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Caspase-8 and caspase-3 are expressed by different populations of cortical neurons undergoing delayed cell death after focal stroke in the rat.
- Source :
-
The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 1999 Jul 15; Vol. 19 (14), pp. 5932-41. - Publication Year :
- 1999
-
Abstract
- A number of studies have provided evidence that neuronal cell loss after stroke involves programmed cell death or apoptosis. In particular, recent biochemical and immunohistochemical studies have demonstrated the expression and activation of intracellular proteases, notably caspase-3, which act as both initiators and executors of the apoptotic process. To further elucidate the involvement of caspases in neuronal cell death induced by focal stroke we developed a panel of antibodies and investigated the spatial and temporal pattern of both caspase-8 and caspase-3 expression. Our efforts focused on caspase-8 because its "apical" position within the enzymatic cascade of caspases makes it a potentially important therapeutic target. Constitutive expression of procaspase-8 was detectable in most cortical neurons, and proteolytic processing yielding the active form of caspase-8 was found as early as 6 hr after focal stroke induced in rats by permanent middle cerebral artery occlusion. This active form of caspase-8 was predominantly seen in the large pyramidal neurons of lamina V. Active caspase-3 was evident only in neurons located within lamina II/III starting at 24 hr after injury and in microglia throughout the core infarct at all times examined. Terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling, gel electrophoresis of DNA, and neuronal cell quantitation indicated that there was an early nonapoptotic loss of cortical neurons followed by a progressive elimination of neurons with features of apoptosis. These data indicate that the pattern of caspase expression occurring during delayed neuronal cell death after focal stroke will vary depending on the neuronal phenotype.
- Subjects :
- Animals
Apoptosis
Brain Ischemia pathology
Caspase 3
Caspase 8
Caspase 9
Caspases biosynthesis
Cell Death
Cerebral Cortex pathology
Functional Laterality
Gene Expression Regulation, Enzymologic
Immunohistochemistry
Ischemic Attack, Transient enzymology
Ischemic Attack, Transient pathology
Male
Neurons pathology
Rats
Rats, Inbred SHR
Reperfusion
Time Factors
Brain Ischemia enzymology
Caspases genetics
Cerebral Cortex enzymology
Neurons enzymology
Subjects
Details
- Language :
- English
- ISSN :
- 1529-2401
- Volume :
- 19
- Issue :
- 14
- Database :
- MEDLINE
- Journal :
- The Journal of neuroscience : the official journal of the Society for Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 10407032