Astroglia protect the brain against ischaemia

Notwithstanding the detrimental effects of profound ischaemia on astroglial cells, the latter still remain the most resistant elements of neural circuits, which protect the brain against injury (Figure 10.4).

First and foremost, astrocytes form the main barrier against glutamate excito-toxicity. Astroglial cells, by virtue of numerous transporters (see Chapters 5.7 and 7.8) expressed in their membrane, act as the main sink for the glutamate in the CNS. Furthermore, the astroglial ability to maintain anaerobic ATP production is of great help, as it allows sustained glutamate transport in hypoxic conditions. Astroglial protection against glutamate excitotoxicity became very obvious from in vitro experiments: withdrawal of astrocytes from neuronal cultures led to a 100-times increase in the vulnerability of neurones to glutamate infusion. Similarly, genetic down-regulation of glial glutamate transporters exacerbates brain ischaemic damage.

Second, astrocytes are powerful scavengers of ROS; the latter being one of the main mediators of ischaemic brain injury. Astrocytes contain high concentrations of glutathione and ascorbate, which are the principal antioxidants in the brain. Ascorbate is a component of neuronal-astroglial exchange, as neurones release oxidized ascorbate, which is accumulated by astrocytes, and subsequently converted into ascorbate ready for a new cycle of ROS scavenging. The ability of astrocytes to protect neurones against ROS has been clearly demonstrated

Energy substrates lactate, alanine a-ketoglutarate

Ascorbate Glutathione Cycle

Ascorbate Glutathione

Figure 10.4 Mechanisms of astroglia-dependent neuroprotection. Astroglial cells act as the main sink for glutamate, buffer extracellular potassium, provide neurones with energy substrates and serve as the main source of reactive oxygen species scavengers

Energy substrates lactate, alanine a-ketoglutarate

ROS scavenging

Ascorbate Glutathione

Figure 10.4 Mechanisms of astroglia-dependent neuroprotection. Astroglial cells act as the main sink for glutamate, buffer extracellular potassium, provide neurones with energy substrates and serve as the main source of reactive oxygen species scavengers in vitro: neuronal-astroglial cultures were much more resistant to injury produced by superoxide or hydrogen peroxide, as compared to purified neuronal cultures.

Third, anaerobic metabolism sustained by astrocytes in hypoxic conditions produces several intermediate substrates, such as lactate, alanine and a-ketoglutarate, which can be fed to neurones and support energy production in conditions of glucose deprivation.

Fourth, astrocytic networks are involved in potassium buffering through either K+ uptake or K+ spatial buffering (Chapter 7.7.1), which by removing the excess of potassium may slow down neuronal depolarization and depolarization-induced glutamate release.

Finally, in the more delayed stages of the infarction, the process of reactive astrogliosis leads to an appearance of a protective astrocyte wall, which isolates the damaged area. Subsequently, the reactive astrocytes produce a scar that fills the core necrotic area.

How To Reduce Acne Scarring

How To Reduce Acne Scarring

Acne is a name that is famous in its own right, but for all of the wrong reasons. Most teenagers know, and dread, the very word, as it so prevalently wrecks havoc on their faces throughout their adolescent years.

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