dc.title: Nanomedicine Strategies to Ameliorate Neuroinflammation and Prevent Secondary Neural Tissue Damage dc.description.abstract: The burden of neurological disease remains a global issue continually rising requiring the need for effective therapeutics to disrupt disease progression. Across neurological diseases, neuroinflammation presents as shared a pathophysiological hallmark presenting a compelling therapeutic target for restoring tissue homeostasis and preventing further tissue damage. Yet, early interventions of neuroinflammation require multifaceted design of Central Nervous System (CNS) delivery systems that overcome the cascade of biological barriers and effectively target the inflamed tissue. We explore the role of CNS delivery in treating neuroinflammation in the CNS tissue caused by different insults (pathogens, mechanical force, dysregulated immune attack) in three exemplary disease states of CNS infections, traumatic brain injury (TBI), and multiple sclerosis (MS). Additionally, we examine the critical design requirements of CNS delivery system to overcome the different biological barriers to reaching the inflamed neural tissue in context of the pathophysiology of neuroinflammation. Moreover, we highlight the emerging nanomedicines that present promising advances to disrupt neuroinflammation and restore the neural tissue in context of CNS infections, TBI, and MS. Our analysis illustrates the continual critical need for multifaceted design of CNS delivery systems in context of the pathophysiology of the source of insult to neural tissue inflammation to improve therapeutic outcomes. Moving forward, the field needs to push forward multifaceted, systematic design of delivery systems that consider less invasive administrative routes and integrate detection with treatment to ultimately provide nanomedicine for successful interventions of neurological diseases.