Interconnection between cells, evidently, has arisen in evolution together with the origin of cells themselves. It seems likely that an early step in the evolution, a multicellular organism represented the association of unicellular organisms that formed colonies. The single-cellular animals when food supplies are exhausted form colonies and show social behavior in a primitive form. Cytokines, cyclic AMP, NO and arachidonic acid regulate colony formation. Injury of a neural system returns inner physiological processes to path of growth and development and activates the same factors. Increased neurotransmitter release (glutamate; substance P and ATP) activate both second order neurons and surrounding glial cells, which produce cytokines and other inflammatory agents: tumor necrosis factor, NO, ATP, etc. [824]. If these ancient processes participate in the cerebral function, they probably play a role in establishment of the background states of a neural system, depending on its current needs, and do not use past experience for upgrading of their activity. For instance, shortage of nutrients consistently causes hunger in spite of when one earlier already experiences this sense. However, more recent defense systems, neuropeptides and, in particular, the opioid system, may more closely be connected with acquired behavior.
Cells in multicellular organisms are incessantly interconnected. During injury, interaction between cells is reorganized and cells begin to express ancient properties. A dynamic process of damage eventually propagates with time from the center of damage to neighboring tissue [532]. Any local injury tends to spread to distant parts of the nervous and non-nervous systems. The extent of severe damage is determined by an outflow of the deleterious contents of dying cells, such as free radicals, and by mediators of cell death such us the inflammatory managers cytokines, retrograde transmitters, etc. These substances are produced by various cells, but especially by glia, for instance, by microglial cells. Compressive injury induces changes in Ca?+ levels in glial cells that can spread through glial networks along the white matter [742]. Experimentally evoked elevation of intracellular Ca2+ in astrocytes evokes elevations in the internal Ca2+ of adjacent neurons [526] and this can aggravate damage. Astrocytes can communicate with each other through Ca2+ waves, providing a potential mechanism for the propagation of information over large distances [27, 526]. Similarly, in response to neuronal activity, elevated Ca2+ in astrocytes leads to glutamate-dependent Ca2+ elevations in neurons and can induce membrane depolarization that eventually can trigger action potential discharges [964]. The spread of cellular damage in the brain increases with the augmentation of intercellular coupling through gap junctions, which provides a fine regulation of surrounding neuronal activity [311, 844, 1011].
Opening of a gap junction can exacerbate cell damage, since when coupled cells have undergone to injury, destructive molecules spread from more to less injured cells helping the former and harming the latter. Health promoting molecules such as necessary metabolites spread from less injured to more injured cells, harming the former and helping the latter [260] and this ameliorates cell injury. In addition, since a gap junction behaves as a resistance connecting two cells, when current flowing from a more injured cell depolarizes a more negative cell, the same current makes the first cell less depolarized [109]. Therefore, when two cells interact through gap junction the damage to the injured cell decreases at the same time as a healthy cell experiences injury. Gap junction, certainly participate in a cell damage, but this participation is ambiguously. Although no direct studies of cognitive or affective effects of coupling have yet been published [257], there are much indirect evidences. By means of gap junctions, cells endure troubles together.
