Development of the brain in staged embryos of the long-tailed monkey (Macaca fascicularis)

Biotherapeutics are pharmaceutical products derived from or synthesized by biological systems. Such molecules carry the potential for immunogenicity which may lead to adverse immune responses. The cynomolgus macaque ( Macaca fascicularis) is the species of choice in nonclinical safety assessment of biotherapeutics. The main aim of this study was to confirm whether mononuclear cell infiltrates at specific locations represent a generic effect of biotherapeutics, and therefore the result of their immunogenicity. Following a review of microscopic findings in studies conducted over a 10-year period at one test facility, 15% of biotherapeutics were reported to have such findings. The most commonly affected site was the choroid plexus and less frequently the meninges and ciliary body. The reporting of such findings as test article–related becomes more subjective as the severity and incidence decreases. To assess the accuracy of such associations, a mathematical approach was employed to determine the probability of obtaining the observed results by chance. There was good agreement between this approach and the original findings. In addition to an increased number and size of mononuclear cell infiltrates in the brain, biotherapeutic administration was strongly associated with the presence of plasma cells and eosinophils.

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Abnormal neuronal and glial argyrophilic fibrillary structures in the brain of an aged albino cynomolgus monkey ( Macaca fascicularis )

Acta Neuropathologica ◽

10.1007/s004010000215 ◽

2000 ◽

Vol 100 (5) ◽

pp. 580-586 ◽

Cited By ~ 13

Author(s):

Wijit Kiatipattanasakul ◽

Hiroyuki Nakayama ◽

Supattra Yongsiri ◽

Somchai Chotiapisitkul ◽

Shin'ichiro Nakamura ◽

...

Keyword(s):

Cynomolgus Monkey ◽

Macaca Fascicularis ◽

The Brain

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Distribution of Relaxin-3 mRNA and Immunoreactivity and RXFP3-Binding Sites in the Brain of the Macaque, Macaca fascicularis

Annals of the New York Academy of Sciences ◽

10.1111/j.1749-6632.2009.03954.x ◽

2009 ◽

Vol 1160 (1) ◽

pp. 256-258 ◽

Cited By ~ 18

Author(s):

Sherie Ma ◽

Pei-Juan Shen ◽

Qian Sang ◽

Jose L. Lanciego ◽

Andrew L. Gundlach

Keyword(s):

Binding Sites ◽

Macaca Fascicularis ◽

The Brain

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Cerebral Infarction in Two Cynomolgus Macaques (Macaca fascicularis) with Hypernatremia

Veterinary Pathology ◽

10.1177/030098589603300410 ◽

1996 ◽

Vol 33 (4) ◽

pp. 431-434 ◽

Cited By ~ 5

Author(s):

E. S. Harber ◽

M. G. O'Sullivan ◽

M. J. Jayo ◽

C. S. Carlson

Keyword(s):

Cerebral Infarction ◽

Water Deprivation ◽

Macaca Fascicularis ◽

Human Beings ◽

Cerebral Lesions ◽

Cynomolgus Monkeys ◽

Cellular Dehydration ◽

Cynomolgus Macaques ◽

Occipital Lobes ◽

The Brain

Hypernatremia resulting in neurologic symptoms ranging from lethargy to coma, and with underlying lesions of cerebral hemorrhage and thrombosis, has been reported in human beings. Herein we report two cases of cerebral infarction with venous thrombosis in cynomolgus monkeys. Both animals were severely hypernatremic because of water deprivation, with serum sodium levels of 185 and 193 meq/liter, respectively. At necropsy, there were bilateral multiple hemorrhagic and malacic areas visible on the surface of the cerebrum and extending into the parenchyma, primarily involving the occipital lobes. These lesions were interpreted microscopically as infarcts because, in addition to hemorrhage and necrosis, multiple thrombi were present in small and medium-sized veins of gray matter and meninges. The pathogenesis of hypernatremia-induced cerebral lesions is believed to involve cellular dehydration that caused shrinkage of the brain. Because the vasculature of the brain is tightly adherent to the skull, this shrinkage results in tearing of blood vessels, with consequent hemorrhage and thrombosis.

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