Chronic ischemic stroke model in cynomolgus monkeys

Behavioral, neuroimaging and anatomical study

Ben Roitberg, Naimath Khan, Eray Tuccar, Katie Kompoliti, Yaping Chu, Noam Alperin, Jeffrey H. Kordower, Marina E. Emborg

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Previous nonhuman primate stroke models have employed temporary occlusion of arteries, had limited behavioral testing and imaging, and focused on the short-term outcome. Our goals were 1. to develop a stable model of chronic stroke in the nonhuman primate, 2. to study in vivo the long-term biochemical changes in the area adjacent to the infarct, using proton magnetic resonance spectroscopy (1H MRS), and 3. evaluate these changes in relation to the histopathological effects of stroke. Four adult cynomologous monkeys had an occlusion of the M1 segment of the right MCA. Behavioral tests included a clinical rating scale, motor planning task, fine motor task, and activity monitoring. Eight months afterwards, MRI and 1H MRS were performed. Following the imaging studies the monkeys were perfused transcardially, their brains extracted and processed. Nissl staining and immunohistochemistry for neuronal markers (NeuN) were performed and used to measure the lesion volume and neuronal optical density (OD). All animals developed a left hemiparesis and were unable to perform a fine motor task with the left hand. There was a significant (31%) decline in the motor planning ability with the nonparetic extremity. Monkeys displayed a stooped posture, episodes of rotation to the side of the lesion, partial left hemianopsia, and transient changes in activity. The clinical signs improved over the first 6-8 weeks but the deficits remained stable for the remaining six months of follow up. MRI demonstrated a subcortical and cortical infarction in the right MCA distribution. 1H MRS data detected a significant decrease in the N-acetyl-aspartate (NAA) /creatine (Cr) ratio in the area adjacent to the infarction (VOI-St) compared to a mirror area in the contralateral hemisphere (VOI-Co). Histopathological measurements revealed a significant decline in neuronal cross-sectional area and neuronal optical density in the region of the VOI-St. We established a stable and reproducible model of chronic stroke in the MCA distribution, in the macaque monkey. Our data indicate that NAA detected by 1H MRS can be used to measure neuronal loss in vivo and help target this area for intervention. Our model may be particularly suitable for studies testing the effects of therapeutic strategies involving neural or stem cell transplantation, trophic factors or gene therapy.

Original languageEnglish
Pages (from-to)68-78
Number of pages11
JournalNeurological Research
Volume25
Issue number1
DOIs
StatePublished - Jan 1 2003
Externally publishedYes

Fingerprint

Macaca fascicularis
Neuroimaging
Stroke
Haplorhini
Primates
Hemianopsia
Aptitude
Neural Stem Cells
Creatine
Cerebral Infarction
Macaca
Stem Cell Transplantation
Therapeutic Uses
Paresis
Posture
Genetic Therapy
Infarction
Motor Activity
Extremities
Hand

Keywords

  • Behavior
  • Middle cerebral artery
  • MR spectroscopy
  • Nonhuman primates
  • Stroke

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Chronic ischemic stroke model in cynomolgus monkeys : Behavioral, neuroimaging and anatomical study. / Roitberg, Ben; Khan, Naimath; Tuccar, Eray; Kompoliti, Katie; Chu, Yaping; Alperin, Noam; Kordower, Jeffrey H.; Emborg, Marina E.

In: Neurological Research, Vol. 25, No. 1, 01.01.2003, p. 68-78.

Research output: Contribution to journalArticle

Roitberg, B, Khan, N, Tuccar, E, Kompoliti, K, Chu, Y, Alperin, N, Kordower, JH & Emborg, ME 2003, 'Chronic ischemic stroke model in cynomolgus monkeys: Behavioral, neuroimaging and anatomical study', Neurological Research, vol. 25, no. 1, pp. 68-78. https://doi.org/10.1179/016164103101200950
Roitberg, Ben ; Khan, Naimath ; Tuccar, Eray ; Kompoliti, Katie ; Chu, Yaping ; Alperin, Noam ; Kordower, Jeffrey H. ; Emborg, Marina E. / Chronic ischemic stroke model in cynomolgus monkeys : Behavioral, neuroimaging and anatomical study. In: Neurological Research. 2003 ; Vol. 25, No. 1. pp. 68-78.
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