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.
Highlights
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)
We aimed to study the cerebral hemodynamic and systemic cardiovascular effects of repeated chemically-induced non-convulsive seizures (NCSz) in a healthy ovine model, as sheep is considered a promising surrogate for modelling human brain diseases[16] and it has already been employed as model for epilepsy[17,18] and to study brain microcirculation[19,20]
We showed that NVC is partially maintained during recurring penicillin-induced seizures in healthy animals, with stable relative ictal variations of both cerebral blood flow velocity (CBFv) and P btO2
Summary
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). Seizures, including non-convulsive seizures (NCSz), cause a dramatic increase in cortical neuronal activity, metabolism and oxygen consumption that is normally supported by a rise in regional cerebral blood flow (CBF)[1], owing to the mechanisms of neurovascular coupling (NVC)[2]. During seizures, an abnormal neurovascular coupling, associated with a BBB dysfunction, was shown in a patient presenting a subarachnoid hemorrhage[8] which can independently alter the NVC9 This progressive reduction in vasodilation was not confirmed by human studies that, instead, showed an increase of CBF in case of non-convulsive status epilepticus[10,11,12]. A sheep model offers numerous technical and theoretical advantages over small animals since it provides a unique opportunity for the transfer of techniques (neuromonitoring and neurosurgical) between animals and humans, making the results more applicable in a clinical s etting[17]
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