Experimental Mild Traumatic Brain Injury Induces Functional Alteration of the Developing Hippocampus

• Published in: Journal of neurophysiology Vol. 103; no. 1; pp. 499 - 510
• Main Authors: Yu, Zhe, Morrison, Barclay, III
• Format: Journal Article
• Language: English
• Published: United States Am Phys Soc 01.01.2010; American Physiological Society
• Subjects: Aging - physiology; Animals; Brain Injuries - physiopathology; CA1 Region, Hippocampal - growth & development; CA1 Region, Hippocampal - injuries; CA1 Region, Hippocampal - physiopathology; CA3 Region, Hippocampal - growth & development; CA3 Region, Hippocampal - injuries; CA3 Region, Hippocampal - physiopathology; Dentate Gyrus - growth & development; Dentate Gyrus - injuries; Dentate Gyrus - physiopathology; Evoked Potentials; Hippocampus - growth & development; Hippocampus - injuries; Hippocampus - physiopathology; In Vitro Techniques; Microelectrodes; Neuronal Plasticity - physiology; Neurons - physiology; Rats; Time Factors
• ISSN: 0022-3077; 1522-1598
• DOI: 10.1152/jn.00775.2009

Columbia University, Department of Biomedical Engineering, New York City, New York Submitted 21 August 2009; accepted in final form 11 November 2009 ABSTRACT It is estimated that 1.5 million Americans suffer a traumatic brain injury (TBI) every year, of which 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. Address for reprint requests and other correspondence: B. Morrison, Dept. of Biomedical Engineering, Columbia University, 1210 Amsterdam Ave., 351 Engineering Terrace, New York, NY 10027 (E-mail: bm2119{at}columbia.edu ).