Affiliations: Northwestern Drug Discovery Program, and Department of
Cell and Molecular Biology, Northwestern University Feinberg Medical School,
Chicago IL, USA | Department of Pediatrics, Children's Memorial
Hospital, Chicago IL, USA
Note: [] Corresponding author: Northwestern University Medical School,
303 E. Chicago Avenue, Ward 4-202, Chicago IL 60611-3008, USA. Tel.: +1 312 503
0697; Fax: +1 312 503 0007; E-mail: [email protected]
Abstract: Glia play active and vital roles in the CNS, including regulation of
brain development, maintenance of cellular homeostasis and reparative responses
to acute and chronic neurologic insults. However, in pathological conditions,
glial function may be dysregulated resulting in enhanced neuroinflammation and
further neurologic injury. The fundamental concept that aberrant regulation of
a normally beneficial process may instead result in pathology is exemplified by
the properties of the glial-derived protein, S100B. In the developing brain and
following acute glial activation in response to injury, S100B acts as a
neurotrophic factor and neuronal survival protein. In contrast, overproduction
of S100B by activated glia can lead to exacerbation of neuroinflammation and
neuronal dysfunction. This duality of S100B actions, both reparative and
degenerative, is consistent with the compelling clinical evidence of the
association between increases in S100B levels and outcome following brain
injury. S100B levels generally correlate with the severity of damage and may
have predictive value for adverse neurological outcomes. The cumulative data
support the potential of S100B as a biomarker for brain damage, implicate glial
activation as a possible treatment target in acute and chronic CNS disorders,
and highlight the dual role of glia in the reparative and pathologic responses
to neurologic injury.
