| First Author | Zhao J | Year | 2020 |
| Journal | Neurotherapeutics | Volume | 17 |
| Issue | 2 | Pages | 710-721 |
| PubMed ID | 31802434 | Mgi Jnum | J:319514 |
| Mgi Id | MGI:6864397 | Doi | 10.1007/s13311-019-00815-3 |
| Citation | Zhao J, et al. (2020) HMGB1 Is a Therapeutic Target and Biomarker in Diazepam-Refractory Status Epilepticus with Wide Time Window. Neurotherapeutics 17(2):710-721 |
| abstractText | Status epilepticus (SE), a life-threatening neurologic emergency, is often poorly controlled by the current pharmacological therapeutics, which are limited to a narrow time window. Here, we investigated the proinflammatory cytokine high mobility group box-1 (HMGB1) as a candidate therapeutic target for diazepam (DZP)-refractory SE. We found that HMGB1 was upregulated and translocated rapidly during refractory SE period. Exogenous HMGB1 was sufficient to directly induce DZP-refractory SE in nonrefractory SE. Neutralization of HMGB1 with an anti-HMGB1 monoclonal antibody decreased the incidence of SE and alleviated the severity of seizure activity in DZP-refractory SE, which was mediated by a Toll-like receptor 4 (TLR4)-dependent pathway. Importantly, anti-HMGB1 mAb reversed DZP-refractory SE with a wide time window, extending the therapeutic window from 30 to 180 min. Furthermore, we found the upregulation of plasma HMGB1 level is closely correlated with the therapeutic response of anti-HMGB1 mAb in DZP-refractory SE. All these results indicated that HMGB1 is a potential therapeutic target and a useful predictive biomarker in DZP-refractory SE. |
