Shelton-Gibbs Synphane, Benderoth Jordan, Gaykema Ronald P, Straub Justyna, Okojie Kenneth A, Uweru Joseph O, Lentferink Dennis H, Rajbanshi Binita, Cowan Maureen N, Patel Brij, Campos-Salazar Anthony Brayan, Perez-Reyes Edward, Eyo Ukpong B
Brain Immunology and Glia Center, University of Virginia, Charlottesville, VA, USA.
Department of Pharmacology, University of Virginia, Charlottesville, Virginia, USA.
bioRxiv. 2023 Mar 6:2023.03.04.531090. doi: 10.1101/2023.03.04.531090.
Seizure disorders are common, affecting both the young and the old. Currently available antiseizure drugs are ineffective in a third of patients and have been developed with a focus on known neurocentric mechanisms, raising the need for investigations into alternative and complementary mechanisms that contribute to seizure generation or its containment. Neuroinflammation, broadly defined as the activation of immune cells and molecules in the central nervous system (CNS), has been proposed to facilitate seizure generation, although the specific cells involved in these processes remain inadequately understood. The role of microglia, the primary inflammation-competent cells of the brain, is debated since previous studies were conducted using approaches that were less specific to microglia or had inherent confounds. Using a selective approach to target microglia without such side effects, we show a broadly beneficial role for microglia in limiting chemoconvulsive, electrical, and hyperthermic seizures and argue for a further understanding of microglial contributions to contain seizures.
癫痫疾病很常见,影响着年轻人和老年人。目前可用的抗癫痫药物对三分之一的患者无效,并且这些药物的研发一直聚焦于已知的以神经为中心的机制,这就增加了对有助于癫痫发作或控制癫痫发作的替代和补充机制进行研究的必要性。神经炎症被广泛定义为中枢神经系统(CNS)中免疫细胞和分子的激活,尽管参与这些过程的具体细胞仍未得到充分了解,但已有研究提出神经炎症会促进癫痫发作。小胶质细胞是大脑中主要的具有炎症能力的细胞,其作用存在争议,因为之前的研究采用的方法对小胶质细胞的特异性较低或存在固有混淆因素。我们使用一种无此类副作用的靶向小胶质细胞的选择性方法,证明了小胶质细胞在限制化学惊厥、电惊厥和热惊厥发作方面具有广泛的有益作用,并主张进一步了解小胶质细胞在控制癫痫发作方面的作用。