Cell volume regulation and transport mechanisms across the blood-brain barrier: implications for the management of hypernatraemic states

Petris, Laura De; Luchetti, Anna; Emma, Francesco

doi:10.1007/s004310000631

Cited by 38 publications

(24 citation statements)

References 35 publications

(90 reference statements)

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“…Alterations in the osmolality and water distribution in the brain and cerebrospinal fluid compartments are a common occurrence in many neuropathological conditions such as brain edema, stroke hyponatremia, head injures, and hydrocephalus (De Petris et al, 2001). Therefore, the osmoregulatory transporters at the BBB play a pivotal role in maintaining osmolality in the brain.…”

Section: Discussionmentioning

confidence: 99%

“…To understand the regulation and physiological and/or pathophysiological functions of system A at the BBB, it is important to identify isoforms of system A and clarify the transport functions of system A at the BBB under disease conditions. The osmo-regulation in the brain may play a role in detoxification in the brain to protect it against adverse events such as brain edema, stroke hyponatremia, head injures, ischemia, and hydrocephalus (Phillis et al, 1999;De Petris et al, 2001).…”

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confidence: 99%

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ATA2 Is Predominantly Expressed as System A at the Blood-Brain Barrier and Acts as Brain-to-Blood Efflux Transport forl-Proline

et al. 2002

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Although system A is present at the blood-brain barrier (BBB), the physiological roles of system A have not been clarified. The efflux transport of the substrates of system A, such as L-proline (L-Pro), glycine (Gly), and ␣-methylaminoisobutyric acid (MeAIB), across the BBB was investigated using the in vivo Brain Efflux Index method. Over a period of 40 min, L 3 H]MeAIB uptake. In light of these observations, our results indicate that L-Pro and Gly are transported from the brain across the BBB, whereas MeAIB is retained in the brain. System A is involved in efflux transport for L-Pro at the BBB. The predominantly expressed ATA2 mRNA at the BBB may play a role in maintaining the concentration of small neutral amino acids and cerebral osmotic pressure in the brain under pathological conditions.The blood-brain barrier (BBB), which is formed by complex tight junctions of the brain capillary endothelial cells, segregates the circulating blood from interstitial fluid in the brain (Cornford, 1985). The BBB is well known to regulate not only the supply of nutrients and drugs to the brain from the circulating blood (Cornford, 1985;Pardridge et al., 1990), but also the efflux transport of compounds, such as P-glycoprotein, which transports anticancer and other drugs (Tsuji et al., 1992;Schinkel et al., 1994). Another transporter at the BBB is system A, a transporter of small neutral amino acids, which accepts L-alanine, L-proline, glycine, and ␣-methylaminoisobutyric acid (MeAIB) as substrates. It has been suggested that system A is present in the abluminal (brain) side of the BBB because MeAIB, which is a specific nonmetabolizable substrate for system A (Norman and Mann, 1986), is taken up in an Na ϩ -dependent manner from the brain side using isolated rat brain capillaries (Betz and Goldstein, 1978) and isolated abluminal membrane vesicles from bovine brain endothelial cells (Sanchez del Pino et al., 1995). Several investigations using brain-uptake methods have established that system A substrates undergo limited influx transport across the BBB (Oldendorf, 1971;Sershen and Lajtha, 1979). These investigations suggest that system A plays a role in the efflux transport of small neutral amino acids at the BBB to maintain their concentration in the brain (Betz and Goldstein, 1978). However, it does not fully explain this hypothesis, because the neutral amino acids are believed to be supplied from the circulating blood (Cornford, 1985). ReThis work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture, Japan. It was also supported in part by the Suzuken Memorial Foundation, the Mochida Memorial Foundation for Medical and Pharmaceutical Research, the Uehara Memorial Foundation, the Novartis Foundation (Japan) for the Promotion of Science, the Nakatomi Foundation, the Japan Society

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

ATA2 Is Predominantly Expressed as System A at the Blood-Brain Barrier and Acts as Brain-to-Blood Efflux Transport forl-Proline

et al. 2002

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“…In chronic hypernatremia, organic osmoles seem to play a much more important role in helping to maintain the osmotic gradient. [37][38][39][40] The temporal dissociation between these 2 adaptive osmoregulating mechanisms, whether at the acute or chronic stage, could account, at least in part, for the nature and severity of neurologic symptoms. General clinical observations suggest that patients with acute hypernatremia or hyponatremia develop a more clinically severe condition and have worse outcomes that those with chronic challenges.…”

Section: Clinical Characteristics Of Patients With Hypernatremic Chalmentioning

confidence: 99%

Clinical Semiology and Neuroradiologic Correlates of Acute Hypernatremic Osmotic Challenge in Adults: A Literature Review

Ismail¹,

Szóllics

Szólics

et al. 2013

AJNR Am J Neuroradiol

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SUMMARY:The complex interplay between hypernatremic osmotic disturbances and cerebral lesions is yet to be clarified. In this review, we discuss, on the basis of the reported data of hypernatremic CNS challenge in the adult population, the clinical and radiologic features of the condition. Our search captured 20 case studies and 1 case series with 30 patients in total who acquired acute hypernatremia due to different etiologies and developed CNS lesions. We explored the associations between premorbid conditions, clinical presentation, hypernatremic state, correction rate, and radiologic appearance, including the localization of brain lesions and the outcomes. The results revealed that altered mental status was the most commonly reported symptom and osmotic demyelination syndrome in the form of extrapontine myelinolysis was the prevailing radiologic pattern. Finally, we contrasted, when appropriate, clinical and experimental data related to hypernatremic and hyponatremic osmotic insults to aid the understanding of the pathophysiology of CNS osmotic brain injury.ABBREVIATIONS: BG ϭ basal ganglia; CPM ϭ central pontine myelinolysis; EPM ϭ extrapontine myelinolysis; GCS ϭ Glasgow Coma Scale; ODS ϭ osmotic

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“…Activation of the regulatory volume decrease will also limit the accumulation of Na ϩ and Ca 2ϩ through the Na ϩ /H ϩ and Na ϩ /Ca 2ϩ exchangers. 34 The second mechanism influencing the status of the ischemic, hypertensive heart is the degree of cell stretching. Figure 1 reveals that an elevation in afterload from 100 to 160 cm H 2 O prevented the reduction in infarct size that was observed in the hearts of the hypertensive rats.…”

Section: Discussionmentioning

confidence: 99%

Effect of Hypertension and Hypertension-Glucose Intolerance on Myocardial Ischemic Injury

Mozaffari

Schaffer

2003

Hypertension

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Abstract-Systemic hypertension and type 2 diabetes mellitus are major risk factors for myocardial infarction. Yet, glucose intolerance, a prelude stage to type 2 diabetes, is associated with reduced infarct size. Since chronic hypertension adversely affects the myocardium, we tested the hypothesis that the coexistence of systemic hypertension and glucose intolerance reverses the cardioprotection associated with impaired glucose tolerance. Hearts from 9-month-old animals were subjected to a 40-minute occlusion of the left coronary artery followed by 2 hours of reperfusion. Before ischemia, similar values for the four experimental groups were observed for the coronary flow, heart rate, and maximum ventricular pressure. During the course of the ischemia-reperfusion insult, the two hypertensive groups displayed greater reductions in contractility than their normotensive counterparts. Infarct size was lower in the normotensive glucose-intolerant rat than in the normotensive control rat. Surprisingly, the hypertrophied hearts of the hypertensive and hypertensive glucose-intolerant rats displayed reduced infarct size (PϽ0.05). However, raising the afterload pressure from 100 to 160 cm H 2 O increased infarct size in the two hypertensive groups. This narrowed the differential between the hypertensive glucose-intolerant (160 cm H 2 O) and the normotensive control (100 cm H 2 O) rats. Nonetheless, at the higher afterload pressure, infarct size was less in the hypertensive glucose-intolerant rats than in their hypertensive counterparts. In conclusion, the impairment in contractile function despite the reduction in infarct size underscores the increased susceptibility of the hypertrophied, hypertensive heart to ischemic injury. Furthermore, exacerbation of cell death at elevated afterload pressure indicates the potential benefit of aggressive antihypertensive therapy.

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Cell volume regulation and transport mechanisms across the blood-brain barrier: implications for the management of hypernatraemic states

Abstract: The basic mechanisms involved in brain ion and water transport are reviewed. A proper understanding of these processes is essential to develop appropriate treatment strategies in managing children with hypernatraemia.

Cited by 38 publications

References 35 publications

ATA2 Is Predominantly Expressed as System A at the Blood-Brain Barrier and Acts as Brain-to-Blood Efflux Transport forl-Proline

ATA2 Is Predominantly Expressed as System A at the Blood-Brain Barrier and Acts as Brain-to-Blood Efflux Transport forl-Proline

Clinical Semiology and Neuroradiologic Correlates of Acute Hypernatremic Osmotic Challenge in Adults: A Literature Review

Effect of Hypertension and Hypertension-Glucose Intolerance on Myocardial Ischemic Injury

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