Jiaqian Ren, Abstract Co-Author: Nothing to Disclose

Shengyong Wu MD,PhD, Presenter: Nothing to Disclose

Jinsheng Yang, Abstract Co-Author: Nothing to Disclose

Charng-Ming Liu, Abstract Co-Author: Nothing to Disclose

Christina Liu, Abstract Co-Author: Nothing to Disclose

Philip Liu, Abstract Co-Author: Nothing to Disclose

We aimed to apply non-invasive MR imaging to investigate adult neurogenesis and its interaction with angiogenesis after cerebral ischemia in a preclinical model of cerebral ischemia-induced brain damage and repair.

Cerebral ischemia was induced in male C57black6 mice or transgenic mice expressing RFG by actin promoter (23±2 gm) via bilateral carotid artery occlusion (BCAO) for 60 minutes (at 37oC or 34oC). Brain injury and the location of repair were evaluated by gene transcript-targeted MRI (GT-tMRI) with 9.4T scanner (Bruker). Brain injury was detected within 24 hours by Gadolinium-enhanced MRI in vivo. We attached superparamagnetic iron oxide nanoparticles (SPIONs) to phosphorothioate-modified micro-DNA (sODN) that targets mRNA of Actin, matrix metalloprotease-9 (MMP-9), glial fibrillary acidic protein (GFAP) or Nestin. We acquired baseline MRI (serial T2*WI) in each mouse then administered SPION-actin (or SPION-mmp9, SPION-gfap or SPION-nestin at 4 mg Fe/kg, i.p. injection). Another post-SPION MRI was acquired one day later starting at the 4th after BCAO). We constructed T2* map and R2* map for all MRI acquired in 26 weeks; then obtained brain tissue sample at the 27th week to compare histology, iron content by Inductively coupled plasma mass spectrometry (ICP-MS) and the distribution of SPION as electron dense nanoparticles (EDN) by transmission electron microscope (TEM) with imaging analysis results.

The surge in cerebral iron content after i.p. delivery of SPION-actin to normal brains was confirmed to be positively corresponding to the increase in the frequency of relaxivity (R2*) in the cortex and striatum. In mice with normal thermia during BCAO, we observed brain injury (BBB leakage and regional elevation in MMP-9 mRNA) and neurological deficit. We showed localization of progenitor cells in the subventricular zone by expression of Actin and Nestin in vivo. Hypothermia reduced injury described above. We showed the presence of EDN or fluorophore-DNA in progenitor cells identified by deltaR2* map with SPION-nestin and -actin. The retention and distribution profiles of both SPION- and fluorophore-sODN reflected positively with mRNA activities.

GT-tMRI detects neuroprotection and/or repair in living brains after ischemia.

A clinical relevant technique for intracellular biomarkers for evaluation of neuroprotection-repair after cerebral ischemia.

Ren, J, Wu, S, Yang, J, Liu, C, Liu, C, Liu, P, Multi-Parameters Evaluation on Adult Neurogenesis with Angiogenesis by Gene Transcript-targeted MR Imaging in Preclinical Cerebral Ischemia-Repair Model.  Radiological Society of North America 2012 Scientific Assembly and Annual Meeting, November 25 - November 30, 2012 ,Chicago IL. http://archive.rsna.org/2012/12031193.html