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Variable response of the Mongolian gerbil to unilateral carotid occlusion: Magnetic resonance imaging and neuropathological characterization

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Abstract

In the present investigation, we estimated both the evolution and the severity of ischemic damage following unilateral carotid occlusion (UCO) in Mongolian gerbils by using conventional magnetic resonance imaging (MRI, i.e. T2 weighted imaging) and histological techniques. Immediately after UCO, the animals showed different clinical effects. The mortality (46%) detected within the first 48h was considered an “stroke-sensitivity”; the “stroke-resistant” animals showed wide variability in terms of both temporal evolution and the extent of ischemic damage. The signal hyperintensity and negative MRI observed during the first 30h after UCO did not always correlate with the cerebral damage presented after 14 days, although a close correlation was established between the T2 weighted images taken more than 30h after UCO and neuropathology: the gerbils negative to imaging showed no morphological changes, whereas an enhanced signal was always prognostic of ischemic injury. Moreover, late MRI documented ventricular dilatation. Histopathology showed that the ischemic damage differed among the stroke-resistant gerbils and was often bilateral. The present study confirms the differences in gerbil susceptibility to hemispheric infarction after permanent UCO and suggests that conventional MRI may be a useful non-invasive method for i) identifying the stroke-resistant animals prone to mature ischemic injury and ii) monitoring the evolution of therapeutic efficacy without sacrificing animals.

Sommario

Nella presente ricerca abbiamo valutato nel gerbillo della Mongolia l'evoluzione e la gravità del danno ischemico dopo chiusura permanente di una delle arterie carotidi comuni (ACC) mediante RM convenzionale (RM con immagini pesate in T2) e analisis istologica.

Subito dopo la chiusura di una ACC, gli animali hanno presentato una differente sintomatologia clinica.

La mortalità (46%) rilevata entro le prime 48 ore è stata considerata un indice di “sensibilità allostroke”. Gli animali “resistenti allostroke” hanno mostrato un'ampia variabilità sia nell'evoluzione che nella gravità del danno ischemico. L'iperintensità del segnale e la negatività all'esame RM osservate entro 30 ore dalla legatura della ACC non sempre correlavano con il danno istologico cerebrale rilevato a 14 giorni.

Una stretta correlazione è stata stabilita tra le immagini pesate in T2 e ottenute dopo 30 ore dalla occlusione della ACC e la neuropatologia. Infatti, i gerbilli negativi alla RM non presentavano lesioni, mentre un'alterazione di segnale era sempre predittiva di danno ischemico.

Inoltre l'esame RM tardivo ha evidenziato dilatazione ventricolare. L'istopatologia ha dimostrato che il danno ischemico differiva tra i gerbilli “resistenti allo stroke” e spesso era bilaterale. Questo studio conferma la diversa suscettibilità all'infarto emisferico dopo chiusura permanente di una ACC e suggerisce che la RM convenzionale potrebbe essere un metodo non invasivo utile per 1) identificare e/o selezionare gli animali inclini a maturare danno ischemico e 2) monitorare l'efficacia di un trattamento terapeutico senza sacrificare gli animali.

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Supported by grants from MURST, Università di Perugia, Italy. Cristiana Gambelunghe was a recipient of Schering-Plough fellowships on “Experimental models for cerebral ischemia”.

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Pelliccioli, G.P., Gambelunghe, C., Ottaviano, P.F. et al. Variable response of the Mongolian gerbil to unilateral carotid occlusion: Magnetic resonance imaging and neuropathological characterization. Ital J Neuro Sci 16, 517–526 (1995). https://doi.org/10.1007/BF02282909

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