title: Astrocyte-specific expression of survivin after intracerebral hemorrhage in mice: a possible role in reactive gliosis?
abstract: Intracerebral hemorrhage (ICH), the most common form of hemorrhagic stroke, accounts for up to 15% of all strokes. Despite maximal surgical intervention and supportive care, ICH is associated with significant morbidity and mortality, in part due to a lack of viable treatment options. Astrogliosis, a key feature of secondary injury that is characterized by glial proliferation, is a poorly-defined process that may produce both beneficial and detrimental outcomes after brain injury. Using a pre-clinical murine model of collagenase-induced ICH, we demonstrate a delayed upregulation of survivin, a key molecule involved in tumor cell proliferation and survival, by 72 h post-ICH. Notably, this increase in survivin expression was prominent in GFAP-positive astrocytes, but absent in neurons. Survivin was not expressed at detectable levels in the striatum of sham-operated mice. The expression of survivin after ICH was temporally and spatially associated with the expression of proliferating cell nuclear antigen (PCNA), an established marker of cellular proliferation. Moreover, the survivin expression was co-localized in proliferating astrocytes as evidenced by triple-label immunohistochemistry. Finally, shRNA-mediated silencing of survivin expression attenuated PCNA expression and reduced cellular proliferation in human glial cells. Together, these data suggest a potentially novel role for survivin in functionally promoting astrocytic proliferation after ICH.
authors.affiliation: Department of Neurosurgery, Georgia Health Sciences University, Augusta, USA. sramesh@georgiahealth.edu
authors.forename: Sangeetha
authors.initials: S
authors.lastname: Sukumari-Ramesh
authors.forename: Cargill H
authors.initials: CH
authors.lastname: Alleyne
authors.forename: Krishnan M
authors.initials: KM
authors.lastname: Dhandapani
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001253:Astrocytes / Q000378:metabolism*; D015153:Blotting, Western; D002455:Cell Division / Q000502:physiology; D002467:Cell Nucleus / Q000502:physiology; D017364:Collagenases; D003600:Cytosol / Q000378:metabolism; D005822:Genetic Vectors; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000473:pathology*; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins / Q000096:biosynthesis* / Q000235:genetics; D020300:Intracranial Hemorrhages / Q000139:chemically induced / Q000378:metabolism*; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D009457:Neuroglia / Q000502:physiology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics; D000077022:Survivin
chemical_list: C117749:Birc5 protein, mouse; D005904:Glial Fibrillary Acidic Protein; D051034:Inhibitor of Apoptosis Proteins; D018809:Proliferating Cell Nuclear Antigen; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D000077022:Survivin; D017364:Collagenases