[Changes of dynorphinA1-13 on the treatment of hypoxic-ischemic brain injury by the brain-derived neurotrophic factor in neonatal rats].
OBJECTIVE
To explore changes and role of dynorphinA(1 - 13) on the experimental treatment of hypoxic-ischemic brain injury (HIBI) by intracerebral transplantation of genetically modified myoblasts expressing and secreting brain-derived neurotrophic factor (BDNF) in neonatal rats.


METHODS
Seven-day-old Sprague-Dawley rats were randomly divided into HIBI + BDNF group (A), HIBI + BDNF + U50, 488H group (B), HIBI group (C) and sham-operated group (D). Pups were intracerebroparenchymally transplanted with either genetically modified myoblasts producing and secreting BDNF (A, B) or their parent cells (C) at 0.8 microl (4 x 10(4)/microl) followed by a cerebroventricular microinjection of opioid kappa receptor agonist U50, 488H (0.5 microg, B) or vehicles (A, C) shortly after HIBI undergone by a permanent ligation of left common carotid artery followed by a 2.5 h inhalation of humidified 8%O(2) + 92%N(2) at 37 degrees C. Water contents of the brain, levels of malondiadehye (MDA) and cell apoptosis were investigated 1 d after the procedure. Contents of dynorphinA(1 - 13)-like immunoreactivity (ir-DynA(1 - 13)) at the left and right cortex and hippocampus were tested by radioimmunoassay 0, 1, 3 d postinjury.


RESULTS
Levels of ir-DynA(1 - 13) in left cortex were markedly increased in group A, B or C when compared to group D different times after the procedure and markedly decreased in group A or B vs group C 1, 3 d after the procedure. Levels of ir-DynA(1 - 13) in left hippocampus were also markedly increased in group A, B and C (0 d), B, C (1 d) and C (3 d) when compared to group D and markedly decreased in group A (1 d) and B (3 d) vs group C, respectively. Water contents, MDA levels and percentage of cell apoptosis were significantly higher in group A, B or C than those in group D and these parameters were obviously lowered in group A compared to group C in the left brain 1 d after the procedure. There were no significant differences of water contents and levels of MDA between group B and C but significantly lowered percentage of cell apoptosis in group B was seen when compared to group C in the left brain.


CONCLUSIONS
It is suggested that dynorphinA(1 - 13) participates in the pathophysiological process of HIBI. One of the pathways of the beneficial effects of intracerebral transplantation of genetically modified myoblasts producing BDNF on HIBI lies on the inhibition of the function of dynorphin A(1 - 13) through the binding of kappa opioid receptor.
Hong
Xinru
X
Department of Pediatrics, Fuzhou General Hospital, Fuzhou 350025, China.
Zheng
Ling
L
Chen
Xinmin
X
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004399:Dynorphins / Q000378:metabolism*; D005260:Female; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D019208:Brain-Derived Neurotrophic Factor; D010446:Peptide Fragments; D008315:Malondialdehyde; C026843:dynorphin (1-13); D004399:Dynorphins; D010100:Oxygen