-transparent.png){kind=logo}
OBJECTIVE The mechanisms of excitotoxic cell death in cerebral ischemia are poorly understood. In addition to necrosis, apoptotic cell death may occur. The purpose of this study was to determine whether an established model of cerebral hypoxia-ischemia in the neonatal rat demonstrates any features of apoptosis. METHODS Seven-day-old neonatal rats underwent bilateral, permanent carotid ligation followed by 1 hour of hypoxia, and their brains were examined 1, 3, and 4 days after hypoxia-ischemia. The severity of ischemic damage was assessed in the dentate gyrus and frontotemporal cortex by light microscopy. Immunocytochemistry was performed to detect the cleavage of actin by caspases, a family of enzymes activated in apoptosis. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) reactivity was examined in the cortical infarction bed and dentate gyrus. Neonatal rat brain DNA was run on agarose gel electrophoresis to detect DNA fragmentation. Ethidium bromide-staining and electron microscopy were used to determine whether apoptotic bodies, 1 of the hallmarks of apoptosis, were present. RESULTS The frontotemporal cortex displayed evidence of infarction, and in most rats the dentate gyrus showed selective, delayed neuronal death. Immunocytochemistry demonstrated caspase-related cleavage of actin. TUNEL and DNA electrophoresis provided evidence of DNA fragmentation. Ethidium bromide-staining and electron microscopy confirmed the presence of chromatin condensation and apoptotic bodies. CONCLUSIONS Features of apoptosis are present in the described model of cerebral hypoxia-ischemia. Apoptosis may represent a mode of ischemic cell death that could be the target of novel treatments that could potentially expand the therapeutic window for stroke.
M R Pulera, and
L M Adams, and
H Liu, and
D G Santos, and
R N Nishimura, and
F Yang, and
G M Cole, and
C G Wasterlain
August 1998,
Zhonghua yi xue za zhi,
M R Pulera, and
L M Adams, and
H Liu, and
D G Santos, and
R N Nishimura, and
F Yang, and
G M Cole, and
C G Wasterlain
August 2008,
Neuroscience letters,
M R Pulera, and
L M Adams, and
H Liu, and
D G Santos, and
R N Nishimura, and
F Yang, and
G M Cole, and
C G Wasterlain
June 2004,
Zhonghua er ke za zhi = Chinese journal of pediatrics,
M R Pulera, and
L M Adams, and
H Liu, and
D G Santos, and
R N Nishimura, and
F Yang, and
G M Cole, and
C G Wasterlain
November 2003,
Journal of applied physiology (Bethesda, Md. : 1985),
M R Pulera, and
L M Adams, and
H Liu, and
D G Santos, and
R N Nishimura, and
F Yang, and
G M Cole, and
C G Wasterlain
April 1995,
Brain research,
M R Pulera, and
L M Adams, and
H Liu, and
D G Santos, and
R N Nishimura, and
F Yang, and
G M Cole, and
C G Wasterlain
December 2001,
Brain research. Developmental brain research,
M R Pulera, and
L M Adams, and
H Liu, and
D G Santos, and
R N Nishimura, and
F Yang, and
G M Cole, and
C G Wasterlain
March 2011,
Stroke,
M R Pulera, and
L M Adams, and
H Liu, and
D G Santos, and
R N Nishimura, and
F Yang, and
G M Cole, and
C G Wasterlain
January 2001,
Biology of the neonate,
M R Pulera, and
L M Adams, and
H Liu, and
D G Santos, and
R N Nishimura, and
F Yang, and
G M Cole, and
C G Wasterlain
January 2014,
Neonatology,
M R Pulera, and
L M Adams, and
H Liu, and
D G Santos, and
R N Nishimura, and
F Yang, and
G M Cole, and
C G Wasterlain
January 2010,
The Journal of neuroscience : the official journal of the Society for Neuroscience,
