Te kikorangi metilīni mō te wharanga roro: te mārama ki ngā taunakitanga i mua i ngā whakamātautau haumanu

Ko te tukinga ki te māhunga, ko te ia-toto kua purua, ko te mate āta whakaheke i ngā pūtau io, ka mutu pea ēnei katoa ki te raruraru kotahi: kua kore i te roro te pūngao hei whakatutuki i āna mahi. Nā taua mutunga ōrite ka kitea tonutia tētahi pūhui i ngā tuhinga rangahau mō ēnei mea e toru. Engari, ehara te mutunga ōrite i te ariā ōrite. Ko te maimoatanga ka hoatu i mua i te wharanga, ko te maimoatanga ka hoatu i te hāora i muri mai, me te maimoatanga ka inea ngā hua i ngā marama i muri mai, e whakamātau ana i ngā whakaaro rerekē, ahakoa he wai kikorangi ōrite kei roto i te pūwero.

E whai ana tēnei tuhinga i te wāhanga wharanga o aua rangahau. Ka arotakehia te tikanga o te kikorangi metilīni mō te wharanga roro i ngā whakamātautau kararehe, ka wehewehea te wharanga nā te pānga kaha i te ikura roro me te hekenga mauroa o ngā pūtau io, ā, ka whakaaturia he aha te wā o te hoatutanga o te horopeta e whakamārama ai i te nuinga o ngā rerekētanga i waenga i ngā rangahau.

E toru ngā momo wharanga, kotahi te korenga pūngao

Kei roto i ngā mitokōria te tukanga e hono ana i ēnei tauira. I te tikanga noa, ka haere ngā irahiko mā te mekameka kawe irahiko hei whakaputa ATP, ā, mā te mekameka ora e whakahaere ngā momo hāora tauhohe. Whai muri i te wharanga, ka ngoikore ētahi wāhanga o te mekameka, ka heke te whakaputanga ATP, ā, ka piki te whakaputanga rāpoi tuwhena. E whakaahua ana te arotake Molecular Neurobiology o 2018 i te kikorangi metilīni hei kaikawe irahiko kē: ka tango irahiko i te NADH, ka tuku atu ki te cytochrome c, mā reira ka piki te mahi a te matatini IV, ka hoki mai hoki te waihangatanga ATP ahakoa kua ngoikore te wāhanga tōmua o te mekameka.

He tau mārama ngā tau i pūrongotia. I ngā whakaritenga pūtau me ngā poro kiko, i piki te mahi a te matatini IV mā te 30 ki te 100 ōrau, ā, i piki tahi te whakamahinga hāora. E tohu ana tēnei i whai hua ngā irahiko tāpiri, kāore i turuturu hei rāpoi tuwhena. I tētahi tauira ikura roro kiore, tata ki te 30 ōrau te pikinga ake o te whakaputanga ATP i te rohe i pāngia, 24 hāora i muri i te maimoatanga, tēnā i ngā kararehe kāore i maimoatia. Ka tāpirihia e te arotake Biochemistry (Moscow) o 2022 ngā pānga ka whai mai: he iti ake te ahotea hāoratanga, te kakātanga o ngā kiko io, me te matenga pūtau kua whakaritea, me ngā pānga ki te monoamine oxidase, te nitric oxide synthase, te waihangatanga mitokōria, te kai-whaiaro a ngā pūtau, me te whakahuihuinga o ngā pūmua hē te pōkai.

Nō reira, he māmā te ariā. Ka aukati te wharanga i te ara noa o ngā irahiko, ā, ka whakarato te kikorangi metilīni i tētahi ara kē. Ko ngā mea katoa ka whai mai he pātai mō te momo wharanga, te wā i hoatu ai, me te āhua i inea ai.

Ehara te wharanga nā te pānga kaha i te ikura roro

I tētahi tauira wharanga roro nā te pānga kaha, ka pā te kaha i te wā kotahi. He pakarutanga ā-tinana te pakarutanga tuatahi: ka haehae te kiko, ka pakaru ngā ia-toto, ā, ka tuwhera te tauārai toto-roro i roto i ngā meneti. Ko te mea e tika ana pea kia pāngia e te kikorangi metilīni ko te ngaru tuarua ka whai mai i roto i ngā hāora me ngā rā, i te ngoikoretanga o ngā mitokōria i te kiko e ora tonu ana, i te horapa o te kakātanga, me te pikinga o te pupuhi nā te wai. E whakaata ana ngā inenga mutunga o ēnei rangahau i taua raupapa: te rōrahi o te wāhi pakaru, te nui o te wai i te roro, te oranga o ngā pūtau io e tata ana ki te tukinga, me ngā whanonga ā muri ake pērā i te hoki mai o te nekeneke, i te ako rānei i te ara rīrapa.

I tētahi tauira ikura roro, korenga toto puta noa rānei, he rerekē kē te āhua o te takahanga. Ka mutu te rere toto, ka whai mai te korenga pūngao i roto i ngā meneti, ā, ka hua ake anō he wharanga i te hokinga mai o te rere toto. I konei ka whakahāngaitia te hoatutanga horopeta ki te takahanga o te ia-toto, he maha ngā wā i roto i ngā meneti i muri i te purunga, i te hokinga mai rānei o te rere toto. Ka ine ngā inenga mutunga i te āhua o te kiko i te wā ohotata, mai i ētahi hāora ki te kotahi, ki te rua rā rānei: te rahi o te kiko mate nā te korenga toto, te rere toto, me te hoki wawe mai o te mahi. Ko tētahi tauira auau i ngā rangahau ikura roro ko te maimoatanga i mua, arā, te hoatu horopeta ki ngā kararehe i mua i te purunga o te ia-toto. Ka whakamātauria e tēnei te ārai i tētahi āhua kāore e tika ā-matatika kia tāruatia i te tangata e ngā whakamātautau wharanga māhunga.

Ko ngā hua ikura roro ngā hua kaha rawa o ngā rangahau wharanga, ā, kei roto hoki te kitenga kore-pānga tino mārama. I ngā kiore i hoatu ai te kikorangi metilīni i te hokinga mai o te rere toto, whai muri i te purunga o te ia-toto roro waenganui mō te kotahi hāora, he 30 ōrau te iti ake o ngā wāhi kiko mate i te rā 2, ā, he nui ake te kiko i whakaorangia i te pūtake me te rohe huri noa e mōrearea ana (Shen, 2013). I kitea e tētahi rangahau purunga pūmau he pōturi ake te hurihanga o te kiko mōrearea hei kiko mate, engari kāore i heke te rōrahi whakamutunga o te kiko mate i te 24 hāora, i tētahi o ngā horopeta e rua i whakamātauria (Rodriguez, 2014). I tētahi rangahau purunga tuatoru, i heke te rahi o te kiko mate ki te āhua haurua i te horopeta waenganui, ā, i tuhia tika te hanganga moroiti rawa o ngā mitokōria me te whakakorenga mitokōria mā te kai-whaiaro i roto tonu i te roro kua kore e whiwhi toto. I pūrongotia hoki te kōrero rerekē i te tūmanako: i piki te matenga pūtau kua whakaritea i te hekenga o te matenga pūtau nā te pakarutanga (Di, 2015). Ā, i te korenga toto puta noa, nā te whāngai pūmau i tētahi horopeta iti i whakahoki te mahi a te cytochrome c oxidase, ngā taumata ATP, me te pūmanawa hiko o te kiriuhi mitokōria i te rohe CA1 whakaraerae o te hippocampus; i pupuri hoki i aua pūtau io, i tiaki hoki i te mahara mokowā (Lu, 2016). He mea nui kia āta whakaaro ki taua inenga CA1: he raraunga tika mō te ATP me te mekameka whakahā mai i roto tonu i tētahi roro whara. I te nuinga o ngā rangahau TBI, ka whakapaetia ēnei, kaua e inea.

He rerekē te hekenga mauroa o ngā pūtau io i ēnei mea e rua. I ngā tauira mate Alzheimer, Parkinson, me Huntington, ka hoatu horopeta ki ngā kararehe mō ngā wiki, mō ngā marama rānei, ka inea te whakahuihuinga pūmua, te whakahaere dopamine, te āta heke rānei o te āheinga hinengaro. He iti rawa ngā mea ōrite i waenga i aua inenga mutunga me tētahi wāhi pakaru ka inea i ngā rā i muri i te tukinga. Ki te whakawhiti te kaipānui i tētahi hua mai i tētahi wāhanga ki tētahi atu, e whakawhiti ana ia i tētahi kitenga ki tua o tētahi rohenga kāore i whakawhitia e ngā whakamātautau. Ka pupuri tā mātou aratohu ki ngā rangahau hekenga pūtau io i aua rangahau wā-roa ki tō rātou ake horopaki, ā, ka wehewehe taipitopito te whakataurite ki ngā taunakitanga mō te ikura roro anake i ngā hoahoa purunga ia-toto i ngā hoahoa tukinga.

Ngā mahi i tino mahia e ngā tauira TBI

Kāore anō kia whakaputaina tētahi whakamātautau tangata o te kikorangi metilīni mō te wharanga roro nā te pānga kaha. He mahi kararehe te katoa o ngā taunakitanga TBI, ko te nuinga he kiore nui, he kiore iti, ā, e aronui ana ki tētahi huinga whakamātautau iti e tika ana kia whakaingoatia, nā te mea he rerekētanga kei ō rātou taipitopito ka ngaro i ngā whakarāpopototanga.

I te rangahau tuatahi mō te tukinga whakahaere ki te kiri roro, i hoatu ki ngā kiore te 1 mg/kg mā te ia-toto kotahi hāora i muri i tētahi tukinga māmā, kātahi ko te 0.5 mg/kg i te toru hāora (Watts, 2014). I noho iti ake te rōrahi o te wāhi pakaru i inea mā te MRI i ngā kararehe i maimoatia, puta noa i ngā wiki e rua o te aroturuki. I tino heke ngā hē takahanga waewae i tētahi whakamātautau hīkoi i ngā rā 1, 2, me 7, engari kāore i te rā 14. I raro i te karu whakarahi i te rā 14, ko te tatau pūtau io e heke ana i te kiri roro whara he 270 ki te 368 i ia āpure tirohanga, ā, ko te tatau whakapoke Nissl rerekē he 41 ki te 73. Arā, he tiakitanga tōmua, engari e memeha ana te painga whanonga i te wiki tuarua.

I tētahi hoahoa wharanga marara, i whakamahia he tukinga pēhanga wai ki te rārangi waenga i ngā kiore iti, me tētahi horopeta kotahi o te 2 mg/kg mā te ia-toto i roto i te haurua hāora (Fenn, 2015). I ngā kararehe i maimoatia, he iti ake te whakapuakitanga o ngā ira e pā ana ki te kakātanga, he iti ake ngā microglia kakā, he iti ake te pupuhi i kitea, ā, kāore he whanonga rite ki te pōuritanga i te rā 7. He mea nui anō ngā kitenga kore-pānga: nā te wharanga tonu i piki paku noa te wai o te roro, ā, kāore te kikorangi metilīni i whakatika i te hekenga taumaha tinana, i te ngoikoretanga rānei o te ruruku nekeneke. Ehara te whakaiti kakātanga i te tino tiaki i ngā mea katoa.

E rua ngā rangahau kiore iti i whakamahi i te hōtaka kotahi: 1 mg/kg i te kotahi hāora, 0.5 mg/kg i te ono hāora, kātahi he horopeta ia rā mō ngā rā e toru. I whakawhānui hoki ēnei i te māramatanga ki te tukanga. I tētahi tauira tukinga kiri roro, nā te maimoatanga i whakaiti te rōrahi o te wāhi pakaru i te 24 hāora, te 72 hāora, me te rā 14, me te pupuri anō i ngā pūtau io me te whakapiki i ngā tohu kai-whaiaro pūtau (Zhao, 2016). I tētahi tauira tukinga pēhanga wai, i whakaitia te matenga pūtau io kua whakaritea, i whakakaha i tētahi tauārai toto-roro turuturu, ā, i pai ake ngā kaute mahi io puta noa i ngā wiki e rua (Shen, 2019). Heoi, kāore he rerekētanga o te nui o te wai i te roro i te 72 hāora i te rangahau Zhao, ā, kāore he rerekētanga o te mahi i te rākau hurihuri i ngā rā 1 me 3 i te rangahau Shen. I rerekē ngā inenga mutunga mō te wāhi pakaru me te oranga pūtau; kāore te pupuhi me ngā inenga nekeneke tōmua i whai i ngā wā katoa.

Ko te whakamātautau hoatutanga horopeta whakaroa te mea motuhake mō te wā (Watts, 2016). I whakamahia taua tauira tukinga anō, engari kāore i hoatu te horopeta tuatahi kia tae rā anō ki te 24 hāora i muri i te wharanga. I te rā 2, i kitea i te rōpū whakaroa ngā hekenga wāhi pakaru e rite ana ki ērā o ngā kararehe i maimoatia i ngā hāora tuatahi, ā, i mau tonu te hekenga i ngā rā 7 me 14. He ngoikore ake te tohu whanonga: ko te pai ake o ngā hē takahanga waewae i te rōpū whakaroa he ia kāore i whai hiranga ā-tatauranga. Kotahi te taiwhanga, kotahi te tauira, kotahi te matapihi 24 hāora. He taunakitanga tūturu tērā ka toro atu te matapihi ki tua o ngā hāora tuatahi, engari koinei anake hoki ngā taunakitanga mō taua whakapae. Kia mataara ki te mahanga o te kupu whakaroa i wāhi kē: i tētahi raupapa rangahau nō Rūhia, e hāngai ana te taitara ki te tiaki pūtau io whakaroa, i hoatu te horopeta i te 30 meneti. I whakamahia te kupu whakaroa hei tohu i ngā hua mauroa, kaua i te tīmatanga tōmuri.

Ka whakaoti tētahi rangahau iti ake mō te wharanga ki tētahi wāhi kotahi i ngā kiore i te tirohanga wā mai i tērā atu taha: nā te hoatu horopeta i mua tonu i te wharanga, me te hoatu i te 30 meneti i muri mai, i whakaiti te ngoikoretanga o ngā peka i ngā wā e rua (Stelmashook, 2019). Ka whai hua te maimoatanga i mua i te taiwhanga nā te mea mā te taiwhanga tonu e whakarite te wā o te wharanga.

He mea nui i konei te āta whakahaere i te horopeta. E whakaahua ana ngā arotake i ngā horopeta iti hei whakaihiihi i te whakahā mitokōria, ā, i ngā horopeta nui hei aukati. Koinei anō te āhua wāhanga-rua e kitea ana puta noa i te mātauranga rongoā kikorangi metilīni. Nā reira, kāore e tika kia pānuitia ngā hua hei mea he nui ake te kikorangi, he nui ake te whakaora. Ka whakamātau ia rangahau i tētahi ira kotahi i runga i tētahi ānau. Ka whai te whakamārama urupare ki te horopeta i taua ānau puta noa i ngā tauira, ā, ka kōrero te tirohanga haumaru me ngā pānga taha mō ngā mahi kē a ngā horopeta nui ake.

Pānuitia whānuitia taua ripanga: kotahi tonu te pūhui, engari e toru ngā karaka rerekē. Kei te rarangi waenganui te ārai, kei ngā rarangi tuatahi e rua te maimoatanga wawe, ā, kei te rarangi tuatahi me te tuatoru ngā hua ā muri ake.

Te ārai, te maimoatanga wawe, ngā hua ā muri ake

Ko te ārai te kerēme māmā rawa kia pōhēhētia. I ngā tauira korenga toto, he pai ake te āhua o ngā kararehe i hoatu ai he horopeta i mua i te purunga ia-toto. I ētahi wā ka whakahuatia taua hua me te mea nei ka tiaki te kikorangi metilīni i ngā roro katoa i ngā takahanga kino katoa o muri mai. Kāore e whakaatu ana i tērā. E whakaatu ana, ki te whakaritea ngā mitokōria mā tētahi ara irahiko kē, ka pai ake tō rātou manawaroa ki tētahi korenga rere toto kua whakaritea te wā. Kāore he tangata e whakarite i te wā mō tētahi wharanga māhunga.

Kei te maimoatanga wawe te nuinga o ngā taunakitanga TBI. Ko te hoatu horopeta i ngā hāora i muri i te tukinga e aro ana ki te raupapa wharanga tuarua i a ia e whanake tonu ana: te korenga pūngao, te ahotea hāoratanga, te kakātanga, te pupuhi. Ko te pai ake o ngā inenga mutunga mō te wāhi pakaru me te pupuhi i konei he pānga maimoatanga tūturu, engari he maimoatanga i tētahi tukanga, ehara i te whakahoki i te kiko kua haehaea ki tōna āhua o mua.

Ko ngā hua ā muri ake te ariā tuatoru. Ko te whanonga ka inea i ngā wiki i muri i te wharanga, ko te whakahaere pūmua rānei ka inea i ngā marama ki roto i tētahi tauira hekenga pūtau io, e whakautu ana mēnā i mau tonu te tiakitanga tōmua, mēnā rānei i panoni te ara o ngā tukanga pōturi. Ko tētahi wāhi pakaru iti ake i te 24 hāora, ko tētahi ia whanonga kāore i whai hiranga ā-tatauranga i muri i te horopeta i whakaroatia mō te 24 hāora, me tētahi pai ake o te mahi ara rīrapa i ngā marama ki roto i te hoatu horopeta mauroa, he kerēme rerekē e toru, he taumata taunakitanga rerekē hoki e toru. I tēnei wā, ko te mea tuatahi anake kua eke ki tōna taumata e hia kē nei ngā wā.

Ngā mea kāore e taea e ēnei taunakitanga te whakaatu

He rohenga ōrite tō ia hua o runga ake nei. Ka urupare ngā mitokōria kiore ki te kikorangi metilīni i ngā āhua tērā pea ka ōrite ki ngā mitokōria tangata. Engari, ehara te kiore i hoatu ai he horopeta mā te ia-toto i ngā meneti i muri i tētahi tukinga kua āta whakatauria tōna kaha, i te tangata ka tae ki te tari ohotata i ngā hāora i muri i tētahi hinganga. Ko te whakamoe mā te rongoā, ko te kaha wharanga kua whakahaerehia, ko ngā kararehe taitamariki hauora, me te wā aroturuki poto, ka whakawhāiti katoa i ngā mea e taea ana te whakawhiti. Kāore rawa he rangahau kikorangi metilīni mō te wharanga nā te pahūtanga, nō reira ko te momo wharanga tino hāngai ki ngā kaipānui hōia te mea iti rawa ngā taunakitanga.

Kāore hoki he tikanga whakawhiti horopeta e whakatakotoria ana. Ka whakamahia e ngā rangahau kararehe ngā ara mā te ia-toto me roto i te kōhao puku, i ngā horopeta i kōwhiria hei whakahaere i te whakamātautau, kaua ko ngā pata mā te waha e hokona ana i ngā toa. Kāore tētahi mea i ēnei rangahau e whakatakoto i tētahi hōtaka maimoatanga tangata, ā, kāore tētahi mea i konei e whakamātau ana i te kikorangi metilīni i te taha o te tiaki wharanga māhunga paerewa.

Nō reira, ka uru te whakarāpopototanga pono ki te kōwae kotahi. I ngā kiore, ka pupuri te kikorangi metilīni i hoatu tata ki te wā o te wharanga roro nā te pānga kaha, nā te korenga toto rānei, i te whakaputanga pūngao mitokōria. Ka whai mai i taua pupuritanga he wāhi pakaru iti ake me ngā kaute whakaora pai ake. I tētahi rangahau tukinga, i mau tonu tētahi wāhanga o te pānga ki te wāhi pakaru ahakoa i whakaroatia te horopeta tuatahi mō te 24 hāora. Kāore anō kia whakamātauria mēnā ka puta tētahi o ēnei mea i ngā roro tangata whara, ā, ka whakamātau ngā rangahau TBI me ngā rangahau ikura roro i ngā wā rerekē ki ngā inenga mutunga rerekē. Ko te tangata e hoko ana i te tino mōhio i runga i ēnei taunakitanga, e tāpiri ana i tētahi kai kāore rawa i roto i ngā whakamātautau.