Complement activation in the human brain after traumatic head injury.
The complement cascade has been suggested to be involved in the development of secondary brain injuries following brain contusions, based on animal experiments. The aim of the present study was to examine the possible involvement of the complement cascade following traumatic head injury in the human brain. Sixteen patients were included in this study, 12-77 years of age, treated at the neurointensive care unit for traumatic brain contusions. All of these patients were operated with frontal or temporal lobe resection due to intractable intracranial hypertension. The resected tissue was analyzed with regard to components related to complement activation. The time interval between accident and operation was 2-82 h. Brain tissue from three patients operated with hippocampectomy due to epilepsy, including temporal lobe resection, were used as controls. We found increased immunoreactivity for complement components C1q, C3b, and C3d and the membrane attack complex (MAC), C5b-9, in the immediate vicinity of neurons in the penumbra area of the contusion. These findings constitute histological evidence for activation of the complement cascade in the penumbra of cortical contusions in the human brain. Using in situ hybridization, we also found C3-mRNA in the penumbra, suggesting a local synthesis of complement. Furthermore, upregulation of the endogenous complement regulator clusterin was found in some neurons in the same area. We suggest that unknown compounds in the debris from injured neurons or myelin breakdown products trigger complement activation, including formation of C5b-9. Activated complement components may stimulate accumulation of inflammatory cells and formation of brain edema, as well as having membrane destructive effects by the end product MAC, thereby being mediators in the development of secondary brain damage.
Bellander
B M
BM
Department of Clinical Neuroscience, Section for Neurosurgery, Karolinska Hospital, Stockholm, Sweden. bob@neuro.ks.se
Singhrao
S K
SK
Ohlsson
M
M
Mattsson
P
P
Svensson
M
M
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D001921:Brain / Q000276:immunology / Q000378:metabolism*; D001930:Brain Injuries / Q000276:immunology / Q000378:metabolism*; D002648:Child; D003167:Complement Activation / Q000502:physiology*; D003165:Complement System Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism
D012333:RNA, Messenger; D003165:Complement System Proteins