IHC on CNS tissues is obviously best done on fixed tissue, with fixation preserving proper cell morphology, and other important morphological features of tissue organization. However, I have noticed that many people have problems with the epitope recovery in fixed CNS tissues. In reality, this is done easily with 2100 Antigen Retriever (http://www.antigen-retriever.com/), as was recently illustrated in the publication of Haley et al. (2013) PLoS ONE 8 (11): e81488. The authors used Amyohen Retriever to recover epitopes of prion (PrPd) in the brain of deers with transmissible spongiform encephalopathies. The new R-universal buffer for 2100 Retriever allows simultaneous recovery of epitopes that normally would require processing in different retrieval buffers (high, low pH,citrate, EDTA etc), thus all the antigens can be detected on the same slide with multicolour immunofluorescence.