Neuronal expression of Fas-associated death domain protein and caspase-8 in the perinidal parenchyma of cerebral arteriovenous malformations.

OBJECTIVE

The expression and localization of phosphorylated Fas-associated death domain protein (pFADD) and cleaved caspase-8 was examined in human cerebral arteriovenous malformations (AVMs). The authors focused on the perinidal parenchyma to clarify the effect of AVMs on perinidal brain tissue.

METHODS

Seventeen cerebral AVMs were analyzed using immunohistochemical methods. Specimens were removed from patients during surgical procedures. The characteristics of the areas that stained positively for pFADD or cleaved caspase-8 were also assessed using an image analysis system. Eleven (65%) of the 17 lesions demonstrated anti-pFADD immunoreactivity and 12 (71%) showed anti-cleaved caspase-8 immunoreactivity. The immunoreactive cells in the perinidal parenchyma demonstrated obvious neuronal morphological characteristics. The characteristics of pFADD-positive and cleaved caspase-8-positive areas were assessed using the image analysis system. The mean distance from the nidus adjacent to either area was not affected by preoperative hemorrhage. The neuronal densities of pFADD-positive and cleaved caspase-8-positive areas were analyzed using the same system. The density of the control area (samples that were pFADD-negative and cleaved caspase-8 negative) was significantly higher when compared with that of pFADD-positive and cleaved caspase-8-positive areas (p < 0.05). The expressions of cleaved caspase-9, cleaved poly(adenosine diphosphate-ribose) polymerase, and apoptotic cells were analyzed using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling method.

CONCLUSIONS

Neuronal areas that stained positively for pFADD and cleaved caspase-8 existed around the nidus of AVMs. In these areas, the neuronal density was lower than that in the other parenchyma around the AVM. Neuronal loss around the nidus may be the origin of brain dysfunction around AVMs.