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

Background: Intracerebral hemorrhage (ICH), a common cerebrovascular disease, seriously threatens human health and has severe secondary injuries, while existing treatment methods have many limitations. alpha 2 delta-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 alpha 2 delta-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 alpha 2 delta-1 and GluN1. KO of Cacna2d1 significantly reduced the ICH-induced apoptosis. The treatment of gabapentin on alpha 2 delta-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.

Automated summary

Cacna2d1 knockout alleviates cerebral hematoma in ICH mice, reduces neuronal apoptosis and inflammation, and restores nerve functions. Loss of Cacna2d1 may provide therapeutic clues for ICH treatment.