Blood-labyrinth Barrier Research Articles

か牛におけるメタンフェタミンの局在

Methamphetamine activates catecholaminergic neurons and releases noradrenalin from their nerve endings in the central nervous system. Many reports have described the distribution of methamphetamine in the central nervous system after systemic administration. However, there have been only a few studies on the effect of this drug on peripheral organs, and known dealing with the inner ear.The authors used immunohistochemical methods to investigate the effect of methamphetamine on the pheripheral auditory system. Methamphetamine was administered to guinea pigs via intraperitoneal injection. The distribution of methamphetamine in the cochlea was studied by light microscopy following its immunohistochemical staining, and the methamphetamine concentration in the serum was also measured.1. Histochemical examination revealed that methamphetamine was present in the hair cells of the organ of Corti, spiral ligament and spiral ganglion cells 30 minutes after administration.2. The drug concentration in the serum rose rapidly, and then dropped in a logarithmic way with time until it became nearly horinzontal after 6 hours.The results suggest that methamphetamine penetrated the blood-labyrinth barrier (BLB) and then reached the organ of Corti, although some methamphetamine took a route to the inner ear via the cerebrospinal fluid. The pharmacological effect of methamphetamine on the cochlea was excitation of the sensory cells, the afferent nerve fibers connecting to them, and the spiral ganglion cells.

Dazoxiben-induced changes in the thromboxane/prostacyclin balance in the lateral cochlear wall of the guinea pig.

Dazoxiben, a thromboxane synthetase inhibitor, was infused i.v. in a first group of guinea pigs. Saline was given to a second group of animals as controls. Subsequently, the lateral cochlear walls of each animal were prepared and analyzed for thromboxane (TXA) and prostacyclin (PGI) using radioimmunoassay. These studies showed that dazoxiben crosses the blood-labyrinth barrier and shifts the TXA2/PGI2 balance in favor of the latter. The effects demonstrated are discussed with respect to the relevance of prostanoids in cochlear physiology.

Barrier systems in the inner ear.

Because of the highly complicated function of the central nervous system and sensory organs, barrier systems have necessarily developed to ensure stability of the extracellular fluids bathing these organs. Several barrier systems which can influence the composition of the inner ear fluids are discussed. They are the 1) blood-labyrinth barrier, 2) cerebrospinal fluid-labyrinth barrier, and 3) middle ear-labyrinth barrier. The experimental data are shown to indicate that these barriers serve to protect the inner ear through selective permeability. Arachidonic acid metabolites, particularly compounds of the prostaglandin series, were identified in perilymph, and were increased by the administration of stress-related hormones, and decreased after aspirin injection. The inner ear fluid composition responds to the changes of the surrounding fluid containing compartments. However, the degree of response appears to depend on the level of changes induced in the surrounding compartments. The concept of a threshold concentration of toxic substances in middle ear effusion to induce inner ear damage is also proposed.

Blood labyrinth barrier and its alteration.

Blood labyrinth barrier and its alteration.

Immunology of the inner ear: response of the inner ear to antigen challenge.

The relationship of the inner ear to host immunity and the immunoresponsiveness of the inner ear to antigen challenge were investigated. A radioimmunoassay was used to quantitate antibody titers to keyhole-limpet hemocyanin generated in the serum, perilymph, and CSF of guinea pigs following systemic or inner ear immunizations. The results of these experiments demonstrate (1) the blood-labyrinth barrier is analogous to the blood-brain barrier with respect to immunoglobulin equilibrium, (2) the inner ear is capable of responding to antigen challenge, and (3) the inner ear is an effective route for systemic immunization.

Nature of blood-labyrinth barrier in experimental conditions.

The blood-labyrinth barrier is concept that has evolved based on marked difference in chemical composition between perilymph and blood. Studies reported here have been designed to manipulate physiologic, metabolic, and pharmacologic conditions in experimental animals in order to determine the characteristics of this regulatory mechanisms. Tracer studies of uptake of sodium, calcium, and albumin from blood into perilymph showed that these substances penetrate into inner ear fluids quite slowly. Injections of ototoxic substances (kanamycin, furosemide) show limited transport of these agents into perilymph. Administration of an osmotic agent (urea) resulted in a parallel but delayed elevation of perilymph concentration. The possible role of a alteration of blood-labyrinth barrier in inner ear disorders has been discussed.

Labyrinthine Barriers and Cochlear Homeostasis

The blood-labyrinth barrier is a concept used to explain the stability of composition of the labyrinthine fluids in spite of systemic alterations in blood composition. This blood-labyrinth barrier concept was tested by injecting various test substances into the systemic circulation of experimental animals and recovering these compounds in perilymph. The concentration of each test substance in perilymph lagged behind that of serum, and the transport of a series of test substances was found to be inversely related to the molecular weight and diameter. Among the osmotic agents injected, glycerol and urea penetrated into perilymph to a considerable degree, however, mannitol did not enter perilymph in any significant amount. This may explain the clinical differences noted with these agents in testing for Meniere's disease. Furosemide, an ototoxic diuretic, was found to penetrate into perilymph after intravenous injection into chinchillas. The concentration of furosemide, measured by high pressure liquid chromatography, was fairly constant at the time of full recovery of endocochlear potential after doses of 50-200 mg/kg. The principle of correlating drug concentration in serum and in inner ear fluids with pathophysiologic effect may provide a prediction of threshold concentration of ototoxic effect by measurement of serum concentration of the drug. More extensive studies are necessary to clarify the role of the blood-labyrinth barrier in the regulatory mechanisms which maintain the homeostasis in the inner ear and the pathology which may follow when this homeostasis is disrupted.

Effect of urea on osmolality of perilymph.

Blood osmolality was altered in chinchillas by intravenous administration of urea. Serum osmolality peaked rapidly at 30 minutes after administration and decreased slightly to a plateau for 180 minutes. Perilymph and CSF osmolality lagged substantially behind the increase in serum osmolality and equaled serum osmolality only after one hour. Perilymph osmolality followed changes in the serum up to 60 minutes with a definite time lag. This phenomenon suggests the existence of a selective blood-labyrinth barrier that is permeable to urea and water. However, the time lag due to the barrier may permit the reduction of hydrostatic pressure in the labyrinth. The results of the present study seem to render partial explanation of improved hearing in patients with Meniere's disease who were treated with urea.

Rate of transport of ototoxic drugs into perilymph

By measuring concentration of kanamycin in perilymph after multiple doses, the accumulation of kanamycin in perilymph was observed. When the correlation between the concentration of kanamycin in perilymph and hair cell damage (by surface preparation technique) was pursued, a dose‐related phenomenon was observed. Furosemide levels have been measured in chinchilla body fluids after 100 mg/kg intravenous injection. The drug has a much longer half‐life in perilymph compared to other body fluid compartments. However, when this same dose is given to animals who had received 25 mg/kg injections every twelve hours for ten doses, no evidence of accumulation in any body fluids was noted. Changes in endocochlear potential (EP) in chinchillas receiving a single IV dose of furosemide 25, 50, of 100 mg/kg showed dose‐dependent changes. The time after administration of drug to initiation of EP recovery was 6, 9, and 19 min for these doses, respectively. The perilymph level of furosemide is 5 μg/ml at the time that recovery of EP is beginning after the 100 mg/kg IV dose. This may represent a threshold level for this drug. These studies support the existence of a blood labyrinth barrier with selective permeability. Kanamycin tends to accumulate in perilymph but furosemide does not. The mechanism underlying these differences in drug accumulation may be a differential toxic effect on membrane permeability or excretion rate from the perilymphatic space. This basic information helps to understand the differences of degree of hearing loss (permanent or temporary) observed in patients receiving antibiotics or diuretics.

Familial balanced translocation 4p+/17q- as a suggested cause of primary trisomy-21 Down's syndrome.

A case is presented in which a 4p+/17q- familial balanced reciprocal translocation in the mother produced a son with primary trisomy-21, as well as the structural chromosomal anomaly. A number of similar situations have been reported, suggesting that the two events are related. In practice, this (as well as other direct risks) should be taken into account when counseling those families in which one parent carries a balanced translocation. A hypothesis, based on experiments in Drosophila, has been put forward by Grell to explain the mechanism which links the balanced structural abnormality to an aneuploidy of chromosomes not taking part in the structural change, and this has been extended to similar human situations.

Osmolality Changes in Perilymph After Systemic Administration of Glycerin

Blood osmolality was altered in guinea pigs by intravenous administration of glycerin (glycerol). After glycerin administration, serum osmolality increased rapidly, reaching a plateau within 15 minutes. Perilymph osmolality lagged significantly behind the increase of serum osmolality and equalled serum osmolality only after one hour. While perilymph osmolality responded to changes of serum osmolality, there was some time lag noted in the response of perilymph, suggesting the existence of a blood-labyrinth barrier. It was observed that this barrier is permeably to glycerin and water, suggesting the possibility of transient reduction of hydrostatic pressure in the labyrinth by the injection of an osmotic agent into the systemic circulation.

Dynamics of permeability of the blood-labyrinth barrier for radioactive phosphorus

Dynamics of permeability of the blood-labyrinth barrier for radioactive phosphorus