Expression of Fas and Fas Ligand After Experimental Traumatic Brain Injury in the Rat

• Published in: Journal of cerebral blood flow and metabolism 2000-04, Vol.20 (4), p.669-677
• Main Authors: Beer, Ronny, Gerhard, Franz, Schöpf, Marion, Reindl, Markus, Zelger, Bernhard, Schmutzhard, Erich, Poewe, Werner, Kampfl, Andreas
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Biological and medical sciences; Blotting, Western; Brain Injuries - metabolism; Brain Injuries - pathology; Brain Injuries - physiopathology; Cerebral Cortex - metabolism; Cerebral Cortex - pathology; Cerebral Cortex - physiopathology; Fas Ligand Protein; fas Receptor - metabolism; Immunohistochemistry; In Situ Nick-End Labeling; Injuries of the nervous system and the skull. Diseases due to physical agents; Male; Medical sciences; Membrane Glycoproteins - metabolism; Rats; Rats, Sprague-Dawley; Traumas. Diseases due to physical agents; Wounds, Nonpenetrating - metabolism; Wounds, Nonpenetrating - pathology; Wounds, Nonpenetrating - physiopathology
• ISSN: 0271-678X; 1559-7016
• DOI: 10.1097/00004647-200004000-00004

Apoptotic cell death plays an important role in the cascade of neuronal degeneration after traumatic brain injury (TBI), but the underlying mechanisms are not fully understood. However, increasing evidence suggests that expression of Fas and its ligand (FasL) could play a major role in mediating apoptotic cell death in acute and chronic neurologic disorders. To further investigate the temporal pattern of Fas and FasL expression after experimental TBI in the rat, male Sprague Dawley rats were subjected to unilateral cortical impact injury. The animals were killed and examined for Fas and FasL protein expression and for immunohistologic analysis at intervals from 15 minutes to 14 days after injury. Increased Fas and FasL immunoreactivity was seen in the cortex ipsilateral to the injury site from 15 minutes to 72 hours after the trauma, respectively. Immunohistologic investigation demonstrated a differential pattern of Fas and FasL expression in the cortex, respectively: increased Fas immunoreactivity was seen in cortical astrocytes and neurons from 15 minutes to 72 hours after the injury. In contrast, increased expression of FasL was seen in cortical neurons, astrocytes, and microglia from 15 minutes to 72 hours after impact injury. Concurrent double-labeling examinations using terminal deoxynucleotidyl tranferase-mediated deoxyuridine-biotin nick end labeling identified Fas- and FasL-immunopostive cells with high frequency in the cortex ipsilateral to the injury site. In contrast, there was no evidence of Fas- and FasL-immunopositive cells in the hippocampus ipsilateral to the injury site up to 14 days after the trauma. Further, Fas and FasL immunoreactivity was absent in the contralateral cortex and hippocampus at all time points investigated. These results reveal induction of Fas and FasL expression in the cortex after TBI in the rat. Further, these data implicate an involvement of Fas and FasL in the pathophysiologic mechanism of apoptotic neurodegeneration after TBI. Last, these data suggest that strategies aimed to repress posttraumatic Fas- and FasL-induced apoptosis may open new perspectives for the treatment of TBI.