Comparative evaluation of cytokine profiles and reactive gliosis supports a critical role for interleukin-6 in neuron-glia signaling during regeneration

Streit, Wolfgang J.; Hurley, Sean D.; McGraw, Tanya S.; Semple‐Rowland, Susan L.

doi:10.1002/1097-4547(20000701)61:1<10::aid-jnr2>3.0.co;2-e

Cited by 119 publications

(52 citation statements)

References 65 publications

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“…The microenvironment for newly generated neurons was characterized by the presence of microglia actively phagocytizing neuronal debris in the dentate. The specific individual roles for microglia initiated cell-cell interactions determining cell death and cell survival have not been elucidated; however, it has been suggested that activated glial cells may exert neuroprotective and pro-regenerative functions that may be essential for the occurrence of neuronal regeneration (Streit et al, 2000). It is possible that glia and the associated inflammatory response both contribute to the induction of neuronal progenitor cells as a mechanism of hippocampal repair.…”

Section: Discussionmentioning

confidence: 99%

Trimethyltin-induced neurogenesis in the murine hippocampus

Harry¹,

McPherson²,

Wine³

et al. 2003

neurotox res

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Neurogenesis continues to occur in the mature rodent brain with one of the most prominent sources for new neurons being the subgranular layer (SGL) of the dentate gyrus (DG) in the hippocampus. A number of factors can stimulate this process including synaptic activity and injury. To determine if this process would occur upon a direct injury to the dentate region, we exposed young, 21 day old male CD-1 mice to the hippocampal toxicant, trimethyltin (TMT). An acute i.p. injection of TMT (2 mg/kg) produced extensive damage and loss of dentate granule neurons within 72 h. This active period of degeneration was accompanied by an increase in the generation of progenitor cells within the SGL as identified by BrdU uptake and Ki-67 immunostaining. As additional markers for neurogenesis, both nestin and doublecortin showed increased staining patterns within the blades of the dentate. In these young weanling mice, the level of proliferation was sufficient to significantly repopulate the dentate region by 4 weeks post-TMT, suggesting a high level of regenerative potential. Our data indicate a significant level of neurogenesis occurring during the active process of degeneration and in an environment of microglia activation. The TMT-induced injury offers a model system for further examination of the process of neurogenesis, neural adaptation, and the influence of inflammatory factors and glia interactions.

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Section: Discussionmentioning

confidence: 99%

Trimethyltin-induced neurogenesis in the murine hippocampus

Harry¹,

McPherson²,

Wine³

et al. 2003

neurotox res

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“…This is claimed to trigger the proliferative aspect of microglia activation, thus having a neuroprotective function. 5,6,98 However, injection of fibroblasts secreting hyperinterleukin-6 (cytokine growth factor, IL-6, and its alpha receptor) did result in a marked increase in number of neutrophils and in the area occupied by activated microglia and macrophages, correlating with a two-fold increase in the lesion size. 99 Following experimental SCI, transcripts of both the proinflammatory cytokines, TNF-a, IL-1b, and IL-6 and the chemokines, MIP-1a and MIP-1b, are upregulated within the first hour postinjury.…”

Section: Regulation Of Cns Inflammationmentioning

confidence: 99%

Post-traumatic inflammation following spinal cord injury

2003

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“…53) Exposure to IL-6 stimulates microglial proliferation. 54) IL-1b induces the elevation of intracellular Ca 2ϩ levels via the dual pathways of Ca 2ϩ entry and Ca 2ϩ mobilization. 55) 3.6.…”

Section: Hiv-related Moleculesmentioning

confidence: 99%