The α2δ‐1/NMDA receptor complex is involved in brain injury after intracerebral hemorrhage in mice

• Published in: Annals of clinical and translational neurology 2021-07, Vol.8 (7), p.1366-1375
• Main Authors: Li, Jingchen, Song, Guoqiang, Jin, Qianxu, Liu, Liqiang, Yang, Liang, Wang, Yuanyu, Zhang, Xuesong, Zhao, Zongmao
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Brain Injuries - metabolism; Brain Injuries - pathology; Calcium Channels - biosynthesis; Calcium Channels - deficiency; Calcium Channels - genetics; Cerebral Hemorrhage - metabolism; Cerebral Hemorrhage - pathology; Cerebral Hemorrhage - prevention & control; Female; Hemoglobin; Hemorrhage; Hospitals; Humans; Laboratory animals; Male; Medical research; Mice; Mice, Inbred C57BL; Mice, Knockout; Mortality; Nerve Tissue Proteins - biosynthesis; Nerve Tissue Proteins - genetics; Nervous system; Proteins; Receptors, N-Methyl-D-Aspartate - biosynthesis; Receptors, N-Methyl-D-Aspartate - genetics; Traumatic brain injury
• ISSN: 2328-9503; 2328-9503
• DOI: 10.1002/acn3.51372

Background Intracerebral hemorrhage (ICH), a common cerebrovascular disease, seriously threatens human health and has severe secondary injuries, while existing treatment methods have many limitations. α2δ‐1 is a subunit of voltage‐gated Ca2+ channels (VGCCs) and can act on glutamate receptor N‐methyl‐D‐aspartate receptors (NMDARs) to relieve neuropathic pain. Methods We first performed ICH modeling on WT mice and Cacna2d1 knockout (KO) mice. The expression levels of GluN1 and α2δ‐1 were measured by Western blot and q‐PCR, and the interaction between the two proteins was evaluated by co‐precipitation. The neuronal apoptosis was detected by the TUNEL assay, and the expression levels of inflammatory factors were assessed by ELISA. The nerve functions of mice were evaluated using behavioral experiments including corner turn test and forelimb use asymmetry. Cerebral hematoma was indicated by brain water content and lesion volume. Results ICH up‐regulated the expression levels of α2δ‐1 and GluN1. KO of Cacna2d1 significantly reduced the ICH‐induced apoptosis. The treatment of gabapentin on α2δ‐1 also significantly reduced the occurrence of apoptosis. KO of Cacna2d1 also reduced the ICH‐induced levels of inflammatory factors. Furthermore, neural functions were also significantly improved. Conclusion Cacna2d1 KO alleviates cerebral hematoma in ICH mice, exhibits a significant regulating effect on its secondary injuries such as neuronal apoptosis and inflammation, and restores the nerve functions of ICH mice. Loss of Cacna2d1 can provide useful therapeutic clues for ICH treatment.