Although global expression profiling has the advantages of being time efficient in analyzing large portions of the transcriptome, there are limitations to the sensitivity and accuracy. It is well documented that SAGE may inconsistently detect low abundance transcripts leaving small genomic expression changes induced by the experimental model or disease undetected. This is evident in examining the epilepsy studies discussed above with each generated database containing 5000 to 14 000 unique tags only, a significant decrease from the estimated size of the entire hippocampal transcriptome being over 30 000 (16, 26) . Furthermore, the sequencing error of SAGE is estimated at an average of 1% per base because of the fact they utilize a single-pass sequence in data processing. This accumulates to roughly 10% per 100 base pairs, leading to lower correct tags counts and artificially inflate the tag counts of already established tags or establish a count of a tag that does not exist. Microarray studies have also been shown to demonstrate significant variations even under the same experimental conditions. As such, validation of global expression profiling results by independent methods, such as real-time polymerase chain reaction (PCR), Northern/Western blotting and immunohistochemical methods, is crucial. In our experience, a significant decrease in the number of differentially expressed genes is demonstrated when validating SAGE results using quantitative real-time polymerase chain reaction (qRT-PCR) with a custom-made, low-density array chip of 94 significant genes as indicated by SAGE (82). Following the changes into the proteomic stage will further validate results of global expression profiling. Translation into functional proteins represents the final pathway of genomic regulation. Quantifying the proteomic changes specimens through immunoperoxidase stainings and in situ hybridizations will not only complete the interrogation process, but also give insights into region-specific changes that may have been missed in interrogation of gross hippocampal, possibly negating the requirement for microdissection of hippocampal subregions (Figure 3) .