Microglia and macrophages associated with the nervous system play a predominant role in neuroinflammatory responses. The neuroinflammatory response of the dorsal cochlear nucleus (DCN) to damage in the auditory system appears complex and has not yet been fully characterized. Under physiological conditions, the distribution of microglial cells at the DCN level is similar to that found in the cerebellar cortex, with a clear division between the molecular layer and the deep layers. The choroid plexus of the fourth ventricle, which overlooks the DCN, also contains macrophages located mainly in the stroma, to a lesser extent to the liquoral surface of the epithelium. Following unilateral cochlear destruction in the rat, we observed changes in the size, shape and distribution of DCN microglial cells, mainly in the molecular layer in contact with the choroid plexus and cerebellum; in addition, the macrophages of the choroid plexus appear distributed in a different way, with a shift to the surface of the epithelium. The machrophages are therefore potentially availlable to reach the surface and the molecular layer of the DCN. Since several drugs are capable of modulating microglia and macrophages associated with the nervous system, especially in the context of sedation and anesthesia techniques, it is necessary to check that the observed effects are not influenced by the agents used for this purpose. In our experiments, cochlear destruction performed using diazepam as an adjuvant for anesthesia. Given that diazepam alone could cause changes in the distribution / activation of DCN microglial cells and choroid plexus macrophages, regardless of cochlear damage, we compared animals treated with diazepam, without cochlear damage, with untreated control animals. The brain stem slices obtained from these animals were marked with Iba-1, to highlight both the microglial cells and the macrophages, and with transthyretin, to mark the epithelium of the chorioid plexus, so as to be able to quantify the distribution and morphology microglial cells and macrophages.
Microglia e macrofagi associati al sistema nervoso giocano un ruolo preponderante nelle risposte neuroinfiammatorie. La risposta neuroinfiammatoria del nucleo cocleare dorsale (DCN) a danni nel sistema uditivo appare complessa e non è ancora stata completamente caratterizzata. In condizioni fisiologiche, la distribuzione delle cellule microgliali a livello del DCN è simile a quella che si trova nella corteccia cerebellare, con chiara divisione tra strato molecolare e strati profondi. Il plesso coroideo del quarto ventricolo, che sovrasta il DCN, contiene inoltre macrofagi localizzati soprattutto nello stroma, ed in misura minore alla superficie liquorale dell’epitelio. In seguito a distruzione cocleare unilaterale nel ratto, abbiamo osservato variazioni nelle dimensioni, nella forma e nella distribuzione delle cellule microgliali del DCN, principalmente nello strato molecolare in contatto con il plesso coroideo e il cervelletto; inoltre, i macrofagi del plesso coroideo appaiono distribuiti in modo diverso, con uno spostamento alla superficie dell’epitelio, e quindi potenzialmente disponibili per raggiungere la superficie e lo strato molecolare del DCN. Dato che diversi farmaci sono in grado di modulare microglia e macrofagi associati al sistema nervoso, soprattutto nell’ambito delle tecniche di sedazione ed anestesia, è necessario controllare che gli effetti osservati non siano influenzati dagli agenti utilizzati a tale scopo. Nei nostri esperimenti, la distruzione cocleare è stata effettuata utilizzando diazepam come adiuvante per l’anestesia. Dato che il diazepam potrebbe da solo provocare cambiamenti nella distribuzione/attivazione delle cellule microgliali del DCN e dei macrofagi del plesso coroideo, indipendentemente dal danno cocleare, abbiamo confrontato animali trattati con diazepam, senza danno cocleare, con animali di controllo non trattati. Le fettine di tronco encefalico ottenute da questi animali sono state marcate con Iba-1, per evidenziare sia le cellule microgliali che i macrofagi, e con transtiretina, per marcare l’epitelio del plesso corioideo, in modo da poter quantificare la distribuzione e la morfologia delle cellule microgliali e dei macrofagi.
Effetto del danno cocleare sulla microglia e sui macrofagi
PISANI, MATILDE
2018/2019
Abstract
Microglia and macrophages associated with the nervous system play a predominant role in neuroinflammatory responses. The neuroinflammatory response of the dorsal cochlear nucleus (DCN) to damage in the auditory system appears complex and has not yet been fully characterized. Under physiological conditions, the distribution of microglial cells at the DCN level is similar to that found in the cerebellar cortex, with a clear division between the molecular layer and the deep layers. The choroid plexus of the fourth ventricle, which overlooks the DCN, also contains macrophages located mainly in the stroma, to a lesser extent to the liquoral surface of the epithelium. Following unilateral cochlear destruction in the rat, we observed changes in the size, shape and distribution of DCN microglial cells, mainly in the molecular layer in contact with the choroid plexus and cerebellum; in addition, the macrophages of the choroid plexus appear distributed in a different way, with a shift to the surface of the epithelium. The machrophages are therefore potentially availlable to reach the surface and the molecular layer of the DCN. Since several drugs are capable of modulating microglia and macrophages associated with the nervous system, especially in the context of sedation and anesthesia techniques, it is necessary to check that the observed effects are not influenced by the agents used for this purpose. In our experiments, cochlear destruction performed using diazepam as an adjuvant for anesthesia. Given that diazepam alone could cause changes in the distribution / activation of DCN microglial cells and choroid plexus macrophages, regardless of cochlear damage, we compared animals treated with diazepam, without cochlear damage, with untreated control animals. The brain stem slices obtained from these animals were marked with Iba-1, to highlight both the microglial cells and the macrophages, and with transthyretin, to mark the epithelium of the chorioid plexus, so as to be able to quantify the distribution and morphology microglial cells and macrophages.È consentito all'utente scaricare e condividere i documenti disponibili a testo pieno in UNITESI UNIPV nel rispetto della licenza Creative Commons del tipo CC BY NC ND.
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https://hdl.handle.net/20.500.14239/11525