Permanent or transient chronic ischemic stroke in the non-human primate: behavioral, neuroimaging, histological, and immunohistochemical investigations

J Cereb Blood Flow Metab. 2010 Feb;30(2):273-85. doi: 10.1038/jcbfm.2009.209. Epub 2009 Sep 30.

Abstract

Using multimodal magnetic resonance imaging (MRI), behavioral, and immunohistochemical analyses, we examined pathological changes at the acute, sub-acute, and chronic stages, induced by permanent or temporary ischemia in the common marmoset. Animals underwent either permanent (pMCAO) or 3-h transient (tMCAO) occlusion of the middle cerebral artery (MCAO) by the intraluminal thread approach. MRI scans were performed at 1 h, 8, and 45 days after MCAO. Sensorimotor deficits were assessed weekly up to 45 days after MCAO. Immunohistological studies were performed to examine neuronal loss, astrogliosis, and neurogenesis. Remote lesions were analyzed using retrograde neuronal tracers. At day 8 (D8), the lesion defined on diffusion tensor imaging (DTI)-MRI and T2-MRI was significantly larger in pMCAO as compared with that in the tMCAO group. At D45, the former still displayed abnormal signals in T2-MRI. Post-mortem analyses revealed widespread neuronal loss and associated astrogliosis to a greater extent in the pMCAO group. Neurogenesis was increased in both groups in the vicinity of the lesion. Disconnections between the caudate and the temporal cortex, and between the parietal cortex and the thalamus, were observed. Sensorimotor impairments were more severe and long-lasting in pMCAO relative to tMCAO. The profile of brain damage and functional deficits seen in the marmoset suggests that this model could be suitable to test therapies against stroke.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / physiology
  • Brain / pathology
  • Callithrix
  • Chronic Disease
  • Immunohistochemistry
  • Ischemic Attack, Transient / pathology*
  • Ischemic Attack, Transient / physiopathology*
  • Magnetic Resonance Imaging
  • Motor Activity
  • Neurogenesis / physiology
  • Recovery of Function / physiology
  • Stroke / pathology*
  • Stroke / physiopathology*