von Roberto Díaz-Peregrino ; Modar Kentar ; Carlos Alberto Trenado Colin ; Renán Sánchez-Porras ; Pablo Albiña-Palmarola ; Francisco L. Ramírez-Cuapio ; Daniel San-Juan ; Andreas Unterberg ; Johannes Woitzik ; Edgar Santos
ECoG recording; Mild hypothermia; power spectrum of frequency bands; Spreading depolarization; Stroke progression
Objective: Characterize the neurophysiological effects of mild hypothermia on stroke and spreading depolarizations (SDs) in gyrencephalic brains. Methods: Left middle cerebral arteries (MCAs) of six hypothermic and six normothermic pigs were permanently occluded (MCAo). Hypothermia began 1 h after MCAo and continued throughout the experiment. ECoG signals from both frontoparietal cortices were recorded. Five-minute ECoG epochs were collected 5 min before, at 5 min, 4, 8, 12, and 16 h after MCAo, and before, during, and after SDs. Power spectra were decomposed into fast (alpha, beta, and gamma) and slow (delta and theta) frequency bands. Results: In the vascular insulted hemisphere under normothermia, electrodes near the ischemic core exhibited power decay across all frequency bands at 5 min and the 4th hour after MCAo. The same pattern was registered in the two furthest electrodes at the 12th and 16th hour. When mild hypothermia was applied in the vascular insulted hemispheres, the power decay was generalized and seen even in electrodes with uncompromised blood flow. During SD analysis, hypothermia maintained increased delta and beta power during the three phases of SDs in the furthest electrode from the ischemic core, followed by the second furthest and third electrode in the beta band during preSD and postSD segments. However, in hypothermic conditions, the third electrode showed lower delta, theta, and alpha power. Conclusion: Mild hypothermia attenuates all frequency bands in the vascularly compromised hemisphere, irrespective of the cortical location. During SD formation, it preserves power spectra more significantly in electrodes further from the ischemic core.
Frontiers in neuroscience Lausanne : Frontiers Research Foundation, 2007 18(2024), Artikel-ID 1302767, Seite 1-15 Online-Ressource
von Renán Sánchez-Porras ; Francisco L. Ramírez‑Cuapio ; Nils Hecht ; Martin Seule ; Roberto Díaz‑Peregrino ; Andreas Unterberg ; Johannes Woitzik ; Jens P. Dreier ; Oliver W. Sakowitz ; Edgar Santos
von Modar Kentar ; Francisco L. Ramirez-Cuapio ; Mildred A. Gutiérrez-Herrera ; Renán Sánchez-Porras ; Roberto Díaz-Peregrino ; Niklas Holzwarth ; Lena Maier-Hein ; Johannes Woitzik ; Edgar Santos
von Renán Sánchez-Porras ; Modar Kentar ; Roland Zerelles ; Martina Geyer ; Carlos Alberto Trenado Colin ; Jed A. Hartings ; Johannes Woitzik ; Jens P. Dreier ; Edgar Santos
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.
von Modar Kentar ; Roberto Díaz-Peregrino ; Carlos Alberto Trenado Colin ; Renán Sánchez-Porras ; Daniel San-Juan ; Francisco L. Ramírez-Cuapio ; Niklas Holzwarth ; Lena Maier-Hein ; Johannes Woitzik ; Edgar Santos
To describe the spatial and temporal electrocorticographic (ECoG) changes after middle cerebral artery occlusion (MCAo), including those caused by spreading depolarization (SD) in the pig brain.
Frontiers in neuroscience Lausanne : Frontiers Research Foundation, 2007 16(2022), Artikel-ID 1025967, Seite 1-12 Online-Ressource
von Edgar Santos ; Arturo Olivares-Rivera ; Sebastian Major ; Renán Sánchez-Porras ; Lorenz Uhlmann ; Kevin Kunzmann ; Roland Zerelles ; Modar Kentar ; Vasilis Kola ; Adrian Hernandez Aguilera ; Mildred A. Gutierrez-Herrera ; Coline L. Lemale ; Johannes Woitzik ; Jed A. Hartings ; Oliver Sakowitz ; Andreas Unterberg ; Jens P. Dreier
Spreading depolarizations (SD) are characterized by breakdown of transmembrane ion gradients and excitotoxicity. Experimentally, N-methyl-d-aspartate receptor (NMDAR) antagonists block a majority of SDs. In many hospitals, the NMDAR antagonist s-ketamine and the GABAA agonist midazolam represent the current second-line combination treatment to sedate patients with devastating cerebral injuries. A pressing clinical question is whether this option should become first-line in sedation-requiring individuals in whom SDs are detected, yet the s-ketamine dose necessary to adequately inhibit SDs is unknown. Moreover, use-dependent tolerance could be a problem for SD inhibition in the clinic.
Critical care London : BioMed Central, 1997 23(2019), Artikel-ID 427, Seite 1-14 Online-Ressource
