Te kikorangi metilīni i te rangahau mō te mate ikura roro me te iti o te rere toto ki te roro: he aha tā ngā tauira e toru e whakaatu ana

He rite pea te āhua o tētahi iatuku kua aukatia, o ngā pūtau whakatipu kua kore he matūkai, me tētahi kiore kua whāiti ōna iatuku kakī ki ngā putanga e toru o te whakamātau kotahi. Heoi, he rerekē ēnei whakamātau. He pātai rerekē tā ia whakamātau, ā, he whakautu rerekē tā te kikorangi metilīni i ia whakamātau. Ki te whakaranua, ka āhua taupatupatu ngā tuhinga rangahau. Ki te wehewehea, ka kitea he tauira mārama, ko te wā hoatu te tino take e whakatau ana i taua tauira.

Ko taua wehewehenga te tino aronga o tēnei arotake. Ko ngā tauira e toru ko te mate ikura roro ohorere ki tētahi wāhi motuhake, ko te korenga hāora me te kūhuka me te whakahokinga hāora ki ngā pūtau whakatipu, me te rere toto iti ki te roro mō ngā wiki maha. E whakaarohia ana he tukanga mitokōria te hononga i waenganui i ēnei, engari ka rerekē ngā putanga nā te rerekē o ngā āhuatanga pākia.

He pātai rerekē tā ngā tauira e toru e whakautu ana

I ngā kiore, ko te tikanga hei whakaputa i te mate ikura roro ohorere ki tētahi wāhi motuhake, he aukati i te iatuku roro waenga. Ko MCAO te whakapotonga mō tēnei. Mā tētahi aukatinga e rite ana ki te katinga toto e hanga he pūtake iskemia, arā, he pūtake kua kore e rawaka te rere toto. Ka karapotia taua pūtake e tētahi rohe paetata, te penumbra, he kiko kei te mōrearea, engari tērā pea ka whakaorangia ki te hoki mai te rere toto. Ko te pātai i konei, mēnā ka pōturi ake te whānuitanga o te wāhi kiko mate nā tētahi wawaotanga, ka tiakina rānei te mahi a te roro i te wā e whakahokia ai te rere toto.

Kei te taumata tino rerekē te korenga hāora me te kūhuka, ko OGD tōna whakapotonga. Ka whakanohoia ngā pūtau roro whakatipu ki tētahi taiao e tata ana te hāora ki te kore, ā, kāore he kūhuka, kātahi ka whakahokia ki te reo whakatipu noa. Kāore he katinga toto, he rere toto mā ngā ara kē, he pēhanga toto, he pūnaha ārai mate rānei. He pātai mō ngā pūtau anake: ka ahatia te hā pūtau, te ATP, me te oranga o ngā pūtau ina ngaro ngā matū e whakamahia ana e te pākia, kātahi ka hoki mai.

Mō te rere toto iti ki te roro mō te wā roa, ka aukatia pūmautia ngā iatuku kakī i ngā taha e rua o ngā kiore. Ko te tauira 2VO te ingoa. Ka heke te rere toto ki te roro o mua, ā, ka noho iti mō ngā wiki maha. Kāore he matenga kiko ohorere ki tētahi wāhi motuhake, kāore hoki he whakahokinga rere toto ohotata. Ko te pātai, mēnā mā te tautoko i te pākia mō ngā wiki maha e tiaki ngā ia toto, ngā mitokōria, me te pūmahara i te wā e iti tonu ana te rere toto.

Nō reira, kāore tētahi pikinga o te pūmahara i muri i te kotahi marama o te maimoatanga i te tauira 2VO e whakaatu tika ana i tētahi mea mō te whakaora i te roro tangata i te wā o tētahi tangohanga katinga toto ohotata. He mea nui tēnei wehewehenga, nā te mea ka waiho ki waho i te nuinga o ngā whakarāpopototanga e whakaatu ana i te tūmanako nui.

Te mate ikura roro ohorere: he whakamarutanga ina whakahokia te rere toto, he whakaroanga ki te kore e whakahokia

Ko te putanga ohorere tino mārama i ahu mai i te MCAO rangitahi me te whakahokinga rere toto. I aukatia te iatuku o ngā kiore mō te 60 meneti, kātahi ka hoatu he horopeta iti o te kikorangi metilīni mā te ia auraki, tīmata ai i te whakahokinga rere toto, me ētahi atu horopeta i te 3 hāora me te rā 2. I whakaatu te MRI kua piki te rahi o te wāhi whara i te rōpū i whiwhi i te wairewa kawe anake mā te 19 ōrau pea i mua i te rā 2, engari kua heke te rahi i te rōpū i whiwhi maimoatanga mā te 17 ōrau pea. He iti iho ngā wāhi kiko mate whakamutunga mā te 30 ōrau pea, ā, he pai ake ngā kaute mahi io i ngā rā 2 me te 7. I kitea i ngā whakaahua he pai ake te oranga o ngā kiko i te pūtake me te rohe paetata. Ka whakatakotoria e ngā tuhinga whānui mō te whakamarutanga io tēnei whakamarutanga i te wā whakahoki rere toto ki te taha o ngā kitenga mō te iskemia whānui me te wharanga.

Ka rerekē te āhua ina noho aukati tonu te iatuku. I tētahi whakamātau MCAO pūmau, nā te kikorangi metilīni i hoatu i te wā e haere tonu ana te iskemia i pōturi ake te whānuitanga o te wāhi whara i kitea mā te whakaahua tōringiringi, ā, i roa ake mō tētahi wā poto te rerekētanga i waenganui i ngā whakaahua rere toto me ngā whakaahua tōringiringi. He paku pai ake hoki te rere toto ā-rohe, engari kāore i tino rerekē te rōrahi whakamutunga o te wāhi kiko mate i te 24 hāora i runga i te ine tauanga. I whakaroatia te hurihanga o te kiko mōrearea hei kiko mate, engari kāore tēnei i whakakapi i te whakatuwhera anō i te ia toto.

Ka tāpiri tētahi rangahau ohorere tuatoru i ngā taipitopito mō te tukanga me te horopeta. I hoatu he horopeta kotahi ki roto i te kōhao puku i muri tonu i te aukatinga. Ko te hekenga nui rawa o te wāhi kiko mate, tata ki te 50 ōrau, i kitea i te horopeta waenga o te 5 mg/kg, kaua i te 1, i te 10 mg/kg rānei, me ngā kaute tairongo me te nekeneke pai ake. I hono ngā kaituhi i tēnei ki te tiakina o te hanganga mitokōria me te pikinga o te mitophagy, arā, te whakakorenga whiriwhiri o ngā mitokōria kua tūkinotia. Nō reira, he mea nui te horopeta, te ara hoatu, me te hōtaka hoatu, ā, ehara ngā uara mg/kg mō ngā kiore i te horopeta mate ikura roro mō te tangata.

Ngā pūtau whakatipu: ka āwhina, ka whakakino rānei te rongoā kotahi i runga i te wā e tae mai ai

Ko te whakamātau pūtau whetū te mea e tino whakamārama ana i te take, ā, koia hoki te mea e tino hē ana te whakahua. I pāngia ngā pūtau whetū taketake o te kiri roro kiore iti e te korenga tino nui o ngā rauemi mō te 6 hāora, i te 0.1 ōrau hāora, i roto i te reo whakatipu kāore he kūhuka, he piruwāti, he serum rānei. Whai muri i tēnā, ka whakahokia te hāora me ngā matū pākia mō te 24 hāora. Tata ki te haurua o ngā pūtau i mate, nō reira he wāhi tō te whakamātau ine hei whakaatu i te pānga pai, i te pānga kino rānei.

I te wā i noho ai te kikorangi metilīni i te wāhanga korenga rauemi, i kino ake te oranga o ngā pūtau. Engari, i te wā i whakaurua ai i te whakahokinga hāora, nā ngā kukū iti i te taumata maikoromōra i pai ake ai te oranga o ngā pūtau, i piki ai hoki te whakamahinga hāora, te tangohanga kūhuka, me te whakaputanga ATP. I ngā āhuatanga noa, nā aua kukū anō i piki ai te tangohanga kūhuka mā te 89 ōrau pea i te 0.1 maikoromōra, me te 200 ōrau pea i te 1 maikoromōra. I tiakina hoki te kūhukōtene me te mahi a te hexokinase i muri i te wharanga, ā, kāore i inea he pikinga o te superoxide.

He māmā ake te mārama ki te tukanga mā te whakataurite ki tētahi pūwhakaputa hiko tāpiri. Ka mahi te kikorangi metilīni hei kaikawe irahiko kē e tango ana i ngā taurite whakaheke me te tuku atu ki te cytochrome c me te matatini IV. Ka tautoko tēnei i te rere irahiko me te waihanga ATP, me te whakaiti i te rerenga irahiko ki waho i ngā wāhanga tōmua o te ara. I te wā o te korenga tino nui o ngā rauemi, he raruraru taua whakaongaonga, nā te mea ka piki te hiahia pākia i te wā e tata ana te hāora me te kūhuka ki te kore. Mā tēnei e tere ake ai te pau o ngā rahui whakamutunga. Ina hoki mai ngā matū pākia, ka whai hua taua āhuatanga anō, nā te mea ka āwhina i ngā mitokōria kua tūkinotia ki te whakamahi tōtika i te hāora me te kūhuka kua whakahokia. Koia hoki te take me whakauru tonu ngā āhuatanga o te korenga rauemi ki ngā whakamāramatanga o ngā kitenga mō te whakawhitinga irahiko mitokōria.

Kotahi te tūpato: nō taua whakaritenga pūtau whetū tēnei ture mō te wā hoatu. I tētahi rangahau pūtau i te taha o tēnei, he momo pūtau kē, he korenga rauemi ngāwari ake, he kukū iti iho hoki i whakamahia. I kitea he whakamarutanga ahakoa i pā te kikorangi metilīni ki ngā pūtau i te wā o te korenga rauemi. Mā te momo pūtau, te hāora e toe ana, te kukū, me te tikanga whakamātau e whakatau mēnā he pai, he kino rānei te pānga.

Te rere toto iti mō te wā roa: te pūmahara, te cytochrome oxidase, me ngā ia toto i roto i ngā wiki maha

I ngā whakamātau mō te wā roa, i whakamahia he maimoatanga horopeta iti ia rā mō ngā wiki maha, ehara i te werohanga ohotata kotahi. I te rangahau tuatahi, i whiwhi ngā kiore kua aukatia pūmautia ngā iatuku kakī i te 4 mg/kg ia rā mō te kotahi marama. I hoatu i muri i ia wā whakangungu o ia rā, kia aro ki te whakapūmau pūmahara, kaua ki te mahi i taua wā tonu. I pōturi ake te ako a ngā kararehe kua aukatia ō rātou iatuku ki ngā mahi wehewehe ā-kanohi, ā, i kino ake ā rātou mahi i tētahi whakamātau pūmahara uaua. Kāore i pāngia te kaha kauhoe, te mahi nekeneke, me te mōhio ki ngā haunga. Nā te maimoatanga ia rā i whakaiti ngā ngoikoretanga ako me te pūmahara, me te kore e whakarerekē i te whanonga nekeneke whānui.

I tētahi rangahau whai muri, i maherehia te cytochrome oxidase, arā, te matatini IV o te mitokōria, puta noa i ngā rohe roro e 44 i muri i taua hōtaka kotahi marama anō. Nā te aukatinga i heke ai te mahi a te whākōkī i te kiri roro kite, te kiri roro o mua, te kiri roro perirhinal, te hippocampus me te amygdala. I ngoikore ake hoki te mahi ngātahi i waenganui i te kiri roro kite me te hippocampus. Nā te maimoatanga i tiaki te mahi whākōkī ā-rohe me te whakapakari i aua hononga pākia i waenganui i ngā rohe, ā, i whai hononga te mahi i tiakina ki te pai ake o te whakatutuki i ngā mahi whakamātau. E whakaahua ana ēnei hononga i te mahi ngātahi a ngā whākōkī pākia, ehara i te ine tika i te tūhononga mahi o te roro tangata. Mā ngā arotake mō te pākia pūngao o te roro e āwhina ki te pupuri i taua wehewehenga.

I tētahi rangahau motuhake mō te kotahi wiki, i whakamahia te 2 mg/kg ia rā, ā, i tāpirihia he matū aukati ara hei whakamātau i te tukanga. I piki te rere toto ki te roro mai i te 60 pea ki te 100 pea mL mō ia 100 g i ia meneti i te maimoatanga, ā, i piki te kiato o ngā ia toto o te hippocampus mai i te 15.1 pea ki te 23 ōrau. I hoki whakamuri ētahi o aua pikinga e rua i te aukatinga o te ara oranga PI3K/Akt, ā, i piki te Akt kua tāpirihia he rōpū pūkōwhai i te maimoatanga. Ko ngā kitenga mō te rere toto, te kiato ia toto, te ārai, me ngā pūtau io e tohu ana i te whakamarutanga o ngā io me ngā ia toto e hono ana ki te tuku tohu PI3K/Akt, kaua ki tētahi pānga pākia anake.

He aha i kore ai ēnei kitenga e rite ki te tiaki ohotata mō te mate ikura roro

Ko te whakahaere pū o ngā āhuatanga taiwhanga te take kāore e taea te whakawhiti tika i ēnei putanga. Kāore he katinga toto, he tukanga tohatoha me te whakakore rongoā rānei o ngā pūtau whakatipu. Ko te tauira 2VO he rere toto iti whānui mō te wā roa, ehara i te katinga ohorere ki tētahi wāhi motuhake nā tētahi embolus, me tētahi rohe paetata nō ngā meneti torutoru noa iho. Ahakoa te MCAO kiore, ka whakamahia ngā kararehe taitamariki hauora, te whakarehu, ngā aukatinga ōrite, me te hoatu horopeta i ngā wā kua tino whakaritea. He rerekē tēnei i ngā tūroro pakeke ake, he rerekē ō rātou katinga toto, he whakapakeketanga iatuku, he pēhanga toto tiketike, he mate huka, ā, kāore e mōhiotia te wā tīmatanga.

Kāore anō tētahi whakamātau matapōkere tangata kua whakaputaina kia whakaū i te kikorangi metilīni hei maimoatanga ohotata mō te mate ikura roro ohorere nā te iskemia. I tētahi rangahau whakaahua roro tangata ka whakahuahia i ētahi wā, e 26 ngā pakeke hauora i whakaurua, ehara i te tūroro mate ikura roro. Nā tētahi horopeta kotahi mā te waha i whakarerekē ngā tohu roro e pā ana ki ngā mahi whakamātau, me tētahi pikinga iti o te kaha maumahara. E whakaatu ana tēnā i tētahi pānga ki te pūnaha io pokapū, ehara i te whaihua mō te mate ikura roro. Ko ngā aratohu ohotata o nāianei e aro kē ana ki te whakahokinga wawe o te rere toto mā te whakarewa katinga toto mā te ia auraki mō ngā tūroro e tika ana, me te tangohanga katinga toto mō ngā aukatinga ia toto nui e tika ana. Ko ngā ara tiaki ohotata paerewa mō te mate ikura roro tonu ngā ara anake kua whakaūngia. Kaua rawa e whakaroa te tiaki mō tētahi mate ikura roro e whakapaetia ana kia hoatu ai te kikorangi metilīni. Mā ngā herenga tūturu o te whakatau horopeta haumanu mai i ngā rangahau i mua i ngā whakamātau haumanu e whakamārama he aha e kore ai e tika te pānui i ngā hōtaka kiore hei hōtaka haumanu.

Ka whakapakari ngā āhuatanga haumaru i taua rohe. He whakatūpato kei roto i tētahi pouaka tō te kikorangi metilīni mā te ia auraki mō te mate serotonin kino, whakamate rānei, ina whakamahia ngātahitia me ngā rongoā e pā ana ki te serotonin, tae atu ki ngā SSRIs, ngā SNRIs, me ngā matū aukati MAO. He tokomaha ngā tūroro kei ngā pakeketanga e pā ai te mate ikura roro e kai ana i ēnei rongoā. Kāore e whakaaetia te whakamahi i te hunga he ngoikore te G6PD nā te mōrearea o te pakarutanga o ngā pūtau toto whero. Ka aukati hoki i te tuku tohu nitric oxide, ā, i ētahi āhuatanga ka piki te ātete o ngā ia toto me te pēhanga. Nō reira, kaua e whakaahua noa hei rongoā whakapiki i te rere toto ki te roro. Ko te hōtaka 1 mg/kg mā te ia auraki kua whakaaetia mō te methemoglobinemia kua puta i muri mai i te whānautanga, ehara i te hōtaka mō te mate ikura roro.

He whāiti te whakarāpopototanga pono, engari he taunakitanga tūturu tōna. I te wā e tata ana ki te whakahokinga rere toto i te iskemia rangitahi ki tētahi wāhi motuhake, nā te horopeta iti o te kikorangi metilīni i whakaiti te whanaketanga o te wāhi whara i ngā kiore. I raro i te aukatinga pūmau, i whakaroatia te matenga kiko, engari kāore i āraitia. I ngā pūtau whetū, i whakakino i te wā o te korenga tino nui o ngā rauemi, ā, i āwhina i te whakahokinga hāora. I te wā o te rere toto iti mō te wā roa, i tiakina te cytochrome oxidase, ngā ia toto, me te pūmahara mō ngā wiki maha. Kotahi te kaikawe, e toru ngā horopaki, e toru ngā whakautu.