An increasing body of evidence associates low vitamin D levels with increased risk of multiple sclerosis (MS), suggesting the possibility of a gene-environment interaction for this environmental factor in MS pathogenesis. Moreover, it has been shown that vitamin D downregulates major histocompatibility complex (MHC) class II expression in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. We here report about the impact of a dietary vitamin D supplementation on EAE in the rat strains having functionally relevant allelic variations in the CIITA ( Mhc2ta ) gene, a master regulator of MHC class II expression. Full length myelin oligodendrocyte glycoprotein (MOG)-EAE was induced in DA.PVG av1 - Vra4 congenic rats harboring the Vra4 locus from PVG strain in the EAE- susceptible DA background, and compared to the parental strains. The congenic rats fed with either vitamin D supplemented, deprived or regular diet developed an intermediate clinical EAE phenotype, in contrast to DA and PVG strains. Immunopathological studies revealed vitamin D dose-dependent effect on demyelination and inflammatory infiltration of the central nervous system (CNS), expression of MHC class II and CIITA, as well as downregulation of a range of pro-inflammatory genes. Taken together, our findings demonstrate an impact of vitamin D on the target tissue pathology and peripheral immune response during EAE in DA.PVG av1 - Vra4 congenic strain. Thereby, our data provide evidence of a modulatory effect of vitamin D in context of genetic variances in the Vra4 locus/ Mhc2ta gene in MS-like neuroinflammation, with potential relevance for the human demyelinating disease.
Obsessive-compulsive disorder (OCD) is characterized by repetitive, persistent and unwanted thoughts and ritualistic, repetitive behaviors. The pathophysiology of OCD involves many distinct cortical and subcortical regions and it has been reported that OCD may occur as a consequence of traumatic brain injury, infections and tumors as well as cerebrovascular insult such as cerebral venous sinus thrombosis (CVST). We here describe the case of a 36-year-old woman who developed OCD at the age of 13 with almost complete remission of the symptoms after a 1 year-long treatment. Interestingly, after suffering CVST at the superior sagittal sinus at the age of 33, she experienced a relapse of OCD. The patient was successfully treated with Sertraline and Clomipramine. Previous studies revealed cases of OCD following different cerebrovascular accidents, i.e. predominantly arterial stroke. However, the present case is the first to describe OCD after venous thrombosis. Based on our clinical experience, the most effective treatment of OCD after CVST represents the combination of the selective serotonin reuptake inhibitor Sertraline and the tricyclic antidepressant Clomipramine. ZusammenfassungDie Zwangsstörung (OCD) ist gekennzeichnet durch sich wiederholende, anhaltende und unerwünschte Gedanken sowie rituelle, sich wiederholende Verhaltensweisen. Die Pathophysiologie der OCD umfasst viele distinkte kortikale und subkortikale Regionen. Berichtet wurde, dass eine OCD als Folge von Infektionen, Tumoren, traumatischen Hirnläsionen und zerebrovaskulären Insulten, beispielweise einer zerebralen Sinusvenenthrombose (CVST), auftreten kann. Wir stellen eine 36-jährige Frau vor, die im Alter von 13 Jahren eine OCD entwickelte, wobei nach einer einjährigen Behandlung eine fast vollständige Remission der Symptome erzielt wurde. Interessanterweise erlitt sie ein Jahr nach einer CVST der V. sagittalis superior im Alter von 33 Jahren ein Rezidiv der OCD. Sie wurde mit einer Kombination aus Sertralin und Clomipramin erfolgreich behandelt. Frühere Studien zeigten Fälle von OCD nach verschiedenen zerebrovaskulären Störungen, vorwiegend nach arteriellem Schlaganfall. Die vorliegende Publikation ist jedoch die erste, in welcher eine OCD nach einer venösen Thrombose beschrieben wird. Nach unserer klinischen Erfahrung besteht die wirksamste Behandlung einer OCD nach CVST in einer Kombination des selektiven Serotoninwiederaufnahmehemmers Sertralin mit dem trizyklischen Antidepressivum Clomipramin. Schlüsselwörter OCD · Zerebraler Insult · Sertralin · Clomipramin · Kombinationstherapie
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