title: The role of microclot formation in an acute subarachnoid hemorrhage model in the rabbit.
abstract: BACKGROUND
  Microvascular dysfunction and microthrombi formation are believed to contribute to development of early brain injury (EBI) after aneurysmal subarachnoid hemorrhage (SAH).
  
  
  OBJECTIVE
  This study aimed to determine (i) extent of microthrombus formation and neuronal apoptosis in the brain parenchyma using a blood shunt SAH model in rabbits; (ii) correlation of structural changes in microvessels with EBI characteristics.
  
  
  METHODS
  Acute SAH was induced using a rabbit shunt cisterna magna model. Extent of microthrombosis was detected 24 h post-SAH (n = 8) by fibrinogen immunostaining, compared to controls (n = 4). We assessed apoptosis by terminal deoxynucleotidyl transferase nick end labeling (TUNEL) in cortex and hippocampus.
  
  
  RESULTS
  Our results showed significantly more TUNEL-positive cells (SAH: 115 ± 13; controls: 58 ± 10; P = 0.016) and fibrinogen-positive microthromboemboli (SAH: 9 ± 2; controls: 2 ± 1; P = 0.03) in the hippocampus after aneurysmal SAH.
  
  
  CONCLUSIONS
  We found clear evidence of early microclot formation in a rabbit model of acute SAH. The extent of microthrombosis did not correlate with early apoptosis or CPP depletion after SAH; however, the total number of TUNEL positive cells in the cortex and the hippocampus significantly correlated with mean CPP reduction during the phase of maximum depletion after SAH induction. Both microthrombosis and neuronal apoptosis may contribute to EBI and subsequent DCI.
authors.affiliation: Department of Neurosurgery, Bern University Hospital, Inselspital Bern, 3012 Bern, Switzerland ; Laboratories for Neuroscience Research in Neurosurgery, Boston Children's Hospital, Boston, MA 02115, USA ; Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Lukas
authors.initials: L
authors.lastname: Andereggen
authors.affiliation: Department of Intensive Care Medicine, Bern University Hospital, Inselspital Bern, 3012 Bern, Switzerland ; Department of Neurosurgery, University Hospital Cologne, 50924 Cologne, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Neuschmelting
authors.affiliation: Institute of Pathology Länggasse, 3012 Bern, Switzerland.
authors.forename: Michael
authors.identifier: 0000-0001-6315-016X
authors.initials: M
authors.lastname: von Gunten
authors.affiliation: Department of Neurosurgery, Bern University Hospital, Inselspital Bern, 3012 Bern, Switzerland.
authors.forename: Hans Rudolf
authors.initials: HR
authors.lastname: Widmer
authors.affiliation: Department of Intensive Care Medicine, Bern University Hospital, Inselspital Bern, 3012 Bern, Switzerland ; Department of Neurosurgery, Kantonsspital Aarau, 5001 Aarau, Switzerland.
authors.forename: Javier
authors.initials: J
authors.lastname: Fandino
authors.affiliation: Department of Intensive Care Medicine, Bern University Hospital, Inselspital Bern, 3012 Bern, Switzerland ; Department of Neurosurgery, Kantonsspital Aarau, 5001 Aarau, Switzerland.
authors.forename: Serge
authors.initials: S
authors.lastname: Marbacher
mesh_terms: D000818:Animals; D017209:Apoptosis; D001777:Blood Coagulation; D002540:Cerebral Cortex / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D009474:Neurons / Q000473:pathology; D011817:Rabbits; D013345:Subarachnoid Hemorrhage / Q000097:blood* / Q000473:pathology* / Q000503:physiopathology
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