The Possible Applications (and Pitfalls!) of Stereological Analysis in Postmortem Brain Research

Stereological analysis represents the "gold standard" for the unbiased assessment of the structural components comprising the brain. Herbert Haug's seminal study highlights the perils of using a ratio estimator, such as density, as an indicator of the total number of neurons in defined brain regions. The less rigorous cutting and sampling regime for typical 2D morphometric approaches may initially represent an avoidable situation, but also one that could be resolved by modifying the procedure for brain banking. Postmortem human tissue is subject to a range of uncontrolled and potentially confounding factors. Autolysis of the brain is believed to commence at death, but its effect on mRNA, proteins and morphometric measures may not be realized until sometime afterward. Optimal analysis of brain tissue using design-based stereology requires proper tissue sampling at dissection.