Mild systemic inflammation and moderate hypoxia transiently alter neuronal excitability in mouse somatosensory cortex
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...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2016-04-01
|
| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996115301224 |
| _version_ | 1818869965661405184 |
|---|---|
| author | Jérôme Mordel Aminah Sheikh Simeon Tsohataridis Patrick O. Kanold Christoph M. Zehendner Heiko J. Luhmann |
| author_facet | Jérôme Mordel Aminah Sheikh Simeon Tsohataridis Patrick O. Kanold Christoph M. Zehendner Heiko J. Luhmann |
| author_sort | Jérôme Mordel |
| collection | DOAJ |
| description | 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 8 mM 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. |
| first_indexed | 2024-12-19T11:59:31Z |
| format | Article |
| id | doaj.art-7154c51df3504a37b5c956832b978c64 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-19T11:59:31Z |
| publishDate | 2016-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-7154c51df3504a37b5c956832b978c642022-12-21T20:22:32ZengElsevierNeurobiology of Disease1095-953X2016-04-01882943Mild systemic inflammation and moderate hypoxia transiently alter neuronal excitability in mouse somatosensory cortexJérôme Mordel0Aminah Sheikh1Simeon Tsohataridis2Patrick O. Kanold3Christoph M. Zehendner4Heiko J. Luhmann5Institute of Physiology, University Medical Center of the Johannes Gutenberg University, 55128 Mainz, GermanyDepartment of Biology, University of Maryland, College Park, MD 20742, USAInstitute of Physiology, University Medical Center of the Johannes Gutenberg University, 55128 Mainz, GermanyDepartment of Biology, University of Maryland, College Park, MD 20742, USAInstitute of Physiology, University Medical Center of the Johannes Gutenberg University, 55128 Mainz, Germany; ZIM III, Department of Cardiology, Institute for Cardiovascular Regeneration, Goethe University Frankfurt, 60590 Frankfurt am Main, GermanyInstitute of Physiology, University Medical Center of the Johannes Gutenberg University, 55128 Mainz, Germany; Corresponding author.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 8 mM 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.http://www.sciencedirect.com/science/article/pii/S0969996115301224HypoxiaSystemic inflammationInterleukin-1βMulti-electrode arrayElectrophysiologyEpileptiform activity |
| spellingShingle | Jérôme Mordel Aminah Sheikh Simeon Tsohataridis Patrick O. Kanold Christoph M. Zehendner Heiko J. Luhmann Mild systemic inflammation and moderate hypoxia transiently alter neuronal excitability in mouse somatosensory cortex Neurobiology of Disease Hypoxia Systemic inflammation Interleukin-1β Multi-electrode array Electrophysiology Epileptiform activity |
| title | Mild systemic inflammation and moderate hypoxia transiently alter neuronal excitability in mouse somatosensory cortex |
| title_full | Mild systemic inflammation and moderate hypoxia transiently alter neuronal excitability in mouse somatosensory cortex |
| title_fullStr | Mild systemic inflammation and moderate hypoxia transiently alter neuronal excitability in mouse somatosensory cortex |
| title_full_unstemmed | Mild systemic inflammation and moderate hypoxia transiently alter neuronal excitability in mouse somatosensory cortex |
| title_short | Mild systemic inflammation and moderate hypoxia transiently alter neuronal excitability in mouse somatosensory cortex |
| title_sort | mild systemic inflammation and moderate hypoxia transiently alter neuronal excitability in mouse somatosensory cortex |
| topic | Hypoxia Systemic inflammation Interleukin-1β Multi-electrode array Electrophysiology Epileptiform activity |
| url | http://www.sciencedirect.com/science/article/pii/S0969996115301224 |
| work_keys_str_mv | AT jeromemordel mildsystemicinflammationandmoderatehypoxiatransientlyalterneuronalexcitabilityinmousesomatosensorycortex AT aminahsheikh mildsystemicinflammationandmoderatehypoxiatransientlyalterneuronalexcitabilityinmousesomatosensorycortex AT simeontsohataridis mildsystemicinflammationandmoderatehypoxiatransientlyalterneuronalexcitabilityinmousesomatosensorycortex AT patrickokanold mildsystemicinflammationandmoderatehypoxiatransientlyalterneuronalexcitabilityinmousesomatosensorycortex AT christophmzehendner mildsystemicinflammationandmoderatehypoxiatransientlyalterneuronalexcitabilityinmousesomatosensorycortex AT heikojluhmann mildsystemicinflammationandmoderatehypoxiatransientlyalterneuronalexcitabilityinmousesomatosensorycortex |