Differential Gene Expression in Hippocampus following Experimental Brain Trauma Reveals Distinct Features of Moderate and Severe Injuries

Abstract

Microarray technology was employed to determine the differential pattern of gene expression within the hippocampus as a result of traumatic brain injury (TBI). The validity of the microarray data was confirmed using real-time RT-PCR. Following either moderate or severe lateral fluid percussion injury, rats were studied 0.5, 4, and 24 h after injury. In general, animals exhibited mRNA up or down regulation of approximately 10% of the genes studied. However, it was clear that the pattern of gene expression was influenced by both the severity of injury and the time after injury at which animals were studied. For example, genes encoding molecules for cellular signaling, synaptic plasticity, metabolism, ion channels and transporters were up regulated following severe injury, but down regulated following moderate injury. Furthermore, moderate injury was associated with an increasing number of responsive genes as a function of time post-injury. However, animals sustaining a severe level of injury exhibited decreasing number of responsive genes during the same post-injury period. The different patterns of gene expression between injury severity and across time after the insult suggests that the pathophysiological cascade induced by TBI is accompanied by a molecular response which, like the other aspects of the cellular response for survival, may indicate a "molecular window" that may offer an opportunity for therapeutic interventions involving gene therapy. Our results also suggest that fundamentally different pathophysiological processes or cascades may be induced by different severities of injury.