Immune Cell Infiltrates in Hippocampal Sclerosis: Correlation With Neuronal Loss

Lu, Jian‐Qiang; Steve, Trevor A.; Wheatley, Matthew; Gross, Donald

doi:10.1093/jnen/nlx001

Cited by 24 publications

(39 citation statements)

References 37 publications

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“…These blood cells invade the hippocampal tissue and induce inflammation. Our data also support those reported by Lu (), who found a correlation between blood cell infiltration in the hippocampus and neuronal loss. This increase in BBB permeability can induce epileptogenesis, and sustain or aggravate epilepsy (Ho et al ), and increased BBB permeability can persist for several weeks, months, or even years after a long‐lasting seizure, and contribute to enhanced brain excitability (van Vliet et al ).…”

Section: Discussionsupporting

confidence: 93%

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Plasma kallikrein‐kinin system contributes to peripheral inflammation in temporal lobe epilepsy

Simões¹,

Zanelatto²,

Assis³

et al. 2019

Journal of Neurochemistry

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Temporal lobe epilepsy (TLE) is a chronic disease, characterized by severe and refractory seizures, triggered in the hippocampus and/or amygdala, disrupting the blood–brain barrier. This disruption can sustain, or aggravate, the epileptic condition. The aim of this study was to evaluate the activation of the kallikrein‐kinin system in patients with TLE, as it relates to the maintenance of blood–brain barrier. Human hippocampal sclerotic tissues removed after surgery for seizure control, plasma, and serum were used in the following assays: immunostaining for white blood cells in the TLE hippocampus, C‐reactive protein in serum, quantification of plasma kallikrein (PKal) and cathepsin B (CatB) activity in serum and plasma, quantification of C1‐inhibitor, analysis of high‐molecular‐weight kininogen (H‐kininogen) fragments, and activation of plasma prekallikrein for comparison with healthy controls. Infiltration of white blood cells in the sclerotic hippocampus and a significant increase in the neutrophil/lymphocyte ratio in the blood of TLE patients were observed. High levels of C‐reactive protein (TLE = 1.4 ± 0.3 µg/mL), PKal (TLE = 5.4 ± 0.4 U/mL), and CatB (TLE = 4.9 ± 0.4 U/mL) were also evident in the serum of TLE patients comparing to controls. A strong linear correlation was observed between active CatB and PKal in the serum of TLE patients (r = 0.88). High levels of cleaved H‐kininogen and free PKal, and low levels of C1‐inhibitor (TLE = 188 ± 12 µg/mL) were observed in the serum of TLE patients. Our data demonstrated that the plasma kallikrein‐kinin system is activated in patients with TLE. Open Science Badges This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/.

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Section: Discussionsupporting

confidence: 93%

“…These blood cells invade the hippocampal tissue and induce inflammation. Our data also support those reported by Lu (2017), who found a correlation between blood cell Fig. 3 Analysis of H-kininogen processing in the serum/plasma of healthy subjects and patients with TLE.…”

Section: Discussionsupporting

confidence: 91%

Plasma kallikrein‐kinin system contributes to peripheral inflammation in temporal lobe epilepsy

Simões¹,

Zanelatto²,

Assis³

et al. 2019

Journal of Neurochemistry

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“…Neuroinflammation with monocyte infiltration and microglial activation, as observed in rodent models of TLE, is also a frequently reported finding in patients with TLE ( 41 – 43 ). Thus, counteracting such inflammatory processes is considered a potential strategy for preventing or modifying epilepsy in patients at risk ( 2 , 3 , 44 – 47 ).…”

Section: Discussionmentioning

confidence: 63%

Chemokine receptors CCR2 and CX3CR1 regulate viral encephalitis-induced hippocampal damage but not seizures

Käufer¹,

Chhatbar

Bröer³

et al. 2018

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

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SignificanceViral encephalitis is a frequent medical emergency, often resulting in acute seizures and brain damage, which reduce quality of life, promote the development of epilepsy, and can cause death. The relative roles of activation of microglia, the brain-resident innate immune cells, versus invasion of blood-borne immune cells such as monocytes in the acute and chronic consequences of viral encephalitis are only incompletely understood. Here we show that lack of the chemokine receptors CCR2 or CX3CR1, which regulate the responses of myeloid cells such as monocytes and microglia, prevents hippocampal damage but not seizures in a mouse model of viral encephalitis. Treatment strategies aimed at inhibiting peripheral immune cells from entering the brain during encephalitis could reduce brain damage.

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“…It is a major finding of the present study that the quantitative RT-PCR data not only confirmed the delayed T-cell response, but was also able to demonstrate that the increase was attributable to an enhanced CD8 + T-cell population. While the pathophysiological role of CD8 + cells has already been suggested in the rodent kainate model [ 34 ], there is recent evidence on the pathogenic role of CD8 + cells in autoimmune anti-GABA-B-receptor encephalitis in humans [ 36 ], but intriguingly, also human temporal lobe epilepsy [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Mycophenolate mofetil prevents the delayed T cell response after pilocarpine-induced status epilepticus in mice

et al. 2017

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Growing clinical and laboratory evidence corroborates a role for the immune system in the pathophysiology of epilepsy. In order to delineate the immune response following pilocarpine-induced status epilepticus (SE) in the mouse, we monitored the kinetics of leukocyte presence in the hippocampus over the period of four weeks. SE was induced following a ramping protocol of pilocarpine injection into 4–5 weeks old C57BL/6 mice. Brains were removed at days 1–4, 14 or 28 after SE, and the hippocampi were analyzed via flow cytometry, via quantitative reverse transcriptase PCR (qRT-PCR) and via immunohistochemistry. Epileptogenesis was confirmed by Timm staining of mossy fiber sprouting in the inner molecular layer of the dentate gyrus. The flow cytometry data revealed a biphasic immune response following pilocarpine-induced SE with a transient increase in activated CD11b+ and F4/80+ macrophages within the first four days replaced by an increase in CD3+ T-lymphocytes around day 28. This delayed T cell response was confirmed via qRT-PCR and via immunohistochemistry. In addition, qRT-PCR data could show that the delayed T cell response was associated with an increased CD8/CD4 ratio indicating a cytotoxic T cell response after SE. Intriguingly, early intervention with mycophenolate mofetil administration on days 0–3 after SE prevented this delayed T cell response. These results show an orchestrated immunological sequela and provide evidence that the delayed T cell response is sensitive to early immunomodulatory intervention.

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Immune Cell Infiltrates in Hippocampal Sclerosis: Correlation With Neuronal Loss

Cited by 24 publications

References 37 publications

Plasma kallikrein‐kinin system contributes to peripheral inflammation in temporal lobe epilepsy

Plasma kallikrein‐kinin system contributes to peripheral inflammation in temporal lobe epilepsy

Chemokine receptors CCR2 and CX3CR1 regulate viral encephalitis-induced hippocampal damage but not seizures

Mycophenolate mofetil prevents the delayed T cell response after pilocarpine-induced status epilepticus in mice

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