Nano‐Engineering in Traumatic Brain Injury

Abstract

Traumatic brain injury (TBI) is a leading cause of mortality and chronic disability worldwide TBI involves an initial primary phase triggered by an impactful force to the brain and a subsequent secondary pathological phase. The secondary phase is characterized by key cellular events such as the release of calcium ions (Ca2+) and a cascade of inflammatory events such as the impairment of mitochondrial function, increase in oxidative stress, activation of glial cells, and impairment of the blood-brain barrier (BBB) causing paracellular leakage. There is no FDA-approved drug for TBI, but current treatment strategies rely on the delivery of small and macromolecular therapies to the brain, and these are severely restricted by the BBB, poor retention, off-target toxicity, and by the complex pathology of TBI. Therefore, there is a growing need for novel therapeutics for the diagnosis and treatment of TBI with effective delivery tactics and treatment paradigms such as nano-engineering nanoparticles (NPs). Nanoparticles sizes range between 1-100 nm and are engineered to form distinct materials such as lipids, organic polymers, and silica and metals complexes providing NPs with characteristics that can mitigate TBI secondary events like BBB breakage, neuroinflammation, oxidative stress, and mitochondrial dysfunction, leading to mitigation of TBI pathology. Limitations of NP technology in the treatment of TBI are related to bioavailability, toxicity load and proinflammatory activity of NPs in the brain. In this chapter, we discuss nanoparticles (NPs) as novel strategies for the treatment of TBI and explore their synthesis, mechanisms of action, and limitations. Understanding the mechanisms and complications of NPs as novel therapeutic strategies will help guide and improve the design of future TBI therapies.