**9. Effect of hypoxia on astrocyte functioning**

Astrocytes have a crucial role in maintaining the normal oxygen levels in the brain. If the PO2 goes less than 17MMHg, astrocytes robust the Calcium ions into the brain; they act as the source of ATP in the hypoxic state of the brain. Astrocytes also have the potential to sense an increase in PCO2 levels too [21]. This chemosensation helps the cells to provide the astroglial networks with ATPS that help spread Ca + 2 activation and excitation. It also increases breathing to maintain homeostasis. It suggests that ATP released helps to keep living in the face of the hypoxia-evoked depression of the respiratory network [55].

In the previous century, it has also become clear that astrocytes can protect neurons under hypoxia conditions. The potential process is similar to "hypoxic preconditioning," in which a temporary interval of moderate hypoxia protects neurons from subsequent ischemia episodes that are generally fatal [56]. Mild hypoxia synthesizes several protective astrocytic factors that help neurons survive. Hypoxia increases the production of specific proteins, such as connexin 43, which may promote ATP/adenosine transit towards the interstitial space [57]. Astrocytes release erythropoietin in reaction to hypoxia, which has a significant neuroprotective impact. The erythropoietin expression in astrocytes is increased once hypoxia-inducible factors are activated. HIF-1α and HIF-2α are two transcription factors. [58]. In an adult brain, astrocytes can alter and monitor synaptic functionality. It was believed that synaptic plasticity is solely based on neurons, but in recent research, it has been found that the glial network and astrocytes alter synaptic transmissions [59]. The activation of metabotropic receptors modulates synaptic alterations by astrocytes. It helps release glutamate, gliotransmitter ATP, and D-serine, which act on neurons [60]. As per Astrocyte-induced pathogenesis, astrocytes can cause adenosine accumulation that affects glial cells and cause sleep deprivation and cognitive impairment [61]. Experimental investigations have found that the astrocytes sense synaptic activity with the help of astrocytic calcium. Astrocytes elevate their Ca + levels to sense neural activity with the help of the Gq-coupled protein pathway [62].
