The LncRNA CRNDE/miR-152-3p/ROCK1 axis aggravates neurological deficits and neuroinflammation in intracerebral hemorrhage.

Objective

Intracerebral hemorrhage (ICH) is a fatal cerebrovascular disease. This study explored the intrinsic relationship between ICH and lncRNA CRNDE.

Methods

Injecting the lentiviral interference vector (sh-CRNDE) into the ICH mice (induced by collagenase). Subsequently, the neurological deficits were evaluated through Garcia scoring, the corner turn test, and the water maze test. The levels of CRNDE and inflammatory factors in the brain tissue were detected by RT-qPCR and ELISA, respectively. In vitro experiments, microglia and neuronal cells were respectively cultured with hemoglobin and Hemin. Subsequently, the level of M1 polarization markers was detected by RT-qPCR. In neuronal cells, the proliferation activity was evaluated by CCK-8. The apoptosis level was comprehensively assessed based on the results of flow cytometry and the level of LDH. Finally, the effects of inhibiting the CRNDE/miR-152-3p axis on ROCK1 and the phenotype of ICH were re-verified in animal models and cell models.

Results

In ICH mice, inhibition of CRNDE prevented the neurological deficits and neuroinflammation. Blocking CRNDE also significantly alleviated the M1 polarization of microglia and the apoptosis of neuronal cells. CRNDE sponges miR-152-3p through the ceRNA mechanism and regulates ROCK1. Inhibition of miR-152-3p or overexpression of ROCK1 weakens the inhibitory effect of sh-CRNDE on neurological deficits, M1 polarization, and the apoptosis of neurons. Moreover, in cell models, inhibition of ROCK1 showed the same protective effect as CRNDE downregulation.

Conclusion

In ICH, CRNDE upregulates ROCK1 by adsorbing miR-152-3p. This regulatory axis exacerbates neuroinflammation and neurofunctional disorders.