4-Hydroxybenzyl Alcohol Prevents Epileptogenesis As Well As Neuronal Damage in Amygdaloid Kindled Seizures

Background: 4-Hydroxybenzyl alcohol (4-HBA), one of the major active phenolic constituents of Gastrodia elata Blume, has been shown to be a neuroprotective agent. Previous studies have demonstrated the anticonvulsive effect of Gastrodia elata, while no studies have investigated the antiepileptogenic effect of 4-HBA. Methods: We examined the effect of 4-HBA (25 mg/kg, 50 mg/kg or 100 mg/kg i.p.) on amygdaloid kindled seizures. Fully kindled seizures were achieved by daily electrical stimulation of the amygdala. Seizure stage and afterdischarge duration (ADD) were assessed daily. The effects of 4-HBA on neuronal loss were observed before kindling and 20 days after kindling by Nissl staining. Results: We found that treatment with 50 mg/kg 4-HBA delayed seizure stage progression, and 25 mg/kg and 50 mg/kg 4-HBA shortened the corresponding ADD. Rats pretreated with 50 mg/kg 4-HBA needed more kindling stimulations to reach stages 4-5 and exhibited more cumulative ADD to stage 5. Pretreatment with 50 mg/kg 4-HBA shortened the number of days in stages 4–5 and decreased the incidence of generalized seizures. Pretreatment with 4-HBA showed no effect on fully kindled rats. Moreover, 50 mg/kg 4-HBA attenuated neuronal loss in the ipsilateral CA1 and the bilateral entorhinal cortex. Conclusion: Our data suggests that 4-HBA can protect against epileptogenesis by preventing the after-discharge propagation in amygdaloid kindled seizures. In addition, the anti-epileptogenic activity may be related to the neuroprotective function of 4-HBA in the late stage of kindling.