West Nile virus (WNV) is the most common mosquito-borne virus in North America. WNV-associated neuroinvasive disease affects all ages, although elderly and immunocompromised individuals are particularly at risk. WNV neuroinvasive disease has killed over 2300 Americans since WNV entered into the United States in the New York City outbreak of 1999. Despite 20 years of intensive laboratory and clinical research, there are still no approved vaccines or antivirals available for human use. However, rapid progress has been made in both understanding the pathogenesis of WNV and treatment in clinical practices. This review summarizes our current understanding of WNV infection in terms of human clinical manifestations, host immune responses, neuroinvasion, and therapeutic interventions.

Therapeutic strategies for traumatic injuries in the central nervous system (CNS) are largely limited to the efficiency of drug delivery. Despite the disrupted blood–CNS barrier during the early phase after injury, the drug administration faces a variety of obstacles derived from homeostatic imbalance at the injury site. In the late phase after CNS injury, the restoration of the blood–CNS barrier integrity varies depending on the injury severity resulting in inconsistent delivery of therapeutics. This review intends to characterize those different challenges of the therapeutic delivery in acute and chronic phases after injury and discuss recent advances in various approaches to explore novel strategies for the treatment of traumatic CNS injury.