CEREBELLAR CORTEX DELAYED MATURATION IN SUDDEN-INFANT-DEATH-SYNDROME

The cerebellum shows afferent and efferent connections with intrinsic bulbar nuclei and plays an important role in respiration and cardiovas cular control. Pathological and neurochemical abnormalities of bulbar nuclei including the arcuate nucleus have been postulated in sudden in fant death syndrome (SIDS). Most of these abnormalities have been rela ted to impairment in brain development. The cerebellar cortex has a we ll-documented evolution from fetal life until infancy; thus, it may be a very good model to assess brain maturation in SIDS. The present stu dy was conducted to investigate changes in the cerebellar cortex in 19 SIDS cases compared with 12 age-related controls using morphological, quantitative, and statistical approaches. Five-mu m paraffin sections from the midsagittal cerebellar vermis were stained with hematoxylin and eosin (H&E). Immunohistochemical staining was carried out using a polyclonal antiserum to glial fibrillary acidic protein (GFAP). Each c ase consisted of a 25-mu m parallel paraffin section stained with H&E, where the cerebellar external granular layer (EGL) cell density was o btained in one field magnification (x1,000) using an optical dissector procedure on the basis of a stereological method. A statistically sig nificant high EGL cell density, mostly related to the presence of imma ture bipolar, elongated neuronal cells of the premigratory zone with h yperchromatic, oval or poor differentiated nuclei, was observed in SID S. In these cases, EGL expressed immunoreactivity for GFAP mainly in t he subpial and the postmitotic zone. These findings demonstrate a dela yed or slower decline in the number of EGL neurons in SIDS, suggesting either a prolongation of the growth phase related to postnatal cerebe llar foliation or a delay in inward migration. These results suggest t hat in SIDS there is delayed maturation of the cerebellar cortex/EGL, which may support the hypothesized cardiopulmonary control dysfunction , leading to death in a vulnerable period of postnatal development.