title: Neuroprotective anti-apoptosis effect of estrogens in traumatic brain injury.
abstract: Traumatic brain injury (TBI) is a leading cause of death and functional disability in western countries, affecting mostly young patients. Despite intense and sustained efforts deployed for the development of new therapeutic strategies, no clinical benefit has been shown by any of the investigated compounds. Increasing attention has been drawn during the past two decades to the neuroprotective effects of estrogens, although most of the available data relate to ischemic brain injury. The purpose of the present study was to investigate the potential neuroprotective value of estrogens in TBI as a therapeutic modality. For this purpose, a contusion was created in the parietal cortex by dynamic cortical deformation in two groups of 10 Sprague-Dawley male rats. Following the injury, treated animals received conjugated estrogens for 3 days, using a subcutaneously implanted osmotic pump. Animals were then sacrificed, and TUNEL, anti-active Caspase 3, bcl-2, and bax labeling were performed in paraffin-embedded brain sections, allowing for comparative and quantitative analysis. In estrogen-treated animals, there was a marked and significant reduction of apoptosis in comparison with non-treated animals. The reduction in TUNEL and active Caspase 3 staining was similar and close to 50%. Optical analysis of histological slides prepared by bcl-2 labeling showed a significant increase in bcl-2 expression in estrogen-treated animals compared to non-treated animals. On the contrary, bax expression was not influenced by hormonal treatment, and no difference could be noticed between the two groups. These results support the potential therapeutic value of estrogens in TBI and further clarify their mode of action.
authors.affiliation: Acute Brain Injury Research Laboratory, Department of Physiology, Bruce Rappaport Faculty of Medicine, Technion, Israel. j_soustiel@rambam.health.gov.il
authors.forename: Jean F
authors.initials: JF
authors.lastname: Soustiel
authors.forename: Eilam
authors.initials: E
authors.lastname: Palzur
authors.forename: Ori
authors.initials: O
authors.lastname: Nevo
authors.forename: Itzhak
authors.initials: I
authors.lastname: Thaler
authors.forename: Eugene
authors.initials: E
authors.lastname: Vlodavsky
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology* / Q000517:prevention & control; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis; D004967:Estrogens / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D051028:bcl-2-Associated X Protein
chemical_list: C494828:Bax protein, rat; D004967:Estrogens; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases