High-density microarray analysis of hippocampal gene expression following experimental brain injury

• Published in: Journal of neuroscience research Vol. 67; no. 5; pp. 646 - 663
• Main Authors: Matzilevich, David A., Rall, Jason M., Moore, Anthony N., Grill, Raymond J., Dash, Pramod K.
• Format: Journal Article
• Language: English
• Published: New York Wiley Subscription Services, Inc., A Wiley Company 01-03-2002
• Subjects: Animals; Blotting, Northern; Brain Injuries - genetics; Brain Injuries - metabolism; Brain Injuries - physiopathology; brain injury; Brain-Derived Neurotrophic Factor - genetics; Brain-Derived Neurotrophic Factor - metabolism; Cell Death - genetics; Cyclooxygenase 2; Down-Regulation - genetics; Gene Expression Regulation - physiology; genes; Genes - physiology; hippocampus; Hippocampus - metabolism; Hippocampus - pathology; Hippocampus - physiopathology; Immunohistochemistry; Isoenzymes - genetics; Isoenzymes - metabolism; Male; Memory Disorders - genetics; Memory Disorders - metabolism; Memory Disorders - physiopathology; microarray; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Neuronal Plasticity - genetics; Neurons - metabolism; Neurons - pathology; Oligonucleotide Array Sequence Analysis; plasticity; Prostaglandin-Endoperoxide Synthases - genetics; Prostaglandin-Endoperoxide Synthases - metabolism; Rats; Rats, Long-Evans; RNA, Messenger - metabolism; spatial memory; Time Factors; Up-Regulation - genetics
• ISSN: 0360-4012; 1097-4547
• DOI: 10.1002/jnr.10157

Behavioral, biophysical, and pharmacological studies have implicated the hippocampus in the formation and storage of spatial memory. Traumatic brain injury (TBI) often causes spatial memory deficits, which are thought to arise from the death as well as the dysfunction of hippocampal neurons. Cell death and dysfunction are commonly associated with and often caused by altered expression of specific genes. The identification of the genes involved in these processes, as well as those participating in postinjury cellular repair and plasticity, is important for the development of mechanism‐based therapies. To monitor the expression levels of a large number of genes and to identify genes not previously implicated in TBI pathophysiology, a high‐density oligonucleotide array containing 8,800 genes was interrogated. RNA samples were prepared from ipsilateral hippocampi 3 hr and 24 hr following lateral cortical impact injury and compared to samples from sham‐operated controls. Cluster analysis was employed using statistical algorithms to arrange the genes according to similarity in patterns of expression. The study indicates that the genomic response to TBI is complex, affecting approximately 6% (at the time points examined) of the total number of genes examined. The identity of the genes revealed that TBI affects many aspects of cell physiology, including oxidative stress, metabolism, inflammation, structural changes, and cellular signaling. The analysis revealed genes whose expression levels have been reported to be altered in response to injury as well as several genes not previously implicated in TBI pathophysiology. © 2002 Wiley‐Liss, Inc.