Most Accessed Articles – Positron Emission Tomography and Autoradiography Imaging of P-selectin Activation Using 68Ga-Fucoidan in Photothrombotic Stroke

Journal Name: Current Neurovascular Research

Author(s): Ina Israel, Felix Fluri, Fabian Schadt, Andreas K. Buck, Samuel Samnick*.

Abstract:

Background: P-selectin is activated early after stroke, followed by a rapid decline. This time course can be used to generate important information on stroke onset. The latter is crucial for therapeutic decision-making of wake-up strokes (i.e. thrombolysis or not). Here, we evaluated the specific p-selectin inhibitor fucoidan labeled with gallium-68 (68Ga-Fucoidan) as an imaging biomarker for assessing p-selectin activation in acute ischemic stroke using Positron Emission Tomography (PET).

Methods: 68Ga-Fucoidan was investigated in rats brain at 2-5 h (n=16), and additionally at 24-26 h (n=9) and 48 h (n=3) after induction of photothrombic stroke or in sham-operated animals (n=6). Correlation of cerebral 68Ga-Fucoidan uptake with p-selectin expression was determined by exposing freshly cut brain cryosections to autoradiography and immunostaining using specific antibodies against p-selectin.

Results: PET scans showed an increased accumulation of 68Ga-Fucoidan in the histologically proven ischemic stroke, as compared to the corresponding contralateral hemisphere in all except one animal. The median ratio between the uptake in the ischemic lesion and the contralateral region was 1.95 (1.45-2.41) at 2-5 h, 1.38 (1.05-1.89) at 24-26 h, and 1.09 (0.81-1.38) at 48 h after stroke, compared to 1.22 (0.99-1.49) for sham-operated animals. In the ex vivo autoradiography, 68Ga-Fucoidan accumulation co-localized with p-selectin as assessed by immunostaining. Control animals and those scanned at 24-26 h and 48 h after stroke exhibited no elevated 68Ga-Fucoidan uptake in either hemisphere.

Conclusion: PET imaging using 68Ga-Fucoidan represents a valuable tool for assessing p-selectin activation in vivo discriminating ischemic stroke early after stroke onset.

 

 

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EDITOR’S CHOICE – The Hippocampal Autophagic Machinery is Depressed in the Absence of the Circadian Clock Protein PER1 that may Lead to Vulnerability During Cerebral Ischemia – Current Neurovascular Research

Journal: Current Neurovascular Research

Author(s): Abdelhaq Rami*, Julia Fekadu, Oliver Rawashdeh

Abstract:

Background: Autophagy is an intracellular bulk self-degrading process in which cytoplasmic contents of abnormal proteins and excess or damaged organelles are sequestered into autophagosomes, and degraded upon fusion with lysosomes. Although autophagy is generally considered to be pro-survival, it also functions in cell death processes. We recently reported on the hippocampal, higher vulnerability to cerebral ischemia in mice lacking the circadian clock protein PERIOD1 (PER1), a phenomenon we found to be linked to a PER1-dependent modulation of the expression patterns of apoptotic/autophagic markers.

Methods: To exclude the contribution of vascular or glial factors to the innate vulnerability of Per1 knockout-mice (Per1^−/−-mice) to cerebral ischemia in vivo, we compared the autophagic machinery between primary hippocampal cultures from wild-type (WT)- and Per1^−/−-mice, using the lipophilic macrolide antibiotic, Rapamycin to induce autophagy.

Results: Development of autophagy in WT cells involved an increased LC3-II-to-LC3-I ratio (microtubule-associated protein 1 light chain 3) and an overall increase in the level of LC3-II. In addition, immunostaining of LC3 in WT cells revealed the typical transformation of LC3 localization from a diffused staining to a dot- and ring-like pattern. In contrast, Per1^−/−-hippocampal cells were resistant to Rapamycin induced alterations of autophagy hallmarks.

Conclusion: Our in vitro data suggests that basal activity of autophagy seems to be modulated by PER1, and confirms the in vivo data by showing that the autophagic machinery is depressed in Per1^−/−-hippocampal neurons.The implication of both autophagy and circadian dysfunction in the pathogenesis of cerebral ischemia suggests that a functional connection between the two processes may exist.

Read more here: http://www.eurekaselect.com/153389

 

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