Co-administration of dl-3-n-butylphthalide and neprilysin is neuroprotective in Alzheimer disease associated with mild traumatic brain injury.

dl-3-n-Butylphthalide is a potent synthetic Chinese celery extract that is highly efficient in inducing neuroprotection in concussive head injury (CHI), Parkinson's disease, Alzheimer's disease, stroke as well as depression, dementia, anxiety and other neurological diseases. Thus, there are reasons to believe that dl-3-n-butylphthalide could effectively prevent Alzheimer's disease brain pathology. Military personnel during combat operation or veterans are often the victims of brain injury that is a major risk factor for developing Alzheimer's disease in their later lives. In our laboratory we have shown that CHI exacerbates Alzheimer's disease brain pathology and reduces the amyloid beta peptide (AβP) inactivating enzyme neprilysin. We have used TiO₂ nanowired-dl-3-n-butylphthalide in attenuating Parkinson's disease brain pathology exacerbated by CHI. Nanodelivery of dl-3-n-butylphthalide appears to be more potent as compared to the conventional delivery of the compound. Thus, it would be interesting to examine the effects of nanowired dl-3-n-butylphthalide together with nanowired delivery of neprilysin in Alzheimer's disease model on brain pathology. In this investigation we found that nanowired delivery of dl-3-n-butylphthalide together with nanowired neprilysin significantly attenuated brain pathology in Alzheimer's disease model with CHI, not reported earlier. The possible mechanism and clinical significance is discussed based on the current literature.