Perifocal and remote blood-brain barrier disruption in cortical photothrombotic ischemic lesion and its modulation by the choice of anesthesia.
We assessed blood-brain barrier (BBB) disruption in early stage of photothrombotic focal cerebral ischemia in the rat. We specifically looked for contralateral changes in BBB permeability and tested the influence of two anesthetics on the results. Adult Wistar rats were randomly anesthetized with pentobarbital (PB) or ketamine-xylazine (KX). Rats received intravenously (i.v.) Rose Bengal followed by Evans Blue (EB). Stereotactically defined spots on denuded skull were irradiated by laser (532 nm) for 18 min. Twenty four hours later, rats were killed, brains perfused, fixated, sectioned and slices analyzed by fluorescence microscopy. Volume of necrosis and volume of EB-albumin extravasation were calculated. Evidence of BBB breakdown in remote brain areas was sought and compared to sham handled controls. BBB disruption was consistently present, frequently with EB-albumin accumulating cells. Total lesion volume did not significantly differ among groups (TLVPB=9.4±1.3 mm³ vs. TLVKX=8.3±2.1 mm³); same was true for the volume of necrosis (NVPB=5.1±0.7 mm³ vs. NVKX=6.3±1.9 mm³). However, volume of EB-albumin extravasation area was significantly smaller in KX group (EBEVPB=4.3±0.8 mm³ vs. EBEVKX=2.0±0.5 mm³; p=0.0293). Median background EB-fluorescence signal density was higher in PB group (p<0.0001). Furthermore, regional increase in EB-fluorescence was found in two animals in PB group. Our study shows that anesthesia with NMDA-antagonist ketamine and α2-adrenergic agonist xylazine may reduce BBB breakdown in photothrombosis. Pentobarbital anesthesia lead to increased BBB permeability in the contralateral hemisphere.
Department of Normal, Pathological and Clinical Physiology, 3rd Faculty of Medicine, Charles University, Prague, Czech Republic. dkrysl@gmail.com
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Deykun
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Lambert
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Pokorny
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Mares
D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology; D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000473:pathology*; D002545:Brain Ischemia / Q000473:pathology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D020767:Intracranial Thrombosis / Q000473:pathology; D007649:Ketamine / Q000494:pharmacology; D007834:Lasers; D008297:Male; D009336:Necrosis / Q000473:pathology; D009588:Nitrogen Mustard Compounds / Q000494:pharmacology; D010424:Pentobarbital / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
D058647:Adrenergic alpha-2 Receptor Agonists; D000777:Anesthetics; D018691:Excitatory Amino Acid Antagonists; D006993:Hypnotics and Sedatives; D009588:Nitrogen Mustard Compounds; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine; C026131:xylamine; D010424:Pentobarbital