In conclusion, we have demonstrated through post-injury TBI treatment that doxycycline may be a viable acute therapy for cerebral edema following TBI in a pre-clinical animal model; and the cellular/molecular mechanism of action is potentially through molecular inhibition of MMP-9 via directly binding to the active site of the enzyme and subsequent preservation of integrity of the BBB from MMP-9-based proteolytic breakdown of tight junction proteins. The gene discussed is MMP9; the disease is edema.