Bone Marrow Mesenchymal Stem Cell Transplantation Increases GAP-43 Expression via ERK1/2 and PI3K/Akt Pathways in Intracerebral Hemorrhage.
Abstract
<h4>Background/aims</h4>Intracerebral hemorrhage (ICH) occurs in hypertensive patients
and results in high rates of mortality and disability. This study determined whether
bone marrow mesenchymal stem cell (BMSC) transplantation affects axonal regeneration
and examined the underlying mechanisms after the administration of PD98059 (p-ERK1/2
inhibitor) or/ and LY294002 (PI3K inhibitor). The hypothesis that was intended to
be tested was that BMSC transplantation regulates the expression of growth-associated
protein-43 (GAP-43) via the ERK1/2 and PI3K/Akt signaling pathways.<h4>Methods</h4>Seventy-five
male rats (250-280 g) were subjected to intracerebral blood injection and then randomly
received a vehicle, BMSCs, PD98059 or LY294002 treatment. Neurological deficits were
evaluated prior to injury and at 1, 3 and 7 days post-injury. The expression of GAP-43,
Akt, p-Akt, ERK1/2, and p-ERK1/2 proteins was measured by western blot analysis.<h4>Results</h4>BMSC
transplantation attenuated neurological deficits 3-7 days post-ICH. The expression
of GAP-43 was increased 3 days following BMSC transplantation. However, this increase
was inhibited by either PD98059 or LY294002 treatment. Treatment with both PD98059
and LY294002 was more effective than was treatment with an individual compound.<h4>Conclusion</h4>BMSC
transplantation could attenuate neurological deficits and activate axonal regeneration
in this rat ICH model. The protective effects might be associated with increased GAP-43
expression by activating both the ERK1/2 and PI3K/Akt signaling pathways.
Type
Journal articleSubject
AxonsBone Marrow Cells
Cells, Cultured
Mesenchymal Stem Cells
Animals
Rats
Rats, Sprague-Dawley
Cerebral Hemorrhage
Disease Models, Animal
Morpholines
Chromones
Flavonoids
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
GAP-43 Protein
Mesenchymal Stem Cell Transplantation
Regeneration
Signal Transduction
Up-Regulation
Male
Proto-Oncogene Proteins c-akt
Phosphatidylinositol 3-Kinases
Phosphoinositide-3 Kinase Inhibitors
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https://hdl.handle.net/10161/23254Published Version (Please cite this version)
10.1159/000477122Publication Info
Cui, Jianzhong; Cui, Changmeng; Cui, Ying; Li, Ran; Sheng, Huaxin; Jiang, Xiaohua;
... Gao, Junling (2017). Bone Marrow Mesenchymal Stem Cell Transplantation Increases GAP-43 Expression via
ERK1/2 and PI3K/Akt Pathways in Intracerebral Hemorrhage. Cellular physiology and biochemistry : international journal of experimental cellular
physiology, biochemistry, and pharmacology, 42(1). pp. 137-144. 10.1159/000477122. Retrieved from https://hdl.handle.net/10161/23254.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Huaxin Sheng
Associate Professor in Anesthesiology
We have successfully developed various rodent models of brain and spinal cord injuries
in our lab, such as focal cerebral ischemia, global cerebral ischemia, head trauma,
subarachnoid hemorrhage, intracerebral hemorrhage, spinal cord ischemia and compression
injury. We also established cardiac arrest and hemorrhagic shock models for studying
multiple organ dysfunction. Our current studies focus on two projects. One is to
examine the efficacy of catalytic antioxidant in treating cerebral is

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