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Objective To explore the effect of leptin on neurorehabilitation and on the expression of dopamine receptor D2 (Drd2) and cytosolic phospholipase A2 (cPLA2) in the cerebral cortex after convulsive brain injury.Methods Five-day-old Sprague-Dawley rats were randomly assigned to a control group (CONT),a leptin injection control group (Leptin),a seizure group (RS),or a seizure with leptin injection group (RS+Leptin).The rats in the RS group and the RS+Leptin group were injected intraperitoneally with lithium chloride (5 mEq/kg) and pilocarpine (320 mg/kg) on day 6,and then scopolamine methyl chloride (1 mg/kg) 30 minutes later to block the peripheral effect of pilocarpine.The animals in the Leptin and RS+Leptin groups were then given leptin (4 mg/kg,i.p.) injections daily from days 8 to 14.The animals' plane righting reflex and negative geotaxis reaction reflex were observed on day 23.The open field test was performed on D30.Real-time reverse-transcription polymerase chain reactions (RT-PCRs) were used to detect the expression of Drd2 and cPLA2 mRNA in the rats' cerebral cortexes on day 34.Results There were significant differences in the plane righting times and negative geotaxis reflexes among the four groups,with those in the RS and RS+Leptin groups significantly longer than among the controls.Both reflexes were significantly quicker in the RS + Leptin group than in the RS group.There were also significant differences in the locomotor scores in the open field test among the four groups,with the average scores in the RS and RS+Leptin groups significantly higher than in the other two groups.The RS+Leptin group's average was significantly higher than that of the RS group.The expression of Drd2 was significantly higher in the leptin,RS and leptin +RS groups than in the control group,and that of the RS and leptin+RS groups was significantly higher than that of the Leptin control group.The expression of cPLA2 in the Leptin and RS groups was significantly higher than in the CONT group,while that of the RS + Leptin group was significantly lower than in the Leptin and RS groups.Conclusions Leptin has a neurorehabilitation effect on the behavioral impairment caused by seizures,at least in neonatal rats.Its neuroprotective mechanism may be related to the regulation of Drd2-mediated cPLA2 expression in the cerebral cortex.
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Objective To explore the intervention effect of ketogenic diet (KD) on neurobehavioral damages after flurothyl-induced neonatal recurrent seizures in rats and on the expression of ZIP7.Methods Postnatal day 8 SD rats (n=24) were divided into four groups randomly:normal group (NS+ND group),non-seizure and ketogenic diet group (NS+KD group),seizure and normal diet group (RS+ND group),seizure and ketogenic diet group (RS+KD group),n=6 in eacb group.At postnatal day 31,the grip-strength test and open field test were monitored.At postnatal day 32,rats were sacrificed and the expression of ZIP7 protein level in cerebral cortex was detected with Western blot.Results (1) The grip-strength test:compared with NS+ND group ((32.67±2.42) s),the time needed to hold on glass bar in RS+ND group ((19.17±2.48) s) was shorter significantly (P＜0.05).Compared with RS+ND group,the time needed to hold on glass bar in RS+KD group ((26.25±2.87) s) was significantly longer (P＜0.05).(2) Open field test:compared with NS+ ND group ((2.00± 0.63) times),the times of grooming in RS+ND group ((4.00±0.63) times) were more (P＜0.05).Compared with RS+ND group,the times of grooming in the RS+KD group ((2.17±0.75) times) were fewer (P＜0.05).(3)Western blot:compared with NS +ND group,the level of ZIP7 of the RS+ND group in cerebral cortex were lower (P＜0.05).Compared with RS+ND group,the level of ZIP7 of the RS+KD group in cerebral cortex were higher (P＜0.05).Conclusion Neonatal recurrent seizures may damage neurobehavior,and the neuroprotective effects of ketogenic diet may be associated with the increasing of ZIP7 in cerebral cortex.
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Objective To systematic evaluation the antiepileptic drug valproic acid and topiramate effects on body weight and plasma leptin levels.Methods By searching the Cochrane Library,PubMed,EMBASE,CNKI,VIP Chinese Scientific Journals Database and Articles Database (from building a database to August 1,2014),qualified RCT was chosen from those articles according to inclusion and exclusion criterias and evaluated their quality.Then the meta-analysis was performed by Rev Man 5.3.Results (1) A total of 70 documents retrieved for the evaluation,12 of the literatures could be incorporated into the Meta-analysis,including a total of 634 participants,9 literatures using valproate to treat epilepsy,4 literatures used topiramate.(2)Meta-analysis:compared with other drugs,valproic acid treatment increased body mass index and leptin level in patients with epilepsy,BMI combined MD=0.88(95％ CI:0.45-1.31),leptin level in the combined MD=0.58(95％ CI:0.07-1.09);compared with other drugs,topiramate affect body mass index and leptin level in patients with epilepsy had no statical difference,BMI combined MD=-0.02 (95％ CI:-0.62-0.58),leptin levels in the combined MD =-0.05(95％ CI:-0.31-0.20).Conclusion Antiepileptic drug valproic acid may increase patients' BMI and serum leptin levels,yet topiramate in do not have influence in patients BMI and serum leptin levels;more basic and clinical researches are needed to explore serum leptin levels and the exact therapy mechanisms of antiepileptic drugs for clinicians to select antiepileptic drugs.
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Objective To investigate dynamic expressions of cortex clusterin (CLU) and intervention effect of ketogenic diet (KD) on neonatal rats with recurrent seizures.Methods Thirty-six-8-day postnatal SD rats were randomly divided into 3 groups:normal control group (NS + ND group,n =12),and the recurrent-seizure and normal diet group (RS + ND group,n =12),and the recurrent-seizure and KD group (RS + KD group,n =12).From 9 d,rats in RS + ND group and RS + KD group were subjected to recurrent seizures induced by volatile flurothyl 30 min each day for consecutive 8 days.Rats in NS + ND group were placed into the container for an equal amount of time to their counterpart without exposure to flurothyl.Scores on neurological behaviors at 35 days postnatally were examined.CLU protein levels in cerebral cortex were determined by Western blot at 58 days postnatally.Results Neurodevelopmental indicators analysis:in the plane righting experiment,there were significant differences between NS + ND group [(1.03 ± 0.54) s],R S + KD group [(0.89 ± 0.16) s] and RS + ND group [(0.64 ± 0.30) s] about the time of plane righting (all P ＜ 0.05) ; in the negative geotaxis reaction experiment,the rats of NS + ND group [(1.92 ± 0.90) s],and RS + KD group [(5.17 ± 0.72) s] about the time of negative geotaxis reaction were significantly different compared with RS + ND gouup [(7.33 ± 0.65) s] (all P ＜ 0.01).In the cliff avoidance test,there were significant differences between NS + ND group,R S + KD group [(4.33 ± 2.54) s,(8.75 ± 2.26) s] and R S + ND group [(16.58 ± 4.25) s] about the time of cliff avoidance (all P ＜ 0.01).Western blot showed that the expression of CLU in cerebral cortex of the RS + ND group [(2.24 ± 0.53) s] was obviously increased compared with NS + ND group [(1.44 ± 0.11) s] (P ＜0.01),and there also had significant difference between RS + KD group [(1.56 ±0.24) s] and RS + ND group (P ＜ 0.05).Conclusions It shows that the up-regulated expression of CLU in cerebral cortex may be associated with recurrent neonatal seizure-induced brain damage,while KD may protect them from recurrent neonatal seizure-induced brain damage by down-regulating expression of CLU.
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Objective To compare the effect of routine ketogenic diet and every other day ketogenic diet on neurobehavioral damage induced by recurrent seizures in neonatal rats.Methods 48 postnatal day 8 (P8) SD rats were randomly divided into four groups with 12 in each group:the control group (CONT),the recurrent seizure group(RS+ND),recurrent seizure + routine ketogenic diet group(RS+KD) and recurrent seizure+ every other day ketogenic diet group(RS+KOD).The recurrent seizures model was induced by flurothyl at p9 and last for 8 days.After a day of fasting the postnatal 28 day rats were placed on either ordinary or ketogenic diet according to packet design.Plane righting experiment,cliff avoidance test and negative geotaxis test were used to assess the neurobehavioral performance at p35.Results (1) Plane righting experiment:the plane fighting time of RS+ ND group ((0.17±0.39) s) was significantly shorter than that of NS+ND group ((0.67 ±0.49) s) (P＜0.05) ; and the plane righting time of RS+KD group((0.58±0.52) s) was significantly longer than that of RS+ND group ((0.17±0.39) s) (P＜0.05).There was no statistical significance between RS+KOD group((0.17±0.39) s) and RS+ND group ((0.17±0.39) s) (P＞0.05).(2) Cliff avoidance test:the cliff avoidance time of RS+ND group ((12.58±4.83) s)was significantly longer than that of NS+ND group ((1.92±0.90) s),RS+KD group((3.33± 1.50)s) and RS+ KOD group (P＜0.05) ;and the cliff avoidance time of RS+KOD group((5.58± 1.93)s) was significant longer than that of RS+KD group ((3.33± 1.50) s) (P＜0.05).(3) Negative geotaxis test:the negative geotaxis time of RS+NDgroup((3.17±1.70)s) was significantly longer than that of NS+ND group((1.42±0.67) s) and RS+KD group ((1.42±0.52)s) (P＜0.05).There was no statistical significance between RS+KOD group and RS+ND group(P＞0.05).Conclusion The ketogenic diet can improve neurobehavioral damage caused by flurothyl-induced recurrent seizures in neonatal rats.The every other day KD group shows a weak intervention effect comparing with the routine KD group.
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Objective To investigate the intervention effect of ketogenic diet (KD) on neurobehavioral demages after flurothyl-induced recurrent neonatal seizures in rats and on the expression of ApoE.Methods Postnatal day 8 (P8) SD rats (quantity:48) were randomly divided into two groups:the non-seizure group (NS group,n =24) and the recurrent-seizure group (RS group,n =24).From P9,rats in RS group were subjected to recurrent seizures induced by volatile flurothyl 30 min each day for consecutive 8 days.While rats in NS group were placed into the container for an equal amount of time to their counterpart without exposuring to flurothyl.At P28,each group was divided into two groups again:non-seizure and normal diet group(NS + ND group,n =12),non-seizure and ketogenic diet group(NS + KD group,n =12),recurrent-seizure and normal diet group (RS + ND group,n =12),recurrent-seizure and ketogenic diet group(RS + KD group,n =12).At P42,neurodevelopmental indicators were monitored.ApoE protein levels in cerebral cortex were determined by western blot at P58.Results Neurodevelopmental indicators were analyzed at P42:in the plane righting experiment,the rats of group NS + ND (1.0 ±0.14) about the time of plane righting was significant different comparing with group RS + ND ((0.75 ±0.32) s) (P ＜ 0.05).There was no significant difference between group RS + KD and group RS + ND about the time of plane righting(P＞ 0.05).In the negative geotaxis reaction experiment,the rats of groups NS + KD and RS + ND((3.17 ± 0.58)s,(6.75 ± 0.75)s) about the time of negative geotaxis reaction were significant different comparing with group NS + ND ((1.58 ±0.52)s) (P＜0.05).Compared with group RS + ND,the group RS + KD in the time of negative geotaxis reaction was obviously shortened (P ＜ 0.05).In the cliff avoidance test,there were significant differences between group NS + ND、RS + KD ((5.75 ± 2.90) s,(9.50 ± 4.36) s) and group RS + ND ((14.00 ± 4.79) s) about the time of cliff avoidance (P ＜ 0.05).In western blot,the expression of ApoE in cerebral cortex in the RS + ND group (1.26 ± 0.30) was obviously increased compared with group NS + ND (0.78 ±0.12) (P＜0.05),and there had also significant difference between group RS + KD (0.89 ±0.10) and group RS + ND (P ＜ 0.05).Conclusion The neuroprotective effects of ketogenic diet on recurrent neonatal seizure-induced neurobehavioral demages may be associated with the reduction of ApoE in cerebral cortex.
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Objective To explore neurobehavioral changes in rats with recurrent seizures and the prevention effect of melatonin.Methods 6-day-old (P6) SD rats were randomly divided into four groups of 24 (n =6):the control group (CONT),melatonin per se group (MEL),recurrent neonatal seizure group (RS) and melatonin administration prior to RS group (RS + MEL).Rats in RS group were subjected to 5 seizures with flurothyl during the first 14 days of life.In RS + MEL group,melatonin was injected at 8:00 before seizures were induced.Neurobehavioral tests including Plane righting experiment,Cliff avoidance test,the grip-strength test and negative geotaxis test were implemented on P24,while open field test on P35.Results (1) Plane righting experiment:the time of plane righting in RS group ((0.33 ± 0.51)s) was significantly shorter than that in the CONT group ((1.17 ± 0.40) s) and RS + MEL group ((0.50 ± 0.54) s) (P ＜ 0.05).(2) Cliff avoidance test:the time of cliff avoidance in RS group ((16.00 ± 6.32) s) was significantly longer than that in CONT group ((4.00 ± 2.60) s)(P ＜ 0.01),while the time of cliff avoidance in RS + MEL group ((7.67 ± 3.26) s) was shorter than that in the RS group (P ＜ 0.05).(3) The grip-strength test:compared with CONT group ((49.50 ± 28.96) s),the time needed to hold on wire in RS group((11.67 ± 7.58)s)was significantly shorter (P ＜ 0.05) and longer in RS+ MEL group ((24.83 ± 6.61) s) (P ＜ 0.05).(4) Negative geotaxis test:the time for rats to turn 180° upward in RS group((7.67 ± 1.36) s) was longer than that in the CONT group ((4.50 ± 2.66) s) and RS + MEL group ((6.17 ± 0.75) s) (P ＜ 0.05).(5) Open field test:the time for rats to begin to run in the RS group ((8.17 ± 3.86) s) was longer than that in the CONT group ((3.00 ± 1.41) s) (P ＜ 0.05).Conclusion The neurobehaviors are damaged following flurothyl-induced recurrent neonatal seizures,and melatonin can reduce the neurobehavioral injury.