| RRC ID |
44130
|
| 著者 |
Fujita Y, Kuchimaru T, Kadonosono T, Tanaka S, Hase Y, Tomimoto H, Hiraoka M, Kizaka-Kondoh S, Ihara M, Takahashi R.
|
| タイトル |
In vivo imaging of brain ischemia using an oxygen-dependent degradative fusion protein probe.
|
| ジャーナル |
PLoS One
|
| Abstract |
Within the ischemic penumbra, blood flow is sufficiently reduced that it results in hypoxia severe enough to arrest physiological function. Nevertheless, it has been shown that cells present within this region can be rescued and resuscitated by restoring perfusion and through other protective therapies. Thus, the early detection of the ischemic penumbra can be exploited to improve outcomes after focal ischemia. Hypoxia-inducible factor (HIF)-1 is a transcription factor induced by a reduction in molecular oxygen levels. Although the role of HIF-1 in the ischemic penumbra remains unknown, there is a strong correlation between areas with HIF-1 activity and the ischemic penumbra. We recently developed a near-infrared fluorescently labeled-fusion protein, POH-N, with an oxygen-dependent degradation property identical to the alpha subunit of HIF-1. Here, we conduct in vivo imaging of HIF-active regions using POH-N in ischemic brains after transient focal cerebral ischemia induced using the intraluminal middle cerebral artery occlusion technique in mice. The results demonstrate that POH-N enables the in vivo monitoring and ex vivo detection of HIF-1-active regions after ischemic brain injury and suggest its potential in imaging and drug delivery to HIF-1-active areas in ischemic brains.
|
| 巻・号 |
7(10)
|
| ページ |
e48051
|
| 公開日 |
2012-1-1
|
| DOI |
10.1371/journal.pone.0048051
|
| PII |
PONE-D-11-07259
|
| PMID |
23094105
|
| PMC |
PMC3477118
|
| MeSH |
Animals
Brain / drug effects
Brain / metabolism*
Brain / pathology
Hypoxia-Inducible Factor 1, alpha Subunit / genetics
Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
Hypoxia-Ischemia, Brain / diagnosis*
Hypoxia-Ischemia, Brain / metabolism
Hypoxia-Ischemia, Brain / pathology
Infarction, Middle Cerebral Artery
Injections, Intravenous
Ischemic Attack, Transient / diagnosis*
Ischemic Attack, Transient / metabolism
Ischemic Attack, Transient / pathology
Male
Mice
Mice, Inbred C57BL
Molecular Imaging / methods*
Molecular Probes / administration & dosage
Molecular Probes / metabolism*
Oxygen / metabolism*
Recombinant Fusion Proteins / administration & dosage
Recombinant Fusion Proteins / metabolism*
|
| IF |
2.74
|
| 引用数 |
5
|
|
WOS 分野
|
CLINICAL NEUROLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
|
