Long-Term Sequelae of Traumatic Brain Injury in Rats: A Morphological, Behavioral, and Electrophysiological Study

Abstract

The long-term sequelae of traumatic brain injury (TBI) in humans are linked with the development of convulsions and cognitive and emotional disorders and are also associated with acceleration of brain aging processes and the formation of hippocampal sclerosis (HS). The mechanisms of these complications remain incompletely understood and treatment is extremely difficult. Existing data obtained using experimental models in animals do not provide a clear assessment of these mechanisms. The present study clarifies the long-term histological, behavioral, and electrophysiological sequelae of TBI in rats. Six months after lateral hydrodynamic blows, animals displayed severe asymmetrical gliosis in hippocampal field CA3 and the dental gyrus in the form of fibrillary astrogliosis, with an increase in the number of glial cells and depletion of the pyramidal layer of field CA3 in the ipsilateral hemisphere (corresponding to type 3 HS in humans); sham-operated animals displayed only symmetrical gliosis (isolated gliosis in the human HS classification). The behavior of the rats six months after TBI and the sham procedure was characterized by decreases in motor activity, which some signs of increased anxiety. Behavioral impairments were more severe in rats after TBI, mainly due to decreases in exploratory activity. The long-term period of TBI was characterized on ECoG by prolonged spike-wave discharges in the cortex and asymmetry of epileptiform spikes in the hippocampus. Two rats in the late period demonstrated epileptic seizures. Intense brain aging processes in rats with TBI and the development of neurodegenerative changes in the hippocampus may be linked with chronic remote neuroinflammation, which plays an important role in the development of posttraumatic epilepsy and dementia.