Immunohistochemical evaluation of the marbled state in childhood hypoxic encephalopathy

We have immunohistochemically analyzed the marbled state in 8 cases of peri natal hypoxic ischemic encephalopathy and 4 cases of infantile hypoxic ence phalopathy, using antibodies against calbindin-D28k (CaBD), glial fibrillar y acidic protein (GFAP), methionine-enkephalin (MEnk), myelin basic protein (MBP), neurofilament (NF), parvalbumin (PV), substance-P (SuP) and synapto physin (SP). The marbled state was found in the thalamus in 11 cases, whose age at death was over 10 years. Four cases demonstrated the marbled state in the cerebral cortex, in addition to the striatum and/or the thalamus. Th e abnormally myelinated fibers in the marbled st;ate were stained with both Kluver-Barrera and Holzer stainings; however, they were partly immunoposit ive for MBP and completely immunonegative for GFAP, CaBD, MEnk, pV, SuP and SP, although some of the neurons and/or fibers showed immunoreactivities f or those calcium-binding proteins and/or neurotransmitters. The axons were visualized in the abnormally myelinated fibers by Bodian staining and/or an ti-NF immunostainings in the cerebral cortex and striatum but not in the th alamus. GFAP-positive astrocytes did not show any continuity with the abnor mally myelinated fibers. These histological features were seen in the cereb ral cortex, striatum and thalamus. Difference of the etiology did not affec t the histological features with the exception of anti-PV staining, in whic h PV-immunopositive neurons were observed only in aged subjects with infant ile hypoxic encephalopathy, and seemed to be more severely affected by hypo xic stress during the perinatal period than the early infantile period. The se data suggest that the site of lesion or the length of survival period af ter brain injury might influence the formation of the marbled st;ate rather than the etiology. And the direct relationship between the abnormally myel inated fiber and astrocytic process was not verified.