In white matter regions of the brain and spinal cord of adult mammals, gap junctions previously were observed linking astrocytes to astrocytes, as well as to oligodendrocytes and ependymacytes. The resulting "functional syncytium" was proposed to modulate the ion fluxes that occur during electrical activity of the associated axons. Gap junctions also have been reported linking neurons with glia, and functional neuronal-glial coupling has been postulated. To investigate the glial syncytium and the neuron-to-glial coupling hypotheses, we used "grid-mapped freeze fracture," conventional thin-section electron microscopy, and light microscope immunocytochemistry to examine and characterize neurons and glia in gray and white matter of adult rat brain and spinal cord. We have obtained quantitative evidence for the abundance and widespread distribution of gap junctions interlinking the three primary types of macroglia throughout both gray and white matter of the mammalian central nervous system (CNS), thereby extending the concept to that of a functional panglial syncytium. In contrast to previous reports, we show that of more than 400 gap junctions in which both participating cells were identified, none were between neurons and glia. Thus, neuronal coupling and glial coupling involved separate and distinct pathways. Finally, putative water channels (i.e., "square arrays") were confirmed to be abundant and in close association with gap junctions in astrocytes and ependymacytes. Because the astrocyte "intermediaries" extend cytoplasmic conduits throughout gray and white matter of brain and spinal cord, from the ependymal layer to the pia-glial limitans, and from oligodendrocytes surrounding axons to astrocyte endfeet surrounding capillaries, the proposed panglial syncytium, with its abundance of water channels and intercellular ion channels, is optimally positioned and equipped to modulate water and ion fluxes across broad regions of the CNS.

(24) (Fig. 1, outlines). Neurons were distinguished from glia based on published criteria (2,3,25,26), including (i) somata >20 p.m in diameter, (ii) nuclei >12 tum in diameter, (iii) cytoplasm with widely spaced ("0.25 ptm) parallel stacks of membranes (i.e., Nissl §To whom reprint requests should be addressed.

Injury to mammalian motor nerves can lead to paralysis, but relatively succul regeneration may occur when conditions are favorable. Elucidation of the mcanism upholding successful regeneration is of theoretical and clincal interest. In this study, the hypothesis that insulin-like growth factor H (IGF-ll) can stimulate motor nerve regeneration was tested. When IGF-H was infused continuously near a site of crush on the sciatic nerve, the distance of motor axon regeneration was increased snlfcantly in rats. In contrast, spontaneous regeneration was inhibited when an anti-IGF-H antiserum was infused through a "window" in the epineurium. Thus, infused IGF-il can increase, and endogenous IGFs can support, the regeneration of motor axons in lesioned nerves.Successful regeneration often is encountered following injury to the peripheral nervous system. Nevertheless, paralysis can result from injury to motor axons in nerves, particularly when lesions are in proximal nerve regions (closer to the spinal cord). Such paralysis might be reduced in incidence someday with improved understanding of the mechanisms supporting successful regeneration. The consequences of motor nerve injury continue to pose a serious medical, economic, and societal problem.The nerve distal to a site of injury contributes to spontaneous regeneration (1, 2). After transection, axons can cross a gap of several millimeters and enter the distal nerve stump, indicating the presence of soluble neurotrophic substances. Supporting cells in the nerve distal to a lesion indeed produce soluble factors, which attract and stimulate neurite growth (3)(4)(5). Freezing the distal nerve greatly reduces the population of Schwann, fibroblast, endothelial, and other cell types and impairs regeneration (6, 7). Motor (8)

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