Department of Neurosurgery, The Second Hospital of Hebei Medical University, 215 Heping Road, Shijiazhuang, 050000, HeBei, China.
Department of Neurosurgery, The First Hospital of Handan City, Handan, 056000, HeBei, China.
Neurochem Res. 2022 Oct;47(10):3063-3075. doi: 10.1007/s11064-022-03657-2. Epub 2022 Jul 9.
Neuroinflammation plays an important role in brain tissue injury during intracerebral hemorrhage. Gabapentin can reduce inflammation and oxidative stress through inhibiting nuclear factor κB (NFκB) signals. Here, we showed that gabapentin reduced brain tissue injury in ICH through suppressing NFκB-mediated neuroinflammation. ICH was induced by injecting collagenase IV into the right striatum of Sprague-Dawley rats. PC12 and BV2 cells injury induced by Hemin were used to simulate ICH in vitro. Inflammation and apoptosis were assessed in rat brain tissue and in vitro cells. The neurobehavioral scores were significantly decreased in ICH rats compared with sham rats. Phosphorylated IκB-α and cleaved caspase3, and apoptosis rate were significantly higher in tissue surrounding the hematoma than in brain tissues from rats subjected to sham surgery. Furthermore, serum IL-6 levels in ICH rats were higher than in sham rats. Gabapentin treatment significantly improved the behavioral scores, decreased levels of phosphorylated IκB-α and cleaved caspase3, apoptosis rate, and serum IL-6 level in ICH rats. Hemin-treated BV2 cells displayed higher levels of phosphorylated IκB-α, cleaved caspase3, and IL-6 in the supernatant compared with vehicle-treated cells. Hemin treatment induced a significantly lower level of peroxisome proliferator-activated receptor γ (PPARγ) in BV2 cells. BV2-PC12 co-culture cells treated by hemin displayed higher levels of cleaved caspase3 in PC12 cells. Furthermore, gabapentin treatment could reduce these effects induced by hemin and the protective effects of gabapentin were significantly attenuated by PPARγ inhibitor. Therefore, gabapentin may reduce inflammation and apoptosis induced by the ICH through PPARγ-NFκB pathway.
神经炎症在脑出血后脑组织损伤中起重要作用。加巴喷丁通过抑制核因子 κB（NFκB）信号通路可以减少炎症和氧化应激。在这里，我们表明加巴喷丁通过抑制 NFκB 介导的神经炎症来减少脑出血后的脑组织损伤。通过向 Sprague-Dawley 大鼠右侧纹状体注射胶原酶 IV 来诱导脑出血。使用血红素诱导 PC12 和 BV2 细胞损伤来模拟脑出血。在大鼠脑组织和体外细胞中评估炎症和细胞凋亡。与假手术大鼠相比，脑出血大鼠的神经行为评分显著降低。与假手术组相比，血肿周围组织中的磷酸化 IκB-α 和 cleaved caspase3 以及细胞凋亡率显著升高。此外，脑出血大鼠的血清 IL-6 水平高于假手术大鼠。加巴喷丁治疗可显著改善脑出血大鼠的行为评分，降低磷酸化 IκB-α 和 cleaved caspase3 水平、细胞凋亡率和血清 IL-6 水平。与 vehicle 处理的细胞相比，血红素处理的 BV2 细胞上清液中 cleaved caspase3 和 IL-6 水平更高。血红素处理可显著降低 BV2 细胞中的过氧化物酶体增殖物激活受体 γ（PPARγ）水平。血红素处理的 BV2-PC12 共培养细胞中 PC12 细胞中的 cleaved caspase3 水平更高。此外，加巴喷丁治疗可降低血红素诱导的这些作用，而 PPARγ 抑制剂可显著减弱加巴喷丁的保护作用。因此，加巴喷丁可能通过 PPARγ-NFκB 通路减轻脑出血引起的炎症和细胞凋亡。
