Liposomal drug delivery systems: from concept to clinical applications.

All cells in living organisms have a limited life span, and when the time set by their biological clocks has run out, they will die , their highly orga­ nized macromolec ular structure will disintegrate, and the low-molec ul ar degrad ation products be­ come part of the disorder of the surroundings . In thermodynamic terms, this series of events consti­ tutes what has been c alled the entropic doom. We know little about those molec ul ar mechanisms that limit the life span of cells in the absence of dise ase. For the clinician, therefore, the important task is to prevent or tre at dise ases that jeopardize the proper functioning and viability of cells whose biologic al clocks have not yet run out . Measures instituted to prevent brain cell death have a special importance . This i s partly due t o the fact that w e equate human life with the functioning of the brain. However, this importance also resides in the v ulnerability of brain cells to conditions that allow cells of most other tissue to survive , and to continue or res ume their activitie s . The clinically most important conditions leading to brain cell death are those associated with cere­ brovascul ar dise ase, particularly stroke, and with head trauma. We will begin, though, by rec alling the traditional view of the occ urrence and loc alization of neuronal damage in four conditions that lead to more disseminated alterations, e specially since they have been considered to c ause nerve cell injury of a

https://journals.sagepub.com/doi/pdf/10.1038/jcbfm.1981.18

Cell Damage in the Brain: A Speculative Synthesis

Effect of anoxia on ion distribution in the brain.

Isozymes of the Na+/K+-ATPase.

Astrocytes are neural cells of ectodermal, neuroepithelial origin that provide for homeostasis and defense of the central nervous system (CNS). Astrocytes are highly heterogeneous in morphological appearance; they express a multitude of receptors, channels, and membrane transporters. This complement underlies their remarkable adaptive plasticity that defines the functional maintenance of the CNS in development and aging. Astrocytes are tightly integrated into neural networks and act within the context of neural tissue; astrocytes control homeostasis of the CNS at all levels of organization from molecular to the whole organ.

Physiology of astroglia

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Addition of norepinephrine or isoproterenol to primary cultures started from the brains of 1-3 day old rats caused up to 200-fold increases in cAMP levels, which reached a maximum by 5-10 min and then declined. This effect was studied in detail for norepinephrine. The rise in cAMP levels was followed by morphological changes, in which up to 65% of the cells exhibited an astrocyte-like morphology, and 2-3 fold increases in carbonic anhydrase and (Na+-K+) ATPase activities. However, morphological transformation also occurred after much smaller increases in total cAMP levels. These effects on cell morphology and enzyme activities reached a maximum 1-2 h after addition of norepinephrine and then declined. Carbonic anhydrase activity was found both in the particulate and post 100,000 g supernatant fractions from homogenates of these cultured cells, and in the latter case the activity was activated 3-fold by addition of cAMP. The significance of these obscrvations on the cellular localization of, and functional role for similar increases in cAMP in brain tissue is discussed.

Robert S. Bourke

Papers

Effects of norepinephrine on the morphology and some enzyme activities of primary monolayer cultures from rat brain

Enzymatic and morphological properties of primary rat brain astrocyte cultures, and enzyme development in vivo.

SITS-inhibitable Cl- transport and Na+-dependent H+ production in primary astroglial cultures.

Cation transport and membrane potential properties of primary astroglial cultures from neonatal rat brains.

Dopamine and norepinephrine uptake and metabolism by astroglial cells in culture.