LAUSR

Secondary brain injury (SBI) refers to new or worsening brain insult after primary brain injury (PBI). Neurophysiological experiments show that calcium (Ca2+) is one of the major culprits that contribute to neuronal damage and death following PBI. However, mechanistic details about how alterations of Ca2+ levels contribute to SBI are not well been characterized. In this paper, we first build a biophysical model for SBI related to calcium homeostasis (SBI-CH)to study the mechanistic details of PBI-induced disruption of CH, and how these disruptions affect the occurrence of SBI. Then, we construct a coupled SBI-CH model by formulating synaptic interactions to investigate how disruption of CH affects synaptic function and further promotes the propagation of SBI between neurons.Our model shows how opening of voltage-gated calcium channels (VGCCs), decreasing of plasma membrane calcium pump (PMCA), and reversal of the Na+/Ca2+ exchanger (NCX) during and following PBI, could induce disruption of CH and further promote SBI.We also show that disruption of CH causes synaptic dysfunction, which further induces loss of excitatory-inhibitory balance in system, and this might promote the prorogation of SBI and cause neighboring tissue to be injured. Our findings offer a more comprehensive understanding of the complex interrelationship between CH and SBI.