| Background and Objective:Glucosamine is an amino monosaccharide with small molecular weight and monomolecular properties.Glucosamine may increase the uptake of glucose by cells through the hexosamine biosynthesis pathway(HBP),thereby affecting the activity of various signal transduction pathways.Glucosamine has been found to have a protective effect in neurological diseases such as neuroinflammation,demyelination and stroke.However,the effects of glucosamine on seizures have not been studied.Seizures are a process of energy accumulation,eruption,and depletion,accompanied by the generation,generalization,and termination of seizures.The energy depletion is the main mechanism of spontaneous termination of epileptic seizures.We aimed to observe the effects of different doses of glucosamine(0.5g/Kg,1.0g/Kg and 2.0g/Kg)on epileptic behavior and electrophysiology in pilocarpine and pentylenetetrazole(PTZ)-induced epileptic model rats.Methods:The experimental animals were divided into five groups:control group,glucosamine 0.5g/Kg group,glucosamine 1.0/Kg group,glucosamine 2.0g/Kg group and glucose 2.0g/Kg group.Glucose(2.0g/Kg)and glucosamine(0,0.5,1.0,and 2.0g/Kg)were added to 2ml drinking water,respectively.The acute epilepsy model of lithium chloridein combination with pilocarpine and PTZ was constructed to observe the effects of different doses of glucosamine on the seizure rate,seizure grade,duration,latency,24h mortality,hippocampal potential and energy density in rats.Meanwhile,the changes of Akt signal were detected by western-blot.Results:Glucosamine(2.0g/Kg)markedly reduced the latency of pilocarpine and PTZ-induced grade 4 to 5 acute seizures,increased Racine score,and increased epileptic seizure duration and the mortality within 24-hours.2.0g/Kg glucosamine shorted the incubation period of epileptic discharge,increased the duration of discharge,enhanced the average energy density of brain electrical activity,increased the energy density of high-frequency oscillations(HFOs)(80Hz-200Hz),and promoted the hyperphosphorylation of protein kinase B(Akt).However,compared with the control group,glucosamine(0.5g/Kg and 1.0/Kg)had no significant effect on the above factors.Conclusion:In this study,we found that different doses of glucosamine have different effects on epileptic activities in rat model.2.0g/Kg glucosamine significantly prolongs the duration of seizures and increases the sensitivity and severity of seizures through activating PI3K/Akt signal.The results provide evidence for the prudent use of glucosamine in epileptic patients. |
