Anti-neutrophil antibody enhances the neuroprotective effects of G-CSF by decreasing number of neutrophils in hypoxic ischemic neonatal rat model.

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 5weeks 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.

Does hyperbaric oxygen therapy have the potential to improve salivary gland function in irradiated head and neck cancer patients?

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.