title: Calcium signaling is implicated in the diffuse axonal injury of brain stem.
abstract: Evaluating diffuse axonal injury (DAI) remains challenging in clinical sciences since the physiopathologic mechanism of DAI is still unclear. The calcium overload in the axoplasm is considered to be crucial for secondary axonal injury. The present study use calcium channel blocker, nimodipine, to explore the influence of Ca2+ in the pathogenesis of rat DAI. In the DAI group, the expressions of β-APP and NF-L in axons were increased from 12 to 72 h. The ultrastructural observation indicated the axon and vessel injury appeared at 12 h post-injury and severely aggravated from 24 to 72 h. The expression of vWF and brain water content was increased at 12 h after injury and further increased at 24 h. Nimodipine decreased the expression of β-APP, NF-L and vWF, and also attenuated the ultrastructural damage of vascular wall and axons. Furthermore, Ca-dependent enzyme, the calcineurin activity were increased in DAI and nimodipine suppressed the activity of calcineurins (CaN). However, the amount of CaN expression was not changed. Our results showed that disturbances of axonal calcium homeostasis play an important role in the secondary damage of the axon, neuron and capillary vessel which may be related with activating CaN during the acute phase of DAI. Nimodipine can alleviate the secondary damage by suppressing the calcineurin activity.
authors.affiliation: Department of Forensic Medicine, Huazhong University of Science and Technology, Tongji Medical College No. 13 Hangkong Lu, Hankou, Wuhan 430030, Hubei, PR China ; Department of Pathology, Hebei North University No. 11 Zuanshinan Lu, Zhangjiakou 075000, Hebei, PR China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Mu
authors.affiliation: Criminal Investigation Brigade of Taicang No. 128 Loujiangbei Lu, Taicang, Suzhou 215400, Jiangsu, PR China.
authors.forename: Yucheng
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Forensic Medicine, Huazhong University of Science and Technology, Tongji Medical College No. 13 Hangkong Lu, Hankou, Wuhan 430030, Hubei, PR China.
authors.forename: Ji
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Forensic Medicine, Huazhong University of Science and Technology, Tongji Medical College No. 13 Hangkong Lu, Hankou, Wuhan 430030, Hubei, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lin
authors.affiliation: Department of Forensic Medicine, Huazhong University of Science and Technology, Tongji Medical College No. 13 Hangkong Lu, Hankou, Wuhan 430030, Hubei, PR China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Dong
mesh_terms: D000818:Animals; D001369:Axons / Q000648:ultrastructure; D015153:Blotting, Western; D001933:Brain Stem / Q000293:injuries* / Q000378:metabolism / Q000648:ultrastructure; D020013:Calcium Signaling / Q000502:physiology*; D020833:Diffuse Axonal Injury / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D046529:Microscopy, Electron, Transmission; D051381:Rats; D017207:Rats, Sprague-Dawley
keywords: Diffuse axonal injury; animal study; calcium signal; nimodipine