title: Delayed administration of basic fibroblast growth factor (bFGF) attenuates cognitive dysfunction following parasagittal fluid percussion brain injury in the rat.
abstract: The present study evaluates the therapeutic effects of delayed administration of bFGF on cognitive dysfunction and histopathological damage following lateral fluid-percussion (FP) brain injury. Male Sprague-Dawley rats were trained to learn a visuospatial task in a Morris Water Maze (MWM) paradigm and then were anesthetized and subjected to either FP brain injury of moderate severity (2.5-2.8 atm, n = 32) or surgery without brain injury (n = 10). Twenty-four hours postinjury, an infusion cannula connected to a mini-osmotic pump was implanted into the area of maximal cortical injury to continuously infuse either bFGF (2.0 g) or vehicle for 7 days. Treatment with bFGF significantly attenuated posttraumatic memory dysfunction in the MWM at 8 days postinjury when compared to vehicle treatment (p < 0.05). The cortical lesion and significant cell loss in the ipsilateral CA3 region of the hippocampus, produced by FP injury, was not affected by bFGF treatment. However, immunohistochemical evaluation of glial fibrillary acidic protein revealed a trend toward increased astrocytosis in the injured cortex of bFGF-treated animals compared to vehicle-treated animals (p < 0.1). These results indicate that bFGF may be efficacious in attenuating cognitive dysfunction associated with traumatic brain injury.
authors.affiliation: Division of Neurosurgery, University of Pennsylvania, Philadelphia 19104-6316, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: McDermott
authors.forename: R
authors.initials: R
authors.lastname: Raghupathi
authors.forename: S C
authors.initials: SC
authors.lastname: Fernandez
authors.forename: K E
authors.initials: KE
authors.lastname: Saatman
authors.forename: A A
authors.initials: AA
authors.lastname: Protter
authors.forename: S P
authors.initials: SP
authors.lastname: Finklestein
authors.forename: G
authors.initials: G
authors.lastname: Sinson
authors.forename: D H
authors.initials: DH
authors.lastname: Smith
authors.forename: T K
authors.initials: TK
authors.lastname: McIntosh
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015415:Biomarkers; D001921:Brain / Q000187:drug effects / Q000473:pathology*; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology; D003072:Cognition Disorders / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D016222:Fibroblast Growth Factor 2 / Q000627:therapeutic use*; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology; D009410:Nerve Degeneration; D010474:Percussion; D017966:Pyramidal Cells / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013788:Thalamus / Q000187:drug effects / Q000473:pathology
chemical_list: D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D016222:Fibroblast Growth Factor 2