Neuroanatomical correlation of behavioral deficits in the CCI model of TBI

Abstract

Traumatic brain injury (TBI) is the leading cause of death and disability both in combat and civilian situations with limited treatment options including surgical removal of hematoma, ventricular drainage and use of hyperosmotic agents that restrict secondary injury following TBI. Availability of appropriate model system with full-range characterization of anatomical and behavioral components correlative with brain injury provides a pre-clinical platform to test candidate therapies for clinical translation. Modeling of TBI using controlled cortical impact injury (CCI) is largely considered to be close to clinical TBI and hence CCI models have been widely used in pre-clinical TBI research. Most studies reported so far using CCI models were presented with a limited behavioral characterization and lacked its correlation with the signature histopathology of TBI. Current investigation validated a detailed sensomotor and cognitive behavioral characterization correlative with diffuse axonal injury—the signature histopathology of TBI, in the CCI mouse model of TBI. Present study offers a comprehensively characterized model of TBI that can be used to investigate cellular and molecular mechanisms underlying TBI and to test candidate therapies in developing novel and effective treatments for TBI.