Epileptiform activity and spreading depolarization in the blood-brain barrier-disrupted peri-infarct hippocampus are associated with impaired GABAergic inhibition and synaptic plasticity
Lippmann K, Kamintsky L, Kim SY, Lublinsky S, Prager O, Nichtweiss JF, Salar S, Kaufer D, Heinemann U, Friedman A (2017)
Publication Type: Journal article
Publication year: 2017
Journal
Book Volume: 37
Pages Range: 1803-1819
Journal Issue: 5
Abstract
Peri-infarct opening of the blood-brain barrier may be associated with spreading depolarizations, seizures, and epileptogenesis as well as cognitive dysfunction. We aimed to investigate the mechanisms underlying neural network pathophysiology in the blood-brain barrier-dysfunctional hippocampus. Photothrombotic stroke within the rat neocortex was associated with increased intracranial pressure, vasogenic edema, and peri-ischemic blood-brain barrier dysfunction that included the ipsilateral hippocampus. Intrahippocampal recordings revealed electrographic seizures within the first week in two-thirds of animals, accompanied by a reduction in gamma and increase in theta frequency bands. Synaptic interactions were studied in parasagittal hippocampal slices at 24 h and seven days post-stroke. Field potential recordings in CA1 and CA3 uncovered multiple population spikes, epileptiform episodes, and spreading depolarizations at 24 h. Input-output analysis revealed that fEPSP-spike coupling was significantly enhanced at seven days. In addition, CA1 feedback and feedforward inhibition were diminished. Slices generating epileptiform activity at seven days revealed impaired bidirectional long-term plasticity following high and low-frequency stimulation protocols. Microarray and PCR data confirmed changes in expression of astrocyte-related genes and suggested downregulation in expression of GABA A -receptor subunits. We conclude that blood-brain barrier dysfunction in the peri-infarct hippocampus is associated with early disinhibition, hyperexcitability, and abnormal synaptic plasticity.
Authors with CRIS profile
Involved external institutions
Charité - Universitätsmedizin Berlin
Germany (DE)
Ben-Gurion University of the Negev (BGU) / אוניברסיטת בן-גוריון בנגב
Israel (IL)
University of California, Berkeley
United States (USA) (US)
Germany (DE)
Ben-Gurion University of the Negev (BGU) / אוניברסיטת בן-גוריון בנגב
Israel (IL)
University of California, Berkeley
United States (USA) (US)
How to cite
APA:
Lippmann, K., Kamintsky, L., Kim, S.Y., Lublinsky, S., Prager, O., Nichtweiss, J.F.,... Friedman, A. (2017). Epileptiform activity and spreading depolarization in the blood-brain barrier-disrupted peri-infarct hippocampus are associated with impaired GABAergic inhibition and synaptic plasticity. Journal of Cerebral Blood Flow and Metabolism, 37(5), 1803-1819. https://dx.doi.org/10.1177/0271678X16652631
MLA:
Lippmann, Kristina, et al. "Epileptiform activity and spreading depolarization in the blood-brain barrier-disrupted peri-infarct hippocampus are associated with impaired GABAergic inhibition and synaptic plasticity." Journal of Cerebral Blood Flow and Metabolism 37.5 (2017): 1803-1819.
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