Acute subdural hematoma: new model delineation and effects of coagulation inhibitors.
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.


CONCLUSIONS
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.
Karabiyikoglu
Murat
M
Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan 48109-0532, USA. karabiyikoglu@yahoo.com
Keep
Richard
R
Hua
Ya
Y
Xi
Guohua
G
D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use*; D001120:Arginine / Q000031:analogs & derivatives; D001522:Behavior, Animal; D004195:Disease Models, Animal; D004224:Diterpenes / Q000627:therapeutic use*; D005121:Extremities / Q000503:physiopathology; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D046934:Ginkgolides; D020199:Hematoma, Subdural, Acute / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D007783:Lactones / Q000627:therapeutic use*; D008297:Male; D009068:Movement / Q000187:drug effects / Q000502:physiology; D010875:Pipecolic Acids / Q000627:therapeutic use*; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D051381:Rats; D015203:Reproducibility of Results; D013449:Sulfonamides; D013997:Time Factors
D000925:Anticoagulants; D004224:Diterpenes; D005343:Fibrinolytic Agents; D046934:Ginkgolides; D007783:Lactones; D010875:Pipecolic Acids; D013449:Sulfonamides; D001120:Arginine; C045856:ginkgolide B; C031942:argatroban