Blood Brain Barrier Breakdown Following Topical Aldara Treatment

Brain inflammation markers are present in several psychiatric and neurodegenerative disorders like major depressive disorder, Alzheimers disease and schizophrenia. Inflammation is also linked to sickness behaviour (social withdrawal, decreased appetite, impaired concentration, irritability), a mechanism by which the body redirects its resources to fight infection and encourage wound healing. The topical application of Aldara triggers systemic type I and II interferon and pro-inflammatory cytokine production, immune cell infiltration into the skin and hyperkeratosis and has been used as a model of psoriasis since 2009(1). We have recently reported that Imiquimod, the active component of Aldara, can enter the brain within 4 hours of topical application(2) and induces a transcriptional interferon and chemokine response in the brain, along with the infiltration of immune cells, a reduction in hippocampal neurogenesis and a reduction in burrowing behaviour(3). To allow us to understand the mechanisms of immune cell entry into the brain following topical Aldara treatment, we investigated blood brain barrier (BBB) integrity using a number of experimental techniques.