To address the increased hazard of repeated loads on the brain, researchers developed a model of cell adhesion molecules kinetics on synapses in the brain that accounts for detachment and rebinding due to mechanical stretch.
Blast-induced traumatic brain injury (bTBI) is a significant risk during military operations and training activities such as heavy weapons training. The transient increase in susceptibility to injury after an impact or blast exposure is an important topic for military and civilian treatment of TBI. In this work, the authors formulated a model of the kinetics of cellular synaptic cell adhesion molecules (CAMs) that addresses the time to recovery and the susceptibility to repeated injury.
The mathematical model considers a single synaptic structure and addresses the effects of mechanical forces on the CAMs in the synaptic cleft. The model describes the kinetics of neurexins, (NX), neuroligins (NL) and NX-NL complexes. Mechanical strain results in forces on the NX-NL complex, leading to an increased un-binding rate of the bonds. The kinetics of detachment and re-attachment due to transient mechanical strain are modelled using kinetic relationships based on literature data. The CAM kinetics predicted in the simulations show time scales that are relevant to clinically observed increases in injury susceptibility.
Modeling studies such as these could identify methods to mitigate the risks of multiple exposure by suggesting treatments that modify the chemical processes in the model. The paper recognizes current limitations of the model and identifies potential improvements.
Gharahi, H., Garimella, H.T., Chen, Z.J., Gupta, R.K., & Przekwas, A. (2023). Mathematical model of mechanobiology of acute and repeated synaptic injury and systemic biomarker kinetics. Frontiers in Cellular Neuroscience, 17:1007062. doi: 10.3389/fncel.2023.1007062.
This work, performed by CFDRC, has been supported by the US DOD Defense Health Agency (DHA) SBIR Phase IIE project titled "Tools for Warfighter Repeated Blast Exposure Monitoring in Military Heavy Weapon Training", Award No. W81XWH-21-C-0020.
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