The neuropathology of septic shock.
The neuropathological correlates of encephalopathy and autonomic dysfunction in septic shock are unclear. We performed post mortem analysis of 5 brain areas susceptible to ischemia and 5 autonomic nuclei (AN) in 23 patients who had died in our intensive care unit (ICU) from septic shock and 8 dying from non-septic shock as well as 5 controls who had died suddenly from extracranial injury. Proinflammatory cytokine (IL1-beta and TNF-alpha) and inducible nitric oxide synthase (iNOS) expression was assessed by immunocytochemistry. Abnormalities in septic shock were: hemorrhages (26%), hypercoagulability syndrome (9%), micro-abscesses (9%), multifocal necrotizing leukoencephalopathy (9%) and ischemia (100%). The incidence of cerebral hemorrhage or hypercoagulability syndrome was not related to clotting disturbances. The intensity of ischemia within susceptible areas was the same in both ICU groups, but more pronounced in the autonomic centers of septic patients (P < 0.0001). Neuronal apoptosis assessed using anti-caspase 3 immunocytochemistry and in situ end labeling was more pronounced in the autonomic nuclei of septic patients. (P < 0.0001). TNF-alpha expression did not differ between groups but vascular iNOS expression assessed by immunocytochemistry was higher in sepsis (P<0.0001) and correlated with autonomic center neuronal apoptosis (P < 0.02). We conclude that septic shock is associated with diffuse cerebral damage and specific autonomic neuronal apoptosis which may be due to circulating factors particularly iNOS.
Service de Reanimation Médicale, Hôpital Raymond Poincaré, Faculté de Médecine Paris-Ile de France Ouest, Garches, France.
Tarek
T
Sharshar
Djillali
D
Annane
Geoffroy Lorin
GL
de la Grandmaison
Jean Philippe
JP
Brouland
Nicholas S
NS
Hopkinson
Gray
G
Françoise
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000502:physiology; D001341:Autonomic Nervous System / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D002545:Brain Ischemia / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002543:Cerebral Hemorrhage / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D012772:Shock, Septic / Q000150:complications / Q000378:metabolism / Q000473:pathology*
D016207:Cytokines; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases