Perifocal and remote blood-brain barrier disruption in cortical photothrombotic ischemic lesion and its modulation by the choice of anesthesia
Abstract
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 mm(3) vs.
TLVKX=8.3 +/- 2.1 mm(3)); same was true for the volume of necrosis (NVPB=5.1 +/- 0.7 mm(3) vs. NVKX=6.3 +/- 1.9 mm(3)).
However, volume of EB-albumin extravasation area was significantly smaller in K X group (EBEVPB=4.3 +/- 0.8 mm(3) vs. EBEVKX=2.0 +/- 0.5 mm(3); 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 alpha 2-adrenergic agonist xylazine may reduce BBB breakdown in photothrombosis. Pentobarbital anesthesia lead to increased BBB permeability in the contralateral hemisphere.