Attenuated Development of Ischemic Brain Edema in Vasopressin-Deficient Rats

Dickinson, Lawrence D.; Betz, A. Lorris

doi:10.1038/jcbfm.1992.93

Cited by 64 publications

(39 citation statements)

References 39 publications

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“…1. Our previous studies have shown that the cerebral blood flow is reduced in the isch emic cortex to -20% of normal in this sample (Martz et aI., 1990;Dickinson and Betz, 1992). Validation of the use of the contralateral tissue as control has been presented previously (Menzies et aI., 1993).…”

Section: Meao and Brain Samplingsupporting

confidence: 70%

“…Since the Kj values measured in this study were <5% of the rate of blood flow that we reported previously (Martz et ai., 1990;Dickinson and Betz, 1992), the Kj values are essentially identical to permeability-surface area (PS) products (Fenstermacher et aI., 1981). The PS product is influenced not only by the BBB permeability (P) of a substance but also by the amount of vascular surface (S) to which it is exposed.…”

Section: Measurement Of Brain Water and Ion Concentrationsmentioning

confidence: 84%

“…Focal cerebral ischemia was produced by right MCAO according to a modification of the method devel oped by Bederson et ai. (1986) as described previously (Martz et aI., 1990;Dickinson and Betz, 1992). For stud ies that were conducted 2 h or later after MCAO, the animals were allowed to recover from the initial anesthe sia and then were reanesthetized.…”

Section: Meao and Brain Samplingmentioning

confidence: 99%

“…dium accumulates in brain is similar in magnitUde to the rate of transport of sodium from blood to brain across the blood-brain barrier (BBB) (Betz et aI., 1989). Furthermore, the permeability of the BBB to sodium increases well before the passive permeabil ity of the BBB increases during ischemia (Betz and Coester, 1990;Ennis et aI., 1990;Schielke et aI., 1991;Dickinson and Betz, 1992). It has been hy pothesized that this increase may result from a stim ulation of Na,K-ATPase in the brain capillary either through free radical-mediated capillary injury (Go toh et aI., 1985) or through the elevated extracellu lar potassium concentration in brain (Schielke et aI., 1991).…”

mentioning

confidence: 99%

“…These results have led us to speculate that it may be possible to reduce edema formation early in isch emia by controlling the rate of ion transport across the BBB (Betz et aI., 1989;Dickinson and Betz, 1992;Menzies et aI., 1993). However, many ques tions remain concerning the mechanisms that are responsible for BBB ion transport and how they are altered by ischemia.…”

mentioning

confidence: 99%

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Blood—Brain Barrier Permeability and Brain Concentration of Sodium, Potassium, and Chloride during Focal Ischemia

Betz

Keep

Beer

et al. 1994

J Cereb Blood Flow Metab

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136

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Summary: Brain edema formation during the early stages of focal cerebral ischemia is associated with an increase in both sodium content and blood-brain barrier (BBB) sodium transport. The goals of this study were to deter mine whether chloride is the principal anion that accumu lates in ischemic brain, how the rate of BBB transport of chloride compares with its rate of accumulation, and whether the stimulation seen in BBB sodium transport is also seen with other cations. Focal ischemia was pro duced by occlusion of the middle cerebral artery (MCAO) in anesthetized rats. Over the first 6 h after MCAO, the amount of brain water in the center of the ischemic cortex increased progressively at a rate of 0.15 ± 0.02 (SE) gig dry wtlh. This was accompanied by a net increase in brain sodium (48 ± 12 j.Lmol/g dry wtlh) and a loss of potassium (34 ± 7 j.Lmol/g dry wt/h). The net rate of chloride accu mulation (16 ± 1 j.Lmol/g dry wt/h) approximated the net rate of increase of cations. Three hours after MCAO, the BBB permeability to three ions e2Na, 36CI, and 86Rb) and two passive permeability tracers WH]a-aminoisobutyric Numerous studies have emphasized the impor tance of cations in the development of brain edema during focal ischemia (Ito et aI., 1979;Schuier and Hossmann, 1980; Gotoh et aI., 1985; Young et aI., 1987; Betz et aI., 1989; Menzies et aI., 1993). For example, during the first 3-6 h of ischemia, water accumulation results from a net increase in brain sodium despite a significant loss of brain potassium (Gotoh et aI., 1985; Young et aI., 1987; Betz et aI., 1989; Menzies et aI., 1993). The rate at which soReceived November 9, 1992; final revision received July 13, 1993; accepted July 16, 1993.Address correspondence and reprint requests to Dr. A. L. Betz at D3227 Medical Professional Building, University of Michigan, Ann Arbor, MI 48109-0718, U. S.A.Abbreviations used: AlB, a-aminoisobutyric acid; BBB, blood-brain barrier; MeAO, middle cerebral artery occlusion. 29acid eH]AIB) and e4C]urea} was determined. Permeabil ity to either passive tracer was not increased, indicating that the BBB was intact. The rate of 36CI influx was 3 times greater and the rate of 22Na influx 1.8 times greater than their respective net rates of accumulation in isch emic brain. The BBB permeability to 22Na relative to that of eRJAIB was significantly increased in the ischemic cortex, the relative permeability to 86Rb was significantly decreased, and the relative permeability to 36CI was un changed. These results indicate that the stimulation in BBB sodium transport is specific for sodium. Further, chloride accumulates with sodium in brain during the early stages of ischemia; however, its rate of accumula tion is low compared with its rate of transport from blood to brain. Therefore, inhibition of BBB sodium transport is more likely to reduce edema formation than is inhibition of BBB chloride transport. Key Words: Brain edema Electrolyte transport-Middle cerebral artery occlu sion-Permeability-surface area product.

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Section: Meao and Brain Samplingsupporting

confidence: 70%

Section: Measurement Of Brain Water and Ion Concentrationsmentioning

confidence: 84%

Section: Meao and Brain Samplingmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Blood—Brain Barrier Permeability and Brain Concentration of Sodium, Potassium, and Chloride during Focal Ischemia

Betz

Keep

Beer

et al. 1994

J Cereb Blood Flow Metab

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136

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Choroid plexus: Target for polypeptides and site of their synthesis

Chodobski

Szmydynger‐Chodobska

2000

Microsc. Res. Tech.

204

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Choroid plexus (CP) is an important target organ for polypeptides. The fenestrated phenotype of choroidal endothelium facilitates the penetration of blood‐borne polypeptides across the capillary walls. Thus, both circulating and cerebrospinal fluid (CSF)‐borne polypeptides can reach their receptors on choroidal epithelium. Several polypeptides have been demonstrated to regulate CSF formation by controlling blood flow to choroid plexus and/or the activity of ion transport in choroidal epithelium. However, many ligand‐receptor interactions occurring in the CP are not involved in the regulation of fluid secretion. Increasing evidence suggests that the choroidal epithelium plays an important role in hormonal signaling via a receptor‐mediated transport into the brain (e.g., leptin) and helps to clear certain CSF‐borne polypeptides (e.g., soluble amyloid β‐protein). Thus, impaired choroidal transport or insufficient clearance of polypeptides may contribute to pathogenesis of systemic or central nervous system (CNS) disorders, such as obesity or Alzheimer's disease. CP epithelium is not only a target but is also a source of neuropeptides, growth factors, and cytokines in the CNS. These polypeptides following their release into the CSF may exert distal, endocrine‐like effects on target cells in the brain due to bulk flow of this fluid. Distinct temporal patterns of choroidal expression of several polypeptides are observed during brain development and in various CNS disorders, including traumatic brain injury and ischemia. Therefore, it is proposed that the CP plays an integral role not only in normal brain functioning, but also in the recovery from the injury. This review attempts to critically analyze the available data to support the above hypothesis. Microsc. Res. Tech. 52:65–82, 2001. © 2001 Wiley‐Liss, Inc.

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