Kev Tshuaj Xyuas Ntawm Cov Kab Ntsig Txawb Ntsig Ntawm Kev Kho Mob Parkinson
Apr 24, 2023
Abstract
Hauv cov qauv tsiaj ntawm Parkinson's disease (PD), spinal cord stimulation (SCS) exhibits neuroprotective effects. Kev nce qib tsis ntev los no hauv SCS thev naus laus zis, qhov tseem ceeb tshaj plaws ntawm lub zog stimulators, tso cai rau cov kev txwv ib txwm siv ntawm SCS xws li lub sij hawm stimulation txwv thiab txwv cov tsiaj txav kom dhau, muab cov kev muaj peev xwm los txhim kho kev kho mob txhais lus rau PD cov neeg mob.
Nyem rau cistanche tubulosa extract rau Alzheimer's kab mob thiab Parkinson tus kab mob
Cov khoom siv me me uas tuaj yeem xa cov SCS mus tas li rau kev ywj pheej ntawm Parkinsonian nas tau pom tias yuav txhim kho tus cwj pwm zoo, khaws cov neurons thiab fibers hauv substantia Nigra / striatum, txo cov microglia infiltration, thiab ua kom cov laminin-zoo ntawm lub paj hlwb cortex. Los ntawm qhov ua tau los tiv thaiv kab mob thiab angiogenic mechanisms, nws tau pom tias muaj kev coj tus cwj pwm thiab cov txiaj ntsig histological rau SCS tas li nyob rau lub sijhawm. Qhov kev tshuaj xyuas no yuav tham txog cov txiaj ntsig ntawm cov thev naus laus zis no nrog rau tsom mus rau cov kev txwv ntawm cov qauv tsiaj tam sim no.
Keywords: 6 hydroxydopamine, hluav taws xob stimulation, neuroinflamation, neuroprotection, Parkinson tus kab mob
Taw qhia
Parkinson tus kab mob (PD) tshwm sim nyob rau hauv lub nigrostriatal system raws li ib tug mob neurodegenerative kab mob tshwm sim los ntawm kev puas tsuaj ntawm dopaminergic (DA) neurons. Bradykinesia, rigidity, so tremors, thiab postural instability yog cov cim tseem ceeb ntawm PD. Kev kho thawj kab rau PD yog kev kho mob levodopa. Kev kho mob ntev ntev, txawm li cas los xij, feem ntau ua rau muaj qhov tshwm sim tsis zoo, suav nrog dyskinesia thiab lub cev muaj zog hloov pauv.
Deep Brain Stimulation rau Parkinson's Disease
Sib sib zog nqus hlwb stimulation (DBS) nyob rau hauv cov neeg mob PD siab heev txhim kho cov tsos mob ntawm lub cev muaj zog. DBS tuaj yeem nce BDNF hauv cov qauv tsiaj ntawm PD thiab tuaj yeem tiv thaiv kev poob ntawm DA neurons hauv substantia nigra pars compacta (SNc). kev cog qoob loo ntawm cov khoom siv stimulator.
Intracranial hemorrhage risk nyob rau hauv DBS yog kwv yees li ntawm 0.8 feem pua mus rau 2.8 feem pua .[4–8] Tsis tas li ntawd, qhov ua tau zoo ntawm DBS zoo li yuav muaj txiaj ntsig tsuas yog thaum muaj kev hloov pauv ntawm lub cev muaj zog teb rau kev kho levodopa, yog li Tsuas yog tsawg tus neeg mob PD thiaj tsim nyog rau DBS.
Spinal Cord Stimulation
Lub stimulation ntawm tus txha caj qaum nyob rau hauv kev kho mob ntawm intractable neuropathic mob qhia tau hais tias ib tug ruaj khov cov ntaub ntawv ntawm kev vam meej thiab kev tiv thaiv. Txawm hais tias tsis ncaj qha tsom rau thaj chaw uas muaj kab mob, peripheral paj hlwb stimulation, xws li lub ntsej muag paj hlwb stimulation, tau pom tias muaj cov txiaj ntsig kho mob rau ischemia los ntawm vasodilation.[9]
Txawm hais tias kev raug mob ntawm lub paj hlwb yog qhov teeb meem loj tshaj plaws ntawm tus txha caj qaum stimulation (SCS), lawv muaj qhov tshwm sim tsawg nrog tus nqi ntawm 0.6 feem pua .[10] Hauv PD tsiaj qauv, SCS txo lub cev muaj zog thiab tiv thaiv dopaminergic neurons. nyob rau hauv lub neostriatum.[11,12] hluav taws xob stimulation ntawm tus txha caj qaum, tshwj xeeb tshaj yog nyob rau hauv tsawg zaus, conferred cov kev pab cuam los ntawm kev nce neuroplasticity hauv PD qauv.[13] Hauv cov neeg mob PD siab heev nrog mob lumbago thiab ceg, SCS muaj txiaj ntsig zoo ntawm kev tswj lub cev muaj zog nrog rau kev sib npaug, kev ruaj ntseg ntawm lub cev, thiab gait.[14]
Tsiaj qauv ntawm Spinal Cord Stimulation
Hauv PD tsiaj qauv, hluav taws xob stimulation ntawm tus txha caj qaum yog ib qho kev ua tau zoo rau kev kho mob. Cov teeb meem, txawm li cas los xij, txwv cov qauv tsiaj ntawm SCS xws li lub sij hawm stimulation luv luv (tsis pub ntau tshaj 1 ha hnub) thiab yam tsawg kawg nkaus pub dawb txav ntawm cov tsiaj (piv txwv li, vim yog tshuaj loog).[1-3,12,15-17] Nrog qhov kev nce qib ntawm cov stimulators me me, tam sim no ua tau rau kev ywj pheej txav Parkinsonian nas kom kho nrog DBS ruaj khov.[18,19]
Cov kev txwv no ntawm preclinical SCS tsiaj qauv tuaj yeem kov yeej hauv kev txhais lus rau qhov chaw kho mob los ntawm repurposing preexisting me me mobile DBS stimulators rau kev siv hauv SCS. Hauv kev tshawb fawb tsis ntev los no, cov khoom siv me me rau kev txuas mus ntxiv SCS hauv kev txav mus los ntawm Parkinsonian nas ywj siab tau tsim tawm.[20] Cov kev tshawb fawb pom tau hais tias ob qho tib si kev xa khoom zoo ntawm SCS los ntawm cov khoom siv txawb me me thiab lub sijhawm nyob ntawm qhov cuam tshuam neuroprotective ntawm nas nrog PD.
Ob pawg ntawm SCS-kho nas feem ntau tau txhim kho kev ua tau zoo hauv ob qho tib si kev tsis ncaj ncees thiab kev sib hloov tshuaj methamphetamine; Txawm li cas los xij, pab pawg 24-teev stimulation tau nthuav tawm cov kev kho mob zoo dua li 8-teev stimulation pawg. Muab piv rau cov nas hauv pawg tswj hwm, ob qho tib si lesioned striatum thiab SNc nthuav tawm qhov txo qis microglial hlwb nrog rau kev ua haujlwm ntev tshaj plaws ntawm SCS.
Cov Khoom Siv Hluav Taws Xob me me rau Kev Nruam Nruam Nruj Ntsig Stimulation
Cov tshuab SCS tsoos tau tso cai tswj qhov ntsuas tsawg kawg nkaus rau kev txhawb nqa thiab txwv tsis pub tsiaj txav. Tam sim no SCS cov cuab yeej muaj xws li lub tshuab hluav taws xob loj thiab lub tshuab hluav taws xob uas tau cog rau hauv cov tsiaj muaj kab mob.[1-3,12,21-23] Lub sijhawm ntev ntawm cov xaim xaim rau hauv daim tawv nqaij tuaj yeem ua rau yaig lossis kab mob hauv cov tsiaj.
Tsis tas li ntawd, kev txav mus los ntawm cov tsiaj dawb yog txwv tsis pub dhau los ntawm kev siv tshuaj loog thaum muab SCS.[12] Qhov cuam tshuam ntawm SCS cov txheej txheem tam sim no zoo li yuav hloov cov txiaj ntsig kev sim. Lub sijhawm thiab lub sijhawm ntawm kev txhawb nqa hluav taws xob tseem txwv rau SCS ib txwm muaj, muab qhov loj ntawm cov stimulators, kev sib txuas ntawm cov stimulator thiab electrodes, kev siv tshuaj loog, thiab kev ua haujlwm invasive.
Cov kev txwv thev naus laus zis ntawm cov tshuab SCS tam sim no tuaj yeem hla dhau los ntawm lub tshuab hluav taws xob compact mobile stimulator. Cov txheej txheem zoo li no twb tau pom tias ua tau zoo rau DBS hauv PD cov tsiaj thiab tam sim no lub teeb yuag, txuas ntxiv SCS lub xov tooj ntawm tes kuj tau tsim. ntawm stimulation tej yam kev mob, thiab muaj zog, ruaj khov stimulation nyob rau hauv PD tsiaj rau tsawg kawg yog 2 lub lis piam [Daim duab 12].
Nco ntsoov, Bluetooth signaling zoo tswj stimulation tsis. Kev nthuav dav ntawm kev siv cov cuab yeej siv me me uas yog siv hauv DBS rau SCS, uas dhau los ntawm cov khoom siv hluav taws xob epidurally implanted ua tiav cov txheej txheem tsis muaj zog thiab kev hloov ntau dua li kev tsom mus rau qhov tob ntawm lub hlwb (xws li thalamus, subthalamic nucleus, thiab globus pallidus).
Nws yog qhov ua tau tias SCS yuav raug siv los teb rau lub sijhawm tiag tiag thiab hauv kev muab qhab nia rau ib tus neeg tus kab mob tshwj xeeb hauv xeev los ntawm kev kaw lub voj kaw uas muaj ob qho kev txhawb nqa thiab tau txais cov haujlwm. Muab cov kev paub dhau los hauv kev txo qis thiab kev sib txuas lus wireless, xws li SCS lub cev muaj peev xwm yuav muaj sai sai.
Txhim kho Cov txiaj ntsig kho mob hauv Parkinson's Disease Tsiaj nrog Lub Ncauj Ncauj Ncauj Ntev
Txawm hais tias PD cov tsiaj tau raug tshaj tawm hauv cov teebmeem neuroprotective ntawm SCS, qhov kev pom zoo rau kev txhawb nqa hluav taws xob tseem tsis paub meej. Tsis muaj xws li mem tes dav (400-1.000 µs), zaus (300–333 Hz), thiab stimulation ntev (30 min ntawm ob zaug / lub lis piam, rau 4.5 feem pua -30 min ntawm ib lub sij hawm txhua lub lim tiam rau 5 lub lis piam) rau kev siv hluav taws xob zoo hauv nas txhua qhov sib txawv.[16,23]
Cov xwm txheej zoo tshaj plaws rau SCS luv luv tawg yav dhau los tau raug txheeb xyuas raws li hauv qab no: Pulse dav, 100 µs; zaus, 2, 50, thiab 100 Hz; thiab lub sijhawm stimulation, 1 h rau 16 hnub sib law liag.[12] Rau qhov "txuas ntxiv" mus rau SCS, qhov zoo tshaj plaws zaus tau raug txheeb xyuas tias yog 50 Hz. Raws li ob pawg nrog lub sijhawm txhawb nqa ntawm 8 h piv rau 24 teev, lub sijhawm nyob ntawm SCS kuj tau pom.
Txawm hais tias kev txhim kho tus cwj pwm, TH-zoo nigral neuron ciaj sia taus, thiab qib angiogenesis tsis txawv ntawm 8 thiab 24-h stimulation pab pawg, ntev SCS khaws cov striatal TH fibers ntau dua li qhov luv SCS kev kho mob thiab nthuav tawm ntau dua ntawm kev tiv thaiv kab mob. Qhov txo qis ntawm kev ua kom cov hlwb microglial los ntawm kev kho SCS uas tau txais txiaj ntsig qhia tau hais tias kev ua kom tsis zoo ntawm cov kab mob neuroinflammation tuaj yeem nrog PD, xav tau kev kho mob kom cais tawm txoj kev tuag ntawm tes tau zoo.[20]
Spinal Cord Stimulation Anti-Inflammatory Effects
Neurodegeneration ntawm PD manifests nws tus kheej ib nrab raws li ib tug ntev neuroinflammation yam ntxwv los ntawm activated microglial hlwb nyob rau hauv lub striatum thiab SNc.[24] Nyob rau hauv cov ntaub ntawv ntawm ib txwm Sprague-Dawley nas, hluav taws xob stimulation tej zaum yuav modulate neuroinflammation -DBS kev kho mob ho txo activated microglia ib puag ncig electrodes.[25]
Hauv cov qauv tsiaj ntawm tus txha caj qaum ischemic reperfusion raug mob, cov kev tshawb fawb tau pom tias kev kho SCS kuj txhawb cov lus teb los tiv thaiv kab mob thiab txo cov microglial activation los ntawm kev txo qis ntawm ERK1/2 txoj hauv kev, ib qho kev taw qhia kev txhawb nqa los ntawm kev tshawb fawb mob.[26-31] Cov kws tshawb fawb ntxiv. pom tias tom qab intrastriatal 6-hydroxydopamine (6-OHDA) kev tswj hwm hauv 24-h stimulation pab pawg, SCS txo tus naj npawb ntawm microglia hlwb los ntawm cov tshuaj tiv thaiv kab mob uas yuav ua rau muaj kev cuam tshuam los ntawm kev qhia txoj hauv kev los ntawm dorsal kem-medial lemniscus, propagating rau hauv SNc thiab stratum[20] Txoj kev tshawb no ntawm cov kab mob tiv thaiv kab mob yuav tsum tau kuaj electrophysiological ntxiv.
Spinal Cord Stimulation Enhances Angiogenesis
Cervical low-frequency SCS txhim kho lub hlwb khiav hauv lub hlwb thiab kav ntev li 15 feeb tom qab SCS raug txiav lawm.[32–34] Txawm li cas los xij, tsis muaj cov ntaub ntawv dhau los uas cuam tshuam txog kev hloov pauv ntawm cerebral vasculostructural thiab SCS. Cov kws tshawb fawb pom tias SCS tau nce cov laminin-zoo thaj chaw nyob rau hauv qhov chaw lesioned ntawm lub hlwb cortex.[20]
Cov kev tshawb pom no qhia tias kev hloov pauv hauv intrastriatal hauv PD nas ntawm cov kab mob vascular endothelial kev loj hlob (VEGF) zais cov hlwb txhim kho angiogenesis.[35] Nyob rau hauv cov ntaub ntawv ntawm PD nas tau txais sporadic SCS (1 h / hnub 7 hnub sib law liag), cov txiaj ntsig no sib npaug ntawm kev tswj hwm ntawm VEGF hauv qhov mob striatum.[12]
Qhov tseeb tias SCS modulates tshwj xeeb kev loj hlob yam cuam tshuam nrog vasculature txhais tau hais tias muaj kev sib txuas ntawm hluav taws xob stimulation thiab kev tso tawm ntawm kev loj hlob, uas tuaj yeem kho qhov pom kev nce hauv laminin-zoo vascular cheeb tsam ntawm SCS-kho PD nas nyob rau hauv cerebral cortex.[36- 40]
Spinal Cord Stimulation Clinical Application in the Future for Parkinson's Disease
Hauv PD pathogenesis, neuroinflammation tuaj yeem suav nrog ntau cov txheej txheem neurodegenerative, xws li o thiab neurotrophic factor downregulation. no neurodegeneration, tus yam ntxwv los ntawm aberrant o thiab dampened neurotrophic yam theem, manifests nws tus kheej raws li ib tug tseem ceeb theem nrab cell tuag txoj kev uas tej zaum yuav yog ib tug muaj peev xwm kho lub hom phiaj.[44-48]
Lub peev xwm ntawm SCS los txwv cov kev tuag ntawm cov xovtooj thib ob no yuav tsum tau soj ntsuam ntxiv rau kev nkag siab txog kev ua kom zoo dua cov txiaj ntsig kho mob thiab nkag siab txog cov txheej txheem ntawm kev txhawb nqa hluav taws xob. Hauv cov neeg mob PD siab heev, DBS muab kev kho tseem ceeb rau cov tsos mob ntawm lub cev. Piv nrog rau DBS, SCS tsis tshua muaj kev cuam tshuam hauv qhov txheej txheem ua rau lub hlwb los ntawm kev phais mob.
Hauv kev txo qis cov cim PD lub cev muaj zog, xws li kev tawm tsam SCS tsawg kawg nkaus yuav ua tiav zoo li DBS. Tseeb tiag nyob rau hauv PD marmosets, SCS relieves motor deficits.[21] Txawm hais tias muaj txiaj ntsig zoo hauv cov tsiaj, txawm li cas los xij, ib daim ntawv tshaj tawm qhia tias SCS hauv ob tus neeg mob PD ua tsis tau zoo los txo qis akinesia lossis rov ua haujlwm, tsa cov lus nug txog kev ua tau zoo ntawm tib neeg.[49] Raws li cov ntaub ntawv muaj, cov txiaj ntsig kho mob ntawm qhov kev txhawb nqa hluav taws xob tsawg tsawg yuav tsum tau ua kom zoo dua los ntawm kev ua kom zoo dua ntawm SCS los ntawm kev siv cov kev txhawb nqa txuas ntxiv los ntawm lub tshuab hluav taws xob me me.
Kev txwv
Txoj kev tshawb fawb soj ntsuam mobile SCS stimulators siv PD daim ntawv ntawm 6-OHDA-induced nas rau kev tshuaj ntsuam.[20] Cov txiaj ntsig tseem ceeb ntawm cov qauv no yog qhov yooj yim ntawm kev tsim cov kab mob uas ua rau poob ntawm striatum dopaminergic fibers thiab substantia nigra dopaminergic neurons; Txawm li cas los xij, muaj qhov teeb meem tseem ceeb ntawm tus qauv no vim tias nws tsis zoo li cov kab mob ib txwm muaj ntawm PD, uas yog qhov kev loj hlob zuj zus ntawm nigrostriatal dopaminergic neuron degeneration los ntawm alpha-synuclein degradation.
Lwm cov qauv PD ntawm neurodegeneration thiab alpha-synucleinopathy yuav tsum tau tshawb xyuas ntxiv txhawm rau ntsuas tus nqi kho mob ntawm SCS. Cov teebmeem neuroprotective ntawm SCS txuas ntxiv tau tshuaj xyuas nrog lub hom phiaj ntawm kev kho mob ntev raws li qhov tseem ceeb. Kev kho mob tau pib sai tom qab tsim cov kab mob 6-OHDA, uas tej zaum yuav tsis siv rau hauv qhov chaw kho mob, vim tias cov tsos mob ntawm PD tsis tshwm sim kom txog thaum tsawg kawg 80 feem pua ntawm cov dopaminergic neurons tau tas lawm.[20] Kev tshawb fawb ntxiv hauv cheeb tsam no feem ntau yuav suav nrog kev sim SCS hauv PD qauv lig.
Lwm qhov tsis zoo yog qhov kev tshawb nrhiav ntxiv yuav tsum tau ua kom paub meej txog kev kho mob ntawm SCS. Kev tshawb fawb tau nthuav tawm tias qhov muaj peev xwm angiogenic ua rau muaj kev cuam tshuam rau neuroprotective, tab sis seb cov teebmeem neuroprotective ntawm SCS thaum lub sij hawm presymptomatic yog khaws cia thaum lub sij hawm cov tsos mob yuav tsum tau soj ntsuam ntxiv. Nyob rau yav tom ntej, kev coj cwj pwm hloov tom qab kev txiav tawm ntawm SCS tuaj yeem nthuav tawm cov txheej txheem ntawm kev ua ntawm PD cov tsos mob nrog rau kev cuam tshuam ntev ntawm SCS.
Xaus
Cov stimulators me me tuaj yeem muab SCS tas li thiab nyob rau lub sijhawm ua haujlwm tawm tsam neuroprotective hauv PD nas. SCS attenuates ob tus cwj pwm thiab histological tsis txaus uas cuam tshuam nrog cov tsos mob ntawm 6-OHDA-induced PD, zoo li los ntawm kev txo qis kev ua kom microglia thaum tib lub sij hawm ntxiv dag zog rau angiogenesis.
Los ntawm kev nkag siab ntxiv ntawm kev sib cuam tshuam los ntawm hluav taws xob stimulation, neurodegeneration, thiab neuronal reconstruction, lub mobile stimulator system rau nruam SCS muab kev pab cuam tseem ceeb ob qho tib si raws li ib tug tseem ceeb cov cuab yeej rau cov kev tshawb fawb theem pib thiab kuj yog ib tug muaj txiaj ntsim kev kho mob modality rau PD.
lub mechanism ntawm Cistanche tiv thaiv Alzheimer's kab mob thiab Parkinson tus kab mob
Cistanche yog cov tshuaj suav tshuaj suav tshuaj uas tau siv ntau pua xyoo los txhim kho lub cev thiab lub hlwb. Kev tshawb fawb tsis ntev los no tau qhia tias Cistanche tuaj yeem muaj cov teebmeem neuroprotective uas tuaj yeem tiv thaiv Alzheimer's thiab Parkinson's disease.
Ib lub tswv yim los ntawm Cistanche tuaj yeem tiv thaiv cov kab mob neurodegenerative no yog los ntawm nws lub peev xwm los nce qib ntawm lub hlwb-derived neurotrophic factor (BDNF) hauv lub hlwb. BDNF yog cov protein uas ua lub luag haujlwm tseem ceeb hauv kev loj hlob thiab ciaj sia ntawm cov neurons. Hauv Alzheimer's disease thiab Parkinson's disease, muaj qhov txo qis hauv BDNF, uas cuam tshuam nrog kev loj hlob ntawm tus kab mob. Cistanche tau pom tias nce qib BDNF, uas tuaj yeem pab tiv thaiv cov neurons los ntawm kev puas tsuaj thiab txhawb lawv txoj sia.
Cistanche kuj muaj cov tshuaj antioxidants thiab cov tshuaj tiv thaiv kab mob uas tuaj yeem pab tiv thaiv lub hlwb. Oxidative stress thiab o yog ob txheej txheem uas koom nrog kev txhim kho Alzheimer's thiab Parkinson's disease. Cov tshuaj antioxidants thiab cov tshuaj tiv thaiv kab mob muaj nyob hauv Cistanche tuaj yeem pab txo cov txheej txheem no, tiv thaiv lub hlwb los ntawm kev puas tsuaj.
Thaum kawg, Cistanche yuav muaj kev tiv thaiv ntawm mitochondria hauv neurons. Mitochondria yog lub zog tsim cov organelles hauv cov hlwb, suav nrog cov neurons. Kev ua haujlwm tsis zoo hauv mitochondria tau cuam tshuam rau kev txhim kho cov kab mob neurodegenerative. Cistanche tau pom los txhim kho mitochondrial muaj nuj nqi, uas tuaj yeem pab tiv thaiv neurons los ntawm kev puas tsuaj.
Zuag qhia tag nrho, cov txheej txheem los ntawm Cistanche tuaj yeem tiv thaiv Alzheimer's kab mob thiab Parkinson tus kab mob yuav muaj ntau yam thiab koom nrog nce BDNF qib, txo oxidative kev nyuaj siab thiab mob, thiab txhim kho mitochondrial muaj nuj nqi.
Cov ntaub ntawv
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Zhen-Jie Wang, Takao Yasuhara1
