Central Nervous System Regenerative Failure: Role of Oligodendrocytes, Astrocytes, and Microglia

Abstract

Animal studies are now showing the exciting potential to achieve significant functional recovery following central nervous system (CNS) injury by manipulating both the inefficient intracellular growth machinery in neurons, as well as the extracellular barriers, which further limit their regenerative potential. In this review, we have focused on the three major glial cell types: oligodendrocytes, astrocytes, and microglia/macrophages, in addition to some of their precursors, which form major extrinsic barriers to regrowth in the injured CNS. Although axotomized neurons in the CNS have, at best, a limited capacity to regenerate or sprout, there is accumulating evidence that even in the adult and, especially after boosting their growth motor, neurons possess the capacity for considerable circuit reorganization and even lengthy regeneration when these glial obstacles to neuronal regrowth are modified, eliminated, or overcome.T he failure of injured central nervous system (CNS) axons to regenerate over long distances and reestablish connections interrupted by traumatic lesions has been known for a very long time. As early as 1890, the striking difference between central axons and the often well-regenerating peripheral nerves was experimentally studied; peripheral nerve grafts were implanted into different parts of the brain, retina, and spinal cord. The results showed that denervated peripheral nerves are excellent growth-promoting substrates for regenerating axons, whether of peripheral or central origin. Santiago Ramó n y Cajal summarized these pioneering studies in his seminal book, Regeneration and Degeneration of the Nervous System (1913 in Spanish; 1928 first English edition; Ramó n y Cajal et al. 1991). He concluded that adult central neurons can be induced to grow long axons by attractive and trophic factors originating from peripheral nerves. He also speculated that the absence of regeneration in CNS tissue would be because of a lack of such factors in the adult brain and spinal cord. Modern tracing

Beneficial effects of IL-37 after spinal cord injury in mice

“…Blood-borne monocytes infiltrating into the injured spinal cord mediate axonal retraction (19,20), and this deleterious effect is due to products released by macrophages or by integral macrophage membrane proteins, which inhibit the growth and guidance of axons (19,20). Other inhibitory molecules include chondroitin sulfate proteoglycans, Nogo, ephrins, and semaphorins, which are expressed at the lesion site by astrocytes, oligodendrocytes, and some precursor cells (7). In addition, adult CNS neurons have a limited ability to switch on the intrinsic regeneration machinery after axotomy (26).…”

“…Indeed, it is currently well accepted that inflammation is a major contributor to secondary cell death after SCI. The damaging effects of inflammation are more pronounced in the central nervous system (CNS) than in other tissues, because of the limited capacity for axon regeneration and replenishment of damaged neurons and glial cells, which leads to irreversible functional disabilities (7,8). Therefore, targeting inflammation is a valuable approach to promoting neuroprotection and limiting functional deficits in SCI.…”

Astrocytic and microglial nicotinic acetylcholine receptors: an overlooked issue in Alzheimer’s disease

“…Receptors residing on glial cells have some physiological role in glial function (Sharma and Vijayaraghavan 2001;Shytle et al 2006;Volterra and Meldolesi 2005). In addition, these receptors are important in AD pathogenesis and treatment (Sadigh-Eteghad et al 2014, 2015a specially those which reside on glial cells (Tuppo and Arias 2005).…”

Role of Mesenchymal Stem Cells (MSC) in the Management of Brain Stroke

“…This is the main reason for extensive morbidity and mortality associated with CNS damage and stroke related conditions. Currently available literature did not document definitive cure for neuronal death [7]. Some amount of cell repair from area of "penumbra" can be achieved with timely intervention.…”