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MR contrast probes that trace gene transcripts for cerebral ischemia in live animals
Author(s) -
Liu Christina H.,
Huang Shuning,
Cui Jiankun,
Kim Young R.,
Farrar Christian T.,
Moskowitz Michael A.,
Rosen Bruce R.,
Liu Philip K.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.07-8203com
Subject(s) - messenger rna , ischemia , pathology , chemistry , medicine , microbiology and biotechnology , biology , gene , biochemistry
The aim of this research was to validate transcription magnetic resonance (MR) imaging (MRI) for gene transcript targeting in acute neurological disorders in live subjects. We delivered three MR probe variants with superparamagnetic iron oxide nanopar‐ticles (SPION’ a T 2 susceptibility agent) linked to a phosphorothioate‐modified oligodeoxynucleotide (sODN) complementary to c‐fos mRNA (SPION‐cfos) or β‐actin mRNA (SPION‐β‐actin) and to sODN with random sequence (SPION‐Ran). Each probe (1 μgFe in 2 μl) was delivered via intracerebroventricular infusion to the left cerebral ventricle of male C57Black6 mice. We demonstrated SPION retention’ measured as decreased T 2 * signal or increased R 2 * value (R 2 * = 1/ T 2 *). Animals that received the SPION‐β‐actin probe exhibited the highest R 2 * values’ followed (in descending order) by SPION‐cfos and SPION‐Ran. SPION‐cfos retention was localiZed in brain regions where SPION‐cfos was present and where hybrids of SPION‐cfos and its target c‐fos mRNA were detected by in situ reverse transcription PCR. In animals that experienced cerebral ischemia, SPION‐cfos retention was significantly increased in locations where c‐fos mRNA increased in response to the ischemic insult;these elevations were not observed for SPION‐β‐actin and SPION‐Ran. This study should enable MR detection of mRNA alteration in disease models of the central nervous system.—Liu C. H., Huang, S., Cui, J., Kim, Y. R., Farrar, C. T., Moskowitz M. A., Rosen B. R., Liu P. K. MR contrast probes that trace gene transcripts for cerebral ischemia in live animals. FASEB J. 21, 3004–3015 (2007)