Cerebral microvascular density, blood-brain barrier permeability, and support for neuroinflammation indicate early aging in a Marfan syndrome mouse model DOI Creative Commons
Tala Curry,

Liam Curtin,

Mitra Esfandiarei

и другие.

Frontiers in Physiology, Год журнала: 2025, Номер 15

Опубликована: Янв. 31, 2025

Introduction Marfan Syndrome (MFS) is a connective tissue disorder due to mutations in fibrillin-1 ( Fbn1 ), where missense mutation C1039G/+ ) can result systemic increases the bioavailability and signaling of transforming growth factor-β (TGF-β). In well-established mouse model MFS C1041G/+ pre-mature aging aortic wall progression root aneurysm are observed by 6-month-of-age. TGF-β has been implicated cerebrovascular dysfunction, loss blood-brain barrier (BBB) integrity, age-related neuroinflammation. We have reported that vascular mice could extend cerebrovasculature, peak blood flow velocity posterior cerebral artery (PCA) 6-month-old (6M) was reduced, similarly 12-month-old (12M) control mice. Case studies patients documented neurovascular manifestations, including intracranial aneurysms, stroke, arterial tortuosity, as well headaches migraines, with incidences pain chronic fatigue. Despite these significant clinical observations, investigation into dysfunction neuropathology remains limited. Methods Using 6M-control C57BL/6 6M-MFS healthy 12M-control male female mice, we test hypothesis abnormal protein expression associated altered microvascular density, BBB permeability, neuroinflammation PCA-perfused hippocampus, all indicative brain phenotype. Glut1 immunostaining used quantify IgG staining assess microglial counts evaluate Results staining, 12M-CTRL present decreased density dentate gyrus (DG), cornu ammonis 1 (CA1), 3 (CA3) regions hippocampus. exhibit increased permeability DG CA3 evident Immunoglobulin G (IgG) staining. No differences were detected between 6M show higher number microglia hippocampus compared age-matched pattern resembling Discussion This study represents first known indicates pathophysiology underlying leads crucial for identifying understanding MFS-associated neurological abnormalities, underscoring need research aimed at improving quality life managing symptoms related disorders.

Язык: Английский

Cerebral microvascular density, blood-brain barrier permeability, and support for neuroinflammation indicate early aging in a Marfan syndrome mouse model DOI Creative Commons
Tala Curry,

Liam Curtin,

Mitra Esfandiarei

и другие.

Frontiers in Physiology, Год журнала: 2025, Номер 15

Опубликована: Янв. 31, 2025

Introduction Marfan Syndrome (MFS) is a connective tissue disorder due to mutations in fibrillin-1 ( Fbn1 ), where missense mutation C1039G/+ ) can result systemic increases the bioavailability and signaling of transforming growth factor-β (TGF-β). In well-established mouse model MFS C1041G/+ pre-mature aging aortic wall progression root aneurysm are observed by 6-month-of-age. TGF-β has been implicated cerebrovascular dysfunction, loss blood-brain barrier (BBB) integrity, age-related neuroinflammation. We have reported that vascular mice could extend cerebrovasculature, peak blood flow velocity posterior cerebral artery (PCA) 6-month-old (6M) was reduced, similarly 12-month-old (12M) control mice. Case studies patients documented neurovascular manifestations, including intracranial aneurysms, stroke, arterial tortuosity, as well headaches migraines, with incidences pain chronic fatigue. Despite these significant clinical observations, investigation into dysfunction neuropathology remains limited. Methods Using 6M-control C57BL/6 6M-MFS healthy 12M-control male female mice, we test hypothesis abnormal protein expression associated altered microvascular density, BBB permeability, neuroinflammation PCA-perfused hippocampus, all indicative brain phenotype. Glut1 immunostaining used quantify IgG staining assess microglial counts evaluate Results staining, 12M-CTRL present decreased density dentate gyrus (DG), cornu ammonis 1 (CA1), 3 (CA3) regions hippocampus. exhibit increased permeability DG CA3 evident Immunoglobulin G (IgG) staining. No differences were detected between 6M show higher number microglia hippocampus compared age-matched pattern resembling Discussion This study represents first known indicates pathophysiology underlying leads crucial for identifying understanding MFS-associated neurological abnormalities, underscoring need research aimed at improving quality life managing symptoms related disorders.

Язык: Английский

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