Browsing by Author "Rovegno Echavarría, David Maximiliano"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Inhibition of astroglial hemichannels prevents synaptic transmission decline during spreading depression
    (2024) Tichauer Calderón, Juan Enrique; Lira Mendieta, Matías Sebastián; Cerpa Nebott, Waldo Francisco; Orellana Roca, Juan Andrés; Sáez Carreño, Juan Carlos; Rovegno Echavarría, David Maximiliano
    Spreading depression (SD) is an intriguing phenomenon characterized by massive slow brain depolarizations that affect neurons and glial cells. This phenomenon is repetitive and produces a metabolic overload that increases secondary damage. However, the mechanisms associated with the initiation and propagation of SD are unknown. Multiple lines of evidence indicate that persistent and uncontrolled opening of hemichannels could participate in the pathogenesis and progression of several neurological disorders including acute brain injuries. Here, we explored the contribution of astroglial hemichannels composed of connexin-43 (Cx43) or pannexin-1 (Panx1) to SD evoked by high-K+ stimulation in brain slices. Results Focal high-K+ stimulation rapidly evoked a wave of SD linked to increased activity of the Cx43 and Panx1 hemichannels in the brain cortex, as measured by light transmittance and dye uptake analysis, respectively. The activation of these channels occurs mainly in astrocytes but also in neurons. More importantly, the inhibition of both the Cx43 and Panx1 hemichannels completely prevented high K+-induced SD in the brain cortex. Electrophysiological recordings also revealed that Cx43 and Panx1 hemichannels critically contribute to the SD-induced decrease in synaptic transmission in the brain cortex and hippocampus. Conclusions Targeting Cx43 and Panx1 hemichannels could serve as a new therapeutic strategy to prevent the initiation and propagation of SD in several acute brain injuries.
  • No Thumbnail Available
    Item
    Role of astrocytes connexins - pannexins in acute brain injury
    (2025) Tichauer Calderón, Juan Enrique; Rovegno Echavarría, David Maximiliano
    Acute brain injuries (ABIs) encompass a broad spectrum of primary injuries such as ischemia, hypoxia, trauma, and hemorrhage that converge into secondary injury where some mechanisms show common determinants. In this regard, astroglial connexin and pannexin channels have been shown to play an important role. These channels are transmembrane proteins sharing similar topology and form gateways between adjacent cells named gap junctions (GJs) and pores into unopposed membranes named hemichannels (HCs). In astrocytes, GJs and HCs enable intercellular communication and have active participation in normal brain physiological processes, such as calcium waves, synapsis modulation, regional blood flow regulation, and homeostatic control of the extracellular environment, among others. However, after acute brain injury, astrocytes can change their phenotype and modify the activity of both channels and hemichannels, which can result in the amplification of danger signals, increased mediators of inflammation, and neuronal death, contributing to the expansion of brain damage and neurological deterioration. This is known as secondary brain damage. In this review, we discussed the main biological mechanism of secondary brain damage with a particular focus on astroglial connexin and pannexin participation during acute brain injuries.