Responses of reactive astrocytes containing S100beta protein and fibroblast growth factor-2 in the border and in the adjacent preserved tissue after a contusion injury of the spinal cord in rats: implications for wound repair and neuroregeneration.
This paper demonstrates glial reaction and changes in the S100beta protein and basic fibroblast growth factor (bFGF, FGF-2) in the border and in the adjacent preserved tissue of the rat spinal cord after a contusion. In view of the expression of FGF-2 and S100beta in reactive glial cells and their ability to promote gliogenesis and neuronal trophism, the molecules have been considered to participate in the wound repair and regenerative events after nervous tissue injury. Adult rats were submitted to a moderate spinal cord (10th thoracic level) contusion induced by a New York University Impactor by dropping a 10 g rod from a distance of 25 mm onto the dorsal surface of the exposed dura spinal cord. Impactor curves and parameters were used to monitor the severity of the trauma. Control rats were submitted to sham operation. The motor behavioral spontaneous recovery was demonstrated by means of a BBB test and the combining behavior score up to 3 weeks after injury. Animals were killed 72 hours, 2, and 3 weeks after surgery and spinal cords were processed for immunohistochemistry to show glial fibrillary acidic protein positive astrocytes and OX-42-positive microglia/macrophages as well as changes in the S100beta and FGF-2 in the border and in the adjacent preserved tissue of the lesioned cords. The changes in the immunoreaction products were quantified by means of morphometric/microdensitometric image analysis, and the cell type expressing S100beta and FGF-2 was analyzed by means of two-color immunofluorescence procedures. Massive increases of S100beta and FGF-2 were found in reactive astrocytes, not in reactive microglia, in the border and in the white and gray matters of adjacent preserved tissue of the contused spinal cord in the periods studied. The results are discussed in view of possible paracrine trophic actions of the reactive astrocytes, mediated by S100beta and FGF-2, triggering wound repair events in the border of the trauma, and also leading to neurotrophism and neuronal plasticity in the adjacent regions. These cellular and molecular responses may interfere with the pattern of behavioral recovery after a contusion injury of the spinal cord.
do Carmo Cunha
Jinger
J
Neuroregeneration Center, Department of Neurology, University of São Paulo School of Medicine, University of São Paulo, São Paulo, Brazil.
de Freitas Azevedo Levy
Beatriz
B
de Luca
Bianca Aparecida
BA
de Andrade
Michele Schultz Ramos
MS
Gomide
Vânia Canterucci
VC
Chadi
Gerson
G
D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D008297:Male; D017628:Microglia / Q000502:physiology*; D009043:Motor Activity / Q000502:physiology; D009414:Nerve Growth Factors / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000502:physiology; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000378:metabolism*; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D013904:Thoracic Vertebrae; D014945:Wound Healing / Q000502:physiology*
D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D016222:Fibroblast Growth Factor 2