Abnormal Rat Cortical Development Induced by Ventricular Injection of rHMGB1 Mimics the Pathophysiology of Human Cortical Dysplasia

• DOI: 10.3389/fcell.2021.634405
• Publication Date: 2021-03-04T05:52:22Z
• Authors: Xiaolin Yang; Xiaoqing Zhang; Yuanshi Ma; Zhongke Wang; Kaixuan Huang; Guolong Liu; Kaifeng Shen; Gang Zhu; Tingting Wang; Shengqing Lv; Chunqing Zhang; Hui Yang; Shiyong Liu
• Keywords: Pathophysiology

Cortical dysplasia (CD) is a common cause of drug-resistant epilepsy. Increasing studies have implicated innate immunity in CD with However, it unclear whether immune factors induce epileptogenic CD. Here, we injected recombinant human high mobility group box 1 (rHMGB1) into embryonic rat ventricles to determine rHMGB1 can pathophysiological characteristics similar those Compared controls and 0.1 μg rHMGB1-treated rats, the cortical organization was severely disrupted 0.2 microgyria heterotopia also emerged; additionally, disoriented deformed neurons were observed lesions heterotopias. Subcortical appeared white matter gray–white junction rats. Moreover, there decreased number layer V–VI an increased astrocytes I V lesions. And HMGB1 antagonist dexmedetomidine alleviated changes induced by rHMGB1. Further, found that TLR4 NF-κB after administration. In addition, excitatory receptors, N -methyl- D -aspartate receptor (NR1), 2A (NR2A), 2B (NR2B) immunoreactivity increased, amino acid transporter (EAAT1) 2 (EAAT2) reduced rats compared controls. While no differences glutamic decarboxylase 65/67 (GAD65/67) between two groups. These results indicate excitation significantly increased. Furthermore, electroencephalogram (EEG) showed shorter latency seizure onset higher incidence status epilepticus rats; frequency amplitude EEG treated than Intriguingly, spontaneous electrographic discharges detected 5 months age, spike-wave approximately 8 Hz most synchronous propagated waves throughout general brain cortex. Taken together, these findings exposure during pregnancy could contribute development CD, which mimicked some