Maonekedwe achipatala a Citicoline akusintha kwambiri, pang'onopang'ono akusintha kuchoka ku "mankhwala adjuvant" kupita ku "core neuroprotective agent". Kusintha kumeneku sikuli kopanda maziko, koma kumachokera ku kusonkhanitsa kosalekeza kwa umboni wa mankhwala ozikidwa pa umboni, kumvetsetsa mozama za njira zake zambiri zomwe zimapangidwira, komanso kuzindikira kwakukulu kwa "zenera la nthawi" pochiza kuvulala kwakukulu kwa mitsempha. Zotsatirazi ndizo maziko ofunikira ndi kusanthula komwe kumathandizira kusinthaku:

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1, Mphamvu yoyendetsera galimoto: Umboni wamphamvu kuchokera kumakina kupita kumayendedwe azachipatala

Kuwunikanso momwe amagwirira ntchito (kupitilira 'thandizo'):

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Membrane phospholipid kukonza core: Cytophosphatidylcholine ndi kalambulabwalo wachindunji wa kaphatikizidwe ka cell membrane phospholipids, monga phosphatidylcholine. Kuwonongeka kwa Membrane phospholipid ndi chochitika choyambirira chovulala pambuyo pa neuronal ischemia/hypoxia. Phosphatidylcholine imatha kuphatikizira mwachindunji zida zamkati za phospholipid, kulimbikitsa kukonza ndi kukhazikika kwa mitsempha ya mitsempha, yomwe ndi maziko ofunikira a neuroprotection.

Multi target neuroprotective zotsatira:

Chepetsani excitotoxicity: kuletsa kutulutsidwa kwakukulu ndi kawopsedwe ka glutamate.

Kupsinjika kwa Antioxidant: kumawonjezera milingo ya glutathione ndikuchotsa ma free radicals.

Kupititsa patsogolo ntchito ya mitochondrial: kusunga mphamvu kagayidwe kachakudya ndikuchepetsa ma cell apoptosis.

Limbikitsani kaphatikizidwe ka ma neurotransmitter: onjezani milingo ya acetylcholine, dopamine, ndi zina zambiri, sinthani kayendedwe ka mitsempha.

Kuchepetsa neuroinflammation: kuletsa kutulutsidwa kwa ma cytokines oyambitsa kutupa.

Njirayi imatsimikizira kuti iyenera kukhala gawo lalikulu la "kulowererapo koyambirira ndi chitetezo chachangu", osati kungothandizira kuchepetsa zizindikiro. pa

Kudziunjikira kwa umboni wapamwamba kwambiri wozikidwa pa umboni (kuphwanya malingaliro a "wothandizira"):

Matenda a ischemic (AIS):

Phunziro la ICTUS (2012): Ngakhale kuti mapeto oyambirira anali oipa, magulu ang'onoang'ono omwe adakonzedweratu (kupweteka kwapang'onopang'ono mpaka koopsa, chithandizo choyambirira) chinasonyeza ubwino waukulu, kutanthauza kuti nthawi ya chithandizo ndi kusankha anthu ndizofunikira.

Phunziro la ECCO 2 (2023): RCT yayikulu yochitidwa mwa anthu aku China (odwala 3947 AIS akuphatikizidwa). Zotsatira zinasonyeza kuti pamaziko a mtsempha wa magazi thrombolysis ndi/kapena endovascular mankhwala oyambirira (pasanathe maola 24 pambuyo chiyambi) mtsempha wa magazi phosphatidylcholine kwa masiku 14 kwambiri anawonjezera gawo la 90 ntchito kudziimira pawokha (mRS 0-1) (43.5% vs 40.0%). Tsimikizirani mphamvu yake yolumikizirana pamaziko a chithandizo chokhazikika cha reperfusion. pa

Kusanthula kwa meta kangapo: kuthandizira mphamvu zake pakuwongolera zotsatira za minyewa komanso kuthekera kwamoyo watsiku ndi tsiku, makamaka kuyambira chithandizo kumayambiriro oyambilira (

Traumatic Brain Injury (TBI):

Kafukufuku wa COBRIT: Zotsatira zake ndi zotsutsana, koma kuwunika kotsatira kukuwonetsa kuti magulu ang'onoang'ono (wapakatikati mpaka owopsa TBI) amapindula.

Kafukufuku weniweni wapadziko lonse & kusanthula kwa meta: Kafukufuku wambiri awonetsa kuti amatha kusintha zotsatira za minyewa komanso kuchira kwachidziwitso mwa odwala TBI.

Matenda a Neurodegenerative (pakufufuza):

Mitsempha yamaganizo (VCI) / vascular dementia (VaD): Kafukufuku wasonyeza kuti akhoza kusintha ntchito yachidziwitso (chidwi, kuphedwa, kukumbukira).

Matenda a Alzheimer's (AD)/Parkinson's (PD): Monga othandizira omwe angasinthe matenda, kafukufuku wina wapang'onoting'ono akuwonetsa kusintha kwa kuzindikira ndi kakhalidwe.

Kafukufuku wazinthu zina monga glaucoma ndi kuvulala kwa msana wawonetsanso kuthekera kwa neuroprotective.

2, Mfundo yofunikira pakuyika kusintha: kuchokera ku "wothandizira" kupita ku "core"

Kupititsa patsogolo nthawi ya chithandizo (chofunikira kwambiri pa "windo la nthawi yagolide"):

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Chinsinsi cha neuroprotection chagona 'koyambirira'. Pambuyo povulala muubongo (monga sitiroko, TBI), kuyankhidwa kovulaza kumayambika mphindi zingapo mpaka maola angapo pambuyo pake.

Dongosolo la phosphatidylcholine limatsimikizira kuti liyenera kugwiritsidwa ntchito kumayambiriro kwa kuvulala koopsa (monga mkati mwa maola a 24 mutangoyamba kumene sitiroko, poyamba bwino) kuti atseke njira yovulalayo ndikuteteza minofu yomwe ili pangozi kwambiri. Izi ndizosiyana kwambiri ndi momwe anthu amakhalira "mankhwala owonjezera adjuvant".

Kupambana kwa kafukufuku wa ECCO 2 kumachokera pamapangidwe a ma protocol oyambilira a intravenous.

Udindo wapakatikati wa njira yamankhwala (yophatikiza ndi reperfusion therapy):

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Kukonzekera kwamankhwala aacute ischemic stroke: Chithandizo chokhazikika ndikubwezeretsanso mitsempha yamagazi (thrombolysis, thrombectomy), koma odwala ambiri amakhalabe ndi chidziwitso choyipa pambuyo poyambiranso (kuvulala kwa reperfusion, palibe chodabwitsa, etc.).

Dongosolo la neuroprotective la phosphatidylcholine (kukhazikika kwa membrane wa cell, antioxidant, anti apoptotic) imatha kuthandizira ndikulumikizana ndi mankhwala obwezeretsanso, kuchepetsa kuvulala kobwerezabwereza komanso kuteteza minofu yaubongo pambuyo pobwezeretsanso.

Kafukufuku wa ECCO 2 watsimikizira kufunika kwake monga gawo lalikulu la neuroprotective mu njira ya "vascular recanalization +", osatinso chowonjezera chothandizira.

Kukhathamiritsa kwa njira zoyendetsera (kutsata bioavailability):

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Oral phosphatidylcholine imakhala ndi bioavailability yochepa (

jakisoni m'mitsempha angapereke bioavailability mkulu, mwamsanga kukwaniritsa ogwira magazi mankhwala ndende, ndi kukwaniritsa zosowa mofulumira neuroprotection mu gawo pachimake.

Kusunthira ku malo a "core" mosakayikira kudzatsagana ndi malingaliro amitundu yamankhwala am'mitsempha kuti agwiritsidwe ntchito pachimake.

3, Kusintha kwa maupangiri / kuvomerezana (zowonetsa kusintha kwamayimidwe)

China:

"Malangizo Opewera ndi Kuchiza Stroke ku China" ndi zolemba zina zawonetsa mphamvu yake yoteteza mitsempha.

Kutengera zotsatira zotsogola za kafukufuku wa ECCO 2, zikuyembekezeredwa kuti mulingo waupangiri ndi malo a phosphatidylcholine (makamaka mtsempha wamagazi omwe amagwiritsidwa ntchito pachimake) mu malangizo aku China adzakhala bwino kwambiri mtsogolo. pa

Zakunja:

Malangizo a AHA/ASA ku United States sanavomerezedwe momveka bwino, koma ndi otseguka kuti afufuze za neuroprotective agents.

Maupangiri ena akumayiko aku Europe amawunika bwino phosphatidylcholine (monga Spain, Portugal).

4. Tanthauzo la kusintha kwa malo azachipatala

Sinthani lingaliro lamankhwala: Neuroprotection ndi mzati wofunikiranso pakuchiza kuvulala koopsa muubongo monga kukonzanso mitsempha.

Konzani ndondomeko ya chithandizo: Limbikitsani chithandizo chachikulu cha phosphatidylcholine (intravenous) monga chithandizo chokhazikika (monga thrombolysis / thrombectomy) mu hyperacute / pachimake gawo la sitiroko / TBI ndi matenda ena.

Kupititsa patsogolo kaganizidwe ka odwala: Kudzera muchitetezo choyambirira komanso chogwira mtima, chikuyembekezeka kupititsa patsogolo kuchuluka kwa kupulumuka komanso kuchira kwa odwala omwe akuvulala kwambiri muubongo, ndikuchepetsa kulumala.

Limbikitsani mayendedwe a kafukufuku ndi chitukuko: Limbikitsani maphunziro apamwamba azachipatala ndikuwunika njira zatsopano zoperekera mankhwala kuti mutetezeke kwambiri.

Chidule ndi Outlook

Kusintha kwa phosphatidylcholine kuchoka ku "adjuvant drug" kupita ku "core neuroprotective agent" ndi zotsatira za kuzama kwa kafukufuku wofunikira, kupititsa patsogolo umboni wachipatala (makamaka kafukufuku wa ECCO 2), ndi malingaliro osinthidwa a chithandizo. Cholinga chake ndi:

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Kuthandizira koyambirira: Tsindikani mankhwala pawindo la nthawi ya golide (acute phase/subacute early stage) pamene kuvulala kwa mitsempha kumayambika.

Kufunika kwa mtsempha: Pagawo lovuta kwambiri lomwe likufunika kuchitapo kanthu mwachangu, kulowetsedwa m'mitsempha ndiyo njira yofunika kwambiri yodzitetezera.

Kupititsa patsogolo luso lophatikizana: Monga gawo lofunika kwambiri la neuroprotection pamaziko a vascular recanalization therapy (stroke) kapena comprehensive treatment (TBI), si bonasi yowonjezera.

Kusintha kumeneku kukuwonetsa kuzindikira kwatsopano komanso kukulitsa mtengo wa phosphatidylcholine pochiza matenda amisala, makamaka pochiza matenda owopsa a ischemic stroke. Monga gawo lofunikira la njira ya "standard reperfusion therapy+core neuroprotection", ikupeza chithandizo chokhazikika chochokera ku umboni komanso kuzindikira zachipatala. M'tsogolomu, ndi chitukuko cha kafukufuku wapamwamba kwambiri ndi zosinthidwa ku malangizo, malo ake oyambirira adzaphatikizidwanso.