I-Microglial Priming kwiCentral Nervous System

Iiseli zeMicroglial zenza malunga ne-10 ukuya kwi-15 ipesenti yazo zonke iiseli zeglial emzimbeni womntu, ezinokufumaneka kwinkqubo ye-nervous central (CNS) kwaye zidlala indima ebalulekileyo kwingqondo yomntu. Iiseli ze-Microglial zinoxanduva lokugcina nokulawula utshintsho kwimeko ye-physiological and pathological ye-CNS ngokuguqula i-morphology yabo, i-phenotype kunye nomsebenzi. Kwimeko ye-physiological avareji, iiseli ze-microglial ziqhuba ngokuqhubekayo ukulawula okusingqongileyo. �

 

Nangona kunjalo, xa i-homeostasis yengqondo iphazamisekile, i-microglia iyatshintsha ibe yinto efana ne-amoeba kwaye phagocyte apho banokubonisa ngokusebenzayo iindidi ze-antigens. Ukuba uphazamiseko lwe-homeostasis kwi-CNS luyaqhubeka, iiseli ze-microglial ziya kuthi ziqale kwindawo eyomeleleyo, eyaziwa ngokuba yi-microglial priming. I-Microglia yi "Bruce Banner" ye-CNS. Nangona kunjalo, nje ukuba bangene kwimo yokukhusela "ye-Hulk", i-microglia ephuculweyo iba buthathaka ngakumbi ekuvuseleleni kwaye banethuba elinamandla lokusabela kuvuselelo, nokusabela kwiiseli eziqhelekileyo. �

 

 

I-Microglial priming ingaba likrele elintlangothi-mbini. Ngokwenyani, i-primed microglia idalwe kwiiphenotypes ezahlukeneyo ze-microglia kwaye i-phenotypes ixhomekeke kumxholo, okuthetha ukuba inxulunyaniswa nolandelelwano kunye nobude bexesha lokuvezwa kwazo kwiintlobo ezahlukeneyo zokuvuselela kwiindlela ezahlukeneyo ze-pathologies. Kwinqaku elingezantsi, siya kubonisa umphumo we-microglial priming kwinkqubo ye-nervous central (CNS), ngakumbi kwizifo ze-neurological. �

 

Indima yeeSeli zeMicroglial kwi-CNS

 

Iiseli ze-Microglial zixhaphake ngokufumaneka kwinkqubo ye-nervous central (CNS), apho zithathwa njengenye yezona ntlobo ziguquguqukayo zeeseli zengqondo. Iiseli ze-Microglial zenziwe kwiiseli ze-precursor ezifunyenwe ngaphakathi mzambim umongo wethambo, okanye ngakumbi ngakumbi afunyenwe kwi-mesodermal yolk sac, kwaye ahlulahlulwe ngokwahlukeneyo kwiindawo ezininzi zobuchopho. Njengoko kukhankanyiwe ngasentla, i-microglia iya kuhlala kwimeko yokulala xa i-homeostasis yobuchopho ihlala izinzile. �

 

I-Microglia inomzimba omncinci weeseli kunye namasebe e-morphological afikelela kuwo onke amacala ukunceda ukugcina nokulawula umsebenzi jikelele we-CNS. Utshintsho kwindalo yabo encinci lunokubangela i-microglia ibe yimeko "esebenzayo". Izifundo zophando zibonise ukuba i-microglia idlala indima ebalulekileyo ekuphuhlisweni kwengqondo kunye nemisebenzi eyahlukeneyo, kuquka ukuthenwa kwe-synaptic kunye nokucoca inkunkuma yeeseli. Ngapha koko, i-microglia idala inkqubo yokujonga amajoni omzimba kwingqondo yomntu kwaye ilawule iinkqubo ezisisiseko ezinxulumene neentlobo ngeentlobo ze-pathologies, kubandakanya nokukhutshwa kunye nokuthathwa kwe-A? kunye neprotheyini ye-tau engaqhelekanga kunye nokuveliswa kwezinto ze-neurotrophic kunye ne-neuroinflammatory factor. �

 

Microglial Priming Overview

 

I-Microglial priming iyasebenza xa uphazamiseko oluqhubekayo kubume bengqondo bubangela impendulo eyomeleleyo yemicroglial xa kuthelekiswa nokuphazamiseka kokuqala okubangela ukuba kusebenze imicroglial. I-Primed microglia kwi-CNS ikwanovakalelo ngakumbi kuvuselelo oluncinci olunokwenzeka. Le mpendulo yandayo ibandakanya ukwanda kwe-microglial, i-morphology, i-physiology, kunye nabamakishi be-biochemical okanye i-phenotype. Nangona kunjalo, olu tshintsho luya kuthi ekugqibeleni lukhuthaze ukwanda kwe-cytokines kunye nemveliso yomlamli wokudumba onokuthi ube nempembelelo enkulu kwi-synaptic plasticity, ukusinda kwe-neuronic, ukuqonda komntu ngamnye kunye nomsebenzi wokuziphatha. Apha ngezantsi kukho umboniso weziphumo ze-microglial priming kwi-CNS. �

 

Iinkqubo zeMicroglial Priming kwi-CNS

 

I-microenvironment ye-central nervous system (CNS), ngokomzekelo, yenye yezinto eziphambili ezinokuchaphazela iiseli ze-microglial. Ukonyuka koxinzelelo lwe-oxidative, i-lipid peroxidation kunye nomonakalo we-DNA ohambelana nokuguga kwengqondo konke kunokubangela ukuqala kwe-microglial. Enye into eqhelekileyo kwi-microglial priming ibandakanya ukwenzakala kwengqondo. Uphononongo lophando lubonise ukuba ukwenzakala okubuhlungu kwe-CNS kwenza i-microglia isebenze kunye nophuhliso lwe-primed microglia. �

 

Uphononongo oluninzi lophando lukwabonisile ukuba zombini ukugxila kunye nokusasaza ukwenzakala kwengqondo kwandisa ukudumba kwingqondo ehambelana ne-microglia kunye ne-astrocytes. Usulelo lwe-CNS lusenokubangela ukuba i-microglial priming apho iintsholongwane zingoyena nobangela wosulelo lwe-CNS. Zombini iintsholongwane ze-DNA kunye ne-RNA zinokuqalisa i-microglial priming kuquka i-microglia kunye ne-astrocytes. Uphononongo lwakutsha nje lubonise ukuba ukungasebenzi kakuhle komphelelisi kunokutshintsha ukubonakaliswa kwee-receptors ezincedisayo kwaye kubangele i-microglial priming emva kokusebenza ngokuqhubekayo kulandela imisebenzi eyahlukeneyo, kubandakanywa ukuvuthwa kwe-synapse, ukukhutshwa kwemveliso ye-immune, ukuhlanganiswa kwe-hematopoietic stem / progenitor cells (HSPC), i-lipid metabolism, kunye ukuvuselelwa kwezicubu. �

 

Ngapha koko, izifundo zophando zibonise ukuba kukho ukonyuka kwe-microglia kwiintlobo ngeentlobo zezifo ze-neurological. Ngokomzekelo, iiseli ze-microglial ezine-phenotype ye-morphological zifumaneka ngamanani amakhulu kwingqondo yomntu. Kwiminyaka eliqela edlulileyo, izifundo zophando zicebise ukuba i-neuroinflammation inokuqhubekeka isebenze i-microglia kwaye ibangele i-microglial priming. Ngapha koko, zonke iimeko ezikhankanywe ngaphambili zinxulunyaniswa ngokusondeleyo ne-neuroinflammation. Uphononongo lophando luye lwabonisa ukuba i-neuroinflammation, kunye ne-microbial debris kunye nemiphumo ye-metabolic, inxulunyaniswa ne-central sensitization kwizifo ze-neurological, ezifana ne-fibromyalgia, ekwabizwa ngokuba "yingqondo emlilweni". �

 

Kwimeko yeemeko zangaphambili ezikhankanywe ngasentla, i-microglia i-primed nangona i-series of pro-inflammatory stimulation, efana ne-lipopolysaccharide (LPS), i-pathogenetic proteins (umz., A?), ?synuclein, i-human immunodeficiency virus (HIV) -Tat, i-mutant huntingtin, i-mutant superoxide dismutase i-1 kunye ne-chromogranin A. Kukho neendlela ezahlukeneyo zokubonisa kwaye ziqhelekile kwiindidi ezahlukeneyo zeeseli ukuvakalisa i-receptors ekhethekileyo yokuqaphela i-pattern (PRRs) enokuchaphazela iindlela zokubonisa ukuvuvukala. Ngokomzekelo, iindlela ezininzi zokubonisa, ezaziwa ngokuba ziipateni zemolekyuli ezihambelana ne-pathogen (PAMPs), ezinokonyuka ngokwesiqhelo kwizicubu ezosulelekileyo, zinokulawula iimolekyuli ezincinci. �

 

Ukongeza, i-peptides okanye i-nucleic acids echongwe njenge-mislocalized iiprotheyini ezingalunganga ngoluhlu lweendlela, ezaziwa njengeepateni zemolekyuli ezinxulunyaniswa nobungozi (DAMPs), zisenokubangela i-microglial priming. Ii-receptors ezinjenge-toll-like (TLRs) kunye ne-carbohydrate-binding receptors ngokuqhelekileyo zisebenza kwezi ndlela. Kukho nee-receptors ezininzi ezahlukeneyo ezifumaneka kwi-microglia, kubandakanywa i-receptors evuselelayo echazwe kwiiseli ze-myeloid (TREM), i-Fc? i-receptors (i-Fc? Rs), i-CD200 receptor (CD200R), i-receptor ye-advanced glycation end products (RAGE), i-chemokine receptors (i-CX3CR1, i-CCR2, i-CXCR4, i-CCR5, kunye ne-CXCR3), enokuthi iqatshelwe kwaye ixutywe kunye nezinye iindlela zokubonisa, nangona ezinye iindlela zingekacaci. �

 

Iziphumo zeMicroglial Priming kwi-CNS

 

I-Microglia ibonisa izinga eliphantsi le-mitosis kwisimo sabo esiqhelekileyo kunye nezinga eliphezulu lokunyuka emva kwe-microglial priming, ebonisa ukuba i-microglia inamandla okuchaphazela ukuguqulwa kweeseli kunye nokuvuselela i-pro-inflammation. Ngokuqhubeka kovuselelo, i-microglia iyasebenza ukusuka kwimeko yabo yokuphumla, itshintsha ibe ziiseli ze-amoeboid microglial kwi-morphology. Nangona kunjalo, utshintsho kwimilo ye-microglia alukwazi ukwahlula iimpawu ze-microglial activation kunye nomsebenzi we-primed microglia kuxhomekeke kwi-phenotypes yabo ehambelana ne-receptors kunye neemolekyuli abazenzayo kwaye baziqaphele. �

 

Iindidi ezahlukeneyo ze-tissue macrophages, phantsi kwempembelelo ye-microenvironmental, ziyakwazi ukwahlula i-M1 kunye ne-M2 phenotypes. Okokuqala, i-M1 polarization, eyaziwa ngokuba yi-activation classical, ekugqibeleni idinga i-interferon-? (IFN-?) ukuba ixutywe ne-TLR4 yokubonisa emva koko ibangela ukuveliswa kwe-inducible nitric oxide synthases (iNOS), iintlobo ze-oksijini ezisebenzayo (ROS), i-cytokines e-proinflammatory, kwaye ekugqibeleni, ekugqibeleni iyanciphisa ukukhululwa kwezinto ze-neurotrophic, ekugqibeleni zibangele ukuvutha kunye ukwanda kweziphawuli ze-main histocompatibility complex II (MHC II), interleukin-1? (IL-1?) kunye ne-CD68. �

 

Ngaphezu koko, i-M2 polarization, eyaziwa ngokuba yi-activation enye, ekugqibeleni ikholelwa ukuba idibene ne-tissue-ixhasayo kwimeko yokuphulukisa isilonda, ukunciphisa ukuvuvukala kunye nokuphucula ukulungiswa kwezicubu ze-collagen ifomu. Baqala ukuphendula kwi-IL-4 kunye ne-IL-13 kwi-vivo. I-M2 polarization ibonakaliswe ngokunyuka kokubonakaliswa kwezinto ze-neurotrophic, i-proteases, i-enzymes i-arginase 1 (ARG1), i-IL-10 yokuguqula ukukhula-? (TGF-?), i-scavenger receptor CD206 kunye ne-coagulation factor kunye nokuphucula umsebenzi we-phagocytic. Njengokuba kunjalo, okwangoku akukho mida ecacileyo phakathi kwee-polarizations ezimbini kunye ne-M1 phenotype yabelana ngeempawu ezininzi ezifanayo kunye ne-phenotype ye-M2. �

 

Enye i-phenotype ye-primed microglia, eyaziwa ngokuba yi-activation efunyenweyo, isandula ukufunyanwa. Le phenotype entsha idibanisa ne-M2 kwaye inamandla okuphucula ukuchasana nokuvuvukala kunye nokubuyiswa komsebenzi. Ukongeza, uphononongo lophando lwenze uhlalutyo lwe-ultra-structural kwaye ichonge i-phenotype entsha kraca, eyaziwa ngokuba �dark microglia�, engafane ibonwe kwindawo yokuphumla yeseli yemicroglial. Ukuvuvukala kwenkqubo kubangela i-microglia ibe yimeko esebenzayo ukukhuthaza ukubuyiswa kweeseli kunye nezicubu kunye nokufezekisa i-homeostasis. I-Microglial priming ekugqibeleni kukuphazamiseka kwesibini kwi-CNS microenvironment. �

 

I-primed microglia likrele elintlangothi-mbini lempilo yengqondo. Uninzi lwezifundo zophando kwi-vivo kunye ne-vitro zibonise ukuba izifo ze-neurological zinxulunyaniswa nokusebenza kwe-microglial. I-phenotypes evuthayo ye-microglia yenza izinto ze-neurotoxic, abalamli kunye ne-ROS ezinokuchaphazela i-CNS. I-Primed microglia idlala indima ebalulekileyo kunye nenzuzo ekuvuseleleni i-neuronal, ukulungiswa, kunye ne-neurogenesis. I-Primed microglia nayo ibuthathaka kakhulu kwaye isabela ngakumbi kukwenzakala kwengqondo, ukudumba, kunye nokuguga kunye nokwandisa ukusebenza kweeseli ze-microglial ngokutshintsha kwi-anti-inflammation, enokuthi ikhuseleke kwiphenotype ukuya kwi-pro-inflammation eyonakalisayo phenotype, njengoko kubonisiwe (Umfanekiso 1). �

 

 

Kwinqanaba lokuqala le-microglial priming, amandla kunye nomsebenzi wokwenza i-phagocytize inkunkuma yeeseli, iiprotheyini eziphosakeleyo, kunye ne-inflammation medium yonyuka apho iimolekyuli ezikhuselayo ezinje nge-IL-4, IL-13, IL-1RA, kunye ne-scavenging receptors, zenziwa. . Utshintsho lunokuchaphazela ukuphulukiswa kwesilonda kunye nomonakalo wokulungiswa kwezicubu, ukukhuselwa kwe-neuron, kunye nokubuyisela i-homeostasis. I-microglia esetyenzisiweyo yeklasikhi (M1) yenza inxalenye enkulu yazo zonke i-microglia kwaye ikhuthaza ukudalwa okwandisiweyo kwezinto ze-neurotoxic, ezifana ne-IL-1?, TNF-?, HAYI kunye ne-H2O2 (6), apho i-microglia engaphezulu iqhutywe ngokukhawuleza emva koko. �

 

Oku kwanda kunye ne-neuroinflammation eyandisiweyo ebangelwa yi-primed microglia inokudityaniswa ekugqibeleni nophuhliso kunye nokuhlanganiswa kweprotein tau kunye ne-A?. Ngaphaya koko, kunokukhokelela ekulahlekelweni kwemithambo-luvo kunye nokuncipha kokusebenza kwengqondo kunye nenkumbulo, njengesifo sika-Alzheimer. Nangona iindlela zingacacanga ngokwaneleyo, abantu baye bafikelela kwisivumelwano sokuba i-primed microglia ibangele impendulo engapheliyo ye-proinflammatory kunye nomjikelo oqhubekayo we-neurotoxicity. Kwaye oku kukholelwa ukuba yeyona nto iphambili kwimiba yempilo yobuchopho ekhokelela kwizifo ze-neurological. �

 

IMicroglia zaziwa njengabakhuseli bobuchopho kwaye zidlala indima ebalulekileyo ekugcineni kunye nokulawula i-homeostasis ye-CNS microenvironment. Ukuvuselela rhoqo kubangela ukuba i-microglia iqalise kwindawo eyomeleleyo, eyaziwa ngokuba yi-microglial priming. Iiseli ze-Microglial yi "Bruce Banner" ye-CNS. Nangona kunjalo, nje ukuba bangene kwimo yokukhusela "ye-Hulk", i-microglia ephuculweyo iba buthathaka ngakumbi ekuvuseleleni kwaye banethuba elinamandla lokusabela kuvuselelo, nokusabela kwiiseli eziqhelekileyo. �- UDkt Alex Jimenez DC, i-CCST Insight

 

Iiseli zeMicroglial zenza malunga ne-10 ukuya kwi-15 ipesenti yazo zonke iiseli zeglial emzimbeni womntu, ezinokufumaneka kwinkqubo ye-nervous central (CNS) kwaye zidlala indima ebalulekileyo kwingqondo yomntu. Iiseli ze-Microglial zinoxanduva lokugcina nokulawula utshintsho kwi-physiological and pathological condition ye-CNS. Umda wolwazi lwethu ukhawulelwe kwi-chiropractic, i-musculoskeletal kunye nemicimbi yezempilo ye-nervous kunye namanqaku amayeza asebenzayo, izihloko kunye neengxoxo. Ukuxubusha ngakumbi ngombandela ongentla, nceda ukhululeke ukubuza uDkt Alex Jimenez okanye uqhagamshelane nathi 915-850-0900 .

 

Ikhethwe nguGqirha Alex Jimenez

 

---

 

Isihloko esongezelelweyo seNgxoxo: kubuhlungu obungapheliyo

 

Intlungu engxamisekileyo yindlela yokuphendula yendalo kwinkqubo yovalo eyanceda ukubonisa ukwenzakala okunokwenzeka. Ngokomzekelo, imiqondiso yentlungu ihamba ukusuka kwindawo eyenzakeleyo ngokuhamba ngeemvakalelo kunye nentambo yomgogodla ukuya kwingqondo. Ubuhlungu buhlala bungaphantsi kakhulu njengobaphilisayo, nangona kunjalo, iintlungu ezingapheliyo zahlukile kunoluhlobo lweentlungu eziphakathi. Ngeentlungu ezingapheliyo, umzimba womntu uya kuqhubeka nokuthumela imiqondiso yentlungu ebuchotsheni, nokuba wenzakele. Intlungu engapheliyo inokuhlala iiveki ezininzi ukuya kwiminyaka eliqela. Ubuhlungu obungapheliyo bunokuchaphazela kakhulu ukuhamba kwesigulana kwaye bunokunciphisa ukuguquguquka, amandla kunye nokunyamezela.

 

 

---

 

I-Neural Zoomer Plus yesifo seNeological

 

Ugqirha Alex Jimenez usebenzisa uthotho lovavanyo ukunceda ukuvavanya izifo ze-neurological. I-Neural Zoomer^TM Ukudibana kuluhlu lwee autoantibodies ze-neurological ezinikezela ukwamkelwa okuthile kwe-anti-to-antigen. I-Vulrant Neural Zoomer^TM Ukudibanisa kuyilelwe ukuvavanya ukwenziwa kwakhona kwe-antigen ye-48 ye-neurological antigens ngokudibana nezifo ezahlukeneyo ezinxulumene nonyango. IVibrant Neural Zoomer^TM Kwaye kujolise ekunciphiseni iimeko zemithambo-luvo ngokuxhobisa abaguli kunye noogqirha ngesixhobo esibalulekileyo sokufumana umngcipheko kwangoko kunye nokugxininiswa okuphuculweyo kuthintelo olusisiseko lomntu.

 

Iifomu zeNkxaso yeMethylation

 

 

XYMOGEN's Iifomula zeeNgqungquthela zodwa zifumaneka ngokukhetha abaqeqeshi bezempilo abanemvume. Intengiso ye-intanethi kunye nokuhlaziywa kwamafomula e-XYMOGEN ayinqatshelwe.

 

Ngebhongo, UDkt. Alexander Jimenez yenza i-XYMOGEN ifomula ifumaneka kuphela kwizigulane ezingaphantsi kwethu.

 

Nceda ufonele iofisi yethu ukuze sikwazi ukudlulisela udokotela ngokubonisana nokufikelela ngokukhawuleza.

 

Ukuba uyigulane Unyango lwezoNyango kunye neChiropractic Klinikhi, unokubuza malunga ne-XYMOGEN ngokubiza 915-850-0900.

 

Ukuze ube lula kwaye uhlaziywe XYMOGEN mveliso nceda uhlolisise le nxu lumene. *I-XYMOGEN-Inkcazo-umxokozelo

 

* Zonke iinkqubo ze-XYMOGEN ezingentla zihlala zisebenza ngokuthe ngqo.

 

---