I wish someone would try this out in humans with a protocol.
http://kenes.com/brain2011/abstracts/pdf/597.pdf
Objectives: Wnt/ beta-catenin signaling is essential for maintaining endogenous neurogenesis
in the adult brain1and enhancing post-stroke neurogenesis has been shown to be beneficial for
recovery2-4. Having established that Wnt/ beta-catenin signaling is present within one of the two adult neurogenic niches: the subventricular zone, SVZ, we examined the dynamics of the
signaling pathway following transient middle cerebral artery occlusion, MCAO. We also
investigated the effect of upregulating the pathway on the endogenous post-stroke
neurogenesis, by employing a novel Wnt-3a liposomal preparation.
Methods: - Young adult male Axin 2 reporter mice for Wnt/ beta-catenin signaling were
subjected to 25 min MCAO and cohorts of 4 mice were sacrificed at 1 day, 3 days, 7 days and
14 days post-stroke. Immunohistochemistry was employed to visualize the cell types
demonstrating Wnt/ beta-catenin signaling. Optical density values of images taken at each time
point were compared using ImageJ in order to evaluate pathway activation levels.
- Wnt-3a liposomes were freshly made 5 and injected intra-parenchymally at 1, 3, 7 and 14 days
post-stroke in two 1.5 ul boluses at 3mm and 1.5 mm depth (1.2 mm laterally, 0.6 mm anterior
of bregma).
- DAB staining and stereology were employed to quantify the number of Doublecortin, DCX,
positive newborn neurons at 1 month after MCAO.
Results: - Wnt/ beta catenin signaling was evident in GFAP, Nestin and Doublecortin cells
present at the SVZ in both naïve and post-stroke animals, as well as in mature NeuN positive
neurons within the cortex and striatum. In post-MCAO animals it was also present in GFAP
positive astrocytes at the penumbra.
- We observed an oscillation in the upregulation pattern of Wnt/ beta-catenin signaling after
stroke, which we are confirming with larger cohorts.
- Wnt-3a liposomes exhibited a potent ability to activate the Wnt/ beta-catenin pathway both in
vivo (5 fold greater than baseline) and in vitro (comparable to recombinant Wnt-3a protein) and
significantly increased the number of Doublecortin positive newborn neurons (up to 20 fold
compared to PBS alone) when injected at 3 and 7 days post -stroke.
Conclusions: Here we show that the Wnt/ beta-catenin signaling pathway is active within the
adult brain and upregulated following stroke. Activation of the pathway, in a novel liposomemediated way, significantly enhances endogenous neurogenesis post-stroke.
http://kenes.com/brain2011/abstracts/pdf/597.pdf
Objectives: Wnt/ beta-catenin signaling is essential for maintaining endogenous neurogenesis
in the adult brain1and enhancing post-stroke neurogenesis has been shown to be beneficial for
recovery2-4. Having established that Wnt/ beta-catenin signaling is present within one of the two adult neurogenic niches: the subventricular zone, SVZ, we examined the dynamics of the
signaling pathway following transient middle cerebral artery occlusion, MCAO. We also
investigated the effect of upregulating the pathway on the endogenous post-stroke
neurogenesis, by employing a novel Wnt-3a liposomal preparation.
Methods: - Young adult male Axin 2 reporter mice for Wnt/ beta-catenin signaling were
subjected to 25 min MCAO and cohorts of 4 mice were sacrificed at 1 day, 3 days, 7 days and
14 days post-stroke. Immunohistochemistry was employed to visualize the cell types
demonstrating Wnt/ beta-catenin signaling. Optical density values of images taken at each time
point were compared using ImageJ in order to evaluate pathway activation levels.
- Wnt-3a liposomes were freshly made 5 and injected intra-parenchymally at 1, 3, 7 and 14 days
post-stroke in two 1.5 ul boluses at 3mm and 1.5 mm depth (1.2 mm laterally, 0.6 mm anterior
of bregma).
- DAB staining and stereology were employed to quantify the number of Doublecortin, DCX,
positive newborn neurons at 1 month after MCAO.
Results: - Wnt/ beta catenin signaling was evident in GFAP, Nestin and Doublecortin cells
present at the SVZ in both naïve and post-stroke animals, as well as in mature NeuN positive
neurons within the cortex and striatum. In post-MCAO animals it was also present in GFAP
positive astrocytes at the penumbra.
- We observed an oscillation in the upregulation pattern of Wnt/ beta-catenin signaling after
stroke, which we are confirming with larger cohorts.
- Wnt-3a liposomes exhibited a potent ability to activate the Wnt/ beta-catenin pathway both in
vivo (5 fold greater than baseline) and in vitro (comparable to recombinant Wnt-3a protein) and
significantly increased the number of Doublecortin positive newborn neurons (up to 20 fold
compared to PBS alone) when injected at 3 and 7 days post -stroke.
Conclusions: Here we show that the Wnt/ beta-catenin signaling pathway is active within the
adult brain and upregulated following stroke. Activation of the pathway, in a novel liposomemediated way, significantly enhances endogenous neurogenesis post-stroke.
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