Figure 2. (1) Recruitment of Parkin by inflammatory agents in the activation process of nuclear factor-kappa B (NF-kB): In the course of the hypoxic-ischemic insult, inflammatory factors are released by glial cells, such as TNF-α, activating a pathway of neural remodeling ^18,20 . In the presence of high levels of TNF-α, it binds to its receptor, TNFR, which recruits the protein kinase interaction receptor (RIPK), which serves as a binding site for Parkin to act. This molecule promotes the activation of nuclear factor-kappa (NF-kB) by promoting the ubiquitination of the gamma (NEMO) subunit of the IkB enzyme complex (IKK) ¹⁴ . Thus, Parkin promotes NEMO labeling and indirectly phosphorylation of the Beta subunit (IKKβ) of the IKK complex by an upstream kinase, activating it ^21,22 . With this activation, IKKβ manages to phosphorylate the inhibitory protein linked to NF-kB, IkBα, which is polyubitkinated and degraded by proteosomes, thus allowing NF-kB, originating from the canonical pathway, to enter the nucleus of neuronal cells in its active form. (2) Role of NF-kB in HIF-1-α mRNA transcription: The NF-kB activated binds to the initiation site of the HIF-1-α precursor DNA molecule, which induces the transcription of the mRNA HIF-1-α ²³ .This binding allows translation of the HIF factor promoter gene, giving rise to the HIF-1-α molecule. This molecule, inside the cell cytoplasm and in the presence of oxygen, is induced to degradation by prolyl hydroxylase (PHD) enzymes and, under hypoxic conditions, allows the HIF molecule to be activated and enter the cell nucleus ¹⁶ . (3) Role of cell growth pathways in HIF activation and production of neural protective factors in MG such as VEGFR-1: Once the HIF molecule is produced, it needs to be stabilized and activated in order to be able to promote the production of neural protective factors such as VEGFR-1. The HIF1-α molecule in the cell cytoplasm is inactive and stabilized by normoxic conditions. For its activation to occur, several factors are related, among them, eukaryotic translation factors/growth factors, which have been shown to contribute to HIF-1-α activation by phosphorylating the molecule and allowing it to enter the nucleus ^24,25 . In this process, neurotrophins are released and bind to the Tyrosine Kinase C (TRK-C) receptor, which is responsible for activating the AKT-3/mTORC-1 pathway and producing eukaryotic translation factors. Inside the nucleus, HIF can produce molecules associated with cellular vascularization — VEGFR-1 — and, therefore, revitalize the tissue by guaranteeing the supply of O2.