A pilot study on transient ischemic stroke induced with endothelin-1 in the rhesus monkeys

Abstract

Endothelin-1 (ET-1), a vasoconstrictor, has recently been used to induce focal ischemia in rodents and marmoset monkeys. The rhesus monkey, however, has numerous advantages to the rodent and marmoset that make it a superior and irreplaceable animal model for studying stroke in the brain. In the present study, after mapping the preferred hand representation in two healthy male monkeys with intracortical micro-stimulation, ET-1 was microinjected into the contralateral motor cortex (M1) to its preferred hand. The monkeys had been trained in three manual dexterity tasks before the microinjection and were tested for these tasks following the ET-1 injection. Brain Magnetic Resonance Imaging scans were performed 1, 7, 14 and 28 days post ischemia. It was found that ET-1 impaired the manual dexterity of the monkeys in the vertical slot and rotating Brinkman board tasks 3–8 days after the injection. Brain imaging found that severe edema was present 7 days after the focal ischemia. This data suggest that ET-1 can induce transient ischemic stroke in rhesus monkey and that ET-1 induced focal ischemia in non-human primates is a potential model to study the mechanism of stroke and brain repair after stroke.

A Reproducible New Model of Focal Ischemic Injury in the Marmoset Monkey: MRI and Behavioural Follow-Up

“…Additionally, the 24h MRI scan allowed us to assess oedema and supply additional corticoids if needed. As reported by others [32] [33], severe vasogenic oedema was still present 1 week post-injury but had resolved within a month. One week after surgery, all animals could eat, climb and move with ease and no major disabilities were observed.…”

Association between Lys198Asn polymorphism of endothelin‐1 gene and ischemic stroke: A meta‐analysis

“…Some studies have found high plasma level (Estrada et al, 2017;Sapira, Cojocaru, Lilios, & Grigorian, 2010;Ziv et al, 1992) and high cerebrospinal fluid (CSF) level (Lampl et al, 1997) of ET-1 in ischemic stroke patients. In a study by Dai et al (2017), injection of ET-1 in rhesus monkey induced transient ischemic attack. Thus ET-1 might have a role in development of ischemic stroke.…”

Preclinical animal studies in ischemic stroke: Challenges and some solutions

“…Marshall and Ridley (2000) developed a test called the six‐tube search task to understand spatial deficits in stroke induced NHPs 86 . The Kluver board task helps to assess the overall strength of the extremity, fine motor function and hemineglect or visual field cuts 87 . Cognitive tasks help to assess memory and learning deficits.…”