| Online-Ressource |
Verfasst von: | Sánchez-Porras, Renán [VerfasserIn]  |
| Kentar, Modar [VerfasserIn]  |
| Zerelles, Roland [VerfasserIn]  |
| Geyer, Martina [VerfasserIn]  |
| Trenado Colin, Carlos Alberto [VerfasserIn]  |
| Hartings, Jed A. [VerfasserIn]  |
| Woitzik, Johannes [VerfasserIn]  |
| Dreier, Jens P. [VerfasserIn]  |
| Santos, Edgar [VerfasserIn]  |
Titel: | Eighteen-hour inhibitory effect of s-ketamine on potassium- and ischemia-induced spreading depolarizations in the gyrencephalic swine brain |
Verf.angabe: | Renán Sánchez-Porras, Modar Kentar, Roland Zerelles, Martina Geyer, Carlos Trenado, Jed A. Hartings, Johannes Woitzik, Jens P. Dreier, Edgar Santos |
E-Jahr: | 2022 |
Jahr: | 5 July 2022 |
Umfang: | 14 S. |
Fussnoten: | Gesehen am 10.11.2022 |
Titel Quelle: | Enthalten in: Neuropharmacology |
Ort Quelle: | Amsterdam [u.a.] : Elsevier Science, 1970 |
Jahr Quelle: | 2022 |
Band/Heft Quelle: | 216(2022), Artikel-ID 109176, Seite 1-14 |
ISSN Quelle: | 1873-7064 |
Abstract: | Spreading depolarizations (SDs) are characterized by near-complete breakdown of the transmembrane ion gradients, cytotoxic edema, and glutamate release. SDs are associated with poor neurological outcomes in cerebrovascular diseases and brain trauma. Ketamine, a N-methyl-d-aspartate receptor antagonist, has shown to inhibit SDs in animal models and in humans. However, little is known about its SD-inhibitory effect during long-term administration. Lissencephalic animal models have shown that ketamine loses its SD-blocking effect after some minutes to hours. Physio-anatomical differences between lissencephalic and the more evolved gyrencephalic animals may affect their SDs-blocking effect. Therefore, information from the last may have more translational potential. Therefore, the aim of this study was to investigate the 18 h-effect of s-ketamine as a basis for its possible long-term clinical use for neuroprotection. For this purpose, two gyrencephalic swine brain models were used. In one, SDs were elicited through topical application of KCl; in the other model, SDs were spontaneously induced after occlusion of the middle cerebral artery. S-ketamine was administered at therapeutic human doses, 2, 4 and 5 mg/kg BW/h for up to 18 h. Our findings indicate that s-ketamine significantly reduces SD incidence and expansion without clear evidence of loss of its efficacy. Pharmacological susceptibility of SDs to s-ketamine in both the ischemic gyrencephalic brain and well-perfused brain was observed. SDs were most potently inhibited by s-ketamine doses that are above the clinically recommended (4 mg/kg BW/h and 5 mg/kg BW/h). Nonetheless, such doses are given by neurointensivists in individual cases. Our results give momentum to further investigate the feasibility of a multicenter, neuromonitoring-guided, proof-of-concept clinical trial. |
DOI: | doi:10.1016/j.neuropharm.2022.109176 |
URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext: https://doi.org/10.1016/j.neuropharm.2022.109176 |
| Volltext: https://www.sciencedirect.com/science/article/pii/S0028390822002350 |
| DOI: https://doi.org/10.1016/j.neuropharm.2022.109176 |
Datenträger: | Online-Ressource |
Sprache: | eng |
Sach-SW: | Electrocorticography |
| Gyrencephalic brain |
| Ketamine |
| Neuromonitoring |
| Spreading depolarization |
| Stroke |
K10plus-PPN: | 1821596137 |
Verknüpfungen: | → Zeitschrift |
Eighteen-hour inhibitory effect of s-ketamine on potassium- and ischemia-induced spreading depolarizations in the gyrencephalic swine brain / Sánchez-Porras, Renán [VerfasserIn]; 5 July 2022 (Online-Ressource)