von Luis Alfredo Navas Contreras ; Vasilis Karantzoulis ; Carlos Alberto Trenado Colin ; Karen Velazquez ; Marcos A. Suárez-Gutiérrez ; Philip Mantilla-Mayans ; Renán Sánchez-Porras ; Edgar Santos ; Farzam Vazifehdan
von Jens P. Dreier ; Svetlana Lublinsky ; Viktor Horst ; Sebastian Major ; Coline L. Lemale ; Vasilis Kola ; Maren K. L. Winkler ; Eun-Jeung Kang ; Karl Schoknecht ; Nils Hecht ; Anna Maslarova ; Edgar Santos ; Johannes Platz ; Christina M. Kowoll ; Oliver Sakowitz ; Erdem Güresir ; Hartmut Vatter ; Christian Dohmen ; Stefan Wolf ; Michael Scheel ; Peter Vajkoczy ; Jed A. Hartings ; Johannes Woitzik ; Peter Martus ; Alon Friedman
Background - We determined the predictive power of semi-automated blood-brain barrier assessment and other variables collected during neurocritical care for the outcome of ‘epilepsy or late death’ following aneurysmal subarachnoid haemorrhage. - Methods - This is a secondary analysis of the prospective, non-interventional, prognostic DISCHARGE-1-cohort from six university hospitals in Germany. All patients who underwent at least one contrast-enhanced MRI during neurocritical care were included. Initial clinical scores and Modified Rankin Scale at day 14 were available. Subdural electrocorticography was scored for seizures and spreading depolarisations. Two MRIs, one post-aneurysm occlusion and another post-neuromonitoring, were semi-automatically segmented into cerebrospinal fluid spaces, normal brain tissue, and abnormal brain tissue. Normal and abnormal tissue were further classified into tissue with “intact” or “dysfunctional” blood-brain barrier. Epilepsy and late death were determined at a median of 3.7 years. - Findings - Abnormal, barrier-dysfunctional tissue as a percentage of intracranial volume on post-monitoring MRI was the only independent predictor of early death within three weeks among 130 patients. In the 121 early survivors, this variable was also the only independent predictor of ‘epilepsy or late death’. This result, obtained by a combination of imputation and the leaving-one-out method, was confirmed in two sensitivity analyses within smaller populations and with fewer missing values. - Interpretation - The study substantiates previous experimental evidence that blood-brain barrier dysfunction plays a key role in epileptogenesis after brain injuries. Contrast-enhanced MRI, a minimally invasive technique, highlighted abnormal, barrier-dysfunctional tissue as a stand-alone independent predictor, underscoring its potential as a ‘precision medicine’ tool in early diagnosis and intervention. - Funding - JPD and AF report a grant from the Era-Net Neuron EBio2 with funds from BMBF 01EW2004 and CIHR Award No. NDD 168164. JPD reports a grant from DFG DR 323/10-2 (project number: 413848220) and EU Horizon MSCA-DN 101119916—SOPRANI. AF reports grants from the Canadian Institutes of Health Research (CIHR) PJT 148896 and Israel Science Foundation (ISF) 2254/20. NH is Berlin Institute of Health Clinical Fellow, funded by Stiftung Charité.
von Edgar Santos ; Juan M. Lopez-Navarro ; Marcos Alejandro Suarez-Gutierrez ; Niklas Holzwarth ; Pablo Albiña-Palmarola ; Thomas Kirchner ; Adrian Hernandez Aguilera ; Jose Antonio Fernandez-Amador ; Farzam Vazifehdan ; Johannes Woitzik ; Lena Maier-Hein ; Renán Sánchez-Porras
von Renán Sánchez-Porras ; Francisco L. Ramírez-Cuapio ; Mildred A. Gutierrez-Herrera ; Ángel Alberto Puig-Lagunes ; Pablo Albiña-Palmarola ; Juan M. López-Navarro ; Marcos Alejandro Suárez-Gutiérrez ; Roberto Díaz-Peregrino ; Diego A. Sandoval-Lopez ; Gregor Fischer ; Farzam Vazifehdan ; Johannes Woitzik ; Edgar Santos
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 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 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.
