Anomaly in aortic arch alters pathological outcome of transient global ischemia in Rhesus macaques

Abstract

We investigated a non-human primate (NHP) transient global ischemia (TGI) model which was induced by clipping the arteries originating from the aortic arch. Previously we demonstrated that our TGI model in adult Rhesus macaques (Macaca mulatta) results in marked neuronal cell loss in the hippocampal region, specifically the cornu Ammonis (CA1) region. However, we observed varying degrees of hippocampal cell loss among animals. Here, we report for the first time an anomaly of the aortic arch in some Rhesus macaques that appears as a key surgical factor in ensuring the success of the TGI model in this particular NHP. Eleven adult Rhesus macaques underwent the TGI surgery, which involved 10-15-minute clipping of both innominate and subclavian arteries. Animals were allowed to survive between 1 day and 28 days after TGI. Because of our experience and knowledge that Japanese macaques exhibited only innominate and subclavian arteries arising from the aortic arch, macroscopic visualization of these two arteries alone in the Rhesus macaques initially assured us that clipping both arteries was sufficient to produce TGI. During the course of one TGI operation, however, we detected 3 arterial branches arising from the aortic arch, which prompted us to subsequently search for 3 branches in succeeding TGI surgeries. In addition, we performed postmortem examination of the heart to confirm the number of arterial branches in the aortic arch. Finally, in order to reveal the pathological effect of the aortic arch anomaly, we compared the hippocampal cell loss between animals found to have 3 arterial branches but had all or only two branches clipped during TGI operation. Post-mortem examination revealed eight NHPs had the typical two arterial aortic branches, but three NHPs displayed an extra arterial aortic branch, indicating that about 30% of Rhesus macaques had 3 arterial branches arising from the aorta. Histological analyses using Nissl staining showed that in NHPs with the aortic arch anomaly clipping only two of three arterial branches led to a partial cell loss and minimal alteration in number of cell layers in the hippocampal region *Address correspondence to: Department of Neurosurgery, University of South Florida College of Medicine, 12901 Bruce B. Downs Blvd., Tampa, FL 33612; cborlong@health.usf.edu; Tel: 813-974-1377; Fax: 813-974-1364. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. when compared with clipping all three branches, with the hippocampal cell death in the latter resembling the pathological outcome achieved by clipping the two arterial branches in NHPs disp...

Endovascular Ischemic Stroke Models in Nonhuman Primates

“…Moreover, ischemic damage of the white matter is a prognostic factor for stroke outcomes. However, only NHP stroke models are able to mimic white matter pathology in stroke patients most closely to pathology seen in humans and is recognized as an important limitation to rodent ischemic stroke models [20][21][22][23][24]. Thus, NHP stroke models have numerous intrinsic advantages over rodents, especially owing to their similarity in different fronts of the human anatomy and physiology, making them an irreplaceable and indispensable animal model for studying cerebral ischemia [25].…”

Angioarchitecture of collateral arteries of the aortic arch of Antillean manatee (Trichechus manatus manatus Linnaeus, 1758)

“…An experimental study conducted by Hara et al (), with adult rhesus monkeys ( Macaca mulatta ), showed the degree of impairment of the nervous tissue, specifically the loss of hippocampal cells in relation to the blood supply by the collateral arteries to the aortic arch. Through histological analyses using the Nissl staining, they verified that animals with two of the three connected arterial branches that were clamped had a partial loss of cells and minimal alteration in the number of cell layers in the hippocampal region when compared to clamping of the three branches, resulting in cell death of the hippocampus.…”

Collateral Arteries of the Aortic Arch in Mongolian Gerbil (Meriones unguiculatus)

“…Em um estudo realizado com macacos Rhesus adultos [16], para avaliar o grau de comprometimento do tecido nervoso, especificamente à perda das células do hipocampo, induzido por clipagem das artérias oriundas do arco aórtico cirurgicamente no tempo de 10 a 15 min, resultando assim na isquemia transitória do tecido, no entanto, durante o experimento observaram por acaso que 30% dos animais apresentaram três artérias colaterais no arco aórtico (tronco braquiocefálico, carótida comum esquerda e subclávia esquerda) ao invés de duas (tronco braquiocefálico e subclávia esquerda). Inicialmente tinham a intenção de clipar as únicas duas artérias colaterais do arco, e no momento que descobriram que existiam animais que possuíam as três artérias, compararam a perda de células do hipocampo entre os animais com 3 ramos arteriais, mas que tiveram todos ou apenas dois ramos cortados durante a operação.…”