Peri-infarct blood-brain barrier dysfunction facilitates induction of spreading depolarization associated with epileptiform discharges

NEUROBIOLOGY OF DISEASE

卷:48

Article

Lapilover, E. G.²  Lippmann, K.²  Salar, S.²  Maslarova, A.²  Dreier, J. P.^4,5,6  Heinemann, U.^2,3  Friedman, A.^1,2 

[1] Ben Gurion Univ Negev, Fac Hlth Sci, Dept Physiol & Neurobiol, Zlotowsky Ctr Neurosci, IL-84105 Beer Sheva, Israel

[2] Charite, Inst Neurophysiol, D-13347 Berlin, Germany

[3] Charite, Neurocure Res Ctr, D-13347 Berlin, Germany

[4] Charite, Ctr Stroke Res Berlin, D-10117 Berlin, Germany

[5] Charite, Dept Expt Neurol, D-10117 Berlin, Germany

[6] Charite, Dept Neurol, D-10117 Berlin, Germany

关键词: Astrocytes;    Blood-brain barrier;    Photothrombosis;    Potassium homeostasis;    Spreading depolarization;    Stroke;   

DOI  :  10.1016/j.nbd.2012.06.024

来源: Elsevier

【 摘 要 】

Recent studies showed that spreading depolarizations (SDs) occurs abundantly in patients following ischemic stroke and experimental evidence suggests that SDs recruit tissue at risk into necrosis. We hypothesized that BBB opening with consequent alterations of the extracellular electrolyte composition and extravasation of albumin facilitates generation of SDs since albumin mediates an astrocyte transcriptional response with consequent disturbance of potassium and glutamate homeostasis. Here we show extravasation of Evans blue-albumin complex into the hippocampus following cortical photothrombotic stroke in the neighboring neocortex. Using extracellular field potential recordings and exposure to serum electrolytes we observed spontaneous SDs in 80% of hippocampal slices obtained from rats 24 hatter cortical photothrombosis. Hippocampal exposure to albumin for 24 h through intraventricular application together with serum electrolytes lowered the threshold for the induction of SDs in most slices irrespective of the pathway of stimulation. Exposing acute slices from naive animals to albumin led also to a reduced SD threshold. In albumin-exposed slices the onset of SDs was usually associated with larger stimulus-induced accumulation of extracellular potassium, and preceded by epileptiform activity, which was also observed during the recovery phase of SDs. Application of ifenprodil (3 mu M), an NMDA-receptor type 2 B antagonist, blocked stimulus dependent epileptiform discharges and generation of SDs in slices from animals treated with albumin in-vivo. We suggest that BBB opening facilitates the induction of pen-infarct SDs through impaired homeostasis of K. (c) 2012 Elsevier Inc. All rights reserved.

【 授权许可】

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