Neuroinflammation and Neuronal Loss in the Hippocampus Are Associated with Immediate Posttraumatic Seizures and Corticosterone Elevation in Rats.

Ilia G. Komoltsev,Mikhail V. Onufriev,Natalia V. Gulyaeva,Margarita R. Novikova,Natalia I. Shirobokova,Julia V. Moiseeva,Aleksandra A. Volkova,Stepan O. Frankevich

doi:10.3390/ijms22115883

Abstract

Hippocampal damage after traumatic brain injury (TBI) is associated with late posttraumatic conditions, such as depression, cognitive decline and epilepsy. Mechanisms of selective hippocampal damage after TBI are not well understood. In this study, using rat TBI model (lateral fluid percussion cortical injury), we assessed potential association of immediate posttraumatic seizures and changes in corticosterone (CS) levels with neuroinflammation and neuronal cell loss in the hippocampus. Indices of distant hippocampal damage (neurodegeneration and neuroinflammation) were assessed using histological analysis (Nissl staining, Iba-1 immunohistochemical staining) and ELISA (IL-1β and CS) 1, 3, 7 and 14 days after TBI or sham operation in male Wistar rats (n = 146). IL-1β was elevated only in the ipsilateral hippocampus on day 1 after trauma. CS peak was detected on day 3 in blood, the ipsilateral and contralateral hippocampus. Neuronal cell loss in the hippocampus was demonstrated bilaterally; in the ipsilateral hippocampus it started earlier than in the contralateral. Microglial activation was evident in the hippocampus bilaterally on day 7 after TBI. The duration of immediate seizures correlated with CS elevation, levels of IL-1β and neuronal loss in the hippocampus. The data suggest potential association of immediate post-traumatic seizures with CS-dependent neuroinflammation-mediated distant hippocampal damage.

Highlights

Traumatic brain injury (TBI) is an important cause of neurological deficit and death [1]
We report differences in time course of neuroinflammation and neurodegeneration in the ipsilateral and contralateral hippocampus and present evidence that immediate posttraumatic seizures may be associated with CS elevation, while both neuroinflammation and neuronal loss in the hippocampus are associated with immediate posttraumatic seizures and CS elevation
We presented a detailed descriptions of immediate seizures following TBI in rats

Summary

Introduction

Traumatic brain injury (TBI) is an important cause of neurological deficit and death [1]. TBI leads to distant hippocampal damage, potentially resulting in post-traumatic epilepsy, depression and cognitive decline [2]. These complications often develop for years after the initial trauma. No detailed analysis of either immediate posttraumatic seizures or their contribution to brain damage has been performed. Posttraumatic pathology, including selective distant hippocampal damage, is explained by both primary and secondary damage [3]. The involvement of the contralateral hippocampus in posttraumatic damage may indicate that local, and systemic mechanisms contribute to hippocampal damage after TBI [4,5]

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