Since its introduction, laser capture microdissection (LCM) methods have been extensively employed to study cell-specific functions in complex, heterogeneous tissues composed of multiple cell types. Laser capture microdissection is particularly suited to studies of the mammalian brain, which, because of its heterogeneity, presents a major challenge in studies that attempt to correlate region or cell type-specific function with distinct gene expression profiles. We have used LCM to study genomic changes in rat brain after experimental traumatic brain injury (TBI). The use of LCM allows precise measures of TBI-induced changes in gene expression in identified populations of brain cells and in anatomically distinct subregions of the rat hippocampus. We have been able to study gene expression in specific populations of dying and surviving hippocampal neurons after TBI and to detect circadian clock dysfunction in the suprachiasmatic nucleus after TBI. We have also used LCM to study epigenetic changes following TBI, mediated in part by small, noncoding microRNAs in different brain regions. We found strikingly different microRNAs are expressed in laser-captured single neurons compared to laser-captured brain areas from which they originate and manually dissected brain areas, indicating the importance of this technology to the study of TBI-induced changes in specific cell types.