Effects of C1-INH Treatment on Neurobehavioral Sequelae and Late Seizures After Traumatic Brain Injury in a Mouse Model of Controlled Cortical Impact

• Published in: Neurotrauma reports Vol. 4; no. 1; pp. 124 - 136
• Main Authors: Chen, Min, Tieng, Quang M, Du, Jiaxin, Edwards, Stephen R, Maskey, Dhiraj, Peshtenski, Emil, Reutens, David
• Format: Journal Article
• Language: English
• Published: United States Mary Ann Liebert, Inc., publishers 01.03.2023; Mary Ann Liebert
• Subjects: C1-INH, epileptogenesis; neurobehavioral sequelae; Original; Original Article; traumatic brain injury; traumatic brain injury; C1-INH, epileptogenesis; neurobehavioral sequelae
• ISSN: 2689-288X; 2689-288X
• DOI: 10.1089/neur.2022.0011

C1 human-derived C1 esterase inhibitor (C1-INH) is a U.S. Food and Drig Administration–approved drug with anti-inflammatory actions. In the present study, we investigated the therapeutic effects of C1-INH on acute and chronic neurobehavioral outcomes and on seizures in the chronic stage in a mouse traumatic brain injury (TBI) model. Adult male CD1 mice were subjected to controlled cortical impact and randomly allocated to receive C1-INH or vehicle solution 1 h post-TBI. Effects of C1-INH treatment on inflammatory responses and brain damage after TBI were examined using the Cytometric Bead Array, C5a enzyme-linked immunosorbent assay, Fluoro-Jade C staining, and Nissl staining. Neurobehavioral outcomes after TBI were assessed with modified neurological severity scores, the rotarod and open field tests, and the active place avoidance task. Video-electroencephalographic monitoring was performed in the 15th and 16th weeks after TBI to document epileptic seizures. We found that C1-INH treatment reduced TNFα expression and alleviated brain damage. Treatment with C1-INH improved neurological functions, increased locomotor activity, alleviated anxiety-like behavior, and exhibited an effect on seizures in the chronic stage after TBI. These findings suggest that C1-INH has beneficial effects on the treatment of TBI.