Mild systemic inflammation and moderate hypoxia transiently alter neuronal excitability in mouse somatosensory cortex.

Abstract

During the perinatal period, the brain is highly vulnerable to hypoxia and inflammation, which often cause white matter injury and long-term neuronal dysfunction such as motor and cognitive deficits or epileptic seizures. We studied the effects of moderate hypoxia (HYPO), mild systemic inflammation (INFL), or the combination of both (HYPO+INFL) in mouse somatosensory cortex induced during the first postnatal week on network activity and compared it to activity in SHAM control animals. By performing in vitro electrophysiological recordings with multi-electrode arrays from slices prepared directly after injury (P8-10), one week after injury (P13-16), or in young adults (P28-30), we investigated how the neocortical network developed following these insults. No significant difference was observed between the four groups in an extracellular solution close to physiological conditions. In extracellular 8mM potassium solution, slices from the HYPO, INFL, and HYPO+INFL group were more excitable than SHAM at P8-10 and P13-16. In these two age groups, the number and frequency of spontaneous epileptiform events were significantly increased compared to SHAM. The frequency of epileptiform events was significantly reduced by the NMDA antagonist D-APV in HYPO, INFL, and HYPO+INFL, but not in SHAM, indicating a contribution of NMDA receptors to this pathophysiological activity. In addition, the AMPA/kainate receptor antagonist CNQX suppressed the remaining epileptiform activity. Electrical stimulation evoked prominent epileptiform activity in slices from HYPO, INFL and HYPO+INFL animals. Stimulation threshold to elicit epileptiform events was lower in these groups than in SHAM. Evoked events spread over larger areas and lasted longer in treated animals than in SHAM. In addition, the evoked epileptiform activity was reduced in the older (P28-30) group indicating that cortical dysfunction induced by hypoxia and inflammation was transient and compensated during early development.

• Authors: Jérôme Mordel, Aminah Sheikh, Simeon Tsohataridis, Patrick O Kanold, Christoph M Zehendner, Heiko J Luhmann
• Journal: Neurobiology of disease (Neurobiol Dis) Vol. 88 Pg. 29-43 (Apr 2016) ISSN: 1095-953X [Electronic] United States
• PMID: 26763603 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical References

• Excitatory Amino Acid Antagonists
• GABA-A Receptor Antagonists
• Potassium Chloride
• 6-Cyano-7-nitroquinoxaline-2,3-dione
• 2-Amino-5-phosphonovalerate
• Bicuculline

Topics

• 2-Amino-5-phosphonovalerate (pharmacology)
• 6-Cyano-7-nitroquinoxaline-2,3-dione (pharmacology)
• Action Potentials (drug effects, physiology)
• Age Factors
• Animals
• Bicuculline (pharmacology)
• Disease Models, Animal
• Excitatory Amino Acid Antagonists (pharmacology)
• Exploratory Behavior (physiology)
• Female
• GABA-A Receptor Antagonists (pharmacology)
• Gene Expression Regulation (physiology)
• Hypoxia (pathology)
• In Vitro Techniques
• Inflammation (pathology)
• Male
• Mice
• Mice, Inbred C57BL
• Neurons (drug effects, physiology)
• Potassium Chloride (pharmacology)
• Somatosensory Cortex (pathology)