Abstract
ObjectiveTo investigate the effect of water extract of Gastrodiae Rhizoma (GR) on the development of acquired temporal lobe epilepsy (TLE) and on regulating the expression of the mammalian target of rapamycin (mTOR) and semaphorin 3F (SEMA3F).MethodsA pilocarpine‐induced status epilepticus (SE) model was adopted to precipitate injury in the limbic systems. GR and carbamazepine (CBZ) treatments were given to mice for 14 days prior to SE induction to demonstrate the antiepileptic effects and continued for 5 more days to illustrate the effects on histologic studies.ResultsOur results consolidated that GR treatment (92.1 minutes) could delay the SE onset in comparison with the control group (61.5 minutes, P = .041). Fewer mice had reached SE with GR treatment (41.7%) when compared with the control group (83.3%, P = .044). GR treatment (2.1 hours/mouse) could suppress the number of acute seizures in post‐SE survival mice when compared with the control group (4.5 hours/mouse, P < .001). The effects of GR treatment were elucidated with the mechanism of actions. GR treatment reduced the overexpression of mTOR (0.27 vs 0.67 AU/mg protein, P = .047). GR treatment increased the underexpression of SEMA3F (0.51 vs 0.16 µg/mg protein, P = .034). In the histochemical study of microtubule‐associated protein 2 (MAP2) staining, our results showed that GR prevented neuronal loss in the GR treatment group (64.8% positively stained pixel area) as compared with the control group (59%, P = .014) in the hippocampus. In glial fibrillary acidic protein (GFAP) staining, the severity of astrogliosis was mitigated by the GR treatment (4.1% positively stained pixel area) when compared to the control group (5.6%, P = .047) in the hippocampus.SignificanceThese results provide preclinical evidence to support the use of GR, which could suppress acute seizures and relieve pathological changes in pilocarpine‐induced TLE mice. We demonstrated that the antiepileptic effects of GR could be accompanied by mTOR reduction and astrogliosis attenuation.
Highlights
Gastrodiae Rhizoma (GR, Tianma) is the rhizome of Gastrodia elata Blume and traditional Chinese medicine (TCM), which is documented in the Chinese Pharmacopoeia
We aimed to investigate the expression of proteins that might relate to epilepsy— mammalian target of rapamycin and semaphorin 3F (SEMA3F), respectively—for establishing the mechanism and explaining the antiepileptic effect of GR
By comparing the naïve group with the control group, similar pathological changes were observed in the hilus of dentate gyrus (DG) (Figure 4B): status epilepticus (SE) decreased the percentage of microtubule-associated protein 2 (MAP2) stained pixel area (51.6 ± 3.8%, P = .002) and increased the percentage of glial fibrillary acidic protein (GFAP)-stained pixel area (5.1 ± 0.6%, P < .001) in the control group (Figure 5B)
Summary
Gastrodiae Rhizoma (GR, Tianma) is the rhizome of Gastrodia elata Blume and traditional Chinese medicine (TCM), which is documented in the Chinese Pharmacopoeia. In a preclinical evaluation of epilepsy treatment, past literature showed that the extracts of GR and its constituents had antioxidant and scavenging free radical activities.[3,4] Studies from Hsieh et al indicated anticonvulsive effects of GR—showing that extract of GR could reduce convulsive syndrome in a pretreatment manner of kainic acid-induced epileptic rat model.[5,6,7] Subsequent studies confirmed that GR might reduce the severity of status epilepticus (SE), as well as seizure frequency, and could protect the neuronal damage against kainic acid in mouse hippocampus.[8,9] Two mechanisms have been proposed for its effects: Hsieh et al suggested a signaling pathway that GR modulated mitogen-activated protein kinase (MAPK) pathway to regulate activator protein 1 (AP-1) expression after SE induction, and Shao et al reported that gastrodin acted on downregulating the expression of Nav1.6 channel protein in pretreatment manner of pilocarpine-induced temporal lobe epilepsy (TLE) in rats.[9,10] recent literature documented that gastrodin ameliorated pentylenetetrazole (PTZ)-induced seizure with an improvement of electroencephalographic outcomes in mice.[11] These results support the potential therapeutic effects of GR in epilepsy Despite these encouraging evidences, the mechanism of GR has not been mapped precisely and remained unclear. SEMA3F governs the axonal growth and synaptic formation, which involves in early axonal sprouting, as
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