Epileptiform activity and spreading depolarization in the blood-brain barrier-disrupted peri-infarct hippocampus are associated with impaired GABAergic inhibition and synaptic plasticity

Kristina Lippmann, Lyn Kamintsky, Soo Young Kim, Svetlana Lublinsky, Ofer Prager, Julia Friederike Nichtweiss, Seda Salar, Daniela Kaufer, Uwe Heinemann, Alon Friedman

نتاج البحث: نشر في مجلةمقالةمراجعة النظراء

ملخص

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.

اللغة الأصليةإنجليزيّة أمريكيّة
الصفحات (من إلى)1803-1819
عدد الصفحات17
دوريةJournal of Cerebral Blood Flow and Metabolism
مستوى الصوت37
رقم الإصدار5
المعرِّفات الرقمية للأشياء
حالة النشرنُشِر - 1 مايو 2017

All Science Journal Classification (ASJC) codes

  • !!Neurology
  • !!Clinical Neurology
  • !!Cardiology and Cardiovascular Medicine

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