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- Mestre, Humberto, et al.
(författare)
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Aquaporin-4-dependent glymphatic solute transport in the rodent brain
- 2018
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Ingår i: eLife. - 2050-084X. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- The glymphatic system is a brain-wide clearance pathway; its impairment contributes to the accumulation of amyloid-β. Influx of cerebrospinal fluid (CSF) depends upon the expression and perivascular localization of the astroglial water channel aquaporin-4 (AQP4). Prompted by a recent failure to find an effect of Aqp4 knock-out (KO) on CSF and interstitial fluid (ISF) tracer transport, five groups re-examined the importance of AQP4 in glymphatic transport. We concur that CSF influx is higher in wild-type mice than in four different Aqp4 KO lines and in one line that lacks perivascular AQP4 (Snta1 KO). Meta-analysis of all studies demonstrated a significant decrease in tracer transport in KO mice and rats compared to controls. Meta-regression indicated that anesthesia, age, and tracer delivery explain the opposing results. We also report that intrastriatal injections suppress glymphatic function. This validates the role of AQP4 and shows that glymphatic studies must avoid the use of invasive procedures.
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- Murawski, Christopher D., et al.
(författare)
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Terminology for osteochondral lesions of the ankle: proceedings of the International Consensus Meeting on Cartilage Repair of the Ankle
- 2022
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Ingår i: JOURNAL OF ISAKOS JOINT DISORDERS & ORTHOPAEDIC SPORTS MEDICINE. - : Elsevier BV. - 2059-7754 .- 2059-7762. ; 7:2, s. 62-66
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Tidskriftsartikel (refereegranskat)abstract
- Background: The evidence supporting best practice guidelines in the field of cartilage repair of the ankle is based on both low quality and low levels of evidence. Therefore, an international consensus group of experts was convened to collaboratively advance toward consensus opinions based on the best available evidence on key topics within cartilage repair of the ankle. The purpose of this article is to report the consensus statements on "terminology for osteochondral lesions of the ankle" developed at the 2019 International Consensus Meeting on Cartilage Repair of the Ankle. Methods: Forty-three international experts in cartilage repair of the ankle representing 20 countries were convened and participated in a process based on the Delphi method of achieving consensus. Questions and statements were drafted within four working groups focusing on specific topics within cartilage repair of the ankle, after which a comprehensive literature review was performed, and the available evidence for each state-ment was graded. Discussion and debate occurred in cases where statements were not agreed on in unanimous fashion within the working groups. A final vote was then held, and the strength of consensus was characterised as follows: consensus, 51%-74%; strong consensus, 75%-99%; unanimous, 100%. Results: A total of 11 statements on terminology and classification reached consensus during the 2019 Interna-tional Consensus Meeting on Cartilage Repair of the Ankle. Definitions are provided for osseous, chondral and osteochondral lesions, as well as bone marrow stimulation and injury chronicity, among others. An osteochondral lesion of the talus can be abbreviated as OLT. Conclusions: This international consensus derived from leaders in the field will assist clinicians with the appro-priate terminology for osteochondral lesions of the ankle.
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- Yasui, Masato
(författare)
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Expression and regulation of water channels and ion transporters : ontogenic aspects
- 1997
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The content and distribution of body water changes dramatically during the perinatal period and in infancy. Transport of water across the cell membrane occurs via diffusion and via specific water channels. Transport via water channels is fast and may be hormonally regulated. The main purpose of this thesis has been to study the peri- and postnatal development and regulation of water channels. Since water movement via water channels is dependent on ionic gradients, I also studied the postnatal expression of some ion transporters. Removal of rat lung liquid at birth was associated with pronounced changes in the expression of water channels, aquaporins (AQP) and ion transporters. The level mRNA levels of AQP1, Na+,K+-ATPase al, and amiloride sensitive sodium channel increased from embryonic day 18 (E18) to birth and continued to increase postnatally. There was a sharp and transient induction of AQP4 mRNA. The AQP4 protein was present in bronchial epithelial cells, where postnatal lung liquid clearance mainly takes place. Exposure of fetal rats (E20) to B-adrenergic agonists or glucocorticoids (GC) significantly increased lung AQP4 mRNA. These observations suggest that AQP4 plays a critical role for absorption of lung fluid at birth. The capacity to concentrate urine develops postnatally and is accelerated in the weaning period in rats. A similar development pattern was found for the AQP2 mRNA expression. The expression of the mRNA of other transporters responsible for medullary hypertonicity, medullary Na+,K+-ATPase al, Na+,K+,2CI~ cotransporter and kidney specific chloride channel also increased during the weaning period. Those parameters were inducible by GC in infant but not in adult rats. The induction was observed after 20 min of GC exposure for Na+,K+-ATPase and after 24 h for the other transporters. Nuclear run-on studies indicated that GC directly stimulated transcription and Na+,K+-ATPase in the infant kidney. The antidiuretic hormone arginine vasopressin (AVP) regulates the urinary concentrating capacity. It is shown here that AVP regulates AQP2 on both a short- and long-term basis. AVP caused a time- and dose-dependent phosphorylation of AQP2 in rat renal papillae via the same pathway. AVP also activated the AQP2 promoter via the V2 receptor-cAMP-PKA pathway. PKA phosphorylated the cAMP-response element-binding protein (CREB) and phosphorylated CREB bound to and activated the AQP2 promoter in LLC-PK1 cells. In conclusion, pronounced changes in the expression of water channels have been observed in the lung around birth and in the kidney during the weaning period, which suggests that they play a role for the transition from a life in fluid to a life in air. Water channels are regulated by hormones and a system by which AVP can regulate AQP2 both on a short- and long-term basis is described. These findings may be of importance for a better understanding of the pathophysiology in infants with lung edema, dehydration and volume expansion and may ultimately lead to improvement of therapy in those conditions.
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