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Glucocorticoid-dependent mechanisms of inflammation-mediated distant hippocampal damage are discussed with a focus on the consequences of traumatic brain injury. The effects of glucocorticoids on specific neuronal populations in the hippocampus depend on their concentration, duration of exposure and cell type. Previous stress and elevated level of glucocorticoids prior to pro-inflammatory impact, as well as long-term though moderate elevation of glucocorticoids, may inflate pro-inflammatory effects. Glucocorticoid-mediated long-lasting neuronal circuit changes in the hippocampus after brain trauma are involved in late post-traumatic pathology development, such as epilepsy, depression and cognitive impairment. Complex and diverse actions of the hypothalamic-pituitary-adrenal axis on neuroinflammation may be essential for late post-traumatic pathology. These mechanisms are applicable to remote hippocampal damage occurring after other types of focal brain damage (stroke, epilepsy) or central nervous system diseases without obvious focal injury. Thus, the liaisons of excessive glucocorticoids/dysfunctional hypothalamic-pituitary-adrenal axis with neuroinflammation, dangerous to the hippocampus, may be crucial to distant hippocampal damage in many brain diseases. Taking into account that the hippocampus controls both the cognitive functions and the emotional state, further research on potential links between glucocorticoid signaling and inflammatory processes in the brain and respective mechanisms is vital.

Time course of changes in neuroinflammatory processes in the dorsal and ventral hippocampus was studied during the early period after lateral fluid percussion-induced neocortical traumatic brain injury (TBI) in the ipsilateral and contralateral hemispheres. In the ipsilateral hippocampus, neuroinflammation (increase in expression of pro-inflammatory cytokines) was evident from day 1 after TBI and ceased by day 14, while in the contralateral hippocampus, it was mainly limited to the dorsal part on day 1. TBI induced an increase in hippocampal corticosterone level on day 3 bilaterally and an accumulation of Il1b on day 1 in the ipsilateral hippocampus. Activation of microglia was observed from day 7 in different hippocampal areas of both hemispheres. Neuronal cell loss was detected in the ipsilateral dentate gyrus on day 3 and extended to the contralateral hippocampus by day 7 after TBI. The data suggest that TBI results in distant hippocampal damage (delayed neurodegeneration in the dentate gyrus and microglia proliferation in both the ipsilateral and contralateral hippocampus), the time course of this damage being different from that of the neuroinflammatory response., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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.

Unprovoked seizures in the late period of traumatic brain injury (TBI) occur in almost 20% of humans and experimental animals, psychiatric comorbidities being common in both situations. The aim of the study was to evaluate epileptiform activity in the early period of TBI induced by lateral fluid percussion brain injury in adult male Srague-Dawley rats and to reveal potential behavioral and pathomorphological correlates of early electrophysiological alterations. One week after TBI the group of animals was remarkably heterogeneous regarding the incidence of bifrontal 7-Hz spikes and spike-wave discharges (SWDs). It consisted of 3 typical groups: a) rats with low baseline and high post-craniotomy SWD level; b)with constantly low both baseline and post-craniotomy SWD levels; c) constantly high both baseline and post-craniotomy SWD levels. Rats with augmented SWD occurrence after TBI demonstrated freezing episodes accompanying SWDs as well as increased anxiety-like behavior (difficulty of choosing). The discharges were definitely associated with sleep phases. The incidence of SWDs positively correlated with the area of glial activation in the neocortex but not in the hippocampus.The translational potential of the data is revealing new pathophysiological links between epileptiform activity appearance, direct cortical and distant hippocampal damage and anxiety-like behavior, putative early predictors of late posttraumatic pathology., Competing Interests: Declaration of Competing Interest None of the authors have potential conflicts of interest to be disclosed., (Copyright © 2020 Elsevier B.V. and Japan Neuroscience Society. All rights reserved.)

Background: In humans, early pathological activity on invasive electrocorticograms (ECoGs) and its putative association with pathomorphology in the early period of traumatic brain injury (TBI) remains obscure., Methods: We assessed pathological activity on scalp electroencephalograms (EEGs) and ECoGs in patients with acute TBI, early electrophysiological changes after lateral fluid percussion brain injury (FPI), and electrophysiological correlates of hippocampal damage (microgliosis and neuronal loss), a week after TBI in rats., Results: Epileptiform activity on ECoGs was evident in 86% of patients during the acute period of TBI, ECoGs being more sensitive to epileptiform and periodic discharges. A "brush-like" ECoG pattern superimposed over rhythmic delta activity and periodic discharge was described for the first time in acute TBI. In rats, FPI increased high-amplitude spike incidence in the neocortex and, most expressed, in the ipsilateral hippocampus, induced hippocampal microgliosis and neuronal loss, ipsilateral dentate gyrus being most vulnerable, a week after TBI. Epileptiform spike incidence correlated with microglial cell density and neuronal loss in the ipsilateral hippocampus., Conclusion: Epileptiform activity is frequent in the acute period of TBI period and is associated with distant hippocampal damage on a microscopic level. This damage is probably involved in late consequences of TBI. The FPI model is suitable for exploring pathogenetic mechanisms of post-traumatic disorders.

Objective: To determine the incidence of non-convulsive status epilepticus, epileptiform activity, rhythmic and periodic patterns in patients with acute stroke., Material and Method: An analysis of electroencephalography (EEG) in 86 stroke patients in the neurointensive care unit of the tertiary medical center was performed. Criteria for starting EEG recording were epileptic seizures or clinical suspicion of uncontrolled epileptic status. The ictal-interictal continuum biomarkers and the diagnostic value of EEG for prediction of survival and recovery were assessed., Results: Pathological changes on EEG were recorded in 84% of patients. These patients showed the absence of the dominant occipital rhythm (66%) and hemispheric slowing (42%). Diffuse slowing below the theta range was observed in 41% of patients. EEG reactivity was absent in 20%. Sporadic epileptiform discharges were recorded in 36% of patients and rhythmic and periodic patterns in 26%. Reliable predictors of the unfavorable outcome were the absence of dominant occipital rhythm, lack of reactivity, and low amplitude of the background EEG. No association between the recording of epileptiform activity and the probability of death was shown., Conclusion: The most useful EEG biomarkers for predicting survival are amplitude, dominant frequency of background EEG activity and reactivity to external stimulus. Sporadic epileptiform discharges, rhythmic, and periodic patterns are not mandatory associated with a negative prognosis in stroke patients.

Background: Establishing the relationship between the damage in the neocortex and the functional manifestations of these lesions is important to understand the mechanisms of acute seizures and their consequences. An analysis of immediate seizures in patients with a traumatic brain injury (TBI) in practice is difficult, however it can be performed in animal models., Aim: To compare the damage to functional neocortical areas with the semiology of immediate seizures and behavioral disturbances in the acute period after lateral fluid percussion (TBI model) in rats., Material and Methods: The study was performed on 48 Wistar rats. TBI was modelled using lateral fluid-percussion injury to the right sensory-motor cortex. To study the semiology of immediate seizures, video recording was performed at the moment of the injury and 5 min after it. After that, a number of behavioral tests were employed., Results and Conclusion: This study presents the first detailed evaluation of damage to the functional neocortical areas in the acute period of TBI using the 'unfolded maps' approach. The focus of damage in the cortex increased from 3rd to 7th day and demonstrated a complex shape, extending far beyond the area of the direct impact. TBI induced immediate seizures with a variability which cannot be explained by the involvement of certain areas of the neocortex alone, as well as behavioral disturbances suggested to reflect developing necrosis predominantly in the sensory area of the neocortex.

Aim: To analyze the pathological electrical activity during the acute period after traumatic brain injury (TBI) and to search for potential morphological correlates of this activity in the neocortex and hippocampus., Material and Methods: The study was performed on male Sprague Dawley rats. TBI was modeled using a lateral hydrodynamic impact in the sensorimotor cortex area. ECoG was continuously recorded one week before and one week after TBI. A histological analysis was performed one week after TBI. Brain slices were Nissl stained as well as immunohistochemically stained for astrocytes (GFAP) and microglia (Isolectin B4). The damage to the neocortex and hippocampus was evaluated., Results and Conclusion: The slowdown of the background activity one and six hours after TBI and appearance of epileptiform activity in a half of animals one week after TBI were shown. The number of discharges was correlated with the area of astrocyte gliosis in the neocortex and with the number of dark (ischemic-like) neurons in the hippocampus. Microglial activation did not correlate with the epileptiform activity. These data are important to understanding early mechanisms of post-trauma epileptogenesis.