Morphological and functional changes of blood–brain barrier in kindled rats with cortical dysplasia

Kaya, Mehmet; Gürses, Candan; Kalayci, Rivaze; Ekizoğlu, Oğuzhan; Ahıshalı, Bülent; Orhan, Nurcan; Oku, Basar; Arıcan, Nadir; Ustek, Duran; Bılgıç, Bilge; Elmas, İmdat; Küçük, Mutlu; Kemikler, Gönül

doi:10.1016/j.brainres.2008.02.101

Cited by 24 publications

(21 citation statements)

References 35 publications

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“…In this study, we used NaFlu dye to detect the disruption of BBB because this hyperpermeability was good models to detect the extravasation of fibrinogen (Kaya et al 2008;Nishioku et al 2009). The administration of 1 mg/kg LPS did not rupture BBB directly because of low dosages.…”

Section: Discussionmentioning

confidence: 99%

Systemic Administration of Lipopolysaccharide Induces Cyclooxygenase-2 Immunoreactivity in Endothelium and Increases Microglia in the Mouse Hippocampus

et al. 2009

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In this study, we observed the effects of lipopolysaccharide (LPS) on neurodegeneration and immune response in the hippocampus. LPS is a gram-negative bacterial cell surface proteoglycan and known as a bacterial endotoxin. For this, we investigated the optimal concentration of LPS influencing the ICR mouse hippocampus to measure the LPS receptor, e.g., toll-like receptor 4 (TLR4), expression in mouse hippocampal homogenates. TLR4 expression was significantly and prominently increased in the hippocampal homogenates of the LPS (1 mg/kg)-treated group. Next, we examined pro-inflammatory response in the hippocampus using cyclooxygenase-2 (COX-2, a marker for inflammatory response) immunohistochemistry after LPS treatment. COX-2 immunoreactivity was significantly increased in the endothelium of blood vessels in the hippocampus 6 h after LPS treatment, judging from double immunofluorescence study with platelet-derived endothelial cell adhesion molecule-1 (PECAM-1, a marker for endothelial cells): it decreased 12 h and disappeared 24 h after LPS treatment. In addition, the ionized calcium-binding adapter molecule 1 (Iba-1)-immunoreactive ((+)) microglia were morphologically activated in the mouse hippocampus after LPS treatment. At 24 h after LPS treatment, Iba-1(+) microglia of activated forms were abundant in the hippocampus. However, NeuN (a neuron-specific soluble nuclear antigen)(+) neurons were not significantly changed in the hippocampus after LPS treatment. Fluoro-jade B (a marker for neuronal degeneration)(+) cells were not detected in the hippocampus at any time after LPS treatment. In addition, there were no significant differences in permeability of blood-brain barriers at any time points after LPS treatment. In brief, our results indicate that intraperitoneal administration of 1 mg/kg LPS effectively induces LPS receptor (TLR4) expression in the hippocampus, and the treatment increases corticosterone levels, inflammation in the blood vessels, and microglial activation in the hippocampus without any neuronal damage.

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Section: Discussionmentioning

confidence: 99%

Systemic Administration of Lipopolysaccharide Induces Cyclooxygenase-2 Immunoreactivity in Endothelium and Increases Microglia in the Mouse Hippocampus

et al. 2009

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“…BBB and BSCB permeability was also assessed using a micromolecular tracer dye sodium fluorescein (NaFlu) (MW, 376; Sigma-Aldrich) according to a modified procedure by Kaya et al (2008). Briefly, NaFlu was administered intravenously (10%; 2 ml/kg) and allowed to circulate for 30 min.…”

Section: Evaluation Of Bscb Permeabilitymentioning

confidence: 99%

Peripheral Nerve Injury Alters Blood-Spinal Cord Barrier Functional and Molecular Integrity through a Selective Inflammatory Pathway

Echeverry¹,

Shi²,

Rivest³

et al. 2011

Journal of Neuroscience

215

201

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Peripheral nerve lesion triggers alterations in the spinal microenvironment that contribute to the pathogenesis of neuropathic pain. While neurons and glia have been implicated in these functional changes, it remains largely underexplored whether the blood-spinal cord barrier (BSCB) is also involved. The BSCB is an important component in the CNS homeostasis, and compromised BSCB has been associated with different pathologies affecting the spinal cord. Here, we demonstrated that a remote injury on the peripheral nerve in rats triggered a leakage of the BSCB, which was independent of spinal microglial activation. The increase of BSCB permeability to different size tracers, such as Evans Blue and sodium fluorescein, was restricted to the lumbar spinal cord and prominent for at least 4 weeks after injury. The spinal inflammatory reaction triggered by nerve injury was a key player in modulating BSCB permeability. We identified MCP-1 as an endogenous trigger for the BSCB leakage. BSCB permeability can also be impaired by circulating IL-1␤. In contrast, antiinflammatory cytokines TGF-␤1 and IL-10 were able to shut down the openings of the BSCB following nerve injury. Peripheral nerve injury caused a decrease in tight junction and caveolae-associated proteins. Interestingly, ZO-1 and occludin, but not caveolin-1, were rescued by TGF-␤1. Furthermore, our data provide direct evidence that disrupted BSCB following nerve injury contributed to the influx of inflammatory mediators and the recruitment of spinal blood borne monocytes/macrophages, which played a major role in the development of neuropathic pain. These findings highlight the importance of inflammation in BSCB integrity and in spinal cord homeostasis.

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“…We then used other methods to assess the BSCB by searching for spinal cord structural changes by histological staining [26] and measuring the extravasation of intravenously administered small molecule fluorescent dyes such as Evans Blue and sodium fluorescein (NaFl) [19,27]. …”

Section: Resultsmentioning

confidence: 99%

Effects of Peripheral Inflammation on the Blood-Spinal Cord Barrier

et al. 2012

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BackgroundChanges in the blood-central nervous system barriers occur under pathological conditions including inflammation and contribute to central manifestations of various diseases. After short-lasting peripheral and neurogenic inflammation, the evidence is mixed whether there are consistent blood-spinal cord changes. In the current study, we examine changes in the blood-spinal cord barrier after intraplantar capsaicin and λ-carrageenan using several methods: changes in occludin protein, immunoglobulin G accumulation, and fluorescent dye penetration. We also examine potential sex differences in male and female adult rats.ResultsAfter peripheral carrageenan inflammation, but not capsaicin inflammation, immunohistochemistry shows occludin protein in lumbar spinal cord to be significantly altered at 72 hours post-injection. In addition, there is also significant immunoglobulin G detected in lumbar and thoracic spinal cord at this timepoint in both male and female rats. However, acute administration of sodium fluorescein or Evans Blue dyes is not detected in the parenchyma at this timepoint.ConclusionsOur results show that carrageenan inflammation induces changes in tight junction protein and immunoglobulin G accumulation, but these may not be indicative of a blood-spinal cord barrier breakdown. These changes appear transiently after peak nociception and may be indicative of reversible pathology that resolves together with inflammation.

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Morphological and functional changes of blood–brain barrier in kindled rats with cortical dysplasia

Cited by 24 publications

References 35 publications

Systemic Administration of Lipopolysaccharide Induces Cyclooxygenase-2 Immunoreactivity in Endothelium and Increases Microglia in the Mouse Hippocampus

Systemic Administration of Lipopolysaccharide Induces Cyclooxygenase-2 Immunoreactivity in Endothelium and Increases Microglia in the Mouse Hippocampus

Peripheral Nerve Injury Alters Blood-Spinal Cord Barrier Functional and Molecular Integrity through a Selective Inflammatory Pathway

Effects of Peripheral Inflammation on the Blood-Spinal Cord Barrier

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