The role of ghrelin in neuroprotection after ischemic brain injury

Sarah J Spencer, Alyson A Miller, Zane B Andrews, Sarah J Spencer, Alyson A Miller, Zane B Andrews

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.

Figures

Figure 1
Figure 1
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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