S100B protein is released by in vitro trauma and reduces delayed neuronal injury.
S100B protein in brain is produced primarily by astrocytes, has been used as a marker for brain injury and has also been shown to be neurotrophic and neuroprotective. Using a well characterized in vitro model of brain cell trauma, we examined the potential role of exogenous S100B in preventing delayed neuronal injury. Neuronal plus glial cultures were grown on a deformable Silastic membrane and then subjected to strain (stretch) injury produced by a 50 ms displacement of the membrane. We have previously shown that this injury causes an immediate, but transient, nuclear uptake of the fluorescent dye propidium iodide by astrocytes and a 24-48 h delayed uptake by neurons. Strain injury caused immediate release of S100-beta with further release by 24 and 48 h. Adding 10 or 100 nm S100B to injured cultures at 15 s, 6 h or 24 h after injury reduced delayed neuronal injury measured at 48 h. Exogenous S100B was present in the cultures through 48 h. These studies directly demonstrate the release and neuroprotective role of S100B after traumatic injury and that, unlike most receptor antagonists used for the treatment of trauma, S100B is neuroprotective when given at later, more therapeutically relevant time points.
Willoughby
Karen A
KA
Department of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, Richmond, Virginia 23298-0613, USA.
Kleindienst
Andrea
A
Müller
Christian
C
Chen
Tao
T
Muir
Judith K
JK
Ellis
Earl F
EF
D000818:Animals; D002452:Cell Count; D002478:Cells, Cultured; D018920:Coculture Techniques; D004334:Drug Administration Schedule; D009414:Nerve Growth Factors / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D013314:Stress, Mechanical; D013997:Time Factors
D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579158:S100b protein, rat