cyclin-d1 and Brain-Infarction

Granulocyte-colony stimulating factor (G-CSF) is an endogenous growth factor that exhibits a diverse range of neuroprotective mechanisms against a variety of neurological disorders including ischemic stroke. We investigated the anti-apoptotic mechanisms of G-CSF against endoplasmic reticulum (ER) stress induced apoptosis. Sprague-Dawley rats were subjected to transient occlusion of the middle cerebral artery (MCAO) for 90 min. Rats were injected with G-CSF (n = 15; 50 μg/kg body weight s.c.) for 4 days, starting 24 h post-MCAO and brains were harvested after 4 days reperfusion (n = 16). Key proteins in ER stress apoptosis were analyzed by immunoblotting. G-CSF reduced infarct volume to 53% and improved neurological deficits. G-CSF treatment significantly (P < .05) attenuated the expression of proteins involved in ER stress apoptosis pathway; ATF4, ATF6, p-p38MAPK, pJNK and CHOP. G-CSF treatment also re-established ER homeostasis evident by the reduction of the intraluminal ER stress sensor, GRP78 as well as reducing the overall cellular stress level protein, HSP27. G-CSF also up-regulated anti-apoptotic proteins pAKT and Bcl-2 while down-regulated the pro-apoptotic protein Bax. G-CSF exerts neuroprotection from cerebral ischemia through the preservation of the ER, resulting in the attenuation of pro-apoptotic proteins and the potentiation of anti-apoptotic proteins.

Topics: Activating Transcription Factor 6; Analysis of Variance; Animals; Apoptosis; bcl-2-Associated X Protein; Brain Infarction; Cyclin D1; Disease Models, Animal; Endoplasmic Reticulum Stress; Granulocyte Colony-Stimulating Factor; Infarction, Middle Cerebral Artery; Male; Neurologic Examination; Neuroprotective Agents; Phosphopyruvate Hydratase; Rats; Rats, Sprague-Dawley; Receptors, Granulocyte Colony-Stimulating Factor; Signal Transduction

The aim of this study is to research the effects of the polyphenol ellagic acid (EA) on brain cells and to explore its mechanism of action, and to evaluate whether EA can be safely utilized by humans as a functional food or therapeutic agent.. A photothrombosis-induced model of brain injury in rats was created, and EA was administered intragastrically to rats on 7 consecutive days post-venous ischemia. An oxygen-glucose deprivation and re-perfusion model was established in neural stem cells in order to research the effects on proliferation after 2 days of EA treatment in vitro. The administration of EA improved the rats' nerve-related abilities, remedied infarct volumes and morphological changes in the brain, and enhanced the content of nestin protein in the brain semidarkness zone. The proliferation of NSCs and the expression of β-catenin and Cyclin D1 genes were also increased in primary cultured NSCs.. EA administration can improve brain injury outcomes and increase the proliferation of NSCs through the Wnt/β-catenin signaling pathway. The presented results represent new insights on the mechanisms of the brain cell protective activity of EA. Thus, EA may be used in functional foods or medicines to help treat nerve dysfunction, neurodegenerative disease and aging.

Topics: Animals; Behavior, Animal; beta Catenin; Brain Infarction; Cell Proliferation; Cyclin D1; Ellagic Acid; Male; Nestin; Neural Stem Cells; Neuroprotective Agents; Rats, Sprague-Dawley; Wnt Signaling Pathway