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The role of ghrelin in neuroprotection after ischemic brain injury.

Spencer SJ, Miller AA, Andrews ZB - Brain Sci (2013)

Bottom Line: Ghrelin, a gastrointestinal peptide with a major role in regulating feeding and metabolism, has recently been investigated for its neuroprotective effects.Specifically, we will discuss evidence showing ghrelin administration can improve neuronal cell survival in animal models of focal cerebral ischemia, as well as rescue memory deficits.We will also discuss its proposed mechanisms of action, including anti-apoptotic and anti-inflammatory effects, and suggest ghrelin treatment may be a useful intervention after stroke in the clinic.

View Article: PubMed Central - PubMed

Affiliation: School of Health Sciences and Health Innovations Research Institute (HIRi), RMIT University, Melbourne, VIC 3083, Australia. Sarah.Spencer@rmit.edu.au.

ABSTRACT
Ghrelin, a gastrointestinal peptide with a major role in regulating feeding and metabolism, has recently been investigated for its neuroprotective effects. In this review we discuss pre-clinical evidence suggesting ghrelin may be a useful therapeutic in protecting the brain against injury after ischemic stroke. Specifically, we will discuss evidence showing ghrelin administration can improve neuronal cell survival in animal models of focal cerebral ischemia, as well as rescue memory deficits. We will also discuss its proposed mechanisms of action, including anti-apoptotic and anti-inflammatory effects, and suggest ghrelin treatment may be a useful intervention after stroke in the clinic.

No MeSH data available.


Related in: MedlinePlus

Ghrelin inhibits apoptosis and protects against inflammation. Ghrelin stimulates extracellular-signalling-regulated-kinase (ERK)1/2, mitogen-activated protein kinase (MAPK), protein kinase A (PKA), and protein kinase C (PKC) pathways to reduce activation of BAX, improve the Bcl2/BAX ratio and thus suppress apoptosis and improve cell survival. Inset; ghrelin inhibits neutrophil, lymphocyte, and microglial activation to suppress pro-inflammatory cytokine production and the secretion of inflammatory neurotoxins.
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brainsci-03-00344-f001: Ghrelin inhibits apoptosis and protects against inflammation. Ghrelin stimulates extracellular-signalling-regulated-kinase (ERK)1/2, mitogen-activated protein kinase (MAPK), protein kinase A (PKA), and protein kinase C (PKC) pathways to reduce activation of BAX, improve the Bcl2/BAX ratio and thus suppress apoptosis and improve cell survival. Inset; ghrelin inhibits neutrophil, lymphocyte, and microglial activation to suppress pro-inflammatory cytokine production and the secretion of inflammatory neurotoxins.

Mentions: When a cell becomes sufficiently depleted of oxygen and nutrients, pro-apoptotic genes involved in cell death are activated. This activation leads to the stimulation of pro-apoptotic BAX and suppression of anti-apoptotic Bcl2. These proteins interact to regulate the permeability of the mitochondrial permeability transition pore [52,53,54,55]. When BAX is activated, cytochrome c is released from the mitochondria and interacts with Apaf-1 such that Apaf-1 forms a complex with pro-caspase 9, leading to activation of caspase-9 and -3. Mitochondrial dysfunction therefore plays an important role in cell survival. Evidence suggests ghrelin inhibits apoptotic mechanisms by activating the extracellular-signalling-regulated-kinase (ERK)1/2, mitogen-activated protein kinase, protein kinase A, and protein kinase C pathways [36,56]. The activation of these pathways is associated with reduced activation of BAX, an improved Bcl2/BAX ratio and suppression of apoptosis/improved cell survival (Figure 1). Ghrelin also suppresses apoptosis by increasing expression of mitochondrial uncoupling protein UCP2. UCP2 elevation effectively buffers production of reactive oxygen species, protecting the cell from oxidative stress and reducing apoptosis [36,57,58]. Protective increases in UCP2 with ghrelin have been observed in traumatic brain injury and PD models [36,58].


The role of ghrelin in neuroprotection after ischemic brain injury.

Spencer SJ, Miller AA, Andrews ZB - Brain Sci (2013)

Ghrelin inhibits apoptosis and protects against inflammation. Ghrelin stimulates extracellular-signalling-regulated-kinase (ERK)1/2, mitogen-activated protein kinase (MAPK), protein kinase A (PKA), and protein kinase C (PKC) pathways to reduce activation of BAX, improve the Bcl2/BAX ratio and thus suppress apoptosis and improve cell survival. Inset; ghrelin inhibits neutrophil, lymphocyte, and microglial activation to suppress pro-inflammatory cytokine production and the secretion of inflammatory neurotoxins.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4061836&req=5

brainsci-03-00344-f001: Ghrelin inhibits apoptosis and protects against inflammation. Ghrelin stimulates extracellular-signalling-regulated-kinase (ERK)1/2, mitogen-activated protein kinase (MAPK), protein kinase A (PKA), and protein kinase C (PKC) pathways to reduce activation of BAX, improve the Bcl2/BAX ratio and thus suppress apoptosis and improve cell survival. Inset; ghrelin inhibits neutrophil, lymphocyte, and microglial activation to suppress pro-inflammatory cytokine production and the secretion of inflammatory neurotoxins.
Mentions: When a cell becomes sufficiently depleted of oxygen and nutrients, pro-apoptotic genes involved in cell death are activated. This activation leads to the stimulation of pro-apoptotic BAX and suppression of anti-apoptotic Bcl2. These proteins interact to regulate the permeability of the mitochondrial permeability transition pore [52,53,54,55]. When BAX is activated, cytochrome c is released from the mitochondria and interacts with Apaf-1 such that Apaf-1 forms a complex with pro-caspase 9, leading to activation of caspase-9 and -3. Mitochondrial dysfunction therefore plays an important role in cell survival. Evidence suggests ghrelin inhibits apoptotic mechanisms by activating the extracellular-signalling-regulated-kinase (ERK)1/2, mitogen-activated protein kinase, protein kinase A, and protein kinase C pathways [36,56]. The activation of these pathways is associated with reduced activation of BAX, an improved Bcl2/BAX ratio and suppression of apoptosis/improved cell survival (Figure 1). Ghrelin also suppresses apoptosis by increasing expression of mitochondrial uncoupling protein UCP2. UCP2 elevation effectively buffers production of reactive oxygen species, protecting the cell from oxidative stress and reducing apoptosis [36,57,58]. Protective increases in UCP2 with ghrelin have been observed in traumatic brain injury and PD models [36,58].

Bottom Line: Ghrelin, a gastrointestinal peptide with a major role in regulating feeding and metabolism, has recently been investigated for its neuroprotective effects.Specifically, we will discuss evidence showing ghrelin administration can improve neuronal cell survival in animal models of focal cerebral ischemia, as well as rescue memory deficits.We will also discuss its proposed mechanisms of action, including anti-apoptotic and anti-inflammatory effects, and suggest ghrelin treatment may be a useful intervention after stroke in the clinic.

View Article: PubMed Central - PubMed

Affiliation: School of Health Sciences and Health Innovations Research Institute (HIRi), RMIT University, Melbourne, VIC 3083, Australia. Sarah.Spencer@rmit.edu.au.

ABSTRACT
Ghrelin, a gastrointestinal peptide with a major role in regulating feeding and metabolism, has recently been investigated for its neuroprotective effects. In this review we discuss pre-clinical evidence suggesting ghrelin may be a useful therapeutic in protecting the brain against injury after ischemic stroke. Specifically, we will discuss evidence showing ghrelin administration can improve neuronal cell survival in animal models of focal cerebral ischemia, as well as rescue memory deficits. We will also discuss its proposed mechanisms of action, including anti-apoptotic and anti-inflammatory effects, and suggest ghrelin treatment may be a useful intervention after stroke in the clinic.

No MeSH data available.


Related in: MedlinePlus