Water channels in the brain and spinal cord—overview of the role of aquaporins in traumatic brain injury and traumatic spinal cord injury

Knowledge about the mechanisms underlying the fluid flow in the brain and spinal cord is essential for discovering the mechanisms implicated in the pathophysiology of central nervous system diseases. During recent years, research has highlighted the complexity of the fluid flow movement in the brain through a glymphatic system and a lymphatic network. Less is known about these pathways in the spinal cord. An important aspect of fluid flow movement through the glymphatic pathway is the role of water channels, especially aquaporin 1 and 4. This review provides an overview of the role of these aquaporins in brain and spinal cord, and give a short introduction to the fluid flow in brain and spinal cord during in the healthy brain and spinal cord as well as during traumatic brain and spinal cord injury. Finally, this review gives an overview of the current knowledge about the role of aquaporins in traumatic brain and spinal cord injury, highlighting some of the complexities and knowledge gaps in the field

Nhe1 is a luminal Na+/H+ exchanger in mouse choroid plexus and is targeted to the basolateral membrane in Ncbe/Nbcn2-null mice

The choroid plexus epithelium (CPE) secretes the major fraction of the cerebrospinal fluid (CSF). The Na+-HCO3− transporter Ncbe/Nbcn2 in the basolateral membrane of CPE cells is important for Na+-dependent pHi increases and probably for CSF secretion. In the current study, the anion transport inhibitor DIDS had no effect on the residual pHi recovery in acidified CPE from Ncbe/Nbcn2 knockout mouse by 2′,7′-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF)-fluorescence microscopy in the presence of CO2/HCO3− (Ncbe/Nbcn2-ko+DIDS 109% of control, P = 0.76, n = 5). Thus Ncbe/Nbcn2 mediates the DIDS-sensitive Na+-dependent pHi recovery in the CPE. The Na+/H+ exchanger-1 Nhe1 is proposed to mediate similar functions as Ncbe/Nbcn2 in CPE. Here, we immunolocalize the Nhe1 protein to the luminal membrane domain in mouse and human CPE. The Na+-dependent pHi recovery of Nhe1 wild-type (Nhe1-wt) mice in the absence of CO2/HCO3− was abolished in the Nhe1 knockout CPE (Nhe1-ko 0.37% of Nhe1-wt, P = 0.0007, n = 5). In Ncbe/Nbcn2-ko mice, Nhe1 was targeted to the basolateral membrane. Nevertheless, the luminal Na+-dependent pHi recovery was increased in Ncbe/Nbcn2-ko compared with wild-type littermates (Nhe1-ko 146% of Nhe1-wt, P = 0.007, n = 5). Whereas the luminal Nhe activity was inhibited by the Nhe blocker EIPA (10 μM) in the Ncbe/Nbcn2-wt, it was insensitive to the inhibitor in Ncbe/Nbcn2-ko (Ncbe/Nbcn2-ko+EIPA 100% of control, P = 0.98, n = 5). This indicates that a luminal EIPA-insensitive Nhe was induced in Ncbe/Nbcn2-ko CPE and that EIPA-sensitive Nhe activity was basolateral. The Nhe1 translocation in Ncbe/Nbcn2-ko CPE may reflect a compensatory response, which provides the cells with better means of regulating pHi or transporting Na+ after Ncbe/Nbcn2 disruption

Renal Type A Intercalated Cells Contain Albumin in Organelles with Aldosterone-Regulated Abundance

<div><p>Albumin has been identified in preparations of renal distal tubules and collecting ducts by mass spectrometry. This study aimed to establish whether albumin was a contaminant in those studies or actually present in the tubular cells, and if so, identify the albumin containing cells and commence exploration of the origin of the intracellular albumin. In addition to the expected proximal tubular albumin immunoreactivity, albumin was localized to mouse renal type-A intercalated cells and cells in the interstitium by three anti-albumin antibodies. Albumin did not colocalize with markers for early endosomes (EEA1), late endosomes/lysosomes (cathepsin D) or recycling endosomes (Rab11). Immuno-gold electron microscopy confirmed the presence of albumin-containing large spherical membrane associated bodies in the basal parts of intercalated cells. Message for albumin was detected in mouse renal cortex as well as in a wide variety of other tissues by RT-PCR, but was absent from isolated connecting tubules and cortical collecting ducts. Wild type I MDCK cells showed robust uptake of fluorescein-albumin from the basolateral side but not from the apical side when grown on permeable support. Only a subset of cells with low peanut agglutinin binding took up albumin. Albumin-aldosterone conjugates were also internalized from the basolateral side by MDCK cells. Aldosterone administration for 24 and 48 hours decreased albumin abundance in connecting tubules and cortical collecting ducts from mouse kidneys. We suggest that albumin is produced within the renal interstitium and taken up from the basolateral side by type-A intercalated cells by clathrin and dynamin independent pathways and speculate that the protein might act as a carrier of less water-soluble substances across the renal interstitium from the capillaries to the tubular cells.</p></div

17 beta-Estradiol induces nongenomic effects in renal intercalated cells through G protein-coupled estrogen receptor 1

Hofmeister MV, Damkier HH, Christensen BM, Olde B, Leeb-Lundberg LM, Fenton RA, Praetorius HA, Praetorius J. 17 beta-Estradiol induces nongenomic effects in renal intercalated cells through G protein-coupled estrogen receptor 1. Am J Physiol Renal Physiol 302: F358-F368, 2012. First published October 12, 2011; doi: 10.1152/ajprenal.00343.2011.-Steroid hormones such as 17 beta-estradiol (E2) are known to modulate ion transporter expression in the kidney through classic intracellular receptors. Steroid hormones are also known to cause rapid nongenomic responses in a variety of nonrenal tissues. However, little is known about renal short-term effects of steroid hormones. Here, we studied the acute actions of E2 on intracellular Ca2+ signaling in isolated distal convoluted tubules (DCT2), connecting tubules (CNT), and initial cortical collecting ducts (iCCD) by fluo 4 fluorometry. Physiological concentrations of E2 induced transient increases in intracellular Ca2+ concentration ([Ca2+](i)) in a subpopulation of cells. The [Ca2+](i) increases required extracellular Ca2+ and were inhibited by Gd3+. Strikingly, the classic E2 receptor antagonist ICI 182,780 also increased [Ca2+](i), which is inconsistent with the activation of classic E2 receptors. G proteincoupled estrogen receptor 1 (G.PER1 or GPR30) was detected in microdissected DCT2/CNT/iCCD by RT-PCR. Stimulation with the specific GPER1 agonist G-1 induced similar [Ca2+](i) increases as E2, and in tubules from GPER1 knockout mice, E2, G-1, and ICI 182,780 failed to induce [Ca2+](i) elevations. The intercalated cells showed both E2-induced concanamycin-sensitive H+-ATPase activity by BCECF fluorometry and the E2-mediated [Ca2+](i) increment. We propose that E2 via GPER1 evokes [Ca2+](i) transients and increases H+-ATPase activity in intercalated cells in mouse DCT2/CNT/iCCD

Extratubular albumin expression.

<p>Immunoperoxidase staining for albumin in the mouse renal cortex with two anti-albumin antibodies. A) Goat anti-albumin labeling of proximal tubules (arrows), as well as peritubular cells (arrow heads). B) Sheep anti-albumin labeling of the same structures. DT = distal tubule, PT = proximal tubule.</p