Endogenous brain protection: what the cerebral transcriptome teaches us.
Despite efforts to reduce mortality caused by stroke and perinatal asphyxia, these are still the 2nd largest cause of death worldwide in the age groups they affect. Furthermore, survivors of cerebral hypoxia-ischemia often suffer neurological morbidities. A better understanding of pathophysiological mechanisms in focal and global brain ischemia will contribute to the development of tailored therapeutic strategies. Similarly, insight into molecular pathways involved in preconditioning-induced brain protection will provide possibilities for future treatment. Microarray technology is a great tool for investigating large scale gene expression, and has been used in many experimental studies of cerebral ischemia and preconditioning to unravel molecular (patho-) physiology. However, the amount of data across microarray studies can be daunting and hard to interpret which is why we aim to provide a clear overview of available data in experimental rodent models. Findings for both injurious ischemia and preconditioning are reviewed under separate subtopics such as cellular stress, inflammation, cytoskeleton and cell signaling. Finally, we investigated the transcriptome signature of brain protection across preconditioning studies in search of transcripts that were expressed similarly across studies. Strikingly, when comparing genes discovered by single-gene analysis we observed only 15 genes present in two studies or more. We subjected these 15 transcripts to DAVID Annotation Clustering analysis to derive their shared biological meaning. Interestingly, the MAPK signaling pathway and more specifically the ERK1/2 pathway geared toward cell survival/proliferation was significantly enriched. To conclude, we advocate incorporating pathway analysis into all microarray data analysis in order to improve the detection of similarities between independently derived datasets.
School for Mental Health and Neuroscience (MHeNS), Maastricht University, Universiteitssingel 50, 6200 MD Maastricht, The Netherlands; Department of Pediatrics, Maastricht University Medical Center (MUMC), postbus 5800, 6202 AZ Maastricht, The Netherlands. Electronic address: kimberly.cox@maastrichtuniversity.nl.
K E M
KE
Cox-Limpens
Department of Pediatrics, Maastricht University Medical Center (MUMC), postbus 5800, 6202 AZ Maastricht, The Netherlands. Electronic address: danilo.gavilanes@mumc.nl.
A W D
AW
Gavilanes
Department of Pediatrics, Maastricht University Medical Center (MUMC), postbus 5800, 6202 AZ Maastricht, The Netherlands. Electronic address: luc.zimmermann@mumc.nl.
L J I
LJ
Zimmermann
Department of Pediatric Neurology, Maastricht University Medical Center (MUMC), P.Debyelaan 25, 6229 HX Maastricht, The Netherlands. Electronic address: jsh.vles@mumc.nl.
J S H
JS
Vles
D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000235:genetics*; D019194:Ischemic Preconditioning; D008297:Male; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D015398:Signal Transduction / Q000235:genetics*; D059467:Transcriptome
Brain protection; Hypoxic/ischemic preconditioning; Microarray analysis; Perinatal asphyxia; Stroke; Whole-genome gene expression