A Novel Neuroprotectant Granulocyte-Colony Stimulating Factor

Solaroğlu, İhsan; Cahill, Julian; Jadhav, Vikram; Zhang, Junyi

doi:10.1161/01.str.0000208205.26253.96

Cited by 115 publications

(90 citation statements)

References 64 publications

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“…Perhaps activation of this pathway alone was not sufficient to afford long-term protection against apoptotic cell death. Notably, we did not detect an increase in either JAK-STAT or ERK 1/2, both of which have been shown to play important roles in G-CSF-related neuroprotection (Solaroglu et al, 2006).…”

Section: Discussioncontrasting

confidence: 70%

“…G-CSF has been shown to be beneficial in animal studies in a variety of brain injury models (Solaroglu et al, 2006), and is presently in Phase I/II trials for ischemic stroke in humans (Shyu et al, 2006, Schabitz et al, 2006. In the present study we found that treatment with G-CSF was associated with a transient improvement in T-maze spontaneous alternation and a trend towards improved body weight, but that it conferred no long-term benefit (Figure 1B,D).…”

Section: Discussionmentioning

confidence: 45%

“…Additionally there was no apparent histological benefit to hippocampal neurons ( Figure 2A, 4A, 4B). These results are somewhat surprising, given that G-CSF has been shown to be neuroprotective in a variety of brain injury models (Solaroglu et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…Multiple animal studies have shown that G-CSF has the capacity to provide significant neuroprotection in cerebral ischemia in vivo, in large measure due to strong anti-apoptotic signaling induced by the hormone in the brain (Solaroglu et al, 2006). A number of studies have shown that G-CSF is potentially neuroprotective in hemorrhagic infarction, traumatic brain injury, and spinal cord injury (Solaroglu et al, 2006, Ren et al, 2005, although there is not universal agreement that G-CSF works in trauma (Sakowitz et al, 2006) or neonatal excitotoxicity models (Keller et al, 2006). In vivo G-CSF treatment of global cerebral ischemia has not been published to date.…”

Section: Introductionmentioning

confidence: 99%

“…Recent work suggests that these intracellular cascades are upregulated selectively in different brain regions, and in different cell types within the brain. In focal ischemia, one of the main mechanisms of G-CSF-induced neuroprotection is inhibition of apoptotic cell death, although other mechanisms such as neurotrophic cell multiplication or anti-inflammatory processes may also be important (Solaroglu et al, 2006). Related growth factors such as Erythropoietin have been shown to be neuroprotective if given before and / or after global cerebral ischemia, in part by anti-apoptotic mechanisms , Calapi et al, 2000.…”

Section: Introductionmentioning

confidence: 99%

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The effect of granulocyte-colony stimulating factor in global cerebral ischemia in rats

Matchett¹,

Calinisan²,

Matchett³

et al. 2007

Brain Research

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Granulocyte-colony stimulating factor (G-CSF) is an endogenous peptide hormone of the hematopoietic system that has entered Phase I/II clinical trials for treatment of ischemic stroke. Severe intraoperative hypotension can lead to global cerebral ischemia and apoptotic neuron loss within the hippocampus. We tested G-CSF in a rat model of global cerebral ischemia. Global cerebral ischemia was induced in male Sprague-Dawley rats (280-330g) with the 2-vessel occlusion model (hemorrhagic hypotension to a mean arterial pressure of 30-35 mmHg and bilateral common carotid artery occlusion for 8 minutes). Three groups of animals were used: global ischemia without treatment (GI, n=49), global ischemia with G-CSF treatment (GI+G-CSF, n=42), and sham surgery (Sham, n = 26). Rats in the treatment group received G-CSF (50 μg / kg, subcutaneously) 12 hours before surgery, on the day of surgery, and on post-operative Day 1, and were euthanized on Day 2, 3, and 14. Mild hyperglycemia was observed in all groups. T-maze testing for spontaneous alternation demonstrated initial improvement in the G-CSF treatment group but no long-term benefit. Measurement of daily body weight demonstrated an initial trend toward improvement in the G-CSF group. Quantitative Nissl histology of the hippocampus demonstrated equivalent outcomes on Day 3 and 14, which was supported by quantitative TUNEL stain. Immunohistochemistry and Western blot demonstrated an initial increase in phosphorylated-AKT in the GI+G-CSF group on Day 2. We conclude that G-CSF treatment is associated with transient early improvement in neurobehavioral outcomes after global ischemia complicated by mild hyperglycemia, but no long-term protection.

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Section: Discussioncontrasting

confidence: 70%

Section: Discussionmentioning

confidence: 45%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The effect of granulocyte-colony stimulating factor in global cerebral ischemia in rats

Matchett¹,

Calinisan²,

Matchett³

et al. 2007

Brain Research

Self Cite

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Autonomic Nervous System and Immune System Interactions

Kenney

Ganta

2014

Comprehensive Physiology

294

218

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The present review assesses the current state of literature defining integrative autonomic-immune physiological processing, focusing on studies that have employed electrophysiological, pharmacological, molecular biological and central nervous system experimental approaches. Central autonomic neural networks are informed of peripheral immune status via numerous communicating pathways, including neural and non-neural. Cytokines and other immune factors affect the level of activity and responsivity of discharges in sympathetic and parasympathetic nerves innervating diverse targets. Multiple levels of the neuraxis contribute to cytokine-induced changes in efferent parasympathetic and sympathetic nerve outflows, leading to modulation of peripheral immune responses. The functionality of local sympathoimmune interactions depends on the microenvironment created by diverse signaling mechanisms involving integration between sympathetic nervous system neurotransmitters and neuromodulators; specific adrenergic receptors; and the presence or absence of immune cells, cytokines and bacteria. Functional mechanisms contributing to the cholinergic anti-inflammatory pathway likely involve novel cholinergic-adrenergic interactions at peripheral sites, including autonomic ganglion and lymphoid targets. Immune cells express adrenergic and nicotinic receptors. Neurotransmitters released by sympathetic and parasympathetic nerve endings bind to their respective receptors located on the surface of immune cells and initiate immune-modulatory responses. Both sympathetic and parasympathetic arms of the autonomic nervous system are instrumental in orchestrating neuroimmune processes, although additional studies are required to understand dynamic and complex adrenergic-cholinergic interactions. Further understanding of regulatory mechanisms linking the sympathetic nervous, parasympathetic nervous, and immune systems is critical for understanding relationships between chronic disease development and immune-associated changes in autonomic nervous system function.

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Seeing old friends from a different angle: Novel properties of hematopoietic growth factors in the healthy and diseased brain

2010

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Hematopoietic growth factors are known for their bolstering effects on the growth, survival, and differentiation of blood progenitor cells. Several of these cytokines also influence the proliferation of neural stem/progenitor cells, paralleling cellular mechanisms in analogy to their function in the hematopoietic system. Erythropoietin (EPO), granulocyte-colony stimulating factor (G-CSF), thrombopoietin (TPO), and their respective receptors are all expressed in the hippocampus of the mammalian brain. Recent studies have confirmed EPO and G-CSF as vital neurotrophic and neuroprotective factors, and ascertained their role in neuroprotection and neuroregeneration as pertaining to the most prominent neurodegenerative diseases. The aims of this review are to discuss newly discovered properties of G-CSF, EPO, and TPO beyond their known functions in the hematopoietic system, to create an overview of the accumulating data on the role of these factors in hippocampal function, and to highlight any potential clinical implications.

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A Novel Neuroprotectant Granulocyte-Colony Stimulating Factor

Cited by 115 publications

References 64 publications

The effect of granulocyte-colony stimulating factor in global cerebral ischemia in rats

The effect of granulocyte-colony stimulating factor in global cerebral ischemia in rats

Autonomic Nervous System and Immune System Interactions

Seeing old friends from a different angle: Novel properties of hematopoietic growth factors in the healthy and diseased brain

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