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Abstract: Stroke can affect females very differently from males, and therefore preclinical research on underlying mechanisms and the effects of interventions should not be restricted to male subjects, and treatment strategies for stroke should be tailored to benefit both sexes. Previously, we demonstrated that a multinutrient intervention (Fortasyn) improved impairments after ischemic stroke induction in male C57Bl/6 mice, but the therapeutic potential of this dietary treatment remained to be investigated in females. We now induced a transient middle cerebral artery occlusion (tMCAo) in C57Bl/6 female mice and immediately after surgery switched to either Fortasyn or an isocaloric Control diet. The stroke females performed several behavioral and motor tasks before and after tMCAo and were scanned in an 11.7 Tesla magnetic resonance imaging (MRI) scanner to assess brain perfusion, integrity, and functional connectivity. To assess brain plasticity, inflammation, and vascular integrity, immunohistochemistry was performed after killing of the mice. We found that the multinutrient intervention had diverse effects on the stroke‐induced impairments in females. Similar to previous observations in male stroke mice, brain integrity, sensorimotor integration and neurogenesis benefitted from Fortasyn, but impairments in activity and motor skills were not improved in female stroke mice. Overall, Fortasyn effects in the female stroke mice seem more modest in comparison to previously investigated male stroke mice. We suggest that with further optimization of treatment protocols more information on the efficacy of specific interventions in stroked females can be gathered. This in turn will help with the development of (gender‐specific) treatment regimens for cerebrovascular diseases such as stroke. This article is part of the Special Issue “Vascular Dementia”. [ABSTRACT FROM AUTHOR]

Abstract: Glycosaminoglycans (GAGs), in particular as part of heparan sulfate proteoglycans, are associated with cerebral amyloid angiopathy (CAA). Similarly, GAGs are also associated with the severe CAA found in patients suffering from hereditary cerebral hemorrhage with amyloidosis of the Dutch type (HCHWA-D), where the amyloid β (Aβ) peptide contains the Dutch mutation (DAβ1-40). This suggests a role for GAGs in vascular Aβ aggregation. It was the aim of this study to investigate the effect of different GAGs (heparin, chondroitin sulfate, heparan sulfate), the macromolecule dextran sulfate and, using desulfated heparins, the role of GAG sulfate moieties on the in vitro aggregation of CAA-associated DAβ1-40 and on DAβ1-40-induced toxicity of cultured cerebrovascular cells. We also aimed to study the in vivo distribution of various sulfated heparan sulfate GAG epitopes in CAA. Of all GAGs tested, heparin was the strongest inducer of aggregation of DAβ1-40 in the different aggregation assays, with both heparin and heparan sulfate reducing Aβ-induced cellular toxicity. Furthermore, (partial) removal of the sulfate moieties of heparin partially abolished the effects of heparin on aggregation and cellular toxicity, suggesting an essential role for the sulfate moieties in heparin. Finally, we demonstrated the in vivo association of sulfated heparan sulfate (HS) GAGs with CAA. We conclude that sulfate moieties within GAGs, like heparin and HS, have an important role in Aβ aggregation in CAA and in Aβ-mediated toxicity of cerebrovascular cells. [Copyright &y& Elsevier]