本文選題：卒中后癲癇 + 神經(jīng)發(fā)生��； 參考：《華中科技大學(xué)》2014年博士論文

【摘要】：[背景] 癲癇是腦卒中后常見(jiàn)的并發(fā)癥。流行病學(xué)調(diào)查發(fā)現(xiàn)腦卒中后癲癇的發(fā)病率超過(guò)10%,占新確診的成年癲癇患者的三分之一；60歲以上新診斷的癲癇患者中,近一半與腦血管病有關(guān)。隨著生活質(zhì)量和醫(yī)療水平的提高,腦卒中患者存活期延長(zhǎng),腦卒中后癲癇的患病率也隨之增加。然而,目前仍然缺乏腦卒中后癲癇有效防治辦法,對(duì)其發(fā)生機(jī)制也不甚了解。成年哺乳動(dòng)物體內(nèi)神經(jīng)祖細(xì)胞主要位于海馬齒狀回顆粒下層和側(cè)腦室的室下區(qū),它們能夠增殖分化成為神經(jīng)元。在新生神經(jīng)元的發(fā)育過(guò)程中,它們逐漸伸出軸突和樹(shù)突,與周圍的細(xì)胞形成功能性突觸聯(lián)系并整合到原有的神經(jīng)環(huán)路中,發(fā)揮相應(yīng)的作用。神經(jīng)發(fā)生過(guò)程受多種因素影響。有研究表明腦卒中的新生大鼠成年后認(rèn)知功能障礙、呈現(xiàn)高度興奮狀態(tài)并伴有癲癇發(fā)生。還有報(bào)道指出,腦卒中促進(jìn)海馬神經(jīng)祖細(xì)胞活化增殖,新生細(xì)胞向損傷部位遷移,參與神經(jīng)功能修復(fù)；腦卒中或癲癇后,海馬新生神經(jīng)元形態(tài)和分布異常。卒中后新生神經(jīng)元的異常是否與癲癇的發(fā)生發(fā)展有關(guān),至今仍是一個(gè)謎。 [目的] 觀察缺血性腦卒中小鼠齒狀回新生神經(jīng)元的形態(tài)和功能以及與癲癇發(fā)生的關(guān)系。 [方法] 通過(guò)大腦中動(dòng)脈栓塞(MCAO)構(gòu)建4月齡小鼠腦缺血模型或相應(yīng)的假手術(shù)對(duì)照,本實(shí)驗(yàn)分別采用了雄性C57BL/6J小鼠、Nestin-Cre小鼠、ChR2小鼠、TeTX小鼠為研究對(duì)象。通過(guò)磁共振(MRI)和Fluoro-Jade C染色檢測(cè)小鼠卒中后腦部受損情況；采用逆轉(zhuǎn)錄病毒(RV-EGFP)、腺相關(guān)病毒(AAV-EGFP)和狂犬病毒(△Rabies-mCherry)感染以及熒光染料顯微注射標(biāo)記新生神經(jīng)元；使用BrdU染色標(biāo)記新生細(xì)胞；利用RT-PCR方法檢測(cè)中間神經(jīng)元、膠質(zhì)細(xì)胞和顆粒細(xì)胞的GAD67、GFAP和Calbindin-D28K的mRNA表達(dá)水平；通過(guò)全細(xì)胞膜片鉗電生理技術(shù)記錄新生顆粒神經(jīng)元與原有顆粒神經(jīng)元的電生理特征；通過(guò)紅藻酸氨(KA)誘發(fā)急性癲癇發(fā)作；通過(guò)視頻腦電圖監(jiān)測(cè)小鼠的癲癇發(fā)作情況。 [結(jié)果] MCAO小鼠反復(fù)自發(fā)癲癇發(fā)作。4月齡雄性C57BL/6小鼠行MCAO (C57-MCAO小鼠)或假手術(shù)(C57-sham小鼠)處理,術(shù)后連續(xù)3個(gè)月記錄腦電圖和癲癇相關(guān)行為,結(jié)果顯示C57-MCAO小鼠術(shù)后1月左右開(kāi)始出現(xiàn)反復(fù)自發(fā)癲癇發(fā)作現(xiàn)象并伴有腦電圖異常。 MCAO小鼠海馬新生神經(jīng)元形態(tài)異常。4月齡雄性C57BL/6小鼠行MCAO (C57-MCAO小鼠)或假手術(shù)(C57-sham小鼠)處理,海馬齒狀回注射逆轉(zhuǎn)錄病毒(RV-EGFP)標(biāo)記新生神經(jīng)元。2周及4周后,觀察新生神經(jīng)元數(shù)量和形態(tài),結(jié)果顯示C57-MCAO小鼠術(shù)后GFP+細(xì)胞數(shù)量顯著增加,雙極細(xì)胞所占比例增加,并出現(xiàn)多個(gè)基樹(shù)突。 MCAO小鼠海馬新生神經(jīng)元突觸連接異常。方法一：4月齡雄性C57BL/6小鼠行MCAO (C57-MCAO小鼠)或假手術(shù)(C57-sham小鼠)處理,海馬齒狀回注射逆轉(zhuǎn)錄病毒(RV-EGFP)標(biāo)記新生神經(jīng)元,術(shù)后4周取動(dòng)物腦片,分別對(duì)GFP+細(xì)胞和GFP-細(xì)胞顯微注射綠色和紅色生物素染料,發(fā)現(xiàn)C57-MCAO小鼠GFP+細(xì)胞軸突纖維深入到分子層。方法二：4月齡雄性C57BL/6小鼠行MCAO (C57-MCAO小鼠)或假手術(shù)(C57-sham小鼠)處理,腹腔注射BrdU標(biāo)記新生細(xì)胞,海馬齒狀回注射AAV-EGFP標(biāo)記所有神經(jīng)元,3周后同樣的部位注射△Rabies-mCherry標(biāo)記已被AAV感染的神經(jīng)元及其上級(jí)神經(jīng)元,此后1周取腦片觀察齒狀回EGFP+/mCherry+、EGFP+/mCherry"和EGFP-/mCherry+細(xì)胞的數(shù)量、形態(tài)和分布,與BrdU是否共定位,結(jié)果顯示大部分EGFP-/mCherry+細(xì)胞是BrdU+細(xì)胞。 MCAO小鼠海馬新生神經(jīng)元異常融入齒狀回神經(jīng)環(huán)路。方法一：4月齡雄性Nes-Cre小鼠行MCAO手術(shù)(Nes-Cre-MCAO小鼠)或假手術(shù)(Nes-Cre-sham小鼠),術(shù)后1周海馬齒狀回注射腺相關(guān)病毒(AAV-ChR2-EGFP),同時(shí)連續(xù)5天腹腔注射BrdU;術(shù)后4周,進(jìn)行NeuN和BrdU染色,觀察兩組動(dòng)物海馬GFP+/NeuN+細(xì)胞和GFP+/NeuN+/BrdU+細(xì)胞的數(shù)量、形態(tài)、分布以及NeuN+/BrdU+細(xì)胞占總GFP+細(xì)胞的比例,結(jié)果顯示Nes-Cre-MCAO小鼠較Nes-Cre-sham小鼠新生神經(jīng)元數(shù)量增加,兩組動(dòng)物NeuN+/BrdU+細(xì)胞數(shù)量沒(méi)有明顯變化。方法二：4月齡雄性ChR2小鼠行MCAO手術(shù)(ChR2-MCAO小鼠)或假手術(shù)(ChR2-sham小鼠),并給予他莫昔芬(TAM)誘導(dǎo)表達(dá)ChR2和EGFP,術(shù)后4周取腦片記錄DG區(qū)ChR2+/EGFP+細(xì)胞與CA3區(qū)以及DG區(qū)的ChR2-/EGFP細(xì)胞之間的突觸聯(lián)系,結(jié)果顯示ChR2-MCAO小鼠與ChR2-sham小鼠CA3區(qū)ChR2-/EGFP-細(xì)胞均可以記錄到EPSCs, ChR2-MCAO組小鼠DG區(qū)ChR2-/EGFP細(xì)胞可以記錄到EPSCs,而在ChR2-sham組小鼠則記錄不到DG區(qū)ChR2-/EGFP細(xì)胞的EPSCs。 MCAO小鼠海馬新生神經(jīng)元與原有成熟顆粒細(xì)胞形成功能性突觸連接。ChR2小鼠持續(xù)給予TAM,行MCAO(ChR2+-MCAO小鼠)或假手術(shù)(ChR2+-sham小鼠),術(shù)后4周,取腦片記錄DG區(qū)ChR2+/EGFP+細(xì)胞與CA3區(qū)以及DG區(qū)的ChR2-/EGFP細(xì)胞之間的突觸聯(lián)系。結(jié)果顯示ChR2+-MCAO組小鼠和ChR2+-sham小鼠CA3區(qū)ChR2-/EGFP-細(xì)胞以及ChR2-MCAO組小鼠DG區(qū)ChR2-/EGFP細(xì)胞可以記錄到EPSCs;該EPSCs與藍(lán)光光強(qiáng)呈線性正相關(guān),對(duì)AMPA受體拮抗劑敏感。 小鼠海馬新生神經(jīng)元中特異性表達(dá)TeTX可特異性阻斷其異常突觸傳遞,并不影響MCAO小鼠新生神經(jīng)元存活和電生理特征。4月齡雄性TeTX小鼠行MCAO處理(TeTX-MCAO小鼠),一組動(dòng)物給予TAM誘導(dǎo)新生神經(jīng)元中表達(dá)TeTX (TeTX+-MCAO小鼠),另外一組動(dòng)物給予正常對(duì)照溶劑(TeTX-MCAO小鼠),4周后,使用Fluoro-Jade C染色了解TeTX對(duì)細(xì)胞存活的影響,結(jié)果表明兩組動(dòng)物F-J+細(xì)胞數(shù)量沒(méi)有明顯差異；進(jìn)一步使用電生理記錄兩組動(dòng)物GFP+和GFP-細(xì)胞的EPSCs和IPSCs,結(jié)果顯示兩組動(dòng)物的GFP+和GFP細(xì)胞的EPSCs之間以及GFP+和GFP-細(xì)胞的IPSCs之間沒(méi)有明顯差異。TeTX小鼠行MCAO (TeTX--MCAO小鼠),術(shù)后1周海馬齒狀回注射腺相關(guān)病毒(AAV-ChR2),4周后,兩組動(dòng)物分別給予多西環(huán)素(DOX)(TeTX+-ChR2+-MCAO-mice)和正常對(duì)照溶劑(vehicle)(TeTX--ChR2+-MCAO-mice)1周,然后第一次記錄光刺激新生神經(jīng)元和電刺激苔蘚纖維時(shí)CA3區(qū)和DG區(qū)的EPSCsNMDA,然后兩組全部更換為正常飲水1周,進(jìn)行第二次記錄(同第一次記錄)。結(jié)果顯示,TeTX--ChR2+-MCAO小鼠可以在CA3區(qū)和DG區(qū)記錄到光刺激和電刺激后的EPSCsNMDA,TeTX+-ChR2+-MCAO小鼠只能在CA3區(qū)記錄到電刺激后的EPSCsNMDA。 特異性阻斷海馬新生神經(jīng)元突觸傳遞能降低MCAO小鼠癲癇發(fā)作的頻率和強(qiáng)度。4月齡雄性TeTX小鼠行MCAO (TeTX-MCAO小鼠)或假手術(shù)(TeTX-sham小鼠)處理,3周后開(kāi)始持續(xù)給予多西環(huán)素(TeTX+-MCAO/sham小鼠)或?qū)φ杖軇?TeTX"-MCAO/sham小鼠),1周后,開(kāi)始連續(xù)觀察腦電圖和行為學(xué)變化。結(jié)果顯示TeTX-sham小鼠無(wú)癲癇發(fā)生；TeTX--MCAO小鼠癲癇有發(fā)作,并且隨著腦缺血恢復(fù)時(shí)間的延長(zhǎng)其發(fā)作次數(shù)增加；TeTX+-MCAO小鼠癲癇發(fā)作次數(shù)和單次發(fā)作持續(xù)時(shí)間較TeTX--MCAO小鼠低。我們也將4月齡雄性TeTX小鼠持續(xù)給予多西環(huán)素(TeTX+小鼠)或?qū)φ杖軇?TeTX小鼠),再行MCAO (TeTX+/--MCAO小鼠)或假手術(shù)(TeTX+/--sham小鼠)處理,給予10-30mg/kg的紅藻氨酸(KA)腹腔注射誘發(fā)急性癲癇發(fā)作,觀察注射KA后各組動(dòng)物腦電圖、癲癇發(fā)作情況以及死亡率。結(jié)果發(fā)現(xiàn)隨著KA劑量的增加,各組動(dòng)物死亡率增加,以TeTX--MCAO小鼠居多；TeTX+/--sham小鼠和TeTX+-MCAO小鼠腦電圖基本正常；TeTX--MCAO小鼠腦電圖波形出現(xiàn)明顯異常,癲癇指數(shù)高于其他組小鼠。進(jìn)一步使用TeTX小鼠行MCAO (TeTX-MCAO小鼠)或假手術(shù)(TeTX-sham小鼠),術(shù)后4周開(kāi)始持續(xù)記錄兩組動(dòng)物(TeTX--MCAO/sham小鼠)癲癇發(fā)作情況4周(第一次記錄,R1),然后兩組動(dòng)物持續(xù)5周給予多西環(huán)素,記錄后四周兩組動(dòng)物(TeTX+-MCAO/sham小鼠)癲癇發(fā)作情況(第二次記錄,R2),然后兩組動(dòng)物持續(xù)5周給予正常飲水,記錄后四周兩組動(dòng)物(TeTX--MCAO/sham小鼠)癲癇發(fā)作情況(第三次記錄,R3)。結(jié)果發(fā)現(xiàn),整個(gè)實(shí)驗(yàn)期間,TeTX+/--sham小鼠幾乎沒(méi)有癲癇發(fā)作；對(duì)于TeTX-MCAO小鼠,R1時(shí),其癲癇發(fā)作強(qiáng)度頻率均明顯高于假手術(shù)組小鼠,R2時(shí),癲癇發(fā)作強(qiáng)度頻率較R1有明顯下降,R3時(shí),癲癇發(fā)作強(qiáng)度頻率恢復(fù)到R1時(shí)的水平。 [結(jié)論] 新生神經(jīng)元異常整合到原有的神經(jīng)環(huán)路是卒中后癲癇反復(fù)發(fā)作的細(xì)胞基礎(chǔ),阻斷該異常突觸連接可以降低MCAO小鼠癲癇發(fā)生頻率和強(qiáng)度。該研究結(jié)果為卒中后癲癇的干預(yù)和治療提供了新的思路。
[Abstract]:[background]
Epilepsy is a common complication after stroke. Epidemiological investigation has found that the incidence of epilepsy after stroke is more than 10%, accounting for 1/3 of the newly diagnosed adult epileptic patients; nearly half of the newly diagnosed epilepsy patients over 60 years old are related to cerebrovascular disease. With the improvement of quality of life and medical treatment, the survival period of stroke patients is prolonged, The incidence of epilepsy after stroke is also increasing. However, there is still a lack of effective prevention and control of epilepsy after stroke, and it is not well understood. The neural progenitor cells in adult mammals are mainly located in the subgranular layer of the dentate gyrus and the subventricular zone in the lateral ventricle, and they can proliferate and differentiate into neurons. During the development of the cells, they gradually extend the axons and dendrites to form functional synapses with the surrounding cells and integrate them into the original nerve loop and play a corresponding role. The process of neurogenesis is influenced by many factors. It is also reported that cerebral apoplexy promotes the activation and proliferation of hippocampal neural progenitor cells, the migration of new cells to the injured part and the repair of neural function. After stroke or epilepsy, the morphology and distribution of newborn neurons in the hippocampus are abnormal. A mystery.
[Objective]
To observe the morphology and function of newborn neurons in dentate gyrus of ischemic stroke and the relationship with the occurrence of epilepsy.
[method]
4 month old mice model of cerebral ischemia or corresponding sham control was constructed by middle cerebral artery embolism (MCAO). Male C57BL/6J mice, Nestin-Cre mice, ChR2 mice and TeTX mice were used to test the brain damage in mice after stroke by magnetic resonance (MRI) and Fluoro-Jade C, and retrovirus was used. (RV-EGFP) infection of adeno-associated virus (AAV-EGFP) and rabies virus (delta Rabies-mCherry) and microinjection of fluorescent dyes for newborn neurons; BrdU staining was used to mark new cells; GAD67, GFAP and Calbindin-D28K in the middle neurons, glia and granulosa cells were detected by RT-PCR. Electrophysiological characteristics of neonatal granular neurons and original granular neurons were recorded by cell patch clamp electrophysiology; acute epileptic seizures were induced by KA, and the epileptic seizures of mice were monitored by video electroencephalogram.
[results]
The.4 month old male C57BL/6 mice of MCAO mice were treated with MCAO (C57-MCAO) or sham operation (C57-sham mice). Electroencephalogram and epilepsy related behavior were recorded for 3 months after operation. The results showed that the spontaneous epileptic seizures and abnormal EEG occurred in the C57-MCAO mice around January.
The morphological abnormalities of hippocampal neurons in MCAO mice were.4 month old male C57BL/6 mice treated with MCAO (C57-MCAO mice) or sham operation (C57-sham mice). Hippocampal dentate gyrus injection retrovirus (RV-EGFP) was used to mark newborn neurons after.2 weeks and 4 weeks. The number and morphology of newborn neurons were observed. The results showed that the number of GFP+ cells in the C57-MCAO mice after operation was significant. The proportion of bipolar cells increased and multiple basal dendrites appeared.
The synaptic connections in the hippocampal neurons of MCAO mice were abnormal. Method 1: 4 month old male C57BL/6 mice were treated with MCAO (C57-MCAO mice) or sham operation (C57-sham mice). The hippocampal dentate gyrus was injected with retrovirus (RV-EGFP) to mark the newborn neurons, and the animal brain slices were taken for 4 weeks after the operation, and the GFP+ cells and GFP- cells were microinjected into green and red respectively. Biotin dye, found that C57-MCAO mice GFP+ cell axon fiber penetrated into the molecular layer. Method two: 4 month old male C57BL/6 mice were treated with MCAO (C57-MCAO mice) or sham operation (C57-sham mice), intraperitoneal injection of BrdU labeled new cells, hippocampal dentate gyrus injected with AAV-EGFP labeled all neurons, 3 weeks after the same site injection of delta Rabies-m. Cherry was labeled with AAV infected neurons and their superior neurons. After 1 weeks, the brain slices were taken to observe the EGFP+/mCherry+ of the dentate gyrus, the number, morphology and distribution of EGFP+/mCherry "and EGFP-/mCherry+ cells, and whether the BrdU was Co located with BrdU, and the results showed that most of the EGFP-/mCherry+ cells were BrdU+ cells.
Method one: 4 month old male Nes-Cre mice were treated with MCAO surgery (Nes-Cre-MCAO mice) or sham operation (Nes-Cre-sham mice). 1 weeks postoperatively, the adenoassociated virus (AAV-ChR2-EGFP) was injected into the sea dentate gyrus, and BrdU was injected intraperitoneally for 5 days. NeuN and BrdU staining was performed at 4 weeks after the operation. The number, morphology and distribution of GFP+/NeuN+ cells and GFP+/NeuN+/BrdU+ cells in the hippocampus of two groups of animals and the proportion of NeuN+/BrdU+ cells to total GFP+ cells were observed. The results showed that the number of newborn neurons in the Nes-Cre-MCAO mice was higher than that of the Nes-Cre-sham mice, and the number of NeuN+/BrdU+ cells in the two groups was not significantly changed. Method two: 4 month old male ChR2. The mice were treated with MCAO operation (ChR2-MCAO mice) or sham operation (ChR2-sham mice), and tamoxifen (TAM) was given to induce the expression of ChR2 and EGFP. The synaptic connections between DG zone ChR2+/EGFP+ cells and CA3 region and ChR2-/EGFP cells in DG region were recorded at 4 weeks after the operation. EPSCs was recorded in DG region ChR2-/EGFP cells of group ChR2-MCAO, but EPSCs. in ChR2-/EGFP group of DG region was not recorded in group EPSCs.
The synaptic connections between the hippocampal neurons of MCAO mice and the original mature granulosa cells formed a functional synaptic connection between.ChR2 mice and TAM. MCAO (ChR2+-MCAO mice) or sham operation (ChR2+-sham mice) were performed. 4 weeks after the operation, the brain slices were taken to record the synaptic connections between the ChR2+/EGFP+ cells of the DG region and the ChR2-/EGFP cells in the CA3 region and DG region. The results showed ChR2+-MCAO The ChR2-/EGFP- cells in the CA3 region of the group of mice and ChR2+-sham mice and the ChR2-/EGFP cells in the DG region of group ChR2-MCAO mice could be recorded to EPSCs; the EPSCs was linearly and positively correlated with the light intensity of blue light, and was sensitive to the AMPA receptor antagonist.
The specific expression of TeTX in the newborn hippocampal neurons of the mice can specifically block the abnormal synaptic transmission, which does not affect the survival and electrophysiological characteristics of the newborn neurons in MCAO mice, and the male TeTX mice of.4 months of age.4 (TeTX-MCAO mice). A group of animals give TAM to express TeTX (TeTX+-MCAO mice) in the newborn neurons, and another group of animals. Given normal control solvent (TeTX-MCAO mice), after 4 weeks, Fluoro-Jade C staining was used to understand the effect of TeTX on cell survival. The results showed that there was no significant difference in the number of F-J+ cells in the two groups. Further electrophysiology was used to record the EPSCs and IPSCs of GFP+ and GFP- cells in two groups of animals, and the results showed EPSCs GFP+ and GFP cells of the two groups of animals. There was no significant difference between the IPSCs and the IPSCs in the GFP+ and GFP- cells..TeTX mice were treated with MCAO (TeTX--MCAO mice), and 1 weeks after the operation, the sea dentate gyrus was injected with adeno-related virus (AAV-ChR2). After 4 weeks, the two groups were given 1 weeks, respectively, DOX (TeTX+-ChR2+-MCAO-mice) and normal control solvent (vehicle) (TeTX--ChR2+-MCAO-mice), and then first. The EPSCsNMDA in CA3 and DG regions was recorded by light stimulation of new neurons and electrical stimulation of moss fibers, and all of the two groups were changed to normal drinking water for 1 weeks, and second records were recorded (the same first record). The results showed that the TeTX--ChR2+-MCAO mice were able to record the EPSCsNMDA, TeTX+-ChR2+-MCAO mice after light stimulation and electrical stimulation in CA3 and DG areas. EPSCsNMDA. can only be recorded in the CA3 area after electrical stimulation
Specifically blocking the synaptic transmission of hippocampal neurons could reduce the frequency and intensity of epileptic seizures in MCAO mice..4 months old male TeTX mice were treated with MCAO (TeTX-MCAO mice) or sham operation (TeTX-sham mice), and 3 weeks later, they began to continue to give doxycycline (TeTX+-MCAO/sham mice) or control solvent (TeTX "-MCAO/sham mice"), and 1 weeks later, it began to connect. The results showed that the electroencephalogram and behavioral changes were observed. The results showed that there was no epilepsy in TeTX-sham mice; TeTX--MCAO mice had seizures and increased with the time of cerebral ischemia. The number of epileptic seizures and the duration of single attack in TeTX+-MCAO mice were lower than that of TeTX--MCAO mice. We also had 4 month old male TeTX mice. Continuous administration of TeTX+ (TeTX mice) or control solvent (TeTX mice), then MCAO (TeTX+/--MCAO mice) or sham operation (TeTX+/--sham mice) treatment, and injection of 10-30mg/kg's kainic acid (KA) intraperitoneally to induce acute epileptic seizures, and observe the electroencephalogram, epileptic seizures and mortality of each group of animals after KA injection. The results were found with K. The increase of A dose increased the mortality of animals in each group, mostly in TeTX--MCAO mice, and the electroencephalogram of TeTX+/--sham mice and TeTX+-MCAO mice was basically normal, and the EEG waveforms of TeTX--MCAO mice were obviously abnormal and the epilepsy index was higher than that of other groups. The TeTX mice were further used for MCAO (TeTX-MCAO mice) or sham operation (TeTX-sham mice). 4 weeks after the operation, the seizures of two groups of animals (TeTX--MCAO/sham mice) were recorded for 4 weeks (the first record, R1), and then the two groups were given doxycycline for 5 weeks. The seizures of two groups of animals (TeTX+-MCAO/sham mice) were recorded (second times, R2), and then the two groups of animals were given normal drinking water for 5 weeks, and the records were recorded. Two groups of animals (TeTX--MCAO/sham mice) were epileptic (third records, R3). The results showed that there were almost no epileptic seizures in TeTX+/--sham mice during the whole period of the experiment. For TeTX-MCAO mice, the frequency of epileptic seizures was significantly higher than that of the sham operation group, while R2, the frequency of epileptic seizures was significantly lower than that of R1, R3, R3. The frequency of seizure intensity returned to R1 level.
[Conclusion]
The abnormal integration of newborn neurons to the original nerve loop is the cell basis of recurrent seizures after stroke. Blocking the abnormal synaptic connection can reduce the frequency and intensity of epilepsy in MCAO mice. The results provide a new way of thinking for the intervention and treatment of epilepsy after stroke.
【學(xué)位授予單位】：華中科技大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2014
【分類號(hào)】：R743.3;R742.1

【共引文獻(xiàn)】

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