Premium
Ablation of Astrocytes in the Paraventricular Nucleus Disrupts the Blood‐Brain Barrier and Increases Blood Pressure in Rats
Author(s) -
Setiadi Anthony,
May Clive N,
Yao Song T
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1010.5
Subject(s) - evans blue , extravasation , blood pressure , blood–brain barrier , medicine , baroreceptor , central nervous system , endocrinology , angiotensin ii , homeostasis , hypothalamus , chemistry , anesthesia , heart rate , pathology
Background Perivascular astrocytes make direct connections to the cerebral vasculature. This close apposition has been shown to be critical for the regulation of blood‐brain barrier (BBB) integrity and function. Recent studies have shown that the BBB becomes disrupted in hypertensive rats, which allows circulating peptides such as angiotensin II, which is normally excluded from the central nervous system, to access brain areas critical for blood pressure control. To date, the association between astrocytes, the BBB and hypertension is still poorly understood. Objective To determine the importance of astrocytes in maintaining BBB integrity and central control of cardiovascular homeostasis. Methods Two groups of male Sprague‐Dawley rats (250–400g), anesthetized (pentobarbital, 60 mg/kg i.p.) and conscious freely‐moving, were bilaterally microinjected with sodium fluoroacetate (50 nL; 10 mM), a specific glial toxin, into the paraventricular nucleus of the hypothalamus (PVN) to ablate perivascular astrocytes. Blood pressure and heart rate were continuously recorded throughout. Evans blue dye (4 mL/kg) was then infused intravenously following microinjections to assess BBB integrity. Changes in baroreceptor reflex function were also studied following fluoroacetate administration. Results Ablation of PVN astrocytes caused a significant increase in Evans Blue dye extravasation (+16.67 ± 4.9 mean density in arbitrary units, P<0.05) when compared with saline injected controls, indicating a compromised BBB. Furthermore, we found a significant increase in mean arterial pressure in anesthetized (+41.02 ± 5.5 mmHg from baseline, P<0.0001) and conscious rats (+23.82.96 ± 7.8 mmHg from baseline, P<0.05) at 100‐minute and 2‐days following fluoroacetate injection, respectively. However, no changes were seen in the baroreceptor reflex control of heart rate. Conclusion Our results show a functional link between astrocytes, BBB disruption and central regulation of cardiovascular function. These findings suggest that a disrupted BBB, via astrocyte dysfunction, may contribute to the pathophysiology of centrally‐induced cardiovascular diseases such as hypertension.