Comparative effect of EB101 vaccine on astrocytosis. Comparative photomicrographs of GFAP immunoreactivity in the hippocampus ((a)–(e), (k)–(o)) and cortical ((f)–(j), (p)–(t)) brain regions at the preventive treatment phase ((a)–(j)) and therapeutic treatment group ((k)–(t)). Preventive treatment: transverse brain sections of 11-month-old mice treated with EB101 show an almost complete prevention of astrocytosis in the detailed sections of the dentate gyrus (a), contrasting with numerous dystrophic reactive astrocytes, typical of an inflammatory reaction, observed in different hippocampal corresponding areas of mouse brains in Group B (Aβ/Lip-treated mice; (b)), Group C (Lip/S1P-treated mice; (c)), Group D (Aβ
42 + CFA/IFA-treated mice; (d)), and Group E (PBS-treated mice, (e)). Immunoreactive astrocytosis in the brain sections of WT mice is absent (data not shown). Detailed sections of the parietal cortex of treated mice show a gradient density of reactive astrocytes immunoreactive to GFAP, indicating a neuroinflammation pattern. Comparative cortical sections show numerous astrocytosis areas in mice Groups C and E ((h), (j)) and wide reactive astrocytes clusters in mice Groups B and D ((g), (i)), while just a few of them are observed in Group A (f). Therapeutic treatment: transverse brain sections of 18-month-old mice of Group A show a notable reduction of astrocytosis in the hippocampal region (k) after EB101 vaccine immunization. Note the astrocytosis contrast density between EB101-treated mice and the other treated groups ((l)–(o)), where numerous immunoreactive GFAP clusters are observed in the correspondent brain sections. A few immunoreactive GFAP clusters are observed in the parietal cortex of EB101 treated mice group, while a moderate ((q), (s)) to high ((r), (t)) density of these neuropathological inflammation clusters is apparent in the other treatment groups (Groups B–E). For abbreviations, see list. Scale bar: 100 μm.