An altered blood–brain barrier contributes to brain iron accumulation and neuroinflammation in the 6-OHDA rat model of Parkinson’s disease

Olmedo-Díaz, Sonia; Estévez-Silva, Héctor; Orädd, Greger; Bjerkén, Sara af; Marcellino, Daniel; Virel, Ana

doi:10.1016/j.neuroscience.2017.08.023

Cited by 52 publications

(40 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…BBB protects the brain from potential neurotoxic molecules in circulation via tightly regulating ion balance, nutrient transport, the entry of plasma components and blood cells [23]. Increasing evidence shows the BBB disruption in patients with PD [3334] and animal models of PD [35363738]. Many studies including ours showed that BBB damage contributes to the degeneration of DA neurons in the SN of MPTP-treated mice [192029] and LPS-treated rats [3940].…”

Section: Discussionmentioning

confidence: 99%

Interleukin-4 Contributes to Degeneration of Dopamine Neurons in the Lipopolysaccharide-treated Substantia Nigra in vivo

et al. 2018

View full text Add to dashboard Cite

The present study investigated the effects of interleukin (IL)-4 on dopamine (DA) neurons in the substantia nigra (SN) in vivo of lipopolysaccharide (LPS)-treated rat. Tyrosine hydroxylase immunohistochemistry showed a significant loss of nigral DA neurons at 3 and 7 day post-LPS. In parallel, IL-4 immunoreactivity was upregulated as early as 1 day, reached a peak at 3 day and remained elevated at 7 day post-LPS. IL-4 immunoreactivity was detected exclusively in microglia. IL-4 neutralizing antibody (NA) significantly increased survival of DA neurons in LPS-treated SN in vivo by inhibiting microglial activation and production of proinflammatory mediator such as IL-1β as assessed by immunihistochemical, RT-PCR and ELISA analysis, respectively. Accompanying neuroprotection are IL-4NA effects on decreased disruption of blood-brain barrier and astrocytes. The present data suggest that endogenously expressed IL-4 from reactive microglia may be involved in the neuropathological processes of degeneration of DA neurons occurring in Parkinson's disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Interleukin-4 Contributes to Degeneration of Dopamine Neurons in the Lipopolysaccharide-treated Substantia Nigra in vivo

et al. 2018

View full text Add to dashboard Cite

show abstract

“…BBB can restrict the entry of peripheral inflammatory cytokines, hemoglobin, albumin and neurotoxic factors into the cerebral parenchyma (Zlokovic, 2008 ; Bell et al, 2010 ), and plays an essential role in maintaining the homeostasis of central nervous system (CNS) microenvironment (Hawkins and Davis, 2005 ). However, the integrity of BBB is vulnerable to pathological insults and can be altered in many CNS diseases, including stroke, Alzheimer’s disease (AD), Parkinson’s disease and acute traumatic brain injury (Hawkins and Davis, 2005 ; Ulrich et al, 2015 ; Nahirney et al, 2016 ; Olmedo-Diaz et al, 2017 ; Zhang et al, 2017 ). Among these diseases, stroke can rapidly cause disruption of BBB.…”

Section: Introductionmentioning

confidence: 99%

Increased BBB Permeability Enhances Activation of Microglia and Exacerbates Loss of Dendritic Spines After Transient Global Cerebral Ischemia

Ran

Zhu

et al. 2018

Front. Cell. Neurosci.

View full text Add to dashboard Cite

Ischemic stroke can induce rapid disruption of blood-brain barrier (BBB). It has been suggested that increased BBB permeability can affect the pathological progression of ischemic tissue. However, the impact of increased BBB permeability on microglial activation and synaptic structures following reperfusion after ischemia remains unclear. In this study, we investigated microglial activation, dendritic damage and plasticity of dendritic spines after increasing BBB permeability following transient global cerebral ischemia in the somatosensory cortices in mice. Bilateral common carotid artery ligation (BCAL) was used to induce transient global cerebral ischemia. Mannitol was used to increase the BBB permeability. Intravital two-photon imaging was performed to image the dendritic structures and BBB extravasation. Microglial morphology was quantitated using a skeletonization analysis method. To evaluate inflammation of cerebral cortex, the mRNA expression levels of integrin alpha M (CD11b), CD68, chemokine (C-X-C motif) ligand 10 (IP10) and tumor necrosis factor alpha (TNF-α) were measured by fluorescent quantitative PCR. Intravital two-photon imaging revealed that mannitol caused a drastic increase in BBB extravasation during reperfusion after transient global ischemia. Increased BBB permeability induced by mannitol had no significant effect on inflammation and dendritic spines in healthy mice but triggered a marked de-ramification of microglia; importantly, in ischemic animals, mannitol accelerated de-ramification of microglia and aggravated inflammation at 3 h but not at 3 days following reperfusion after ischemia. Although mannitol did not cause significant change in the percentage of blebbed dendrites and did not affect the reversible recovery of the dendritic structures, excessive extravasation was accompanied with significant decrease in spine formation and increase in spine elimination during reperfusion in ischemic mice. These findings suggest that increased BBB permeability induced by mannitol can lead to acute activation of microglia and cause excessive loss of dendritic spines after transient global cerebral ischemia.

show abstract

“…[10][11][12] In a recent 6-OHDA rat model study, Olmedo-Diaz et al found that iron inclusions were closely associated with active microglia, indicating a role for microglia in brain iron accumulation and dopamine neurodegeneration. 13 Therefore, the iron accumulation in microglia may mainly affect the T Ã 2 value. In our previous study, we found that PD could be strongly suspected when the FA value in the cranial part of the SNc was lower than 0.224.…”

Section: Parameters As a New Diagnostic Methods In Therapeutic Evaluatmentioning

confidence: 99%

“…Furthermore, the

{normalT}_{2}^{*}

parameter, sensitive to the macroscopic and microscopic inhomogeneities of the magnetic field, could also serve as a new biomarker in PD diagnosis . In a recent 6‐OHDA rat model study, Olmedo‐Diaz et al found that iron inclusions were closely associated with active microglia, indicating a role for microglia in brain iron accumulation and dopamine neurodegeneration . Therefore, the iron accumulation in microglia may mainly affect the

{normalT}_{2}^{*}

value.…”

mentioning

confidence: 99%

Role of the combination of FA and parameters as a new diagnostic method in therapeutic evaluation of parkinson's disease

Fang

Zheng

Liu

et al. 2017

Magnetic Resonance Imaging

View full text Add to dashboard Cite

show abstract

An altered blood–brain barrier contributes to brain iron accumulation and neuroinflammation in the 6-OHDA rat model of Parkinson’s disease

Cited by 52 publications

References 51 publications

Interleukin-4 Contributes to Degeneration of Dopamine Neurons in the Lipopolysaccharide-treated Substantia Nigra in vivo

Interleukin-4 Contributes to Degeneration of Dopamine Neurons in the Lipopolysaccharide-treated Substantia Nigra in vivo

Increased BBB Permeability Enhances Activation of Microglia and Exacerbates Loss of Dendritic Spines After Transient Global Cerebral Ischemia

Role of the combination of FA and parameters as a new diagnostic method in therapeutic evaluation of parkinson's disease

Contact Info

Product

Resources

About