AUTHOR=Lin Muh-Shi , Chiu I-Hsiang , Lin Chai-Ching 

TITLE=Ultrarapid Inflammation of the Olfactory Bulb After Spinal Cord Injury: Protective Effects of the Granulocyte Colony-Stimulating Factor on Early Neurodegeneration in the Brain

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=Volume 13 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2021.701702

DOI=10.3389/fnagi.2021.701702

ISSN=1663-4365

ABSTRACT=A growing body of literature reveals the respective relationship of olfactory dysfunction and spinal cord injury (SCI) between subjective cognitive decline and neurodegenerative dementia. Since impaired olfaction is regarded as a marker for brain degeneration, whether SCI can lead to olfactory dysfunction is an important issue that should be clarified. We screened the brain of mice that underwent spinal cord hemisection injury through microarray. We found that the mRNA expression of olfactory receptors in the brain began to decline 8 hours (hs) after SCI. Furthermore, SCI was shown to cause neuroinflammation, reduced expression of olfactory receptors and neural stem cells (NSCs), as well as attenuated production of neurotrophic factors in the olfactory bulbs at an early phase (8 hs) following SCI. Specifically, mice experienced with SCI showed elevated mRNA and protein expression of glial fibrillary acidic protein (GFAP; marker of astrocyte reactivation), proinflammatory mediators, including IL-1β, IL-6, and Nestin (marker of NSC) in the olfactory bulb, when compared to sham control. Decreased mRNA expression of olfactory receptors, including olfr 1494, 1324, 1241, 979, and neurotrophic factors, including brain derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF), and nerve growth factor (NGF) were found in the olfactory bulb of SCI mice 8 hs after SCI. The administration of granulocyte colony stimulating factor (G-CSF) in SCI mice was demonstrated to attenuate the above-mentioned pathological manifestation of the olfactory bulb 8 hs after SCI. These results once again confirmed our observation that olfactory bulb is vulnerable to environmental stimuli, even if this damage comes from the remote spinal cord, and pathological processes including inflammatory response and hindered neurogenesis, can initiate at an early stage. This discovery helps to investigate the pathological mechanisms of early neurodegenerative diseases originating from the olfactory bulb, as well as to provide information on early clinical drug prevention.