• Hong-Cai Wang, Cheng-Feng Sun, Hai Chen, Mao-Song Chen, Gang Shen, Yan-Bin Ma, and Bo-Ding Wang.
• Department of Neurosurgery, Li Hui Li Hospital of Medical Centre of Ningbo , Ningbo , PR China and.
• Brain Inj. 2014 Jan 1;28(12):1491-503.

BackgroundTraumatic brain injury (TBI) contributes to a substantial number of deaths and cases of disability. Despite well-established experimental models and years of carefully conducted research, a clinical therapeutic breakthrough in TBI has lagged. This may be due, in part, to the discrepancies between commonly used experimental models and clinical scenarios.MethodSecondary insults, such as hypotension and hypoxemia, have been well demonstrated as powerful determinants of outcomes from TBI. Despite the frequency of secondary insults in patients with TBI, they are rarely incorporated into most existing models of TBI. This review focuses on the combined injury models, especially coupled with systemic secondary insults, and aims to provide a new view to guiding future research endeavors in this field.ResultsA growing number of experimental models of TBI complicated by certain secondary insult have been gradually introduced and characterized. Correspondingly, the pathophysiological changes following combined injuries and the interactive effects of primary injury with secondary insults can be studied more in-depth.ConclusionA more complete understanding of the interactions between the injured brain and secondary insults represents a potentially fruitful avenue that may increase the likelihood of developing effective therapies. Experimental models of TBI should not only attempt to model the focal or diffuse changes resulting from external forces, but also integrate, when appropriate, secondary insults reminiscent of human situations.

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