Cerebral and systemic hemodynamic effect of recurring seizures

Abstract

The increase in neuronal activity induced by a single seizure is supported by a rise in the cerebral blood flow and tissue oxygenation, a mechanism called neurovascular coupling (NVC). Whether cerebral and systemic hemodynamics are able to match neuronal activity during recurring seizures is unclear, as data from rodent models are at odds with human studies. In order to clarify this issue, we used an invasive brain and systemic monitoring to study the effects of chemically induced non-convulsive seizures in sheep. Despite an increase in neuronal activity as seizures repeat (Spearman’s ρ coefficient 0.31, P < 0.001), ictal variations of cerebral blood flow remained stable while it progressively increased in the inter-ictal intervals (ρ = 0.06, P = 0.44 and ρ = 0.22; P = 0.008). We also observed a progressive reduction in the inter-ictal brain tissue oxygenation (ρ = − 0.18; P = 0.04), suggesting that NVC was unable to compensate for the metabolic demand of these closely repeating seizures. At the systemic level, there was a progressive reduction in blood pressure and a progressive rise in cardiac output (ρ = − 0.22; P = 0.01 and ρ = 0.22; P = 0.01, respectively), suggesting seizure-induced autonomic dysfunction.

Sepsis modulates cortical excitability and alters the local and systemic hemodynamic response to seizures

“…Animal model procedures have been previously described 9 , 16 . Briefly, the Institutional Review Board for Animal Care of the Free University of Brussels (Belgium) approved all experimental procedures (number of Ethical Committee approval: 675 N), which were also in compliance with ARRIVE (Animal Research: Reporting in Vivo Experiments) guidelines.…”

“…Animals were allocated with a 1:1:1 ratio to a sham procedure (n = 6), early sepsis assessment (n = 6) and septic shock assessment (n = 6) groups. Sample sizes were based on previous studies from our laboratory using the same animal model 16 . After randomization, animals were excluded if they presented a hemoglobin level below 8 g/dL or systemic signs of infection at time of delivery to the laboratory.…”

“…Monitoring protocol has been previously published 9 , 16 . Briefly, a continuous IV infusion of ketamine, morphine, and midazolam was used as general anesthesia throughout the entire experiment adjusting initial doses to achieve a nearly continuous EEG background 68 .…”

“…Cerebral and systemic parameters were analyzed as previously described 16 . All analyses were performed off-line, using built-in and custom functions in Matlab (The MathWorks, Natick, MA, USA).…”

“…We employed a well-controlled ovine model of sepsis that has already been used in previous studies on cerebral circulation and seizures 15 , 16 . Fecal peritonitis is characterized by a polymicrobial infectious focus that provides a scenario that is more similar to human sepsis, in term of clinical phases 17 and cytokine profiles 18 , than systemic application of pro-inflammatory bacterial products (i.e.…”