RT Journal Article
SR Electronic
T1 Caspase-8 and Caspase-3 Are Expressed by Different Populations of Cortical Neurons Undergoing Delayed Cell Death after Focal Stroke in the Rat
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 5932
OP 5941
DO 10.1523/JNEUROSCI.19-14-05932.1999
VO 19
IS 14
A1 James J. Velier
A1 Julie A. Ellison
A1 Kristine K. Kikly
A1 Patricia A. Spera
A1 Frank C. Barone
A1 Giora Z. Feuerstein
YR 1999
UL http://www.jneurosci.org/content/19/14/5932.abstract
AB 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.