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.
Highlights
Been a few non-human primate studies utilizing ET-1 induced cerebral ischemia models developed in marmoset monkeys[12,13]
ET-1 was found to induce focal ischemia and lead to impairments in the manual dexterity of rhesus monkeys assessed in the vertical slot and rotating Brinkman board tasks 3 and 8 days after the ET-1 injection
In Virley et al.’s study, a craniotomy was made and ET-1 at different doses was applied to the M2 portion of the middle cerebral artery (MCA) in marmosets
Summary
Been a few non-human primate studies utilizing ET-1 induced cerebral ischemia models developed in marmoset monkeys[12,13]. ET-1 intracortically injected into the primary visual cortex of adult and neonatal marmosets induced posterior cerebral arterial occlusions and developed a highly reproducible and survivable model of focal ischemia[13]. These results suggested that a marmoset model of ET-1 induced ischemia has the potential to assess long-term effects of stroke and to gauge the efficacy of novel therapeutic strategies targeted to treat clinical stroke[12,13]. The correlations between the behavioral change and the edema in the cortex were further estimated in brain MRIs in order to develop an efficient non-human primate model for studying strokes
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