title: A novel experimental in vivo model of cerebral immunomodulation induced by inactivated Staphylococcus epidermidis.
abstract: The genesis and appropriate treatment of neuroinflammation in various infectious and non-infectious disorders of the central nervous system is still a matter of debate. We introduce an alternative and simple experimental model for the investigation of the cellular inflammatory response to bacterial antigens by stereotactic intracerebral injection of heat-inactivated Staphylococcus epidermidis (HISE). HISE-injection resulted in well-circumscribed intraparenchymal deposits encompassed by an early micro- and astroglial response and a selective but sustained opening of the blood-brain barrier (BBB). After 24h, the HISE collections were densely infiltrated by granulocytes and few circumjacent macrophages that became the predominating immunocompetent cell type from day 4 on. CD8a+ lymphocytes peaked at day 4, whereas CD4+ and CD20+ lymphocytes increased gradually in number, developing a scattered infiltrate until day 17, indicating the initiation of an adaptive immune response. MHC class II presenting cells were abundantly recruited from day 1 and eventually shaped an increasingly dense accumulation within the lesion. Intracerebral HISE administration provides a controlled, highly reproducible and well defined influx of immunocompetent cells across the BBB leading to a distinct and condensed inflammatory reaction. The technique is straightforward, easily feasible and may significantly enable further investigations of the initiation, maintenance and therapeutic modulation of acute neuroinflammation.
authors.affiliation: Neurosurgical Oncology Laboratory, Department of General Neurosurgery, University Hospital Cologne, Kerpener Strasse 62, 50924 Cologne, Germany. loehr.m@nch.uni-wuerzburg.de
authors.forename: Mario
authors.initials: M
authors.lastname: Löhr
authors.forename: Marek
authors.initials: M
authors.lastname: Molcanyi
authors.forename: Werner
authors.initials: W
authors.lastname: Stenzel
authors.forename: Harald
authors.initials: H
authors.lastname: Seifert
authors.forename: Georgios
authors.initials: G
authors.lastname: Tzouras
authors.forename: Gabriele
authors.initials: G
authors.lastname: Röhn
authors.forename: Daud
authors.initials: D
authors.lastname: Mohseni
authors.forename: Jürgen A
authors.initials: JA
authors.lastname: Hampl
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004660:Encephalitis / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D056747:Immunomodulation / Q000276:immunology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013212:Staphylococcus epidermidis / Q000276:immunology*