Vascular tight junction disruption and angiogenesis in spontaneously hypertensive rat with neuroinflammatory white matter injury
Vascular cognitive impairment is a major cause of dementia caused by chronic hypoxia, producing progressive damage to white matter (WM) secondary to blood-brain barrier (BBB) opening and vascular dysfunction. Tight junction proteins (TJPs), which maintain BBB integrity, are lost in acute ischemia. A...
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| Format: | Article |
| Language: | English |
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Elsevier
2018-06-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996118300445 |
| _version_ | 1818648890543439872 |
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| author | Yi Yang Shihoko Kimura-Ohba Jeffrey F. Thompson Victor M. Salayandia Melissa Cossé Limor Raz Fakhreya Y. Jalal Gary A. Rosenberg |
| author_facet | Yi Yang Shihoko Kimura-Ohba Jeffrey F. Thompson Victor M. Salayandia Melissa Cossé Limor Raz Fakhreya Y. Jalal Gary A. Rosenberg |
| author_sort | Yi Yang |
| collection | DOAJ |
| description | Vascular cognitive impairment is a major cause of dementia caused by chronic hypoxia, producing progressive damage to white matter (WM) secondary to blood-brain barrier (BBB) opening and vascular dysfunction. Tight junction proteins (TJPs), which maintain BBB integrity, are lost in acute ischemia. Although angiogenesis is critical for neurovascular remodeling, less is known about its role in chronic hypoxia. To study the impact of TJP degradation and angiogenesis during pathological progression of WM damage, we used the spontaneously hypertensive/stroke prone rats with unilateral carotid artery occlusion and Japanese permissive diet to model WM damage. MRI and IgG immunostaining showed regions with BBB damage, which corresponded with decreased endothelial TJPs, claudin-5, occludin, and ZO-1. Affected WM had increased expression of angiogenic factors, Ki67, NG2, VEGF-A, and MMP-3 in vascular endothelial cells and pericytes. To facilitate the study of angiogenesis, we treated rats with minocycline to block BBB disruption, reduce WM lesion size, and extend survival. Minocycline-treated rats showed increased VEGF-A protein, TJP formation, and oligodendrocyte proliferation. We propose that chronic hypoxia disrupts TJPs, increasing vascular permeability, and initiating angiogenesis in WM. Minocycline facilitated WM repair by reducing BBB damage and enhancing expression of TJPs and angiogenesis, ultimately preserving oligodendrocytes. |
| first_indexed | 2024-12-17T01:25:37Z |
| format | Article |
| id | doaj.art-0696f5953c6b43d99919b767572da97c |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-17T01:25:37Z |
| publishDate | 2018-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-0696f5953c6b43d99919b767572da97c2022-12-21T22:08:41ZengElsevierNeurobiology of Disease1095-953X2018-06-0111495110Vascular tight junction disruption and angiogenesis in spontaneously hypertensive rat with neuroinflammatory white matter injuryYi Yang0Shihoko Kimura-Ohba1Jeffrey F. Thompson2Victor M. Salayandia3Melissa Cossé4Limor Raz5Fakhreya Y. Jalal6Gary A. Rosenberg7Department of Neurology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA; Memory and Aging Center, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA; Corresponding author at: Department of Neurology, MSC11 6035, 1 University of New Mexico, Albuquerque, NM 87131-0001, USA.Department of Neurology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USAMemory and Aging Center, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USADepartment of Neurology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USADepartment of Neurology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USADepartment of Neurology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USADepartment of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab EmiratesDepartment of Neurology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA; Memory and Aging Center, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA; Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA; Department of Neurosciences, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USAVascular cognitive impairment is a major cause of dementia caused by chronic hypoxia, producing progressive damage to white matter (WM) secondary to blood-brain barrier (BBB) opening and vascular dysfunction. Tight junction proteins (TJPs), which maintain BBB integrity, are lost in acute ischemia. Although angiogenesis is critical for neurovascular remodeling, less is known about its role in chronic hypoxia. To study the impact of TJP degradation and angiogenesis during pathological progression of WM damage, we used the spontaneously hypertensive/stroke prone rats with unilateral carotid artery occlusion and Japanese permissive diet to model WM damage. MRI and IgG immunostaining showed regions with BBB damage, which corresponded with decreased endothelial TJPs, claudin-5, occludin, and ZO-1. Affected WM had increased expression of angiogenic factors, Ki67, NG2, VEGF-A, and MMP-3 in vascular endothelial cells and pericytes. To facilitate the study of angiogenesis, we treated rats with minocycline to block BBB disruption, reduce WM lesion size, and extend survival. Minocycline-treated rats showed increased VEGF-A protein, TJP formation, and oligodendrocyte proliferation. We propose that chronic hypoxia disrupts TJPs, increasing vascular permeability, and initiating angiogenesis in WM. Minocycline facilitated WM repair by reducing BBB damage and enhancing expression of TJPs and angiogenesis, ultimately preserving oligodendrocytes.http://www.sciencedirect.com/science/article/pii/S0969996118300445Magnetic resonance imagingChronic hypoxiaBBB permeabilityTight junction proteinsAngiogenesisVascular cognitive impairment and dementia |
| spellingShingle | Yi Yang Shihoko Kimura-Ohba Jeffrey F. Thompson Victor M. Salayandia Melissa Cossé Limor Raz Fakhreya Y. Jalal Gary A. Rosenberg Vascular tight junction disruption and angiogenesis in spontaneously hypertensive rat with neuroinflammatory white matter injury Neurobiology of Disease Magnetic resonance imaging Chronic hypoxia BBB permeability Tight junction proteins Angiogenesis Vascular cognitive impairment and dementia |
| title | Vascular tight junction disruption and angiogenesis in spontaneously hypertensive rat with neuroinflammatory white matter injury |
| title_full | Vascular tight junction disruption and angiogenesis in spontaneously hypertensive rat with neuroinflammatory white matter injury |
| title_fullStr | Vascular tight junction disruption and angiogenesis in spontaneously hypertensive rat with neuroinflammatory white matter injury |
| title_full_unstemmed | Vascular tight junction disruption and angiogenesis in spontaneously hypertensive rat with neuroinflammatory white matter injury |
| title_short | Vascular tight junction disruption and angiogenesis in spontaneously hypertensive rat with neuroinflammatory white matter injury |
| title_sort | vascular tight junction disruption and angiogenesis in spontaneously hypertensive rat with neuroinflammatory white matter injury |
| topic | Magnetic resonance imaging Chronic hypoxia BBB permeability Tight junction proteins Angiogenesis Vascular cognitive impairment and dementia |
| url | http://www.sciencedirect.com/science/article/pii/S0969996118300445 |
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