Temporal and Spatial Changes in Glial Cells During Chronic Hypobaric Hypoxia: Role in Neurodegeneration

Ascend to high altitude results in a drastic change in the environmental conditions an individual is exposed to. As the altitude increases there is a decrease in partial pressure of oxygen leading to a unique condition known as hypobaric hypoxia (HH). Brain is highly vulnerable to hypoxia and it has been well established that hypobaric hypoxia leads to neurodegeneration in different brain regions. However, the response of glial cells during hypobaric hypoxia needs to be explored yet. The present study was aimed to understand the role of glial cells viz. astrocytes, microglia and oligodendrocytes in HH-induced neuronal death. The study aims to understand the effect of HH exposure on glial physiology in a time-dependent (0, 1, 3, 7 and 14 days of HH exposure) and region-dependent (CA1, CA3 and DG regions of hippocampus) manner. We examined the morphological changes and activation of glial cells along with pro-inflammatory cytokine levels. Results indicated that chronic hypobaric hypoxia (7 and 14 days exposure) causes activation of both astrocytes (GFAP-positive cells) and microglia (IBA-1-positive cells) but oligodendrocytes (M-PLP-positive cells) expression was found to be significantly reduced. The results obtained were found to be more profound in the CA1 region of hippocampus, indicating its vulnerability to hypoxia. Neuroinflammation was suggested by elevated IL-β1, IL-6 and TNF-α cytokine levels upon chronic HH. The study also explored the role of microglia and A1 astrocyte interplay in HH-induced neurodegeneration and demyelination. This study explores the shift in role of glial cell toward neurodegeneration under chronic hypobaric hypoxia stress. Chronic stress results in glial activation which leads to neuroinflammation a plausible factor in HH-induced neurodegeneration.