Platelet and leukocyte adhesion in the microvasculature at the cerebral surface immediately after subarachnoid hemorrhage.
OBJECTIVE
Pathophysiology after subarachnoid hemorrhage (SAH) caused by aneurysmal rupture has not been well examined. The purpose of this study was to observe platelet-leukocyte-endothelial cell interactions as indexes of inflammatory and prothrombogenic responses in the acute phase of SAH, using an in vivo cranial window method.


METHODS
Subarachnoid hemorrhage was induced in C57Bl/6J mice by using the endovascular perforation method. Intravital microscopy was used to monitor the rolling and adhesion of platelets and leukocytes that were labeled with different fluorochromes. Regional cerebral blood flow was measured with laser Doppler flowmetry. The platelet-leukocyte-endothelial cell interactions were observed 30 minutes, 2 hours, and 8 hours after SAH. The effect of P-selectin antibody and apocynin, an inhibitor of nicotinamide adenine dinucleotide phosphate oxidase, on these responses was examined at 2 hours after SAH, and compared with a different SAH model in which autologous blood was injected into the foramen magna.


RESULTS
SAH was accompanied by a 60% decrease in regional cerebral blood flow, whereas no changes in regional cerebral blood flow were observed on the contralateral side. SAH elicited time- and size-dependent increases in rolling and adherent platelets and leukocytes in cerebral venules. All of these interactions were attenuated by treatment with a P-selectin antibody or apocynin. There was no significant blood cell recruitment observed in the blood-injected SAH model.


CONCLUSIONS
SAH at the skull base induced P-selectin- and oxygen radical-mediated platelet-leukocyte-endothelial cell interactions in venules at the cerebral surface. These early inflammatory and prothrombogenic responses may cause a whole-brain injury immediately after SAH.
Ishikawa
Mami
M
Department of Neurosurgery, Saitama Medical Center, Jichi Medical University, Saitama, Japan. m.ishikawa@jichi.ac.jp
Kusaka
Gen
G
Yamaguchi
Noriyuki
N
Sekizuka
Eiichi
E
Nakadate
Hiromichi
H
Minamitani
Haruyuki
H
Shinoda
Soji
S
Watanabe
Eiju
E
D000818:Animals; D001921:Brain / Q000276:immunology* / Q000473:pathology; D002448:Cell Adhesion / Q000276:immunology*; D002560:Cerebrovascular Circulation / Q000276:immunology*; D007962:Leukocytes / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008833:Microcirculation / Q000276:immunology*; D055806:Microvessels / Q000276:immunology*; D010973:Platelet Adhesiveness / Q000276:immunology*; D013345:Subarachnoid Hemorrhage / Q000276:immunology* / Q000473:pathology