» arhiv
Možnosti:
[Prikaži v obliki za tiskanje]
[Poišči nalogo v zbirki Cobiss]
ID naloge: 61 Letnik: 1999 Predmet: patofiziologija
Pomen Schwannovih celic za vzdrževanje regeneracije senzoricnih aksonov pri podgani
Avtor: Iztok Gril, Marko Jug
Mentor: prof.dr. Janez Sketelj
Somentor: as. mag. Fajko Bajrovic
Izhodišce. Dobro regeneracijo aksonov po poškodbi perifernega živca omogocajo razmnožene Schwannove celice (SC) v distalnem krnu, ki izlocajo topne spodbujevalne dejavnike, in bazalne lamine SC. Le-te tvorijo nevrilemske cevke, ki predstavljajo ugodno rastno podlago za aksone. Rezultati raziskav o relativnem pomenu topnih dejavnikov in rastne podlage so delno protislovni. Novejša študija je pokazala, da se senzoricni aksoni med regeneracijo skozi brezcelicni distalni krn po relativno hitri rasti v prvem tednu po poškodbi ustavijo. Vodeci aksoni se nato retrahirajo proti mestu poškodbe. Nova rast se vzpostavi samo, ce je možna migracija SC iz proksimalnega krna. Dosedanji rezultati kažejo, da bi za zaustavitev rasti aksonov lahko bila odgovorna degeneracija rastne podlage v odsotnosti SC.
Namen. Preverili bomo naslednje hipoteze:
1. Ustavitev rasti in retrakcija senzoricnih aksonov v drugem tednu regeneracije v odsotnosti celicne podpore nista posledici trajnejše "izcrpanosti" v telesu nevrona, ampak odsev neustreznih razmer v mikrookolju regenerirajocih se aksonov.
2. Ob ohranitvi primerne rastne podlage se lahko rast aksonov vzdržuje tudi v drugem tednu po poškodbi, oz. ne pride do njihove retrakcije, tudi ob trajni odsotnosti SC.
3. Z dodajanjem topnih dejavnikov SC lahko vzdržujemo rast aksonov, oz. preprecimo njihovo retrakcijo, tudi med podaljšano regeneracijo skozi brezcelicni odsek kljub delno degenerirani rastni podlagi.
Metode. Suralni živec podgane smo poškodovali z aksonotmezo. V prvi skupini živali smo celice v distalnem odseku živca z enkratnim zmrzovanjem unicili vse do konca odseka, kontinuiteta cevk BL pa ni bila prekinjena. V drugi skupini živali smo zmrzovali le 10 oz. 15 mm dolg odsek živca za mestom aksonotmeze in pustili celice distalno ohranjene. V tretji skupini živali smo distalni odsek dvakrat zapored zmrzovali v razmaku štirih dni. Drugo zmrzovanje je zajelo odsek distalno od prvega. V cetrti skupini smo v celoti zmrzovani distalni odsek n. suralisa ovili v degeneriran odsek n. peroneusa. Hitrost regeneracije najhitrejših aksonov smo testirali s testom všcipa živca. Aksone smo na precnem prerezu živca prikazali z imunohistokemicno reakcijo na nevrofilament.
Rezultati. Potrdili smo, da se zacetna hitra rast senzoricnih aksonov skozi popolnoma brezcelicni odsek distalno od aksonotmeze po osmih dneh ustavi. Ustavitvi rasti sledi retrakcija vodecih aksonov. Pri regeneraciji skozi 10 oz. 15 mm dolg brezcelicni odsek do ustavitve rasti ne pride. Rast aksonov skozi dvakrat zapored zmrzovani odsek živca se v drugem tednu ne ustavi, je pa pocasnejša. Elongacija aksonov skozi brezcelicni odsek, obložen z degeneriranim živcnim odsekom, se v drugem tednu ne ustavi, se pa upocasni.
Sklep. Ustavitev rasti aksonov skozi brezcelicni distalni odsek živca je posledica neugodnih razmer v mikrookolju regenerirajocih se aksonov. Z ohranjanjem dobre rastne podlage lahko vzdržujemo rast dalj casa kljub stalni odsotnosti celicne podpore. Z dodajanjem topnih dejavnikov SC lahko vzdržujemo rast med podaljšano regeneracijo skozi brezcelicni distalni odsek živca tudi ob delno degenerirani rastni podlagi
«»
[Abstract / English version]
The role of Schwann cells in maintaining regeneration of sensory axons in the rat
Author: Iztok Gril, Marko Jug
Mentor: prof.dr. Janez Sketelj
Co-mentor: as. mag. Fajko Bajrovic
Background. Satisfactory regeneration of axons after crush injury of periferal nerve is supported by proliferating Schwann cells (SC) in the distal stump and their basal laminae. SC secrete diffusable growth promoting substances, whereas basal laminae provide good growth substratum within the neurilemmal tubes. The results of previous studies about the relative importance of diffusable growth promoting substances and growth substratum are partly controversial. A recent study showed that sensory axons, regenerating through the acellular distal nerve segment, elongated fairly rapidly during the first week after axonotmesis, but then cease to grow. Leading axons retracted towards the site of axonotmesis. Subsequent elongation was possible only with concomitant migration of SC from the proximal stump. Previous experiments indicated that degeneration of growth substratum in the absence of Schwann cells could be responsible for cessation of axonal growth.
Objectives. Our goal was to examine the following hypotheses:
1. Cessation of axonal growth and retraction of sensory axons during the second week of regeneration in the absence of cell support is a consequence of unfavourable microenviroment of the regenerating axons and is not due to permanent "exhaustion" of neuron cell body.
2. If adequate growth substratum is maintained, axons continue to grow and there is no retraction during the second week after axonotmesis, even in the absence of SC.
3. Elongation of axons can be maintained and their retraction prevented during prolonged regeneration through acellular distal nerve segment by providing diffusable growth promoting substances of SC, even though the growth substratum is partly degenerated.
Methods. Rat sural nerve was crushed. In the first group of animals the cells in the distal stump were killed by freezing the whole distal segment at once. In the second experimental group, only 10 or 15 mm long segment of the nerve adjacent to the crush site was frozen, to leave the cells distally alive. Nerves in the third group of animals were frozen twice with an interval of four days in between. The second freeezing was applied to the nerve segment distally to the first. In the fourth group, a nerve sandwich was composed of the frozen sural nerve wrapped in a degenerated segment of the peroneal nerve. Elongation rate of regenerating axons was monitored by nerve pinch test. Axons in the nerve cross-sections were demonstrated by imunnohistochemical staining against neurofilament.
Results. We confirmed that rapid initial growth of sensory axons through the completely acellular distal nerve segment stopped after eight days. Thereafter the leading axons began to retract. When regeneration of axons through 10 or 15 mm long acellular segments was examined, there was no reduction in elongation rate. Growth of axons along successivly frozen nerve segments did not stop during the second week, although it was slowed down. Elongation of axons through the nerve sandwich was slowed down during the second week but it did not stop.
Conclusions. Cessation of growth of axons through an acellular distal nerve segment in crushed nerves is a consequence of unfavourable microenviroment of the regenerating axons. By maintaining good growth substratum, the growth can be sustained, even though viable cells are not present. By providing diffusable growth promoting factors (secreted by SC), we enabled the axons to elongate during prolonged regeneration even in the presence of partly degenerated growth substratum.
|
|
 |
Išči po nalogah
Brskaj po nalogah
Prijava na obvestila
|
