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  • 1
    Online Resource
    Online Resource
    Blood‐brain barrier dysfunction in canine epileptic seizures detected by dynamic contrast‐enhanced magnetic resonance imaging
    Wiley ; 2019
    In:  Epilepsia Vol. 60, No. 5 ( 2019-05), p. 1005-1016
    Details
    In: Epilepsia, Wiley, Vol. 60, No. 5 ( 2019-05), p. 1005-1016
    Abstract: Dogs with spontaneous or acquired epilepsy exhibit resemblance in etiology and disease course to humans, potentially offering a translational model of the human disease. Blood‐brain barrier dysfunction ( BBBD ) has been shown to partake in epileptogenesis in experimental models of epilepsy. To test the hypothesis that BBBD can be detected in dogs with naturally occurring seizures, we developed a linear dynamic contrast‐enhanced magnetic resonance imaging ( DCE ‐ MRI ) analysis algorithm that was validated in clinical cases of seizing dogs and experimental epileptic rats. Methods Forty‐six dogs with naturally occurring seizures of different etiologies and 12 induced epilepsy rats were imaged using DCE ‐ MRI . Six healthy dogs and 12 naive rats served as control. DCE ‐ MRI was analyzed by linear‐dynamic method. BBBD scores were calculated in whole brain and in specific brain regions. Immunofluorescence analysis for transforming growth factor beta (TGF‐β) pathway proteins was performed on the piriform cortex of epileptic dogs. Results We found BBBD in 37% of dogs with seizures. A significantly higher cerebrospinal fluid to serum albumin ratio was found in dogs with BBBD relative to dogs with intact blood‐brain barrier (BBB) . A significant difference was found between epileptic and control rats when BBBD scores were calculated for the piriform cortex at 48 hours and 1 month after status epilepticus. Mean BBBD score of the piriform lobe in idiopathic epilepsy ( IE ) dogs was significantly higher compared to control. Immunohistochemistry results suggested active TGF ‐β signaling and neuroinflammation in the piriform cortex of dogs with IE , showing increased levels of serum albumin colocalized with glial acidic fibrillary protein and pSMAD2 in an area where BBBD had been detected by linear DCE ‐ MRI . Significance Detection of BBBD in dogs with naturally occurring epilepsy provides the ground for future studies for evaluation of novel treatment targeting the disrupted BBB . The involvement of the piriform lobe seen using our linear DCE ‐ MRI protocol and algorithm emphasizes the possibility of using dogs as a translational model for the human disease.
    Type of Medium: Online Resource
    ISSN: 0013-9580 , 1528-1167
    URL: Issue
    URL: Article
    DOI: 10.1111/epi.2019.60.issue-5
    DOI: 10.1111/epi.14739
    RVK:
    XA 10000
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 2002194-X
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  • 2
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    Paroxysmal slow cortical activity in Alzheimer’s disease and epilepsy is associated with blood-brain barrier dysfunction
    American Association for the Advancement of Science (AAAS) ; 2019
    In:  Science Translational Medicine Vol. 11, No. 521 ( 2019-12-04)
    Details
    In: Science Translational Medicine, American Association for the Advancement of Science (AAAS), Vol. 11, No. 521 ( 2019-12-04)
    Abstract: A growing body of evidence shows that epileptic activity is frequent but often undiagnosed in patients with Alzheimer’s disease (AD) and has major therapeutic implications. Here, we analyzed electroencephalogram (EEG) data from patients with AD and found an EEG signature of transient slowing of the cortical network that we termed paroxysmal slow wave events (PSWEs). The occurrence per minute of the PSWEs was correlated with level of cognitive impairment. Interictal (between seizures) PSWEs were also found in patients with epilepsy, localized to cortical regions displaying blood-brain barrier (BBB) dysfunction, and in three rodent models with BBB pathology: aged mice, young 5x familial AD model, and status epilepticus–induced epilepsy in young rats. To investigate the potential causative role of BBB dysfunction in network modifications underlying PSWEs, we infused the serum protein albumin directly into the cerebral ventricles of naïve young rats. Infusion of albumin, but not artificial cerebrospinal fluid control, resulted in high incidence of PSWEs. Our results identify PSWEs as an EEG manifestation of nonconvulsive seizures in patients with AD and suggest BBB pathology as an underlying mechanism and as a promising therapeutic target.
    Type of Medium: Online Resource
    ISSN: 1946-6234 , 1946-6242
    URL: Article
    DOI: 10.1126/scitranslmed.aaw8954
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2019
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