title: Nestin expression after experimental intracerebral hemorrhage.
abstract: The current study examines nestin expression after intracerebral hemorrhage (ICH), the role of different blood components in nestin upregulation, and the possibility that low doses of thrombin that induce tolerance to brain injury (thrombin preconditioning) might also induce nestin expression. Adult male Sprague-Dawley rats received an intracaudate injection of either whole blood, thrombin (1 or 5 U) or red blood cells (RBCs). Animals were sacrificed for single and double labeling immunohistochemistry to identify which cells express nestin, and for Western blotting to quantify nestin expression. By immunohistochemistry, nestin immunoreactivity was present in large numbers of astrocytes, surrounding the hematoma from day 3 to 1 week after ICH. After 2 weeks, nestin immunoreactivity was co-localized with a neuronal marker (neuronal specific enolase). By Western blot analysis, nestin was strongly expressed at day 3 (P<0.01) and 1 week (P<0.01), and expression persisted for at least 1 month (P<0.05). Intracerebral injection of thrombin or lysed RBCs resulted in a marked increase in nestin expression. Interestingly, injection of a low dose of thrombin that induces brain tolerance also upregulated nestin. The ICH-induced nestin expression in astrocytes may reflect an early response of these cells to injury, while the delayed expression in neurons might be a part of the adaptative response to injury perhaps leading to recovery of function. Nestin induction by a low dose of thrombin suggests that specific receptor-mediated pathways are involved in inducing nestin expression and that nestin may play a role in thrombin preconditioning.
authors.affiliation: Department of Neurosurgery, University of Michigan, 5550 Kresge I, Ann Arbor, MI 48109-0532, USA.
authors.forename: Takehiro
authors.initials: T
authors.lastname: Nakamura
authors.forename: Guohua
authors.initials: G
authors.lastname: Xi
authors.forename: Ya
authors.initials: Y
authors.lastname: Hua
authors.forename: Julian T
authors.initials: JT
authors.lastname: Hoff
authors.forename: Richard F
authors.initials: RF
authors.lastname: Keep
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001479:Basal Ganglia / Q000378:metabolism / Q000473:pathology; D001804:Blood Transfusion, Autologous / Q000379:methods / Q000662:veterinary; D015153:Blotting, Western; D002543:Cerebral Hemorrhage / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000378:metabolism; D007839:Functional Laterality; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins / Q000378:metabolism*; D008297:Male; D009419:Nerve Tissue Proteins; D064231:Nestin; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013917:Thrombin / Q000009:adverse effects*; D013997:Time Factors
chemical_list: D005904:Glial Fibrillary Acidic Protein; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; D013917:Thrombin; D010751:Phosphopyruvate Hydratase