Ghrelin Therapy Decreases Incidents of Intracranial Hemorrhage in Mice after Whole-Body Ionizing Irradiation Combined with Burn Trauma

Abstract

Nuclear industrial accidents and the detonation of nuclear devices cause a variety of damaging factors which, when their impacts are combined, produce complicated injuries challenging for medical treatment. Thus, trauma following acute ionizing irradiation (IR) can deteriorate the IR-induced secondary reactive metabolic and inflammatory impacts to dose-limiting tissues, such as bone marrow/lymphatic, gastrointestinal tissues, and vascular endothelial tissues, exacerbating the severity of the primary injury and decreasing survival from the exposure. Previously we first reported that ghrelin therapy effectively improved survival by mitigating leukocytopenia, thrombocytopenia, and bone-marrow injury resulting from radiation combined with burn trauma. This study was aimed at investigating whether radiation combined with burn trauma induced the cerebro-vascular impairment and intracranial hemorrhage that could be reversed by ghrelin therapy. When B6D2F1 female mice were exposed to 9.5 Gy Cobalt-60 γ-radiation followed by 15% total skin surface burn, cerebro-vascular impairment and intracranial hemorrhage as well as platelet depletion were observed. Ghrelin treatment after irradiation combined with burn trauma significantly decreased platelet depletion and brain hemorrhage. The results suggest that ghrelin treatment is an effective therapy for ionizing radiation combined with burn trauma.

Ghrelin therapy mitigates bone marrow injury and splenocytopenia by sustaining circulating G-CSF and KC increases after irradiation combined with wound

“…The latter induces side effects including appetite loss and edema [ 55 ]. Ghrelin administration accelerates body weight recovery and is found no edema [ 31 ].…”

“…It is reported that human ghrelin decreased organ injury and increased survival by 30% above the vehicle-treated mice after RI combined with severe sepsis in rats [ 14 ]. Kiang et al [ 24 ] reported that ghrelin therapy was efficacious in a mouse model of radiation combined with wound or burn by increasing survival, body weight, wound healing, bone marrow cell counts, neutrophil recovery and platelet recovery on day 30 post CI as well as inhibiting brain hemorrhage [ 31 ]. Ghrelin blocks NF-κB activation, decreased TNF-α and IL-6 concentrations in lung of septic rats and inhibited nucleotide-binding oligomerization domain-containing protein 2 [NOD2, also known as caspase recruitment domain-containing protein 15 (CARD15) or inflammatory bowel disease protein 1 (IBD1)] [ 32 ].…”

A novel therapy, using Ghrelin with pegylated G-CSF, inhibits brain hemorrhage from ionizing radiation or combined radiation injury

“…23 Our laboratory recently reported that brain hemorrhage was observed on days 13-16 after irradiation in an experimental animal model of radiation combined with burn trauma. 24 In that report, when mice were exposed to 15% total skin surface burn following 9.5 Gy 60 Cobalt-γ photon radiation, extracranial hemorrhage and intracranial hemorrhage were found. Extracranial hemorrhage was observed in the olfactory lobe, mid-brain, and cerebellum.…”

Self-Assembling Peptide Scaffold Carrying Neural-Cell Adhesion Molecule-Derived Mimetic-Peptide Transplantation Promotes Proliferation and Stimulates Neurite Extension by Modulating Tau Phosphorylation and Calpain/Glycogen Synthase Kinase 3 beta (GSK-3β) in Neurons

“…Peptides are an important topic in the biomedical field and have been extensively proven to be an ideal therapeutic strategy for many diseases [ 1 , 2 ]. Peptides are used in the treatment of cancers [ 3 ], diabetes [ 4 ], and cerebrovascular disorders [ 5 ]. However, they are easily cleaved by circulating proteases and thus are short-lived [ 6 ].…”