Impact of anaesthetic agents on CSF macro- and microcirculation

Position du problème et objectif(s) de l’étude

Assessing the intra-parenchymal circulation of cerebrospinal fluid (CSF) is a technical challenge. MRI allows contrast agent penetration tracking throughout the brain after injection into the CSF on sedated animals to ensure immobility. Conclusions drawn are limited to the comparison of anaesthetics without awake control animals despite controversy over the effect of anaesthesia on this system more commonly known as the glymphatic system. Here, we compare the effects of anaesthetics most widely used in clinical practice on CSF circulation versus awake state with an MRI restraint method developed in our laboratory.

Matériel et méthodes

Experiments were performed in Swiss mice. Each mouse was fitted with a cranial prosthesis enabling its head to be immobilized in the MRI antenna after a protocol of habituation to the restraint over 3 weeks. A cannula implanted in the cisterna magna allowed a contrast agent (GadospinDTM, MW~17,000 g.mol-1, 1µL) leak-free injection into the CSF. Iterative quantitative T1-weighted MRI sequences were carried out on a 7T MRI over 40min (Figure 1). The anaesthetics tested were isoflurane (halogenated gas), propofol, midazolam and ketamine intravenous. The results are presented as the area under the curve at 40min (AUC). The statistical analysis was performed by Kruskal-Wallis test followed by Bonferroni correction (p significant < 0.05). The project has been approved by the ethics committee (DAP # 32700). This abstract has also been submitted for presentation at JNRB 2025 (Journée Normande de Recherche Biomédicale).

Résultats & Discussion

Cortex show clear uptake and loss in awake mice with an intra-parenchymal concentration peak at 25 min after injection (Figure 2, n=4, AUC 0,10+/-0,03 µM.min). Under isoflurane (n=4, AUC 0,006+/-0,007 µM.min*), CSF circulation in the ventricular system and in the brain parenchyma is dramatically reduced. Sedation with midazolam (n=5, AUC 0,18+/-0,07 µM.min*) and ketamine (n=5, AUC 0,17+/-0,09 µM.min*) appears to slow down but increase intraparenchymal contrast penetration. Propofol anaesthesia (n=5, AUC 0,09+/-0,09 µM.min) presents the profile closest to the physiology of the awake animal.

Conclusion

Intraparenchymal CSF circulation appears to be an active and rapid process in awake animals. Impact of anaesthetic agents does not appear to be unequivocal with a marked alteration in the circulation of the contrast agent in animals sedated with halogenated gas. This challenge our clinical habits, especially in patients whose glymphatic system is impaired, such as elderly or demented patients.

Auteurs

Jennifer BOURGÈS (1) , Audrey CHAGNOT (2), Clément GAKUBA (3) - (1)Chu/inserm Umr-S U1237, Caen, France, (2)Uk Dementia Research Institute, Edinburgh, Royaume-Uni, (3)Chu/inserm Umr-S U1237, Caen, Royaume-Uni

Orateur(s)

Jennifer BOURGES (Caen)