Microglial cell population dynamics in the injured adult central nervous system

Ladeby, Rune; Wirenfeldt, Martin; Garcı́a-Ovejero, Daniel; Fenger, Christina; Dissing-Olesen, Lasse; Dalmau, Ishar; Finsen, Bente

doi:10.1016/j.brainresrev.2004.12.009

Cited by 299 publications

(233 citation statements)

References 99 publications

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“…S3). There was no evidence of gliosis, which typically accompanies neurodegeneration (11,12). Instead, the B-vitamin-deficient and high methionine diets significantly suppressed the population of microglial cells in hippocampus.…”

mentioning

confidence: 90%

B-vitamin deficiency causes hyperhomocysteinemia and vascular cognitive impairment in mice

Troen

Shea‐Budgell²,

Shukitt‐Hale³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

166

133

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In older adults, mildly elevated plasma total homocysteine (hyperhomocysteinemia) is associated with increased risk of cognitive impairment, cerebrovascular disease, and Alzheimer's disease, but it is uncertain whether this is due to underlying metabolic, neurotoxic, or vascular processes. We report here that feeding male C57BL6/J mice a B-vitamin-deficient diet for 10 weeks induced hyperhomocysteinemia, significantly impaired spatial learning and memory, and caused a significant rarefaction of hippocampal microvasculature without concomitant gliosis and neurodegeneration. Total hippocampal capillary length was inversely correlated with Morris water maze escape latencies (r ‫؍‬ ؊0.757, P < 0.001), and with plasma total homocysteine (r ‫؍‬ ؊0.631, P ‫؍‬ 0.007). Feeding mice a methionine-rich diet produced similar but less pronounced effects. Our findings suggest that cerebral microvascular rarefaction can cause cognitive dysfunction in the absence of or preceding neurodegeneration. Similar microvascular changes may mediate the association of hyperhomocysteinemia with human age-related cognitive decline. cerebrovascular ͉ homocysteine ͉ mouse ͉ nutrition

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mentioning

confidence: 90%

B-vitamin deficiency causes hyperhomocysteinemia and vascular cognitive impairment in mice

Troen

Shea‐Budgell²,

Shukitt‐Hale³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

166

133

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“…The brain response to ischemia is characterized by a reactive microgliosis [33,75,77] that is associated with a robust induction of the transmembrane receptor Toll-like receptor 2 (TLR2). While it has been widely established that TLRs are the key mediators in the response to invading pathogens, there is a growing line of evidence suggesting that TLRs can be activated by endogenous "danger signals" released from the injured or necrotic cells.…”

Section: Tlrs Response To Ischemic Injury and Neurogenesismentioning

confidence: 99%

Inflammation, plasticity and real-time imaging after cerebral ischemia

2009

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With an incidence of approximately 350 in 100,000, stroke is the third leading cause of death and a major cause of disability in industrialized countries. At present, although progress has been made in understanding the molecular pathways that lead to ischemic cell death, the current clinical treatments remain poorly eVective. There is mounting evidence that inXammation plays an important role in cerebral ischemia. Experimentally and clinically, brain response to ischemic injury is associated with an acute and prolonged inXammatory process characterized by the activation of resident glial cells, production of inXammatory cytokines as well as leukocyte and monocyte inWltration in the brain, events that may contribute to ischemic brain injury and aVect brain recovery and plasticity. However, whether the post-ischemic inXammatory response is deleterious or beneWcial to brain recovery is presently a matter of debate and controversies. Here, we summarize the current knowledge on the molecular mechanisms underlying post-ischemic neuronal plasticity and the potential role of inXammation in regenerative processes and functional recovery after stroke. Furthermore, because of the dynamic nature of the brain inXammatory response, we highlight the importance of the development of novel experimental approaches such as real-time imaging. Finally, we discuss the novel transgenic reporter mice models that have allowed us to visualize and to analyze the processes such as neuroinXammation and neuronal repair from the ischemic brains of live animals.

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“…Although microglial cells are the first inflammatory cells to respond to cerebral ischemia, the responses of astrocytes to pro-inflammatory signals may also be relevant to brain injury (13)(14)(15). However, the association between inflammatory glial cells and TLR4 has not been fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

Protective role of isoflurane pretreatment in rats with focal cerebral ischemia and the underlying molecular mechanism

Xiao

Ren

Yang

et al. 2012

Molecular Medicine Reports

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Abstract. Inflammation and immunity are important in the pathogenesis of cerebral ischemia. Toll-like receptor 4 (TLR4) is involved in the inflammatory responses of injured brain tissues. Emerging studies have focused on the effect of isoflurane (ISO) pretreatment on cerebral ischemia, however, the association between ISO pretreatment and TLR4 during cerebral ischemia remains to be elucidated. In the present study, the protective role of ISO pretreatment in rats with focal cerebral ischemia reperfusion was investigated and the molecular mechanism was discussed. Using a middle cerebral artery occlusion (MCAO) model, triphenyltetrazolium chloride staining was utilized to measure the infarct volume and brain edema and immunofluorescence staining was used to detect the MCAO-induced TLR4 expression and localization. Western blot analyses were conducted to quantify the protein expression levels of TLR4, myeloid differentiation primary response 88 (MyD88) and nuclear factor (NF)-κB in ischemic brain tissue at different time points. The results demonstrated that, following ISO pretreatment, the neurological deficits, brain edema and cerebral infarct size caused by ischemia/reperfusion were attenuated. The astrocyte and microglial activation in the brain tissue was decreased. In addition, the expression levels of TLR4, MyD88 and NF-κB were decreased. The present study indicated that ISO pretreatment may protect the brain from ischemic damage by downregulating the expression levels of TLR4, MyD88 and NF-κB.

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Microglial cell population dynamics in the injured adult central nervous system

Cited by 299 publications

References 99 publications

B-vitamin deficiency causes hyperhomocysteinemia and vascular cognitive impairment in mice

B-vitamin deficiency causes hyperhomocysteinemia and vascular cognitive impairment in mice

Inflammation, plasticity and real-time imaging after cerebral ischemia

Protective role of isoflurane pretreatment in rats with focal cerebral ischemia and the underlying molecular mechanism

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