Neuropediatrics 2012; 43 - WS17_04
DOI: 10.1055/s-0032-1307171

Fetuin A: a new neuroprotective serum protein?

M Häusler 1, J Elsas 1, 3, B Sellhaus 2, A Kinkeldey 3, M Herrmann 3, J Weis 2, W Jahnen-Dechent 3
  • 1Kinder- und Jugendmedizin, UK/RWTH Aachen, Aachen, Germany
  • 2Institut für Neuropathologie, UK Aachen, Aachen, Germany
  • 3Institut für Biomedizinische Technologien RWTH Aachen, Aachen, Germany

Aims: Fetuin A is a serum protein, essential for mineral homeostasis, showing immunomodulatory functions mediated by spermine-like polycations as well as TGF beta. It was neuroprotective in a rat model of acute stroke and reduces lethality after systemic LPS challenge. Serum fetuin A concentrations are highest during early intrauterine life and are depressed during acute phase (negative acute phase protein). Expression of fetuin A in the preterm brain has already been shown. This study aimed at specifying the cerebral expression pattern of fetuin A.

Methods: Histopathological studies on rats (age P0 to P28) and human cerebral tissues (20 to 40 weeks of gestation) derived from routine autopsies.

Results: In human and rat brain, fetuin A is expressed in cortex, white matter, subplate, hippocampus (dentate gyrus, hilus, CA3, CA1), subventricular zone, and ependymal cells. In different brain areas, the expression pattern changes with time, the number of fetuin A-positive cells decreases throughout the observation period. For the longest period of time fetuin A expression is found in hippocampal cells and in the periventricular stem cell layer. In ependymal cell layers, fetuin A expression is restricted to distinct cells, suggesting active transependymal transport from the cerebrospinal fluid. According to double immunofluorescence studies, fetuin A colocalizes with NeuN (mature neurons), beta III tubulin (immature neurons), GFAP (astrocytes) and CD68 (activated microglia).

Conclusion: Cerebral fetuin A expression is observed from preterm age to term born neonates. It affects neuronal, glial, and immune cells in a differentiated and time-related pattern, suggesting specific functions in different brain areas at different stages of brain maturation. Its potential role in the physiology and pathology (asphyxia, cerebral bleeding) of brain development will be studied in a fetuin-A deficient mouse model.

Fetuin A - preterm infant - brain maturation - immunohistochemistry - neuroprotection