Seizure‐Promoting Effect of Blood–Brain Barrier Disruption

Marchi, Nicola; Angelov, Lilyana; Masaryk, Thomas; Fazio, Vincent Di; Granata, Tiziana; Hernandez, Nadia; Hallene, Kerri; Diglaw, Tammy; Franic, Linda; Najm, Imad; Janigro, Damir

doi:10.1111/j.1528-1167.2007.00988.x

Cited by 451 publications

(434 citation statements)

References 33 publications

(55 reference statements)

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“…Tissue samples of MTS have been shown to present a striking lack of peri‐vascular AQP4 water channels that mediates the glymphatic water clearance (Eid et al., 2005). The absence of AQP4 channels in MTS areas could lead to altered extracellular electrolyte concentrations that sensitizes neuronal tissue to seizures (Eid et al., 2005; Lundgaard et al., 2017; Marchi et al., 2007). …”

Section: Discussionmentioning

confidence: 99%

Altered physiological brain variation in drug‐resistant epilepsy

et al. 2018

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IntroductionFunctional magnetic resonance imaging (fMRI) combined with simultaneous electroencephalography (EEG‐fMRI) has become a major tool in mapping epilepsy sources. In the absence of detectable epileptiform activity, the resting state fMRI may still detect changes in the blood oxygen level‐dependent signal, suggesting intrinsic alterations in the underlying brain physiology.MethodsIn this study, we used coefficient of variation (CV) of critically sampled 10 Hz ultra‐fast fMRI (magnetoencephalography, MREG) signal to compare physiological variance between healthy controls (n = 10) and patients (n = 10) with drug‐resistant epilepsy (DRE).ResultsWe showed highly significant voxel‐level (p < 0.01, TFCE‐corrected) increase in the physiological variance in DRE patients. At individual level, the elevations range over three standard deviations (σ) above the control mean (μ) CVMREG values solely in DRE patients, enabling patient‐specific mapping of elevated physiological variance. The most apparent differences in group‐level analysis are found on white matter, brainstem, and cerebellum. Respiratory (0.12–0.4 Hz) and very‐low‐frequency (VLF = 0.009–0.1 Hz) signal variances were most affected.ConclusionsThe CVMREG increase was not explained by head motion or physiological cardiorespiratory activity, that is, it seems to be linked to intrinsic physiological pulsations. We suggest that intrinsic brain pulsations play a role in DRE and that critically sampled fMRI may provide a powerful tool for their identification.

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Section: Discussionmentioning

confidence: 99%

Altered physiological brain variation in drug‐resistant epilepsy

et al. 2018

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“…Degradation of the BBB can occur after insults to the brain, including seizures (6,40,41). Serum albumin was detected by Western blot analysis in the PBS solution-perfused cortex four days following pilocarpine-induced SE in wild-type mice, compared with minimal albumin in saline solution-treated wild-type animals (Fig.…”

Section: Se (mentioning

confidence: 99%

Infiltrating monocytes promote brain inflammation and exacerbate neuronal damage after status epilepticus

Varvel

Neher

Bosch

et al. 2016

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

287

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The generalized seizures of status epilepticus (SE) trigger a series of molecular and cellular events that produce cognitive deficits and can culminate in the development of epilepsy. Known early events include opening of the blood-brain barrier (BBB) and astrocytosis accompanied by activation of brain microglia. Whereas circulating monocytes do not infiltrate the healthy CNS, monocytes can enter the brain in response to injury and contribute to the immune response. We examined the cellular components of innate immune inflammation in the days following SE by discriminating microglia vs. brain-infiltrating monocytes. Chemokine receptor 2 (CCR2 + ) monocytes invade the hippocampus between 1 and 3 d after SE. In contrast, only an occasional CD3 + T lymphocyte was encountered 3 d after SE. The initial cellular sources of the chemokine CCL2, a ligand for CCR2, included perivascular macrophages and microglia. The induction of the proinflammatory cytokine IL-1β was greater in FACS-isolated microglia than in brain-invading monocytes. However, Ccr2 knockout mice displayed greatly reduced monocyte recruitment into brain and reduced levels of the proinflammatory cytokine IL-1β in hippocampus after SE, which was explained by higher expression of the cytokine in circulating and brain monocytes in wild-type mice. Importantly, preventing monocyte recruitment accelerated weight regain, reduced BBB degradation, and attenuated neuronal damage. Our findings identify brain-infiltrating monocytes as a myeloid-cell subclass that contributes to neuroinflammation and morbidity after SE. Inhibiting brain invasion of CCR2 + monocytes could represent a viable method for alleviating the deleterious consequences of SE. myeloid cell heterogeneity | epileptogenesis | neuroprotection | seizure | microgliosis S tatus epilepticus (SE) is a serious medical emergency that triggers a series of cellular and molecular events that can result in the development of epilepsy, a chronic neurological disorder characterized by a persistently lowered seizure threshold (1). The early consequences of SE in rodents include a robust neuroinflammatory response, selective neuronal degeneration, and transient opening of the blood-brain barrier (BBB), leading to later cognitive decline. Although the neuroinflammatory features of SE in man are less well known, extravasation of albumin into the brain was observed for patients who died in SE (2), elevated cerebrospinal fluid levels of the cytokines IL-6, IL-8, and CXCL10 are typically found in patients with refractory SE compared with patients with other inflammatory neurologic disorders (3), and intense gliosis (both astrocytes and microglia) was observed in the temporal cortex of a patient with new-onset focal seizures that progressed to refractory SE (4). These admittedly sparse clinical findings are consistent with the much more extensive animal literature in demonstrating a florid inflammatory response of the brain to SE (5). We and others have provided evidence in animal models of epilepsy that quenching inflamma...

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“…Experimental evidence also supports a role of intravascular inflammation, often associated with BBB damage, in seizure disorders (Marchi et al, 2007a;Marchi et al, 2009;Seiffert et al, 2004;van Vliet et al, 2007). Recently, the association between circulating immune cells, their interaction with the BBB, and seizure propensity was proposed; leukocyte adhesion was shown to directly support ictogenesis in the pilocarpine model of seizures (Fabene et al, 2008).…”

Section: Blood-brain Barrier Dysfunction In Epilepsy: Experimental Anmentioning

confidence: 99%

“…After injury, local compromise of BBB integrity is common (Abbott et al, 2010;Cacheaux et al 2009;Oby and Janigro, 2006), as revealed by ultrastructural studies of animal and human epileptic tissue in multiple forms of epilepsy. Marchi et al, 2007a;van Vliet et al, 2007), and BBB opening may specifically serve as a trigger event leading to epilepsy. However, the research field has recently considered the fact that damage to the cerebral vasculature could be involved in the pathogenesis of seizures (Oby & Janigro, 2006).…”

Section: Blood-brain Barrier Dysfunction In Epilepsy: Experimental Anmentioning

confidence: 99%