OBJECTIVES: To evaluate the histological changes of tracheal cartilage and epithelium caused by tracheal occlusion at different gestational ages in a fetal rat model. METHODS: Rat fetuses were divided into two groups: a) External control, composed of non-operated rats, and b) Interventional group, composed of rats operated upon on gestational day 18.5 (term = 22 days), divided into triads: 1) Tracheal occlusion, 2) Internal control and 3) Sham (manipulated but not operated). Morphological data for body weight, total lung weight and total lung weight/body weight ratio were collected and measured on gestational days 19.5, 20.5 and 21.5. Tracheal samples were histologically processed, and epithelial, chondral and total tracheal thicknesses were measured on each gestational day. RESULTS: The tracheal occlusion group exhibited an increase in total lung weight/body weight ratio (p<0.001). Histologically, this group had a thicker epithelial thickness (p<0.05) and thinner chondral (p<0.05) and total tracheal thicknesses (p<0.001). These differences were more prominent on gestational days 20.5 and 21.5. CONCLUSION: Tracheal occlusion changed tracheal morphology, increased epithelial thickness and considerably decreased total tracheal thickness. These changes in the tracheal wall could explain the development of tracheomegaly, recently reported in some human fetuses subjected to tracheal occlusion.

O gliotóxico brometo de etídio (BE) foi utilizado para o estudo da resposta macrofágica e astrocitária sob imunossupressão com ciclofosfamida (CY). Investigou-se a imunorreatividade astrocitária à proteína glial fibrilar ácida (GFAP) e à vimentina (VIM), e a imunorreatividade macrofágica ao ED1 após injeção do BE. Foram utilizados ratos Wistar adultos injetados na cisterna basal com salina a 0,9% (grupo I), BE a 0,1% (grupo II) e BE a 0,1%, imunossuprimidos com CY (grupo III). Fragmentos do tronco encefálico foram colhidos do 1º ao 21º dia pós-injeção para estudo imuno-histoquímico da GFAP, VIM e ED1. Nos grupos II e III, observou-se imunorreatividade aumentada para GFAP e re-expressão de VIM. No grupo II, células ED1-positivas foram observadas a partir do 2º dia e no grupo III, a partir do 3º dia. Aos 14 dias pós-injeção, havia mais células ED1-positivas no grupo III. A CY aparentemente não alterou a resposta astrocitária.

The gliotoxic ethidium bromide (EB) was used to study morphologically the macrophagic and astrocytic response under immunosuppression by cyclophosphamide (CY). Astrocyte immunoreactivity to glial fibrillary acidic protein (GFAP) and vimentin (VIM) and macrophagic immunoreactivity to ED1 were investigated after EB injection. Male Wistar rats were injected with 0.9% saline solution (group I), 0.1% BE (group II) and 0.1% EB associated with CY treatment (group III). Brainstem samples were collected from the 1st to the 21st day post-injection for GFAP, VIM and ED1 immunostaining. In groups II and III, it was observed increased immunoreactivity to GFAP and reexpression of VIM. In group II, ED1-positive cells were noted after the 2nd day and in group III, after the 3rd day. On the 14th day post-injection, it was observed a greater quantity of ED1- positive cells in group III than in group II. Apparently, CY did not change the astrocytic response pattern.

A remielinização do sistema nervoso central após desmielinização tóxica é um processo bem conhecido. No encéfalo, os oligodendrócitos remielinizam uma área maior do que na medula espinhal, onde as células de Schwann são preponderantes. Embora esses fatos sejam bem conhecidos, ainda não se conhece com certeza a origem das células remielinizantes. Esta investigação foi desenhada para esclarecer a participação de oligodendrócitos maduros na reconstrução das bainhas perdidas após a desmielinização induzida por brometo de etídio (BE) no tronco encefálico de ratos Wistar normais e imunossuprimidos com ciclosporina A. Trinta ratos fêmeas adultas foram divididos em três grupos experimentais. No grupo 1, os ratos receberam uma injeção de 10 miL de BE em 0,9% salina (n=10) na cisterna basal; no grupo 2, os ratos receberam a injeção de BE e foram tratados com ciclosporina A (n=10); no grupo 3 os ratos receberam uma injeção de 10 miL de 0,9% salina e foram tratados com ciclosporina A. Os ratos foram sacrificados aos 15, 21 e 31 dias após a injeção. A partir dos 15 dias muitas células da periferia das lesões tiveram marcação positiva para OSP (proteína específica do oligodendrócito), marcador de oligodendrócitos maduros e mielina. Assim, foi possível comprovar que células maduras da linhagem oligodendroglial participam do processo de remielinização neste modelo gliotóxico.

Central nervous system (CNS) remyelination following toxically-induced demyelination is a well known process. Oligodendrocytes constitute the bulk of the myelinating cells in the brain whereas Schwann cells overwhelm oligodendrocytes numbers in spinal cord remyelination. Despite the common knowledge of these facts, we still do not know completely the origin of both remyelinating cells. The present study investigated the participation of mature oligodendrocytes in remyelination after ethidium-bromide (EB) induced demyelination in the brainstem of normal and cyclosporin A-immunosuppressed Wistar rats. Thirty adult female rats were divided into three experimental groups. In group 1 the rats received a single intracisternal injection of 10 muL of 0.1% ethidium bromide (EB) in 0.9% saline (n=10); in group 2 the rats received the EB injection while immunosuppressed with cyclosporin A (n=10); in group 3 the rats received a single 10 muL injection of 0.9% saline while treated with cyclosporin A. The rats were killed at 15, 21 and 31 days after injection. Within the EB lesions, from 15 days onward many cells within the periphery of the lesions stained positive for OSP (oligodendrocyte specific protein) a marker for mature oligodendrocytes and myelin. This cell marking signals that, at least, part of the process of repairing the myelin sheaths is carried out by mature cells of the oligodendrocyte lineage.

Oligodendrócitos e células de Schwann realizam a produção e manutenção das bainhas de mielina, respectivamente no sistema nervoso central (SNC) e periférico (SNP). As células de Schwann, à diferença dos oligodendrócitos, são capazes de invadir o SNC para remielinizar axônios desmielinizados, sempre que os astrócitos tenham sido destruídos. O brometo de etídio é uma droga gliotóxica usada para induzir desmielinização com o desaparecimento precoce de astrócitos, de modo que as células de Schwann têm liberdade para invadir o SNC. Em ratos Wistar normais, a remielinização é detectada treze dias após desmielinização; em ratos Wistar imunossuprimidos com ciclofosfamida a reparação do tecido é tardia, enquanto que em animais tratados com ciclosporina ela é acelerada. O objetivo do artigo é discutir todas as etapas do processo de destruição e reparação da mielina em um modelo experimental de desmielinização em ratos.

Oligodendrocytes and Schwann cells are engaged in myelin production, maintenance and repairing respectively in the central nervous system (CNS) and the peripheral nervous system (PNS). Whereas oligodendrocytes act only within the CNS, Schwann cells are able to invade the CNS in order to make new myelin sheaths around demyelinated axons. Both cells have some limitations in their activities, i.e. oligodendrocytes are post-mitotic cells and Schwann cells only get into the CNS in the absence of astrocytes. Ethidium bromide (EB) is a gliotoxic chemical that when injected locally within the CNS, induce demyelination. In the EB model of demyelination, glial cells are destroyed early after intoxication and Schwann cells are free to approach the naked central axons. In normal Wistar rats, regeneration of lost myelin sheaths can be achieved as early as thirteen days after intoxication; in Wistar rats immunosuppressed with cyclophosphamide the process is delayed and in rats administered cyclosporine it may be accelerated. Aiming the enlightening of those complex processes, all events concerning the myelinating cells in an experimental model are herein presented and discussed.