Dynamics of functional impairments during focal transient ischemia in three-dimensional cortical space
- Authors: Vinokurova D.E.1, Zakharov A.V.1,2, Mingazov B.R.1, Khazipov R.N.3
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Affiliations:
- Kazan Federal University
- Kazan State Medical University
- INMED, Aix-Marseille University
- Issue: Vol 18, No 4 (2023)
- Pages: 691-693
- Section: Conference proceedings
- URL: https://genescells.ru/2313-1829/article/view/623414
- DOI: https://doi.org/10.17816/gc623414
- ID: 623414
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Abstract
Ischemic injury in the cerebral cortex results in decreased electrical activity across all frequency bands and the emergence of abnormal electrophysiological patterns, including spreading depolarization (SD) and negative ultraslow potential (NUP) [1, 2]. Despite this, the specific dynamics of these changes in electrical activity within the three-dimensional cortical space during ischemia remain incompletely described and poorly understood.
To simultaneously investigate changes in electrical activity across the layers of the cerebral cortex and in the horizontal cortical space, we used two linear 16-channel silicone probes (Neuronexus, USA) in combination with a flexible transparent 60-channel matrix of subdural electrodes (MIPT, Russia) and intrinsic optical signal imaging (IOS, 665 nm, transillumination mode) during focal ischemia induced by intracortical injection of the potent vasoconstrictor endothelin-1 (ET-1, 1 μL, 1 μM). These experiments were carried out in head-restrained rats under urethane anesthesia (1.5 g/kg).
Formation of the ischemic lesion following ET-1 administration was correlated with clusters of SDs that demonstrated considerable variability in their propagation patterns within both vertical and horizontal planes. The initial SDs originated from the injection site of ET-1 and diffused across all cortical layers. Subsequently, the initiation point of the ensuing SDs gradually shifted towards the deeper layers while the electrical activity showed inadequate recovery between SDs within the injection site. SDs originating in the surrounding cortex did not invade the area near the injection point. Instead, they tended to spread around, often compartmentalizing in the superficial layers of the cortex. Some SDs were observed deep in the cortex, while others were detected on the surface via superficial electrodes and IOS, without leaving typical intracortical electrode traces. Electrographic activity was significantly depressed, especially in the superficial layers around the injection site, three hours after ET-1 administration. However, it returned to pre-ET-1 levels at the remote site, with a spatial gradient observed in subdural electrodes. Functional impairments corresponded to the histological lesion observed in coronal brain sections. Recently discovered NUPs were initiated by SD and were most prominent in the electrodes closest to the ET-1 injection site. These NUPs reached their maximal amplitude at one hour and subsided three hours after ET-1 injection.
Our research indicates intricate dynamics in the creation of an ischemic focal point. The data gathered suggest that the emergence of cerebral harm during focal ischemia is associated with the growth of a focus extending both horizontally and vertically across cortical dimensions. This growth is fueled by the generation of SDs within the ischemic penumbra.
Full Text
Ischemic injury in the cerebral cortex results in decreased electrical activity across all frequency bands and the emergence of abnormal electrophysiological patterns, including spreading depolarization (SD) and negative ultraslow potential (NUP) [1, 2]. Despite this, the specific dynamics of these changes in electrical activity within the three-dimensional cortical space during ischemia remain incompletely described and poorly understood.
To simultaneously investigate changes in electrical activity across the layers of the cerebral cortex and in the horizontal cortical space, we used two linear 16-channel silicone probes (Neuronexus, USA) in combination with a flexible transparent 60-channel matrix of subdural electrodes (MIPT, Russia) and intrinsic optical signal imaging (IOS, 665 nm, transillumination mode) during focal ischemia induced by intracortical injection of the potent vasoconstrictor endothelin-1 (ET-1, 1 μL, 1 μM). These experiments were carried out in head-restrained rats under urethane anesthesia (1.5 g/kg).
Formation of the ischemic lesion following ET-1 administration was correlated with clusters of SDs that demonstrated considerable variability in their propagation patterns within both vertical and horizontal planes. The initial SDs originated from the injection site of ET-1 and diffused across all cortical layers. Subsequently, the initiation point of the ensuing SDs gradually shifted towards the deeper layers while the electrical activity showed inadequate recovery between SDs within the injection site. SDs originating in the surrounding cortex did not invade the area near the injection point. Instead, they tended to spread around, often compartmentalizing in the superficial layers of the cortex. Some SDs were observed deep in the cortex, while others were detected on the surface via superficial electrodes and IOS, without leaving typical intracortical electrode traces. Electrographic activity was significantly depressed, especially in the superficial layers around the injection site, three hours after ET-1 administration. However, it returned to pre-ET-1 levels at the remote site, with a spatial gradient observed in subdural electrodes. Functional impairments corresponded to the histological lesion observed in coronal brain sections. Recently discovered NUPs were initiated by SD and were most prominent in the electrodes closest to the ET-1 injection site. These NUPs reached their maximal amplitude at one hour and subsided three hours after ET-1 injection.
Our research indicates intricate dynamics in the creation of an ischemic focal point. The data gathered suggest that the emergence of cerebral harm during focal ischemia is associated with the growth of a focus extending both horizontally and vertically across cortical dimensions. This growth is fueled by the generation of SDs within the ischemic penumbra.
ADDITIONAL INFORMATION
Funding sources. This work was supported by Russian Science Fundation (grant No. 22-15-00236).
About the authors
D. E. Vinokurova
Kazan Federal University
Author for correspondence.
Email: AnVZaharov@kpfu.ru
Russian Federation, Kazan
A. V. Zakharov
Kazan Federal University; Kazan State Medical University
Email: AnVZaharov@kpfu.ru
Russian Federation, Kazan; Kazan
B. R. Mingazov
Kazan Federal University
Email: AnVZaharov@kpfu.ru
Russian Federation, Kazan
R. N. Khazipov
INMED, Aix-Marseille University
Email: AnVZaharov@kpfu.ru
France, Marseille
References
- Dreier JP, Reiffurth C. The stroke-migraine depolarization continuum. Neuron. 2015;86(4):902–922. doi: 10.1016/j.neuron.2015.04.004
- Vinokurova D, Zakharov A, Chernova K, et al. Depth-profile of impairments in endothelin-1 – induced focal cortical ischemia. J. Cereb. Blood Flow Metab. 2022;42(10):1944–1960. doi: 10.1177/0271678X221107422
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