Inflammation mediates varying effects in neurogenesis: relevance to the pathogenesis of brain injury and neurodegenerative disorders

Abstract

Brain inflammation is a complex cellular and molecular response to stress, injury or infection of the CNS in attempt to defend against insults, clear dead and damaged neurons and return the CNS to a normal state. Inflammation in the CNS is driven by the activation of resident microglia, astrocytes and infiltrating peripheral macrophages, which release a plethora of anti‐ and pro‐inflammatory cytokines, chemokines, neurotransmitters and reactive oxygen species. This inflammatory state inadvertently causes further bystander damage to neurons and produces both detrimental and favorable conditions for neurogenesis. Inflammatory factors have varying effects on neural progenitor cell proliferation, migration, differentiation, survival and incorporation of newly born neurons into the CNS circuitry. The unique profile of inflammatory factors, which depends on the severity of inflammation, can have varying consequences on neurogenesis. Inflammatory factors released during mild acute inflammation usually stimulate neurogenesis; where as the factors released by uncontrolled inflammation create an environment that is detrimental to neurogenesis. This review will provide a summary of current progress in this emerging field and examine the potential mechanisms through which inflammation affects neurogenesis during neurological complications.

Evaluating the role of Toll-like receptors in diseases of the central nervous system

“…While neurogenesis occurs primarily in development, the growth of new neurons occurs throughout adult life. The inflammatory mediators released during mild acute inflammation promote neurogenesis, while the inflammatory mediators released during prolonged inflammation inhibits neurogenesis [21].…”

“…Not alone do neurons need to be newly generated but these neurons must differentiate, migrate, survive and integrate correctly into the CNS circuitry in order to be functionally relevant and therefore constitute successful neurogenesis [21]. For example although in Alzheimer's disease (AD) there is an increase in neurogenesis, these neurons do not mature and survive [21].…”

“…For example in ischaemic models it has been shown that new neurons are not only generated but also functionally integrate and enhance cognative function which suggests that the use of drugs that trigger neurogenesis may be beneficial in stroke [21]. Alternatively the introduction of transplanted NPC from transdifferentiated stem cells from non-neural tissue such as the skin may be used.…”

“…The use of NPC transdifferentiated from the patient's own non-neural stem cells to generate new neurons would avoid problems associated with host-versus-donor rejection [21]. In addition to this much work will be required to 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 32 understand how new neurons survive and integrate in order to be properly functional, therefore the processes following neuronal generation may be manipulated therapeutically in diseases of the CNS [21]. The finding that TLRs modulate adult neurogenesis [108] suggests that TLR manipulation may, in the future, be beneficial in therapies aimed at enhancing neurogenesis.…”

Cymbopogon citratus as source of new and safe anti-inflammatory drugs: Bio-guided assay using lipopolysaccharide-stimulated macrophages

“…Chronic inflammation is one of the leading causes of mortality in the western world and is associated with several pathologies like cancer (Porta et al, 2009), rheumatoid arthritis, diabesity (Schmidt and Duncan, 2003), cardiovascular and neurodegenerative diseases (Hunter and Doddi, 2010;Whitney et al, 2009). However, the current anti-inflammatory drugs have several limitations such as lack of responsiveness, side effects, delivery problems and cost of manufacture.…”