Establishment and evaluation of a monkey acute cerebral ischemia model

OBJECTIVES: Cerebral ischemia seriously threatens human health and is characterized by high rates of incidence, disability and death. Developing an ideal animal model of cerebral ischemia that reflects the human clinical features is critical for pathological studies and clinical research. The goal of this study is to establish a local cerebral ischemia model in rhesus macaque, thereby providing an optimal animal model to study cerebral ischemia. METHODS: Eight healthy rhesus monkeys were selected for this study. CT scans were performed before the operation to exclude cerebral vascular and intracranial lesions. Under guidance and monitoring with digital subtraction angiography (DSA), a microcatheter was inserted into the M1 segment of the middle cerebral artery (MCA) via the femoral artery. Then, autologous white thrombi were introduced to block blood flow. Immediately following embolization, multisequence MRI was used to monitor cerebrovascular and brain parenchymal conditions. Twenty-four hours after embolization, 2 monkeys were sacrificed and subjected to perfusion, fixation and pathological examination. RESULTS: The cerebral ischemia model was established in 7 rhesus monkeys; one animal died during intubation. DSA and magnetic resonance angiography (MRA) indicated the presence of an arterial occlusion. MRI showed acute local cerebral ischemia. HE staining revealed infarct lesions formed in the brain tissues, and thrombi were present in the cerebral artery. CONCLUSION: We established a rhesus macaque model of local cerebral ischemia by autologous thrombus placement. This model has important implications for basic and clinical research on cerebral ischemia. MRI and DSA can evaluate the models to ensure accuracy and effectiveness.

Canine model of ischemic stroke with autologous thrombus in three dogs; Magnetic resonance imaging features and histopathological findings / 동물의과학연구지

Ischemic stroke is the most common type of stroke in humans. The purpose of this study was to evaluate the diagnostic value of magnetic resonance imaging (MRI) in a canine model of stroke. Ischemic stroke was induced by using prepared autologous thrombus. The dogs were placed in lateral recumbency on the operation table and the cervical area of each dog was sterilized by using alcohol. After making a cervical incision, the common carotid artery and internal carotid artery (a branch of the common carotid artery that supplies an anterior part of the brain) were exposed. A 200 microL injection of the autologous thrombus prepared 24 hr prior to surgery was delivered with a 20 gauge venous catheter through an internal carotid artery. After successful delivery of the autologous thrombus, the venous catheter was removed, and the cervical incision was sutured. Neurologic signs including generalized seizures, tetraparesis, and altered mental status, were observed in all 3 dogs after induction of ischemic stroke and the signs manifested immediately after awakening from anesthesia. T1- and T2-weighted images and fluid-attenuated inversion recovery (FLAIR) images of the brain were acquired 1 day before and 1 day after surgery. On the day following ischemic stroke induction, MRI revealed multifocal lesions in the cerebral cortex and subcortex such as T1 hypointensity, T2 hyperintensity, FLAIR hyperintensity, and diffusion-weighted hyperintensity in all 3 dogs. Upon postmortem examination, ischemic lesions were found to be consistent with the MRI findings and they were unstained with 2% triphenyltetrazolium chloride. Histologic features of the earliest neuronal changes such as cytoplasmic eosinophilia with pyknotic nuclei were identified. Neuropil spongiosis and perivascular cuffing were also prominently observed at the infarcted area. The present study demonstrated the features of MRI and histopathologic findings in canine ischemic stroke models.