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Intracerebral hemorrhage-induced neuronal death.
- Source :
-
Neurosurgery [Neurosurgery] 2001 Apr; Vol. 48 (4), pp. 875-82; discussion 882-3. - Publication Year :
- 2001
-
Abstract
- Objective: The mechanisms underlying neural injury in intracerebral hemorrhage (ICH) remain uncertain. The present two-part study investigated cell death in the region of ICH and its association with caspase-3 activation.<br />Methods: ICH was produced in adult rats by injection of 100 microl of autologous blood or saline into the right basal ganglia. The animals' brains were removed at 6 hours or at 1, 3, 7, or 14 days after hemorrhage. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin in situ nick end-labeling (TUNEL) was used to detect deoxyribonucleic acid (DNA) fragmentation. TUNEL-positive cells were quantified. Caspase-3 activation was measured by Western blotting and immunohistochemistry. Double labeling was used to compare TUNEL with caspase-3 distribution and to identify the cell types affected. TUNEL-positive cells were also quantified at 6 hours, 1 day, and 3 days after injection of 5 U of thrombin into the right basal ganglion.<br />Results: At 6 hours, TUNEL-positive cells appeared in the ICH model (but not in the saline control brains) and were present for more than 2 weeks after ICH, peaking at 3 days. Western blot analysis revealed that the increase in immunoreactivity for the activated caspase-3 precedes that of DNA fragmentation, peaking at 1 day after ICH and declining thereafter. Immunohistochemistry analysis showed nucleus translocation of caspase-3 after ICH. Double-labeling studies demonstrated that both neurons and astrocytes surrounding the clot were TUNEL-positive. In addition, TUNEL and caspase-3 were colocalized in the same cells. Intracerebral thrombin injection elicited DNA fragmentation similar to that observed after the injection of blood.<br />Conclusion: Double-strand breaks in genomic DNA and induction of caspase-3 were demonstrated adjacent to parenchymal hematoma in the animals' brains. These results provide evidence that cell loss after ICH is associated with activation of caspase-3.
Details
- Language :
- English
- ISSN :
- 0148-396X
- Volume :
- 48
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Neurosurgery
- Publication Type :
- Academic Journal
- Accession number :
- 11322448
- Full Text :
- https://doi.org/10.1097/00006123-200104000-00037