Neuroprotective effect of cycloheximide on hypoxic-ischemic brain injury in neonatal rats.
This study was done to determine the neuroprotective effect of cycloheximide on neonatal hypoxic-ischemic brain injury. Seven day-old newborn rat pups were subjected to 90 min of 8% oxygen following a unilateral carotid artery ligation. The extent of cerebral infarction was evaluated at 1 and 4 week of recovery. Apoptosis was identified by performing terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining and flow cytometry with a combination of fluoresceinated annexin V and propidium iodide. Brain infarction area was significantly increased at 4 week compared to 1 week after hypoxia-ischemia in the control group. With cycloheximide treatment, the number of TUNEL positive cells in the ipsilateral cerebral cortex at 48 hr and peri-infarct area at 1 and 4 week of recovery was significantly reduced, both apoptotic and necrotic cells by flow cytometry 48 hr after the injury were significantly reduced, and the extent of cerebral infarction at 1 and 4 week of recovery was also significantly attenuated compared to the hypoxia-ischemia control group. In summary, our data suggest that apoptosis plays an important role in the development of delayed infarction, and inhibition of apoptosis with cycloheximide significantly reduces the ensuing cerebral infarction in a newborn rat pup model of cerebral hypoxia-ischemia.
Park
Won Soon
WS
Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul, Korea.
Sung
Dong Kyung
DK
Kang
Saem
S
Koo
Soo Hyun
SH
Kim
Yu Jin
YJ
Lee
Jang Hoon
JH
Chang
Yun Sil
YS
Lee
Munhyang
M
D000818:Animals; D000831:Animals, Newborn; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D020520:Brain Infarction / Q000473:pathology / Q000517:prevention & control; D003513:Cycloheximide / Q000494:pharmacology*; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020287:In Situ Nick-End Labeling; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011419:Propidium; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D017304:Annexin A5; D018696:Neuroprotective Agents; D011419:Propidium; D003513:Cycloheximide