Objectives Neonatal hypoxia ischemia (HI) is an injury that can lead to neurological impairments such as behavioral and learning disabilities. Granulocyte-colony stimulating factor (G-CSF) has been demonstrated to be neuroprotective in ischemic stroke however it has also been shown to induce neutrophilia, ultimately exacerbating neuronal injury. Our hypothesis is that coadministration of anti-neutrophil antibody (Ab) with G-CSF will decrease blood neutrophil counts thereby reducing infarct volume and improving neurological function post HI brain injury. Methods Rat pups were subjected to unilateral carotid artery ligation followed by 2.5h of hypoxia. Animals were randomly assigned to five groups: Sham (n=15), Vehicle (HI, n=15), HI with G-CSF treatment (n=15), HI with G-CSF+Ab treatment (n=15), and HI with Ab treatment (n=15). Ab (325μg/kg) was administered intraperitoneally while G-CSF (50μg/kg) was administered subcutaneously 1h post HI followed by daily injections for 3 consecutive days. Animals were euthanized at 96h post HI for blood neutrophil counts and brain infarct volume measurements as well as at 5 weeks for neurological function testing and brain weight measurements. Lung and spleen weights at both time points were further analyzed. Results The G-CSF treatment group showed tendencies to reduce infarct volume and improve neurological function while significantly increasing neutrophil counts. On the other hand, the G-CSF+Ab group significantly reduced infarct volume, improved neurological function and decreased neutrophil counts. The Ab alone group showed reversal of the neuroprotective effects of the G-CSF+Ab group. No significant differences were found in peripheral organ weights between groups. Conclusion Our data suggest that coadministration of G-CSF with Ab not only prevented brain atrophy but also significantly improved neurological function by decreasing blood neutrophil counts. Hence the neuroprotective effects of G-CSF may be further enhanced if neutrophilia is avoided.
Following radiotherapy, many patients with osteoradionecrosis suffer from xerostomia, thereby decreasing their quality of life. Patients can develop problems with speech, eating, increased dental caries, dysphagia, fractured dentition, chronic refractory osteomyelitis and osteoradionecrosis. Symptoms associated with salivary gland dysfunction can be severe enough that patients terminate the course of their radiotherapy prematurely due to the decrease in their quality of life. Currently, the only treatments available to patients are palliative. A definitive treatment has yet to be discovered. Head and neck cancers, which comprise 5% of overall cancer treatments, rank 8th most expensive to treat in the United States today. Hyperbaric oxygen is being considered for the therapy of radiated salivary glands because it has been shown to stimulate capillary angiogenesis and fibroplasia in radiation treated tissues. It has been hypothesized that salivary acinar cells undergo apoptosis following radiation therapy. The purpose of this paper is to discuss the mechanisms of salivary gland injury and evaluate whether hyperbaric oxygen therapy improves salivary gland function in patients who develop xerostomia and osteoradionecrosis following head and neck radiation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.