[Neuroprotective effect of naloxone in brain damage caused by repeated febrile seizure].
OBJECTIVE
The brain damage caused by repeated febrile seizure (FS) during developing age is harmful to the intellectual development of children. So how to decrease the related damage is a very important issue. The main purpose of the present study was to find out whether the non-specific opiate antagonist naloxone at low dose has the neuroprotective effect on seizure-induced brain damage.


METHODS
Warm water induced rat FS model was developed in this study. Forty-seven rats were randomly divided into two groups: normal control group (n = 10) and hyperthermic seizure groups (n = 37). The latter was further divided into FS control group (n = 13) and naloxone-treated group (n = 24). The dose of naloxone is different in two naloxone-treated groups (12/each group), in one group the dose was 1 mg/kg, in the other one 2 mg/kg. Seven febrile seizures were induced in each rat of hyperthermic seizure groups with the interval of 2 days. The rats were weighed and injected intraperitoneally with naloxone once the FS occurred in naloxone-treated group, while the rats of the other groups were injected with 0.9% sodium chloride. Latency, duration and grade of FS in different groups were observed and compared. HE-staining and the electron microscopy (EM) were used to detect the morphologic and ultrastructural changes of hippocampal neurons.


RESULTS
In naloxone-treated group, the rats' FS duration and FS grade (5.02 +/- 0.63, 2.63 +/- 0.72) were significantly lower (t = 5.508, P < 0.01; t = 8.439, P < 0.01) than those in FS control group (7.70 +/- 2.25 min, 4.52 +/- 0.49), although no significant gap was observed on FS latency between them. In FS control group, HE-staining pattern of hippocampal CA(1) and CA(2) showed lots of disordered neurons with confused polarity and vacuoles formed. Nuclei were with various size, some rounded and some oblong. While in naloxone-treated groups, the arrangement of neurons was regular, only a small quantity of neurons had changed polarity and vacuoles formed. Most nuclei were oblong and in the same size. In hippocampal CA(1) region and dentate gyrus of rats from FS control group, EM showed that the most mitochondrion volumes obviously increased with vacuoles formed, the matrix condensed, the ridge obscured or disappeared, apoptosis body emerged. Minor to moderate dilation of rough endoplasmic reticulum and Golgi's complex was also observed. However, in naloxone-treated groups, the number of neurons with swollen mitochondrion and endoplasmic reticulum was much fewer than that in FS control group. No apoptosis body was observed. The comparison between them showed much lighter brain damage in naloxone-treated groups than in FS control group.


CONCLUSIONS
Although low-dose naloxone could not totally stop the occurrence of febrile seizure, it could lighten the brain damage resulted from repeated FS to some extent.
Shan
Ying
Y
Department of Pediatrics, First Hospital, Peking University, Beijing 100034, China.
Qin
Jiong
J
Chang
Xing-zhi
XZ
Yang
Zhi-xian
ZX
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D008297:Male; D023421:Models, Animal; D009270:Naloxone / Q000494:pharmacology* / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D003294:Seizures, Febrile / Q000188:drug therapy* / Q000503:physiopathology; D016896:Treatment Outcome
D009292:Narcotic Antagonists; D018696:Neuroprotective Agents; D009270:Naloxone