Editorial [Hot Topic: Analysis of Progenitor Cells in the Brain before and after Treatment (Guest Editors: M.A. Curtis and L. Paulson)]

In 1913, Santiago Ramon Y Cajal, one of the fathers of neuroscience and a Nobel prize laureate, wrote “... the functional specialization of the brain imposes on the neurons two great lacunae; proliferation inability and irreversibility of intraprotoplasmic differentiation. It is for this reason that, once the development was ended, the founts of growth and regeneration of axons and dendrites dried up irrevocably. In adult centers, the nerve paths are something fixed, ended and immutable. Everything may die, nothing may be regenerated. It is for the science of the future to change, if possible, this harsh decree”. However, today, in what Cajal may have termed the future, neuroscientists know that this ‘harsh decree’ is not as harsh as first thought. Rather, the brain's ability to produce new neurons via neurogenesis in the two developmentally active germinal zones is highly regulated and appears vital for cognition, memory and for the repair and replacement of damaged neurons after injury. Although the first studies showing that progenitor cell proliferation and neurogenesis occur in the mammalian brain were first reported in the 60's, these studies did not receive the attention they deserved and until the 90's, we were on the heel of the learning curve that was about to become exponential. In particular, it was the demonstration by Eriksson et al. in 1998 that neurogenesis occurs in the human hippocampus that first made the field realise that these germinal zone cells might be useful for the treatment of disease in humans. Although neuroscientists tend to focus on the advances in biology, it is very evident that many biological advances occur subsequent to the development of technology. In this edition of JCPB, we will focus on the studies performed and the methods used to analyse progenitor cell populations in vivo and in vitro. Our review series begins by defining the progenitor cell populations and clarifying the potentially confusing nomenclature used in stem and progenitor cell biology. We also review the techniques used to examine the unique cohort of proteins that progenitor cells express, thus making them distinct as a cell population. Then our series examines the pitfalls that have entrapped many, when using double and triple labelling techniques, due to confounding artefacts. The next review describes neurosphere formation as a measure of self-renewal and differentiation capacity of progenitor/stem cells in vitro with comparison to the in vivo situation. Then fluorescence activated cell sorting (FACS) is reviewed as a method for the detection of specific cell populations based on cell surface markers; these techniques appear to be coming of age in the field of neural progenitor cells also. From there, our series focuses on the temporal expression of endogenous cell cycle proteins through the progenitor cell cycle and reveals how the analysis of these proteins may take us ‘beyond BrdU’. We have also included a review of microarrays for high throughput detection of differentially expressed RNA and DNA in different progenitor cell lines. Then, the techniques used and the results reported for analysing progenitor cell migration in vivo and in vitro are reviewed- this detailed review is not to be missed. The final review is focused on progenitor cells from hippocampi donated by patients that undergo temporal lobectomy for intractable epilepsy. This final review hits the core of practical progenitor cell biology; the results reviewed do not present a model or theory but rather an insight into a human neurological disease itself and the effect the disease has on progenitor cells, or vice versa. We hope that you find these reviews both timely and interesting. We also hope that from these reviews you will be inspired with new approaches and ideas for answering the many questions that remain concerning progenitor cells in the brain.