TY - ABST

T1 - A rat model for embolic encephalitis

AU - Astrup, Lærke Boye

AU - Agerholm, Jørgen Steen

AU - Aalbæk, Bent

AU - Rasmussen, Rune Skovgaard

AU - Johansen, Flemming Fryd

AU - Iburg, Tine Moesgaard

PY - 2011/5/25

Y1 - 2011/5/25

N2 - Objective: To establish a rat model for embolic encephalitis. Methods: 63 Male Sprague-Dawley rats were randomly assigned to three groups: control, sterile and septic. The right external carotid artery (ECA) was catheterized after anesthesia and 300µl blood was aspired. The blood was mixed with 30µl thrombin (2.5 IU/ml) in a catheter until coagulated. A sterile fibrin-clot of 5 mm was selected for embolization and injected via the ECA catheter. The common carotid artery was clamped during injection thereby directing the embolus via the internal carotid artery to the brain. The clot-diameter ensures occlusion at the origin of the middle cerebral artery. Occlusion was verified by angiography. In the septic group Staphylococcus aureus was added to the clot-mixture resulting in 600 CFU/5 mm fibrin clot. The control-group received no embolus. The body temperature was kept at 37.0 ±0.5°C during anesthesia. Animals were killed after 48 hours. Within each group animals were randomly assigned into two sub-groups, one formalin-perfused and one snap-frozen. Formalin fixed brains were cut into coronal sections and stained by haematoxylin & eosin and by immunohistochemistry. Results: 11 animals in each group completed the survival period. Premature death occurred more than 2.5 times as often in the septic group than in the sterile group. Bacteriological cultivation showed rapid growth of bacteria in the brain during the survival time. Histology of the formalin-fixed brains showed uni-or bi-focal abscesses in the right hemisphere in the septic group. The abscesses stained positively for Staphylococcus aureus antigen in the center of the abscesses. Histology showed sterile infarction in the right hemisphere in the sterile group. No brain lesions were detected in the control animals. Conclusions: We hereby present a novel animal model of haematogenous brain infection. A model of cerebral ischemia was modified to haematogenously introduce bacteria to an area of brain necrosis and damage to the blood-brain-barrier. Our model has several advantages: the surgical intervention is minimized, the bacteria gain access to the brain by the circulation and, no foreign materials other than bacteria are implated in the brain. This ensures high face-validity and high construct-validity of the model for three reasons: 1) Cerebral infarction by thrombosis or disseminated intravascular coagulation is a key mechanism involved in neurologic complications to human bacteriaemia. 2) Staphylococcus aureus is a leading cause of human brain abscesses. 3) Human brain abscesses are primarily confined to one anatomical site in the frontal lobe. This model therefore offers a tool for several scientific areas within research of brain infection and inflammation. References: Sharma, R. et al. (2009): Infection Kielian, T. et al. (2004): Journal of Neuropathology and Experimental Neurology. Rasmussen, RS. et al. (2003): Acta Neurol Scand Syrjänen, J. (1989): Scand J Infect Dis

AB - Objective: To establish a rat model for embolic encephalitis. Methods: 63 Male Sprague-Dawley rats were randomly assigned to three groups: control, sterile and septic. The right external carotid artery (ECA) was catheterized after anesthesia and 300µl blood was aspired. The blood was mixed with 30µl thrombin (2.5 IU/ml) in a catheter until coagulated. A sterile fibrin-clot of 5 mm was selected for embolization and injected via the ECA catheter. The common carotid artery was clamped during injection thereby directing the embolus via the internal carotid artery to the brain. The clot-diameter ensures occlusion at the origin of the middle cerebral artery. Occlusion was verified by angiography. In the septic group Staphylococcus aureus was added to the clot-mixture resulting in 600 CFU/5 mm fibrin clot. The control-group received no embolus. The body temperature was kept at 37.0 ±0.5°C during anesthesia. Animals were killed after 48 hours. Within each group animals were randomly assigned into two sub-groups, one formalin-perfused and one snap-frozen. Formalin fixed brains were cut into coronal sections and stained by haematoxylin & eosin and by immunohistochemistry. Results: 11 animals in each group completed the survival period. Premature death occurred more than 2.5 times as often in the septic group than in the sterile group. Bacteriological cultivation showed rapid growth of bacteria in the brain during the survival time. Histology of the formalin-fixed brains showed uni-or bi-focal abscesses in the right hemisphere in the septic group. The abscesses stained positively for Staphylococcus aureus antigen in the center of the abscesses. Histology showed sterile infarction in the right hemisphere in the sterile group. No brain lesions were detected in the control animals. Conclusions: We hereby present a novel animal model of haematogenous brain infection. A model of cerebral ischemia was modified to haematogenously introduce bacteria to an area of brain necrosis and damage to the blood-brain-barrier. Our model has several advantages: the surgical intervention is minimized, the bacteria gain access to the brain by the circulation and, no foreign materials other than bacteria are implated in the brain. This ensures high face-validity and high construct-validity of the model for three reasons: 1) Cerebral infarction by thrombosis or disseminated intravascular coagulation is a key mechanism involved in neurologic complications to human bacteriaemia. 2) Staphylococcus aureus is a leading cause of human brain abscesses. 3) Human brain abscesses are primarily confined to one anatomical site in the frontal lobe. This model therefore offers a tool for several scientific areas within research of brain infection and inflammation. References: Sharma, R. et al. (2009): Infection Kielian, T. et al. (2004): Journal of Neuropathology and Experimental Neurology. Rasmussen, RS. et al. (2003): Acta Neurol Scand Syrjänen, J. (1989): Scand J Infect Dis

KW - Former LIFE faculty

M3 - Conference abstract for conference

ER -