Citation

Hansen KR, DeWalt GJ, Mohammed AI, Tseng HA, Abdulkerim ME, Bensussen S, Saligrama V, Nazer B, Eldred WD, Han X. J. Neurotrauma 2018; 35(13): 1523-1536.

Affiliation

Boston University, 1846, Biomedical Engineering, Boston, Massachusetts, United States ; xuehan@bu.edu.

Copyright

(Copyright © 2018, Mary Ann Liebert Publishers)

DOI

10.1089/neu.2017.5029

PMID

29343209

Abstract

Mild traumatic brain injury (mTBI) represents a serious public health concern. While much is understood about long term changes in cell signaling and anatomical pathologies associated with mTBI, little is known about acute changes in neuronal function. Using large scale Ca2+ imaging in vivo, we characterized the intracellular Ca2+ dynamics in thousands of individual hippocampal neurons using a repetitive mild blast injury model where blasts were directed onto the cranium of unanesthetized mice on two consecutive days. Immediately following each blast event, neurons exhibited two types of changes in Ca2+ dynamics at different time scales. One was a reduction in slow Ca2+ dynamics that corresponded to shifts in basal intracellular Ca2+ levels at a time scale of minutes, suggesting a disruption of biochemical signaling. The second was a reduction in the rates of fast transient Ca2+ fluctuations at the sub-second time scale that are known to be closely linked to neural activity. Interestingly, the blast-induced changes in basal Ca2+ levels were independent of the changes in the rates of fast Ca2+ transients, suggesting that blasts had heterogeneous effects on different cell populations. Both types of changes recovered after about an hour. Together, our results demonstrate that mTBI induced acute, heterogeneous changes in neuronal function, altering intracellular Ca2+ dynamics across different time scales, which may contribute to the initiation of longer term pathologies.

Language: en

Keywords

HEAD TRAUMA; IN VIVO STUDIES; TRAUMATIC BRAIN INJURY