[Ephedrine and naloxone promote nerve remodeling after cerebral ischemia].
OBJECTIVE
To investigate the effects of ephedrine combined with various doses of naloxone on neural plasticity in rats after cerebral ischemia/reperfusion injury to explore the possibility of synergistic effect about ephedrine combined with naloxone, promoting the optimum ratio of neural remodeling and its molecular mechanism.


METHODS
A total of 192 healthy adult Sprague-Dawley rats, 220-250 g, were used to establish models of left middle cerebral artery occlusion using the suture occlusion method. Were randomly divided into 8 groups: the rats were intraperitoneally injected with 1.5 mg x kg(-1) x d(-1) ephedrine (ephedrine group), with 0.1, 0.2, 0.3 mg x kg(-1) x d(-1) naloxone (low, moderate and high doses of naloxone groups) , with 1.5 mg x kg(-1) x d(-1) ephedrine + 0.1, 0.2, 0.3 mg x kg(-1) x d(-1) naloxone (ephedrine + low, moderate and high doses of naloxone groups), and with 0.5 mL saline (model group), respectively. At 1-4 weeks following cerebral ischemia, sensorimotor integration in rats was assessed using the beam walking test, brain-derived neurotrophic factor (BDNF) expression was detected in the hippocampal CA3 area using immunohistochemistry 1-4 weeks after surgery, immunofluorescence method of detecting ischemic hemisphere hippocampal expression, The number of nerve cells apoptosis was detected using TUNEL assay.


RESULTS
BWT, BDNF, TUNEL assay results showed three doses of naloxone group had no significant effect, the effects increased together with the quantitative ephedrine, and had the amount-effect relationship, in which ephedrine + high dose of naloxone group the recovery of movement was fastest, BDNF expression in the best and ischemic apoptosis in the hippocampus at least, ischemic injury to the minimum, speed up the process of neural remodeling.


CONCLUSIONS
The ephedrine and ephedrine + naloxone groups were accelerated motor function recovery rate in rat after cerebral ischemia, and the promotion of neural remodeling is closely related to the expression of BDNF, inhibit apoptosis in ischemic area, and with the increase of naloxone amount of additives, its role more clearly, the mechanism may be related to the dose of naloxone can significantly inhibit the ischemic area of apoptosis in early cerebral ischemia, so had the positive synergy effect with ephedrine to speed up the formation of neural remodeling.
Chen
Yuxia
Y
Department of Convalescent Center, Children's Hospital, Chongqing Medical University, Chongqing 400014, China.
Xiao
Nong
N
Lin
Liyun
L
Liu
Ling
L
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004809:Ephedrine / Q000008:administration & dosage*; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D008297:Male; D009270:Naloxone / Q000008:administration & dosage*; D009473:Neuronal Plasticity / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D019208:Brain-Derived Neurotrophic Factor; D009270:Naloxone; D004809:Ephedrine