BACKGROUND: In human autopsy studies, 70% to 80% of patients with aneurysmal subarachnoid hemorrhage (SAH) showed infarcts in cerebral cortex covered by subarachnoid blood. Thus far, no animal model of SAH is known to produce this peculiar infarct pattern, and its pathogenesis remains enigmatic. OBJECTIVE: To investigate whether such infarcts occur in the clot model of SAH in primates. METHODS: We performed a retrospective pathological review of 16 primate brains. In 13 cynomolgus monkeys, a blood clot was placed around the middle cerebral artery after additional removal of the arachnoid membrane from the basal surface of the frontal and temporal cortexes. Three animals underwent sham surgery without placement of a blood clot (controls). The brains were harvested between days 1 and 28 after SAH and examined by a neuropathologist blinded to study group. RESULTS: We identified 2 types of cortical infarcts. A band of selective cortical laminar necrosis parallel to the cortical surface ("horizontal") was found in 5 animals. The second category of cortical lesions had a "vertical" extension. It included wedge-shaped (n = 2) or pillarlike (n = 2) necrosis. Both horizontal and vertical infarcts were located exclusively in areas adjacent to subarachnoid blood. The presence of a cortical infarct did not correlate with the degree of middle cerebral artery vasospasm (r2 = .24, P = .13). CONCLUSION: The presence of cortical infarcts suggests that a modified nonhuman primate model of SAH is suitable to examine the pathogenesis of proximal vasospasm and permits investigation of cortical lesions similar to those reported in patients after SAH. Furthermore, it indicates that direct effects of the blood clot on the brain and microcirculation contribute to the development of cortical infarcts after SAH.
BACKGROUND: In human autopsy studies, 70% to 80% of patients with aneurysmal subarachnoid hemorrhage (SAH) showed infarcts in cerebral cortex covered by subarachnoid blood. Thus far, no animal model of SAH is known to produce this peculiar infarct pattern, and its pathogenesis remains enigmatic. OBJECTIVE: To investigate whether such infarcts occur in the clot model of SAH in primates. METHODS: We performed a retrospective pathological review of 16 primate brains. In 13 cynomolgus monkeys, a blood clot was placed around the middle cerebral artery after additional removal of the arachnoid membrane from the basal surface of the frontal and temporal cortexes. Three animals underwent sham surgery without placement of a blood clot (controls). The brains were harvested between days 1 and 28 after SAH and examined by a neuropathologist blinded to study group. RESULTS: We identified 2 types of cortical infarcts. A band of selective cortical laminar necrosis parallel to the cortical surface ("horizontal") was found in 5 animals. The second category of cortical lesions had a "vertical" extension. It included wedge-shaped (n = 2) or pillarlike (n = 2) necrosis. Both horizontal and vertical infarcts were located exclusively in areas adjacent to subarachnoid blood. The presence of a cortical infarct did not correlate with the degree of middle cerebral artery vasospasm (r2 = .24, P = .13). CONCLUSION: The presence of cortical infarcts suggests that a modified nonhuman primate model of SAH is suitable to examine the pathogenesis of proximal vasospasm and permits investigation of cortical lesions similar to those reported in patients after SAH. Furthermore, it indicates that direct effects of the blood clot on the brain and microcirculation contribute to the development of cortical infarcts after SAH.
Authors: Jed A Hartings; Jonathan York; Christopher P Carroll; Jason M Hinzman; Eric Mahoney; Bryan Krueger; Maren K L Winkler; Sebastian Major; Viktor Horst; Paul Jahnke; Johannes Woitzik; Vasilis Kola; Yifeng Du; Matthew Hagen; Jianxiong Jiang; Jens P Dreier Journal: Brain Date: 2017-10-01 Impact factor: 13.501
Authors: Jens P Dreier; Martin Fabricius; Cenk Ayata; Oliver W Sakowitz; C William Shuttleworth; Christian Dohmen; Rudolf Graf; Peter Vajkoczy; Raimund Helbok; Michiyasu Suzuki; Alois J Schiefecker; Sebastian Major; Maren Kl Winkler; Eun-Jeung Kang; Denny Milakara; Ana I Oliveira-Ferreira; Clemens Reiffurth; Gajanan S Revankar; Kazutaka Sugimoto; Nora F Dengler; Nils Hecht; Brandon Foreman; Bart Feyen; Daniel Kondziella; Christian K Friberg; Henning Piilgaard; Eric S Rosenthal; M Brandon Westover; Anna Maslarova; Edgar Santos; Daniel Hertle; Renán Sánchez-Porras; Sharon L Jewell; Baptiste Balança; Johannes Platz; Jason M Hinzman; Janos Lückl; Karl Schoknecht; Michael Schöll; Christoph Drenckhahn; Delphine Feuerstein; Nina Eriksen; Viktor Horst; Julia S Bretz; Paul Jahnke; Michael Scheel; Georg Bohner; Egill Rostrup; Bente Pakkenberg; Uwe Heinemann; Jan Claassen; Andrew P Carlson; Christina M Kowoll; Svetlana Lublinsky; Yoash Chassidim; Ilan Shelef; Alon Friedman; Gerrit Brinker; Michael Reiner; Sergei A Kirov; R David Andrew; Eszter Farkas; Erdem Güresir; Hartmut Vatter; Lee S Chung; K C Brennan; Thomas Lieutaud; Stephane Marinesco; Andrew Ir Maas; Juan Sahuquillo; Markus A Dahlem; Frank Richter; Oscar Herreras; Martyn G Boutelle; David O Okonkwo; M Ross Bullock; Otto W Witte; Peter Martus; Arn Mjm van den Maagdenberg; Michel D Ferrari; Rick M Dijkhuizen; Lori A Shutter; Norberto Andaluz; André P Schulte; Brian MacVicar; Tomas Watanabe; Johannes Woitzik; Martin Lauritzen; Anthony J Strong; Jed A Hartings Journal: J Cereb Blood Flow Metab Date: 2016-01-01 Impact factor: 6.200