Inflammation and Stem Cell Therapy Group, Wallenberg Neuroscience Center, Division of Clinical Neurophysiology, Lund University, Sweden; Lund Epilepsy Center, Lund University, SE-221 84 Lund, Sweden.
Inflammation and Stem Cell Therapy Group, Wallenberg Neuroscience Center, Division of Clinical Neurophysiology, Lund University, Sweden; Lund Epilepsy Center, Lund University, SE-221 84 Lund, Sweden.
Neurobiol Dis. 2015 Feb;74:194-203. doi: 10.1016/j.nbd.2014.11.009. Epub 2014 Nov 21.
Temporal lobe seizures lead to an acute inflammatory response in the brain primarily characterized by activation of parenchymal microglial cells. Simultaneously, degeneration of pyramidal cells and interneurons is evident together with a seizure-induced increase in the production of new neurons within the dentate gyrus of the hippocampus. We have previously shown a negative correlation between the acute seizure-induced inflammation and the survival of newborn hippocampal neurons. Here, we aimed to evaluate the role of the fractalkine-CX3CR1 pathway for these acute events. Fractalkine is a chemokine expressed by both neurons and glia, while its receptor, CX3CR1 is primarily expressed on microglia. Electrically-induced partial status epilepticus (SE) was induced in adult rats through stereotaxically implanted electrodes in the hippocampus. Recombinant rat fractalkine or CX3CR1 antibody was infused intraventricularly during one week post-SE. A significant increase in the expression of CX3CR1, but not fractalkine, was observed in the dentate gyrus at one week. CX3CR1 antibody treatment resulted in a reduction in microglial activation, neurodegeneration, as well as neuroblast production. In contrast, fractalkine treatment had only minor effects. This study provides evidence for a role of the fractalkine-CX3CR1 signaling pathway in seizure-induced microglial activation and suggests that neuroblast production following seizures may partly occur as a result of microglial activation.
颞叶癫痫发作会导致大脑出现急性炎症反应，主要表现为实质内小胶质细胞的激活。同时，锥体神经元和中间神经元发生退化，并且海马齿状回中的新生神经元在癫痫发作后增加。我们之前已经证明，急性癫痫发作引起的炎症与新生海马神经元的存活呈负相关。在这里，我们旨在评估趋化因子 fractalkine-CX3CR1 通路在这些急性事件中的作用。 fractalkine 是一种由神经元和神经胶质细胞表达的趋化因子，而其受体 CX3CR1 主要表达在小胶质细胞上。通过立体定向植入海马中的电极，在成年大鼠中诱导电诱导部分癫痫持续状态（SE）。在 SE 后一周内，通过脑室内输注重组大鼠 fractalkine 或 CX3CR1 抗体。在 SE 后一周内，齿状回中观察到 CX3CR1 的表达显著增加，但 fractalkine 没有增加。CX3CR1 抗体治疗导致小胶质细胞激活、神经退行性变和神经母细胞生成减少。相比之下， fractalkine 治疗只有较小的作用。这项研究为 fractalkine-CX3CR1 信号通路在癫痫发作引起的小胶质细胞激活中的作用提供了证据，并表明癫痫发作后神经母细胞的产生可能部分是由于小胶质细胞的激活。
