Disruption of intestinal barrier and endotoxemia after traumatic brain injury: Implications for post‐traumatic epilepsy

Abstract

Objective Traumatic brain injury (TBI) may lead to the disruption of the intestinal barrier (IB), and to the escape of products of commensal gut bacteria, including lipopolysaccharide (LPS), into the bloodstream. We examined whether lateral fluid percussion injury (LFPI) and post‐traumatic epilepsy (PTE) are associated with the increased intestinal permeability and endotoxemia, and whether these events in turn are associated with PTE. Methods LFPI was delivered to adult male Sprague‐Dawley rats. Before, 1 week, and 7 months after LFPI, the IB permeability was examined by measuring plasma concentration of fluorescein isothiocyanate–labeled dextran (FD4) upon its enteral administration. Plasma LPS concentration was measured in the same animals, using enzyme‐linked immunosorbent assay. PTE was examined 7 months after LFPI, with use of video‐EEG (electroencephalography) monitoring. Results One week after LFPI, the IB disruption was detected in 14 of 17 and endotoxemia – in 10 of 17 rats, with a strong positive correlation between FD4 and LPS levels, and between plasma levels of each of the analytes and the severity of neuromotor deficit. Seven months after LFPI, IB disruption was detected in 13 of 15 and endotoxemia in 8 of 15 rats, with a strong positive correlation between plasma levels of the two analytes. Five of 15 LFPI rats developed PTE. Plasma levels of both FD4 and LPS were significantly higher in animals with PTE than among the animals without PTE. The analysis of seven rats, which were examined repeatedly at 1 week and at 7 months, confirmed that late IB disruption and endotoxemia were not due to lingering of impairments occurring shortly after LFPI. Significance LFPI leads to early and remote disruption of IB and a secondary endotoxemia. Early and late perturbations may occur in different subjects. Early changes reflect the severity of acute post‐traumatic motor dysfunction, whereas late changes are associated with PTE.

Cerebral Intraparenchymal Hemorrhage Changes Patients’ Gut Bacteria Composition and Function

“…( Kashyap et al., 2013 ; Gensollen et al., 2016 ; Zhu et al., 2018 ; Hanscom et al., 2021 ). Previous studies have proved that acute brain injury induces specific changes in the mice gut microbiota that affects the outcome in mice ( Benakis et al., 2016 ; Houlden et al., 2016 ; Mazarati et al., 2021 ). However, whether gut microbiota dysbiosis occurs in patients with acute cerebrovascular events remains unknown.…”

The microbiota‐gut‐brain axis and epilepsy from a multidisciplinary perspective: Clinical evidence and technological solutions for improvement of in vitro preclinical models

“…The attention has been mainly focused on dietary modification, microbiome supplementations, or manipulation of gut microbiota from mouse models, to evaluate pathological outcomes such as a reduction in seizures' frequency 16 . On the other hand, the number of studies demonstrating a link between gut microbiota alterations and increased neuronal excitability and seizures is constantly increasing, shedding light on the potential mechanisms, pharmacological targets, and treatments 31–34 . It is worth noting that literature studies can be divided into those demonstrating a direct or an indirect impact of microbiota manipulation on epilepsy features.…”

Peripheral Infection after Traumatic Brain Injury Augments Excitability in the Perilesional Cortex and Dentate Gyrus

“…CNS infections co-occurred with epilepsy, but the association between epilepsy and infections was not specifically analyzed [ 22 ]. A recent study demonstrated that elevated systemic levels of lipopolysaccharide (LPS), a component of the outer membrane of Gram-negative bacteria, due to the breakdown of the gastrointestinal barrier was associated with PTE in a rat lateral fluid-percussion injury (FPI) model [ 23 ]. Despite the important clinical ramifications, little is known about whether or not the re-activation of inflammation by peripheral infection in an adult TBI-primed brain facilitates epileptogenesis.…”