The role of trapidil on neuronal apoptosis in neonatal rat model of hypoxic ischemic brain injury.
BACKGROUND
Hypoxic ischemic brain injury (HIBI) is a common cause of neonatal mortality and morbidity. Trapidil is an antiplatelet agent and several studies demonstrate the beneficial effect of trapidil in various forms of tissue injury. The effects of trapidil on neuronal apoptosis in HIBI have not been reported previously.


OBJECTIVE
The aim of this study is to evaluate the effect of trapidil on neuronal apoptosis in neonatal rat model of HIBI.


METHODS
Seven-day-old Wistar rat pups were subjected to right common carotid artery ligation and hypoxia (92% nitrogen and 8% oxygen) for 2h. They were treated with trapidil or saline either immediately before or after hypoxia. In sham group animals, neither ligation, nor hypoxia were performed. Neuronal apoptosis was evaluated by the terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) and caspase-3 staining methods.


RESULTS
Trapidil treatment either before or after hypoxia results in significant reduction of the numbers of apoptotic cells in both hemispheres, when it is compared with saline treatment group. The numbers of apoptotic cells in right hemispheres in all groups are significantly higher than that in the left hemispheres.


CONCLUSIONS
These results show that trapidil administration either before or after hypoxia reduces neuronal apoptosis and we propose that trapidil may be a novel approach for the therapy of HIBI.
Atici
Aytug
A
Department of Pediatrics, Division of Neonatology, University of Mersin School of Medicine, Mersin, Turkey. aatici@superonline.com
Bozlu
Gulcin
G
Turhan
Ali Haydar
AH
Polat
Ayse
A
Nayci
Ali
A
Okuyaz
Cetin
C
Taskinlar
Hakan
H
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism; D002452:Cell Count; D004195:Disease Models, Animal; D005260:Female; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar; D014192:Trapidil / Q000008:administration & dosage* / Q000627:therapeutic use; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000627:therapeutic use
D014665:Vasodilator Agents; D053148:Caspase 3; D014192:Trapidil