The Role of Transient Receptor Potential Channels in Blood-Brain Barrier Dysfunction after Ischemic Stroke

Huang, Qingxia; Wang, Xiaoyu; Lin, Xiao; Zhang, Jianmin; You, Xin; Shao, Anwen

doi:10.1016/j.biopha.2020.110647

Cited by 17 publications

(11 citation statements)

References 120 publications

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“…Ca 2+ modulation has been known to be an important factor in maintaining the function of brain microvessel endothelial cells (BMEC) forming blood-brain barrier (BBB) (Brown and Davis, 2002;De Bock et al, 2013). By modulating Ca 2+ trafficking into BMEC, a growing evidence has been achieved that TRP channels may have a critical role on the BBB properties including its permeability, angiogenesis and inflammatory responses (Berrout et al, 2012;Huang et al, 2020). However, the expression or functionality of TRPV in BBB was much less studied than in non-cerebral endothelial cells.…”

Section: Introductionmentioning

confidence: 99%

Molecular and Functional Study of Transient Receptor Potential Vanilloid 1-4 at the Rat and Human Blood–Brain Barrier Reveals Interspecies Differences

Luo

Saubaméa

Chasseigneaux

et al. 2020

Front. Cell Dev. Biol.

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Transient receptor potential vanilloid 1-4 (TRPV1-4) expression and functionality were investigated in brain microvessel endothelial cells (BMEC) forming the blood–brain barrier (BBB) from rat and human origins. In rat, Trpv1-4 were detected by qRT-PCR in the brain cortex, brain microvessels, and in primary cultures of brain microvessel endothelial cells [rat brain microvessel endothelial cells (rPBMEC)]. A similar Trpv1-4 expression profile in isolated brain microvessels and rPBMEC was found with the following order: Trpv4 > Trpv2 > Trpv3 > Trpv1 . In human, TRPV1-4 were detected in the BBB cell line human cerebral microvessel endothelial cells D3 cells (hCMEC/D3) and in primary cultures of BMEC isolated from human adult and children brain resections [human brain microvascular endothelial cells (hPBMEC)], showing a similar TRPV1-4 expression profile in both hCMEC/D3 cells and hPBMECs as follow: TRPV2 > > TRPV4 > TRPV1 > TRPV3 . Western blotting and immunofluorescence experiments confirmed that TRPV2 and TRPV4 are the most expressed TRPV isoforms in hCMEC/D3 cells with a clear staining at the plasma membrane. A fluorescent dye Fluo-4 AM ester was applied to record intracellular Ca 2+ levels. TRPV4 functional activity was demonstrated in mediating Ca 2+ influx under stimulation with the specific agonist GSK1016790A (ranging from 3 to 1000 nM, EC 50 of 16.2 ± 4.5 nM), which was inhibited by the specific TRPV4 antagonist, RN1734 (30 μM). In contrast, TRPV1 was slightly activated in hCMEC/D3 cells as shown by the weak Ca 2+ influx induced by capsaicin at a high concentration (3 μM), a highly potent and specific TRPV1 agonist. Heat-induced Ca 2+ influx was not altered by co-treatment with a selective potent TRPV1 antagonist capsazepine (20 μM), in agreement with the low expression of TRPV1 as assessed by qRT-PCR. Our present study reveals an interspecies difference between Rat and Human. Functional contributions of TRPV1-4 subtype expression were not identical in rat and human tissues reflective of BBB integrity. TRPV2 was predominant in the human whereas TRPV4 had a larger role in the rat. This interspecies difference from a gene expression point of view should be taken into consideration when modulators of TRPV2 or TRPV4 are investigated in rat models of brain disorders.

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Section: Introductionmentioning

confidence: 99%

Molecular and Functional Study of Transient Receptor Potential Vanilloid 1-4 at the Rat and Human Blood–Brain Barrier Reveals Interspecies Differences

Luo

Saubaméa

Chasseigneaux

et al. 2020

Front. Cell Dev. Biol.

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“…At 16 wk old, WT and TRPC6 KO mice were anesthetized with 2% isoflurane and a telemetry probe (TA11PA-C10, Data Science) was implanted in the left carotid artery and advanced into the aorta. Seven to ten days after recovery from the surgery, MAP and HR were measured by telemetry 24 h/day for 5 consecutive days using computerized methods for data collection as previously described ( 10 , 13 ). Daily MAP and HR were obtained from the average of 12:12-h light-dark recording using a sampling rate of 1 Hz and a duration of 30 s every 10 min.…”

Section: Methodsmentioning

confidence: 99%

“…A growing interest in the potential role of TRPC6 channels in kidney injury emerged after the discovery that gain-of-function mutations in TRPC6 cause focal segmental glomerulosclerosis (9). Increased expression of TRPC6 was also found in podocytes of patients and animals with diabetic proteinuric kidney disease, consistent with the possibility that excessive activation of TRPC6 and subsequent Ca 2 þ influx may be a common pathway for glomerular dysfunction (7,10).…”

Section: Introductionmentioning

confidence: 97%

Transient receptor potential cation channel 6 contributes to kidney injury induced by diabetes and hypertension

Wang

Carmo

et al. 2022

American Journal of Physiology-Renal Physiology

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Diabetes (DM) and hypertension (HTN) are major risk factors for chronic kidney injury, together accounting for >70% of end-stage renal disease. In this study, we assessed whether DM and HTN interact synergistically to promote kidney dysfunction and if Transient Receptor Potential Cation Channel 6 (TRPC6) contributes to this synergism. In wild type (WT; B6/129s background) and TRPC6 knockout (KO) mice, DM was induced by streptozotocin injection to increase fasting glucose levels to 250-350 mg/dL. HTN was induced by aorta constriction (AC) between the renal arteries. AC increased blood pressure (BP) by ~25 mmHg in the right kidney (above AC) while BP in the left kidney (below AC) returned to near normal after 8 weeks, with both kidneys exposed to the same levels of blood glucose, circulating hormones, and neural influences. Kidneys of WT mice exposed to DM or HTN alone had only mild glomerular injury and urinary albumin excretion. In contrast, kidneys exposed to DM plus HTN (WT-DM+AC mice) for 8 weeks had much greater increases in albumin excretion and histological injury. Marked increased apoptosis was also observed in the right kidneys of WT-DM+AC mice. In contrast, in TRPC6 KO-DM+AC mice, the right kidneys exposed to the same levels of high BP and high glucose had lower albumin excretion, less glomerular damage and apoptotic cell injury compared to right kidneys of WT-DM+AC mice. Our results suggest that TRPC6 may contribute to the interaction of DM and HTN to promote kidney dysfunction and apoptotic cell injury.

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“…The BBB controls the exchange of substances between blood and brain tissue, allows nutrients to pass and prevents harmful substances from entering, thereby protecting the CNS. Given that the secondary injuries after cerebral ischemia is closely related to the morphological and structural destruction of BBB, protecting the integrity of the latter and alleviating cerebral edema are increasingly being considered as treatment options for ischemic stroke ( Huang et al, 2020 ; Parvez et al, 2022 ). Apelin-13 can reduce BBB permeability and brain vasogenic edema after ischemia by mitigating oxidative stress, and inhibiting the expression of matrix metalloproteinases (MMP) and endothelin-B receptor ( Gholamzadeh et al, 2021a ).…”

Section: Apelin-13 and Cerebral Ischemiamentioning

confidence: 99%

The beneficial roles of apelin-13/APJ system in cerebral ischemia: Pathogenesis and therapeutic strategies

Chen

et al. 2022

Front. Pharmacol.

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The incidence of cerebral ischemia has increased in the past decades, and the high fatality and disability rates seriously affect human health. Apelin is a bioactive peptide and the ligand of the G protein-coupled receptor APJ. Both are ubiquitously expressed in the peripheral and central nervous systems, and regulate various physiological and pathological process in the cardiovascular, nervous and endocrine systems. Apelin-13 is one of the subtypes of apelin, and the apelin-13/APJ signaling pathway protects against cerebral ischemia by promoting angiogenesis, inhibiting excitotoxicity and stabilizing atherosclerotic plaques. In this review, we have discussed the role of apelin-13 in the regulation of cerebral ischemia and the underlying mechanisms, along with the therapeutic potential of the apelin-13/APJ signaling pathway in cerebral ischemia.

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The Role of Transient Receptor Potential Channels in Blood-Brain Barrier Dysfunction after Ischemic Stroke

Cited by 17 publications

References 120 publications

Molecular and Functional Study of Transient Receptor Potential Vanilloid 1-4 at the Rat and Human Blood–Brain Barrier Reveals Interspecies Differences

Molecular and Functional Study of Transient Receptor Potential Vanilloid 1-4 at the Rat and Human Blood–Brain Barrier Reveals Interspecies Differences

Transient receptor potential cation channel 6 contributes to kidney injury induced by diabetes and hypertension

The beneficial roles of apelin-13/APJ system in cerebral ischemia: Pathogenesis and therapeutic strategies

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