Fas system activation in perihematomal areas after spontaneous intracerebral hemorrhage.
OBJECTIVE
Apoptosis has been implicated as the prominent form of cell death in the brain perihematomal region in animal models and in autopsy or postsurgical human studies. Both the Fas system and caspase activation play a central role in apoptotic pathways. The aims of this study were to investigate soluble Fas (s-Fas) plasma levels after acute intracerebral hemorrhage (ICH), to determine its influence on clinical and radiologic features, and to assess Fas receptor and Fas ligand (Fas-L) protein expression in human ICH brain tissue.


METHODS
s-Fas plasma levels were determined on admission in 78 consecutive ICH patients and serially in a subgroup of 21 of them, at the time of neurologic assessment, by means of ELISA. ICH and perihematomal edema volumes were determined at baseline and on follow-up computed tomography scans, and ICH and perihematomal edema growth was calculated. The presence of Fas receptor and Fas-L was assessed in different brain tissue samples by immunoblotting from 6 deceased ICH patients and from 2 control subjects.


RESULTS
Mortality reached 20.5% of patients at the third month, and 48% of survivors had an unfavorable outcome (modified Rankin Scale score >/=3). The baseline s-Fas level in ICH patients was significantly lower than in healthy controls [160 (160-245) vs 269 (230-332) pg/mL, P<0.001], returning to normal values by 24 hours (P<0.05 for all determinations). Regarding radiologic features, the baseline s-Fas value was found to be inversely correlated to perihematomal edema growth at follow-up (r=-0.33, P=0.041). Finally, Fas-L content was highest in the perihematomal area compared with contralateral and remote ipsilateral areas in ICH patient and control samples.


CONCLUSIONS
A decreased plasma s-Fas level together with an increased Fas-L amount in perihematomal brain tissue suggest Fas-mediated apoptosis involvement in this disease.
Delgado
Pilar
P
Neurovascular Research Laboratory. Hospital Vall d'Hebron, Passeig Vall d'Hebron 119-129, 08035 Barcelona, Spain. 35070pdm@comb.es
Cuadrado
Eloy
E
Rosell
Anna
A
Alvarez-Sabín
José
J
Ortega-Aznar
Arantxa
A
Hernández-Guillamón
Mar
M
Penalba
Anna
A
Molina
Carlos A
CA
Montaner
Joan
J
D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging / Q000473:pathology; D001929:Brain Edema / Q000097:blood* / Q000150:complications / Q000503:physiopathology; D020520:Brain Infarction / Q000097:blood / Q000209:etiology / Q000503:physiopathology; D002543:Cerebral Hemorrhage / Q000097:blood* / Q000150:complications / Q000503:physiopathology; D053418:Death Domain Receptor Signaling Adaptor Proteins / Q000378:metabolism; D018450:Disease Progression; D015536:Down-Regulation / Q000502:physiology; D053222:Fas Ligand Protein / Q000032:analysis / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009410:Nerve Degeneration / Q000097:blood* / Q000209:etiology / Q000503:physiopathology; D011237:Predictive Value of Tests; D012016:Reference Values; D014057:Tomography, X-Ray Computed; D015854:Up-Regulation / Q000502:physiology; D019014:fas Receptor / Q000032:analysis / Q000097:blood*
D015415:Biomarkers; D053418:Death Domain Receptor Signaling Adaptor Proteins; C491901:FAS protein, human; D053222:Fas Ligand Protein; D019014:fas Receptor