Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids (CLIPPERS) is a recently described inflammatory CNS disorder. It is characterized by 1) subacute onset of cerebellar and brainstem symptoms, 2) peri- pontine contrast-enhancing perivascular lesions with a “salt-and- pepper” appearance on MRI, and 3) angiocentric, predominantly T lymphocytic infiltration as revealed by brain biopsy. Inflammatory diseases including neuroinfections, CNS lymphoma and neuro- sarcoidosis must be excluded. Currently it is not well established, whether the inflammation is truly restricted to the brain stem, or also involves other brain areas with normal MRI appearance. Moreover, based on case descriptions it has been suggested that CLIPPERS might be a pre-lymphoma state. In this study we have investigated four Danish cases of CLIPPERS, three of which have been confirmed by brain biopsy, and one confirmed by both biopsy and autopsy. In the autopsy case, we have compared differences in immunohis- tochemical stainings for CD45 (lymphocytes), CD3 (T cells), CD4 and CD8 (T cell subsets), CD20 (B cells) and IBA1 (microglia/macrophages) between brain stem and normal appearing cerebral cortex. To investigate the possibility of a pre-lymphoma condition, we have moreover stained for light-chain restriction (kappa-smi and lambda-smi) and done lymphoma stainings (CD10, Bcl6 and MUM-1) in all four cases. As expected, we found a pronounced perivascular infiltration of predominantly CD4-positive T cells in the brain stem. Infiltration of CD8-positive T cells was less pronounced, and only a few CD20 positive B cells were observed. A similar, but less prominent T-cell infiltration was found in the normal appearing cerebral cortex, suggesting a more generalized inflammation. We found no evidence for pre-lymphoma or lymphoma in any of the four cases. We conclude that the inflammation pattern seen in CLIPPERS is most prominent in the MRI-positive brain stem structures, but the predom- inantly CD4-postive T cell infiltration is also seen in apparently normal brain tissue including cortex. Our study does not suggest that CLIPPERS is a pre-lymphoma condition. doi:10.1016/j.jneuroim.2014.08.369 437 Sex dependent influences of apolipoprotein E on the expression ATP-binding cassette transporters during experimental autoimmune encephalomyelitis Anne Böhme, Lisa Schrewe, Ralf Gold, Andrew Chan Department of Neurology, Ruhr-Universität Bochum, Bochum, Germany Introduction: Apolipoprotein E (apoE) has different sex specific immunomodulatory functions in vitro. In addition, apoE is known to regulate multi drug resistance transporters of the ATP-binding cassette (ABC) family in an experimental model of acute ischemic stroke. ABC transporters are active cellular efflux pumps with substrate specificity also for different therapeutics used in Multiple Sclerosis. It is currently unknown whether therapeutically relevant ABC-transporters are also regulated in chronic neuroinflammatory disease. Objective: To investigate the sex-specific influence of apoE genotype on protein expression of ABC-transporters abcb1 and abcg2 at different time points during experimental autoimmune encephalomyelitis (EAE) in different compartments. Material and methods: Chronic EAE was induced in wild type (WT) and apoE-/- C57/BL6-mice by immunization with myelin oligodendrocyte glycoprotein (MOG33-55). Animals were scored daily using the 10 grade score. Mice were sacrificed during the acute and chronic phase of EAE (days 17, 35). Abcb1 and abcg2 were investigated in spinal cord (SC), SC isolated microvessels (SCMV) and liver by Western blot. Protein levels of ABC-transporters were normalized to beta-actin. Images were analyzed by densitometry. Results: In MOG-immunized wild type female mice, abcg2 protein was reduced in spinal cord during chronic EAE (44.7% reduction as compared to healthy female wild type mice, p b 0.01 (unpaired t- test)). These differences were not observed in male animals of either genotype. Also no differences were found in abcb1 expression in SC tissue regardless of sex, genotype or phase of disease. In contrast, in SCMV, pilot experiments indicate an increase of abcb1 in male apoE-/- mice during chronic EAE (9-fold increase compared to healthy male apoE-/- mice, p b 0.001 (unpaired t-test)). Discussion: Whereas we observed a gender specific effect on abcg2 regulation in SC during the chronic phase of EAE, there was no additional effect of apoE genotype on ABC-transporter expression. This may indicate that regulation of abc transporters in a chronic neuroinflammatory model is different to an acute disease model such as experimental ischemic stroke. Feasibility of therapeutic, e.g. neuroprotective strategies using ABC-transporter substrates may therefore differ in these models. doi:10.1016/j.jneuroim.2014.08.370 568 Maternal obesity decreases GFAP expression in hypothalamic astrocytes from rat pups Andreia Joaquim a , Cideli de Paula Coelho a , Maria de Fátima Monteiro Martins a , Elizabeth Teodorov b , Eduardo Fernandes Bondan a , Leoni Vilano Bonamin a , Maria Martha Bernardi a a Paulista University, Department of Veterinary Medicine, São Paulo, Brazil; b Federal University of ABC, Mathematics, Computing and Cognition Center, São Paulo, Brazil Obesity is associated with a chronic and low-grade inflammation in several tissues, including the hypothalamus. Hypothalamic inflamma- tion is an early factor for the onset of obesity, which occurs even before body weight gain. Within the hypothalamus, microglia and astrocytes produce cytokines that drive inflammatory response. A wide range of nutritional interventions in pregnancy and lactation, including mater- nal obesity, can lead to a range of metabolic disorders in offspring, which are mediated in part by epigenetic mechanisms. Evidences suggest that developmental programming should be regarded as a transgenerational phenomenon and is therefore often viewed as a form of epigenetic inheritance, either via the maternal or paternal line. The objective of this study was to investigate the influence of maternal hypercaloric diet on behavior, body and abdominal fat weights, adipose histology and astrocyte reaction in response to lipopolysaccharide (LPS) in the first generation (F1). Female Wistar rats received hypercaloric (group H) or normocaloric (group N) diet from postnatal day (PND) 23 to 65. The litters of F1 generation from N and H females were weighed at PND 2 and, at weaning (PND21). On PND50, the male pups were weighed again and some received 100 μg/kg of LPS, by intraperitoneal route, 12 h before open field test for sickness behavior. After euthanasia, abdominal fat was used for morphometric studies. Immunohistochem- ical investigation was done for glial fibrillary acidic protein (GFAP) expression in hypothalamic astrocytes. Results show that rats from H dams presented higher weights at birth, although such difference was no more found at weaning and adult age, and a higher number of large adipocytes in hypodermis. After LPS inoculation, these rats presented anxiety behavior instead of sickness behavior. Although LPS adminis- tration increased astrocytic expression of GFAP in the F1 from N and H Abstracts 138