title: Intraventricular infusion of the neurotrophic protein S100B improves cognitive recovery after fluid percussion injury in the rat.
abstract: Elevated serum S100B levels have been shown to be a predictor of poor outcome after traumatic brain injury (TBI). Experimental data, on the other hand, demonstrate a neuroprotective and neurotrophic effect of this calcium-binding protein. The purpose of this study was to examine the role of increased S100B levels on functional outcome after TBI. Following lateral fluid percussion or sham injury in male Sprague Dawley rats (n = 56), we infused S100B (50 ng/h) or vehicle into the cerebrospinal fluid of the ipsilateral ventricle for 7 days using an osmotic mini-pump. Assessment of cognitive performance by the Morris water maze on days 30-34 after injury revealed an improved performance of injured animals after S100B infusion (p < 0.05), when compared to vehicle infusion. Blood samples for analysis of clinical markers of brain damage, S100B and neuron specific enolase, taken at 30 min, 3 h, 4 h, 2 days, or 5 days showed a typical peak 3 h after injury (p < 0.01), and higher serum levels correlated significantly with an impaired cognitive recovery (p < 0.01). The correlation of higher serum S100B levels with poor water maze performance may result from injury induced opening of the blood-brain barrier, allowing the passage of S100B into serum. Thus while higher serum levels of S100B seem to reflect the degree of blood-brain barrier opening and severity of injury, a beneficial effect of intraventricular S100B administration on long-term functional recovery after TBI has been demonstrated for the first time. The exact mechanism by which S100B exerts its neuroprotective or neurotrophic influence remains unknown and needs to be elucidated by further investigation.
authors.affiliation: Division of Neurosurgery, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298-0508, USA. akleindienst@vcu.edu
authors.forename: Andrea
authors.initials: A
authors.lastname: Kleindienst
authors.forename: Harlan B
authors.initials: HB
authors.lastname: Harvey
authors.forename: Ann C
authors.initials: AC
authors.lastname: Rice
authors.forename: Christian
authors.initials: C
authors.lastname: Müller
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Hamm
authors.forename: Michael R
authors.initials: MR
authors.lastname: Gaab
authors.forename: M Ross
authors.initials: MR
authors.lastname: Bullock
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000097:blood / Q000188:drug therapy*; D003071:Cognition / Q000187:drug effects*; D007276:Injections, Intraventricular; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009414:Nerve Growth Factors / Q000008:administration & dosage* / Q000097:blood; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010751:Phosphopyruvate Hydratase / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000008:administration & dosage* / Q000097:blood
chemical_list: D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579158:S100b protein, rat; D010751:Phosphopyruvate Hydratase