Inter-alpha Inhibitor Proteins (IAIPs) are a family of related serine protease inhibitors. IAIPs are important components of the systemic innate immune system. We have identified endogenous IAIPs in the central nervous system (CNS) of sheep during development and shown that treatment with IAIPs reduces neuronal cell death and improves behavioral outcomes in neonatal rats after hypoxic-ischemic brain injury. The presence of IAIPs in CNS along with their exogenous neuroprotective properties suggests that endogenous IAIPs could be part of the innate immune system in CNS. The purpose of this study was to characterize expression and localization of IAIPs in CNS. We examined cellular expressions of IAIPs in vitro in cultured cortical mouse neurons, in cultured rat neurons, microglia, and astrocytes, and in vivo on brain sections by immunohistochemistry from embryonic (E) day-18 mice and postnatal (P) day-10 rats. Cultured cortical mouse neurons expressed the light chain gene Ambp and heavy chain genes Itih-1, 2, 3, 4, and 5 mRNA transcripts and IAIPs proteins. IAIP proteins were detected by immunohistochemistry in cultured cells as well as brain sections from E18 mice and P10 rats. Immunoreactivity was found in neurons, microglia, astrocytes and oligodendroglia in multiple brain regions including cortex and hippocampus, as well as within both the ependyma and choroid plexus. Our findings suggest that IAIPs are endogenous proteins expressed in a wide variety of cell types and regions both in vitro and in vivo in rodent CNS. We speculate that endogenous IAIPs may represent endogenous neuroprotective immunomodulatory proteins within the CNS.

Background:While many studies have previously focused on fingolimod's effect on immune cells, the effect it has on circulating and local central nervous system platelets (Plts) has not yet been investigated. This study will elucidate what effects fingolimod treatment has on multiple sclerosis (MS) patients’ plasma Plt levels. In addition, it will propose possible reasoning for these effects and suggest further investigation into this topic.Methods:This quasi-experimental study used patients from the Isfahan Multiple Sclerosis Society to produce a subject pool of 80 patients, including 14 patients who ceased fingolimod use due to complications. The patients had their blood analyzed to determine Plt levels both 1-month prior to fingolimod treatment and 1-month after fingolimod treatment had been started.Results:The mean level of Plts before initiation of fingolimod therapy (Plt1) among these MS patients was 256.53 ± 66.26. After 1-month of fingolimod treatment, the Plt level yielded an average of 229.96 ± 49.67 (Plt2). This number is significantly lower than the average Plt count before treatment (P < 0.01).Conclusions:MS patients taking oral fingolimod treatment may be at risk for side-effects caused by low Plt levels. This may not be a factor for patients with higher or normal Plt levels. However, a patient with naturally low Plt levels may experience a drop below the normal level and be at risk for excessive bleeding. In addition to these possible harmful side-effects, the decreased Plt population may pose positive effects for MS patients.