Experimental mild traumatic brain injury induces functional alteration of the developing hippocampus

It is estimated that approximately 1.5 million Americans suffer a traumatic brain injury (TBI) every year, of which approximately 80% are considered mild injuries. Because symptoms caused by mild TBI last less than half an hour by definition and apparently resolve without treatment, the study of mild TBI is often neglected resulting in a significant knowledge gap for this wide-spread problem. In this work, we studied functional (electrophysiological) alterations of the neonatal/juvenile hippocampus after experimental mild TBI. Our previous work reported significant cell death after in vitro injury >10% biaxial deformation. Here we report that biaxial deformation as low as 5% affected neuronal function during the first week after in vitro mild injury of hippocampal slice cultures. These results suggest that even very mild mechanical events may lead to a quantifiable neuronal network dysfunction. Furthermore, our results highlight that safe limits of mechanical deformation or tolerance criteria may be specific to a particular outcome measure and that neuronal function is a more sensitive measure of injury than cell death. In addition, the age of the tissue at injury was found to be an important factor affecting posttraumatic deficits in electrophysiological function, indicating a relationship between developmental status and vulnerability to mild injury. Our findings suggest that mild pediatric TBI could result in functional deficits that are more serious than currently appreciated.