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Noninvasive delivery of gene targeting probes to live brains for transcription MRI
Author(s) -
Liu Christina H.,
You Zerong,
Ren JiaQian,
Kim Young R.,
EikermannHaerter Katharina,
Liu Philip K.
Publication year - 2008
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.07-9557com
Subject(s) - gliosis , glial fibrillary acidic protein , pathology , cortical spreading depression , medicine , magnetic resonance imaging , blood–brain barrier , immunohistochemistry , central nervous system , radiology , migraine
We aimed to test the feasibility of detecting gliosis in living brains when the blood‐brain barrier (BBB) is disrupted. We designed a novel magnetic resonance (MR) probe that contains superparamag‐netic iron oxide nanoparticles (SPION, a T2 susceptibility contrast agent) linked to a short DNA sequence complementary to the cerebral mRNA of glial fibrillary acidic protein (GFAP) found in glia and astrocytes. As a control, we also used a sequence complementary to the mRNA of β‐actin. Our objectives are to demonstrate that this new probe, SPION‐gfap, could be delivered to the brain when administered by eyedrop solution to the conjunctival sac. We induced BBB leakage by puncture wound, global cerebral ischemia, and cortical spreading depression in C57BL6 mice;1 day after probe delivery we acquired T2* MR images and R2* (R2* = 1/T2*) maps using a transcription MRI technique in live mice. We found that the SPION‐gfap probe reported foci with elevated signal in subtraction R2* maps and that these foci matched areas identified as having extensive glial network (gliosis) in postmortem immunohistochemistry. Similarly, animals adminis‐tered the control probe exhibited foci of R2* elevation that matched β‐actin‐expressing endothelia in the vascular wall. We conclude that our modular MR probe, delivered in an eyedrop solution, effectively reports gliosis associated with acute neurological disorders in living animals. As BBB leakage is often observed in acute neurological disorders, this study also served to validate noninvasive delivery of MR probes to the brains of live animals after acute neurological disorders. Liu C. H., You, Z., Ren JQ., Kim, Y. R., Eikermann‐Haerter, K., Liu P. K. Noninvasive delivery of gene targeting probes to live brains for transcription MRI. FASEB J. 22, 1193–1203 (2008)