Sources of endothelin-1 in hippocampus and cortex following traumatic brain injury.
Endothelin 1 (ET-1) exerts normally a powerful vasoconstrictor role in the control of the brain microcirculation. In altered states, such as following traumatic brain injury (TBI), it may contribute to the development of ischemia and/or secondary cell injury. Because little is known of ET-1's cellular compartmentalization and its association to vulnerable neurons after TBI, we assessed its expression (both mRNA and protein) in cerebral cortex and hippocampus using correlative in situ hybridization and immunocytochemical techniques.Sprague-Dawley male rats were killed at 4, 24 or 48 h after TBI (450 g from 2 m, Marmarou's model). Semiquantitative analysis of our in situ hybridization results indicated a 2.5- and a 2.0-fold increase in ET-1 mRNA content in the hippocampus and cortex respectively which persisted up to 48 h post TBI. At 4 and 24 h after TBI enzyme-linked immunosorbent assay showed a tendency for increased ET-1 synthesis. In animals subjected to TBI, qualitative immunocytochemical analysis revealed a shift in ET-1 expression from astrocytes (in control animals) to endothelial cells, macrophages and neurons. Astrocytes and macrophages were identified unequivocally by using double immunofluorescence revealing ET-1 and glial fibrillary acidic protein or ED-1, respectively, the markers being specific for these cellular types. While this redistribution was most prominent at 4 and 24 h post TBI, at 48 h the endothelial cells remained strongly ET-1 immunopositive. The results suggest that cellular types which in the intact animal synthesize little or no ET-1 provide novel sources of the peptide after TBI. These sources may contribute to the sustained cerebrovascular hypoperfusion observed post TBI.
Petrov
Th
T
Department of Anatomy and Cell Biology, Wayne State University School of Medicine, 540 East Canfield Avenue, Detroit, MI 48201, USA. tpetrov@med.wayne.edu
Steiner
J
J
Braun
B
B
Rafols
J A
JA
D000818:Animals; D001930:Brain Injuries / Q000378:metabolism*; D002540:Cerebral Cortex / Q000737:chemistry / Q000378:metabolism*; D019332:Endothelin-1 / Q000032:analysis* / Q000096:biosynthesis / Q000502:physiology; D006624:Hippocampus / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley
D019332:Endothelin-1; D012333:RNA, Messenger