Downregulation of water channel aquaporin-4 in rats with experimental autoimmune encephalomyeritis induced by myelin basic protein

Kaneyama, Tomoki; Takizawa, Sho; Tsugane, Sayaka; Yanagisawa, Satoshi; Takeichi, Naoya; Ehara, Takashi; Ichikawa, Motoki; Koh, Chang−Sung

doi:10.1016/j.cellimm.2013.01.003

Cited by 5 publications

(5 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Aquaporin 4 is the main water channel protein of astrocytes within the CNS, with a high density at the glia limitans [22]. The expression can be negatively impacted by inflammation [22]. In the present study, it was seen that the expression of aquaporin 4 is downregulated within inflammatory hippocampal lesions after TMEV infection, irrespective of tamoxifen application (Figure 4).…”

Section: Figuresupporting

confidence: 53%

See 1 more Smart Citation

Tamoxifen Application Is Associated with Transiently Increased Loss of Hippocampal Neurons following Virus Infection

Hülskötter

Lühder

Flügel

et al. 2021

IJMS

View full text Add to dashboard Cite

Tamoxifen is frequently used in murine knockout systems with CreER/LoxP. Besides possible neuroprotective effects, tamoxifen is described as having a negative impact on adult neurogenesis. The present study investigated the effect of a high-dose tamoxifen application on Theiler’s murine encephalomyelitis virus (TMEV)-induced hippocampal damage. Two weeks after TMEV infection, 42% of the untreated TMEV-infected mice were affected by marked inflammation with neuronal loss, whereas 58% exhibited minor inflammation without neuronal loss. Irrespective of the presence of neuronal loss, untreated mice lacked TMEV antigen expression within the hippocampus at 14 days post-infection (dpi). Interestingly, tamoxifen application 0, 2 and 4, or 5, 7 and 9 dpi decelerated virus elimination and markedly increased neuronal loss to 94%, associated with increased reactive astrogliosis at 14 dpi. T cell infiltration, microgliosis and expression of water channels were similar within the inflammatory lesions, regardless of tamoxifen application. Applied at 0, 2 and 4 dpi, tamoxifen had a negative impact on the number of doublecortin (DCX)-positive cells within the dentate gyrus (DG) at 14 dpi, without a long-lasting effect on neuronal loss at 147 dpi. Thus, tamoxifen application during a TMEV infection is associated with transiently increased neuronal loss in the hippocampus, increased reactive astrogliosis and decreased neurogenesis in the DG.

show abstract

Section: Figuresupporting

confidence: 53%

“…Tamoxifen-treated animals also showed increased numbers of neurotropic A2 astrocytes compared to untreated mice with no lesions (Figure 4). Aquaporin 4 is the main water channel protein of astrocytes within the CNS, with a high density at the glia limitans [22]. The expression can be negatively impacted by inflammation [22].…”

Section: Figurementioning

confidence: 99%

Tamoxifen Application Is Associated with Transiently Increased Loss of Hippocampal Neurons following Virus Infection

Hülskötter

Lühder

Flügel

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…Altered polarization of AQP4, that is, an elevation in nonvascular associated protein, is observed in neurodegenerative disorders, impairs glymphatic influx, and subsequently attenuates waste clearance from the CNS. [156][157][158][159] Given the inflammatory nature of SAH, it is unsurprising then that similar defects in astrocytic polarization, as well as general astrogliosis, are seen following SAH induction by autologous blood, limiting clearance of toxic waste matter from the brain. 154 Lymphatic drainage appears, at least partially, coupled with functional glymphatic flow.…”

Section: Potential Glymphatic Alterationsmentioning

confidence: 99%

Cerebrovascular Anomalies: Perspectives From Immunology and Cerebrospinal Fluid Flow

Rustenhoven

Tanumihardja

Kipnis

2021

Circulation Research

View full text Add to dashboard Cite

Appropriate vascular function is essential for the maintenance of central nervous system homeostasis and is achieved through virtue of the blood-brain barrier; a specialized structure consisting of endothelial, mural, and astrocytic interactions. While appropriate blood-brain barrier function is typically achieved, the central nervous system vasculature is not infallible and cerebrovascular anomalies, a collective terminology for diverse vascular lesions, are present in meningeal and cerebral vasculature supplying and draining the brain. These conditions, including aneurysmal formation and rupture, arteriovenous malformations, dural arteriovenous fistulas, and cerebral cavernous malformations, and their associated neurological sequelae, are typically managed with neurosurgical or pharmacological approaches. However, increasing evidence implicates interacting roles for inflammatory responses and disrupted central nervous system fluid flow with respect to vascular perturbations. Here, we discuss cerebrovascular anomalies from an immunologic angle and fluid flow perspective. We describe immune contributions, both common and distinct, to the formation and progression of diverse cerebrovascular anomalies. Next, we summarize how cerebrovascular anomalies precipitate diverse neurological sequelae, including seizures, hydrocephalus, and cognitive effects and possible contributions through the recently identified lymphatic and glymphatic systems. Finally, we speculate on and provide testable hypotheses for novel nonsurgical therapeutic approaches for alleviating neurological impairments arising from cerebrovascular anomalies, with a particular emphasis on the normalization of fluid flow and alleviation of inflammation through manipulations of the lymphatic and glymphatic central nervous system clearance pathways.

show abstract

“…24) On the other hand, microglia produces neurotrophic factor such as brain derived neurotrophic factor (BDNF), and acts as neuroprotective in the middle or late phase of EAE. 25) No obvious suppression of IVIg on the Iba1-positive area on day 21 (late phase) was observed, suggesting the possibility that IVIg do not affect neuroprotective microglia. Collectively, neuroprotective effects of IVIg may be due to anti-inflammation including microglial suppression, and direct protection of the optic nerve.…”

Section: Discussionmentioning

confidence: 97%

Prophylactic Treatment with Intravenous Immunoglobulin Attenuates Experimental Optic Neuritis in Mice

Takahashi

Okuda

Tamura

et al. 2019

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Optic neuritis is characterized by optic nerve inflammation, demyelination and axonal loss. Intravenous immunoglobulin (IVIg) has been reported to be effective for steroid-resistant patients. However, there is no report investigating the histopathological efficacy of IVIg in optic neuritis models. In this study, we examined the effects of IVIg on optic neuritis of experimental autoimmune encephalomyelitis (EAE) and experimental autoimmune optic neuritis (EAON). Inflammation, demyelination and axonal loss were assessed in the optic nerve sections. IVIg showed dose-dependent prevention of clinical symptoms in EAON. IVIg provided an anti-inflammatory effect in both EAE and EAON, associated with improved demyelination. Axonal loss in EAE was also significantly attenuated. These results suggest that IVIg has neuroprotective properties in experimental optic neuritis, and is a promising new treatment for optic neuritis.

show abstract

Downregulation of water channel aquaporin-4 in rats with experimental autoimmune encephalomyeritis induced by myelin basic protein

Cited by 5 publications

References 31 publications

Tamoxifen Application Is Associated with Transiently Increased Loss of Hippocampal Neurons following Virus Infection

Tamoxifen Application Is Associated with Transiently Increased Loss of Hippocampal Neurons following Virus Infection

Cerebrovascular Anomalies: Perspectives From Immunology and Cerebrospinal Fluid Flow

Prophylactic Treatment with Intravenous Immunoglobulin Attenuates Experimental Optic Neuritis in Mice

Contact Info

Product

Resources

About