色发现 Con 组和 Rap+Nec-1 组受压皮质中 RIPK3 的荧光强度较弱。
