OBJECTIVE: To develop a highly reproducible rat model and behavioral tests for acute subdural hematoma (ASDH) and to investigate the role of intravascular coagulation and thrombin in the pathogenesis of brain injury in this model. METHODS: A new method was implemented to inject 200 microl of autologous blood subdurally in rats. Immunohistochemistry was used to investigate intravascular fibrin deposition and thrombin levels in the cortex underlying the ASDH. Effectiveness of systemic heparin, argatroban, or ginkgolide B treatment was determined by histological lesion volume, number of occluded microvessels, and neurological deficits. Neurological deficits were monitored for 7 days after ASDH by use of forelimb placing, forelimb use asymmetry, and corner turn tests. RESULTS: Consistent brain damage and sensorimotor deficits were observed in all animals with ASDH. Histological analysis demonstrated occluded microvessels and enlarged perivascular spaces in the underlying cortex starting 1 hour after hematoma induction. Fibrin and thrombin immunoreactivity were increased in the lesioned cortical parenchyma at 4 and 24 hours. However, no intravascular fibrin deposition was detected. Heparin induced hemorrhagic transformation in the cortical lesion and did not attenuate microvessel occlusion. Argatroban and ginkgolide B did not induce hemorrhage but failed to improve microvessel occlusion, lesion volume, and neurological deficits. CONCLUSION: Intravascular coagulation and thrombin are not the major mediators of brain damage after ASDH. The model and behavioral tests presented in this study can be used to investigate other putative mechanisms of injury and to test future therapeutic interventions in ASDH.
OBJECTIVE: To develop a highly reproducible rat model and behavioral tests for acute subdural hematoma (ASDH) and to investigate the role of intravascular coagulation and thrombin in the pathogenesis of brain injury in this model. METHODS: A new method was implemented to inject 200 microl of autologous blood subdurally in rats. Immunohistochemistry was used to investigate intravascular fibrin deposition and thrombin levels in the cortex underlying the ASDH. Effectiveness of systemic heparin, argatroban, or ginkgolide B treatment was determined by histological lesion volume, number of occluded microvessels, and neurological deficits. Neurological deficits were monitored for 7 days after ASDH by use of forelimb placing, forelimb use asymmetry, and corner turn tests. RESULTS: Consistent brain damage and sensorimotor deficits were observed in all animals with ASDH. Histological analysis demonstrated occluded microvessels and enlarged perivascular spaces in the underlying cortex starting 1 hour after hematoma induction. Fibrin and thrombin immunoreactivity were increased in the lesioned cortical parenchyma at 4 and 24 hours. However, no intravascular fibrin deposition was detected. Heparin induced hemorrhagic transformation in the cortical lesion and did not attenuate microvessel occlusion. Argatroban and ginkgolide B did not induce hemorrhage but failed to improve microvessel occlusion, lesion volume, and neurological deficits. CONCLUSION:Intravascular coagulation and thrombin are not the major mediators of brain damage after ASDH. The model and behavioral tests presented in this study can be used to investigate other putative mechanisms of injury and to test future therapeutic interventions in ASDH.
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: Nina Eriksen; Bente Pakkenberg; Egill Rostrup; David O Okonkwo; Bruce Mathern; Lori A Shutter; Anthony J Strong; Johannes Woitzik; Clemens Pahl; Jens P Dreier; Peter Martus; Martin J Lauritzen; Martin Fabricius; Jed A Hartings Journal: Neurocrit Care Date: 2019-06 Impact factor: 3.210