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A Weerasuriya

Publications and source records attributed to A Weerasuriya.

At least 19 recordsLinked to original sources

GABA receptor-mediated inhibition of reflex deglutition in the cat.

In anesthetized cats, swallowing elicited by electrical stimulation of the superior laryngeal nerves (SLNs) was inhibited by the GABA-mimetic muscimol and by diazepam, an action that was reversed by picrotoxin and bicuculline. This inhibition supports the involvement of GABA receptors, specifically those of the GABAA subtype which both antagonists have been shown to block in various areas of the central nervous system. The inhibition of reflex swallowing and its reversal were unaltered by a transection of the brainstem at a midcollicular level. Stimulation of the SLNs also caused a bradycardia that was inhibited by both muscimol and diazepam and was restored by both GABA antagonists. Data from these experiments provide suggestive evidence for a role of GABA-ergic transmission in the central control of the deglutitory reflex.

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Perineurial permeability to sodium during Wallerian degeneration in rat sciatic nerve.

In rat sciatic nerves, the effect of Wallerian degeneration on the rate of transperineurial passage of sodium between the endoneurium and the epineurial extracellular space was investigated. In nerves transected and ligated at the sciatic notch, an in situ technique was used to measure the permeability coefficient-surface area product (PS) of the mid-thigh portion of the perineurium to 22Na. Sampling times ranged from one day to sixteen weeks after the lesion. Additionally, endoneurial water content (an indicator of nerve edema) was also measured in transected, degenerating nerves at the same sampling times. Endoneurial water content increased significantly by the fourth day after transection, peaked at four weeks, and then remained elevated through 16 weeks of post-lesion measurement. The PS of the perineurium to 22Na on the 4th day after transection was significantly greater than that of control animals. This increase then declined to normal levels through the 2nd week, and finally increased to values that were 3-fold to 4-fold of control values for the remainder of the observation period. The earlier, short lasting increase in perineurial PS is probably associated with the inflammatory response to nerve section, and proliferation of perineurial layers and cells. The later increase in perineurial permeability is proposed to play a role in the dissipation of endoneurial hydrostatic pressure and clearance of myelin debris from the endoneurium. In view of the complex changes in perineurial permeability described herein, it would seem inappropriate to consider these phenomena merely as passive breakdowns of the barrier properties of the perineurium.

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Endoneurial blood flow in rat sciatic nerve during development.

1. Endoneurial blood flow (EBF) in the sciatic nerve of rats aged 2-12 weeks was studied using microelectrode H2 polarography. 2. EBF is highest in 2-week-old rats and progressively declines during development. Mean arterial pressure (MAP) is low at 2 weeks of age, gradually increases through the next 4 weeks, and is relatively constant thereafter. The decrease in EBF, in spite of an increase in MAP, occurs because the endoneurial vascular resistance is increasing faster than the MAP. 3. The higher EBF in younger rats is not due to the smaller diameter of their nerves. Sural and tibial nerves of 12-week-old rats, with diameters comparable to that of the sciatic nerve of a 3-week-old rat, have EBFs similar to that of the sciatic nerve of a 12-week-old rat. 4. There was no compelling evidence of autoregulation of EBF in 3-week-old rats over a MAP range from -40 to +30 mmHg of the normal value. 5. The increase of nerve vascular resistance with maturation is probably due to a decrease in capillary density and, to a lesser extent, to an increase in plasma viscosity and haematocrit. 6. The higher EBF in immature rats is likely to be a developmentally adaptive mechanism which permits greater blood-nerve exchange of material to accommodate the greater metabolic needs of rapidly elongating and myelinating axons and proliferating Schwann cells.

Aging↗

Developmental changes in blood-nerve transfer of albumin and endoneurial albumin content in rat sciatic nerve.

The rate of entry of albumin into the endoneurial space and its content within that compartment during development were investigated by measuring the permeability coefficient-surface area product to 125I-albumin (PSA) of the blood-nerve interface (BNI), endoneurial residual plasma volume (Vp), blood-nerve interface index to albumin, and endoneurial water content in sciatic nerves of rats ranging in age from 1 to 24 weeks. There was a 30-fold reduction in PSA and a 4-fold decrease in Vp from 2 to 24 weeks, indicating that the endoneurial capillaries and perineurium become less permeable during development. On the other hand, the Alb-BNI index was relatively small at 1 week, increased to a peak value around 6-8 weeks, and then decreased to adult values by 13 weeks. The smaller Alb-BNI index in the neonatal period is consistent with endoneurial albumin being cleared across a permeable perineurium by epineurial lymphatics. Subsequently, as the perineurium becomes less permeable, endoneurial albumin content increases. It then decreases as the endoneurial capillary permeability also decreases. Additionally, metabolic clearance of albumin, especially during the first 2-3 weeks, by axons and glia to meet the nutritive requirements of rapid axonal growth and myelination could be partly responsible for a lower Alb-BNI index. It is suggested that in the developing nerve, the combination of epineurial lymphatics and a relatively permeable perineurium, together with axonal and glial uptake and protein catabolism aid in the clearance of plasma-derived osmolytes from the endoneurial space, and thus prevent the elevation of endoneurial hydrostatic pressure and onset of oedema that would have been seen in an adult nerve with a comparably permeable BNI.

Aging↗

Physiological changes in the sciatic nerve endoneurium of lead-intoxicated rats: a model of endoneurial homeostasis.

The effects of inorganic lead (Pb) on peripheral nerves were studied by measuring the permeability coefficient-surface area product to albumin (PSA) of the blood-nerve interface (BNI), water and Pb content of endoneurium, and residual endoneurial plasma volume (Vp) of sciatic nerves of adult rats maintained on a 4% Pb diet for 2-12 weeks. Additionally, body weight, haematocrit, and blood Pb levels were also monitored. Within 1 week, both blood and endoneurial Pb levels had increased significantly above background levels and continued to increase up to the 6th week. Thereafter, over the next 6 weeks, the blood Pb levels were relatively stable, while the endoneurial Pb levels decreased sharply to a quarter of their peak values. The wet/dry weight ratio of the endoneurium, an indicator of nerve oedema, increased by about 30% from the 4th to 12th week, reaching a water content of 75% corresponding to a 24% increase of the total fascicular area. PSA increased only by the 8th week, without an accompanying increase in Vp. This suggests that the increase in PSA reflects an increase in the permeability of the BNI. Furthermore, the moderate 3-fold increase in PSA is more consistent with an adaptive response of the BNI to changes in the endoneurial microenvironment rather than a massive breakdown or disruption of the BNI. This is supported by the inconsistent or mild leakage of horseradish peroxidase from endoneurial capillaries observed in Pb-intoxicated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

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Patterns of change in endoneurial capillary permeability and vascular space during nerve regeneration.

In frog sciatic nerve crushed and allowed to regenerate, an in situ perfusion technique was used to measure the permeability coefficient-surface area product (PS) of endoneurial capillaries to [14C]sucrose and endoneurial vascular space (V) at intervals of 3 days to 12 weeks post-crush. Additionally, the amplitude and latency of the compound action potential (CAP) of the regenerating nerve were also monitored. There was a delayed increase of both PS and V which peaked at 2-3 weeks after the crush and then declined. This is strikingly similar to the pattern seen in transected nerves. Whereas both PS and V reached near normal levels 6 weeks after transection, in regenerating nerves V continued toward normal levels but PS increased again to peak around 9 weeks post-crush. This second peak of PS coincided with a rapid increase of the CAP amplitude and a sharp decline of its latency. As is the case for transected nerves, the initial increase of PS is probably induced by breakdown products of axons or chemical signals from attendant Schwann cells and related to the clearance of debris from the endoneurium. The later increase of PS may be an endoneurial homeostatic mechanism to increase blood-nerve exchange during rapid axonal growth and remyelination.

Action Potentials↗

Responses of medullary neurons to moving visual stimuli in the common toad. I. Characterization of medial reticular neurons by extracellular recording.

The concept of coded 'command releasing systems' proposes that visually specialized descending tectal (and pretectal) neurons converge on motor pattern generating medullary circuits and release--in goal-specific combination--specific action patterns. Extracellular recordings from medullary neurons of the medial reticular formation of the awake immobilized toad in response to moving visual stimuli revealed the following main results. (i) Properties of medullary neurons were distinguished by location, shape, and size of visual receptive fields (ranging from relatively small to wide), by trigger features of various moving configural stimulus objects (including prey- and predator-selective properties), by tactile sensitivity, and by firing pattern characteristics (sluggish, tonic, warming-up, and cyclic). (ii) Visual receptive fields of medullary neurons and their responses to moving configural objects suggest converging inputs of tectal (and pretectal) descending neurons. (iii) In contrast to tectal monocular 'small-field' neurons, the excitatory visual receptive fields of comparable medullary neurons were larger, ellipsoidally shaped, mostly oriented horizontally, and not topographically mapped in an obvious fashion. Furthermore, configural feature discrimination was sharper. (iv) The observation of multiple properties in most medullary neurons (partly showing combined visual and cutaneous sensitivities) suggests integration of various inputs by these cells, and this is in principle consistent with the concept of command releasing systems. (v) There is evidence for reciprocal tectal/medullary excitatory pathways suitable for premotor warming-up. (vi) Cyclic bursting of many neurons, spontaneously or as a post-stimulus sustaining event, points to a medullary premotor/motor property.

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Blood-nerve transfer of albumin and its implications for the endoneurial microenvironment.

Blood-nerve transfer of plasma albumin was studied by measuring the permeability coefficient-surface area (PS) product of the blood-nerve barrier (BNB) to 125I-albumin in rat sciatic nerve using the i.v. bolus injection method. The calculated PS was 6.3 +/- 0.5 (S.E.M.) x 10(-7) ml.g-1.s-1. This value is smaller by more than an order of magnitude of that measured for sucrose and confirms the relative impermeance of the BNB to blood-borne solutes. From a review of the available evidence, it is concluded that normal blood-nerve exchange occurs predominantly across the endoneurial microvasculature, and the PS of the BNB reflects the permeability of capillaries to a greater extent than that of the perineurium. The only capillaries found to be less permeable than these are the cerebral capillaries. Proximo-distal differences (sciatic vs tibial) of the PS could not be detected. Blood-nerve albumin transfer was calculated at 1.2 mg.g-1.day-1, and the daily turnover of endoneurial albumin to be about 30%. It is postulated that small increases in PS of BNB to albumin lead to an elevation of endoneurial albumin concentration and, through the operation of Starling forces, subsequently produce endoneurial oedema. A major question posed by the results of this study is the identity of pathways for clearance of albumin and other macromolecules from the endoneurium.

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Patterns of change in endoneurial capillary permeability and vascular space during Wallerian degeneration.

In degenerating frog sciatic nerves an in situ perfusion technique was used to measure the permeability coefficient-surface area product (PA) of endoneurial capillaries to [14C]sucrose, and the endoneurial vascular space (V). Both PA and V started to increase after the 3rd day of degeneration. The increase in PA peaked around the 14th day of degeneration and then declined to reach near normal levels at 6 weeks post-transection. V increased until about the end of the 3rd week of degeneration and then declined to near normal levels at 6 weeks after transection. The delayed increase in capillary permeability may reflect an adaptive reorganization of endoneurial capillary structure and function in response to altered conditions of the endoneurial microenvironment, and it is suggested that this permeability increase is induced by breakdown products of axons or chemical signals from Schwann cells enveloping transected axons. Fluid extravasation from these leaking capillaries is probably responsible for the endoneurial oedema observed in Wallerian degeneration. The recovery of endoneurial capillary tone to near-normal levels at 6 weeks after transection leads to the intriguing conclusion that healthy nerve fibers are not essential for the maintenance of normal endoneurial capillary permeability.

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Permeability of endoneurial capillaries to K, Na and Cl and its relation to peripheral nerve excitability.

The permeability coefficient-surface area products (PA) of frog sciatic nerve endoneurial capillaries to K, Na and Cl were measured with an in situ perfusion technique and found to be 40.3, 24.6 and 32.8 X 10(-5) ml . g-1 . s-1, respectively. PAs to [14C]sucrose and 42K, when measured simultaneously, and their ratio were independent of perfusate K concentration (0.1-10.0 mM). Simultaneous measurements with 36Cl and 42K indicated that the Cl/K permeability ratio was significantly smaller than the mobility ratio of these two ions in free solution. On the other hand, comparable experiments with 22Na and 42K revealed that the K/Na permeability ratio was not significantly different from its respective mobility ratio. Thus, these results provide no evidence of facilitated transport of K by endoneurial capillaries, and suggest that K, Na and Cl traverse the endoneurial capillary wall by a paracellular route which is weakly selective for cations. The minimum extracellular K concentration (Ke) capable of producing a depolarization conduction block in frog sciatic nerve was between 12.5 and 15.0 mM. When the vasculature of this nerve was perfused with a hyperkalaemic (20.0 mM) Ringer solution, a conduction block developed in 7.9 min. Comparison of this time with the theoretically predicted rate of change of endoneurial Ke (induced by a comparable change of intravascular K concentration) indicated that an increase of endoneurial Ke is transmitted directly to the paranodal spaces of nerve fibres so as to immediately influence axonal excitability.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

Endoneurial capillary permeability to [14C]sucrose in frog sciatic nerve.

Using an in situ perfusion technique, we measured the [14C]sucrose permeability-surface area product (PA) in endoneurial capillaries of 48 frog sciatic nerves, as 6.6 +/- 0.6 (S.E.M.) X 10(-5) s-1, and the vascular space as 1.31 +/- 0.10%. Assuming A = 30 cm2/g, P = 2.2 X 10(-6) cm/s. P for sucrose was greater than P in some barrier tissues with tight junctions, but was less than P in all capillaries examined so far except rat cerebral capillaries. These observations demonstrate that endoneurial capillaries are an effective part of the blood-nerve barrier to water-soluble non-electrolytes. The findings are consistent with capillary impermeability to microperoxidase and with capillary ultrastructure.

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AC impedance of the perineurium of the frog sciatic nerve.

The AC impedance of the isolated perineurium of the frog sciatic nerve was examined at frequencies from 2 Hz to 100 kHz. A Nyquist plot of the imaginary and real components of the impedance demonstrated more than 1 capacitative element, and a DC resistance of 478 +/- 34 (SEM, n = 27) omega cm2. Transperineurial potential in the absence of externally applied current was 0.0 +/- 0.5 mV. The impedance data were fitted by nonlinear least squares to an equation representing the generalized impedance of four equivalent circuits each with two resistive and two capacitative elements. Only two of these circuits were consistent with perineurial morphology, however. In both, the perineurial cells were represented by a resistive and capacitative element in parallel, where capacitance was less than 0.1 microF/cm2. The extracellular matrix and intercellular junctions of the perineurium were represented as single resistive and capacitative elements in parallel or in series, where capacitance exceeded 2 microF/cm2. Immersion of the perineurium in low conductance Ringer's solution increased DC resistive elements as compared with their values in isotonic Ringer's solution, whereas treatment for 10 min with a hypertonic Ringer's solution (containing an additional 1.0 or 2.0 mol NaCl/liter of solution) reduced DC resistive elements, consistent with changes in perineurial permeability. The results indicate that (a) perineurial impedance contains two time constants and can be analyzed in terms of contributions from cellular and extracellular elements, and (b) transperineurial DC resistance, which is intermediate between DC resistance for leaky and nonleaky epithelia, represents intercellular resistance and can be experimentally modified by hypertonicity.

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Ionic permeabilities of the frog perineurium.

Ionic permeation was investigated across the perineurium of the frog sciatic nerve, under normal conditions and following treatment by hypertonic Ringer, ouabain or amiloride. A cylindrical segment of perineurium removed from the nerve and mounted in vitro on two cannulae was continuously perfused. Permeation rates of 22Na and 42K across the perineurium were the same in either direction and were unaffected by the drugs. The mean 22Na permeability coefficient at the perineurium equaled 1.68 +/- 0.08 (S.E.M.) X 10(-6) cm/sec. Simultaneous measurement of transperineurial fluxes of 22Na, 42K and 36Cl indicated that the K/Na permeability ratio exceeded the ratio of limiting conductances of these ions in free solution, but that the Cl/K permeability ratio did not differ from the respective limiting conductance ratio. Immersion of the perineurial cylinder in Ringer, made hypertonic by addition of NaCl, increased the absolute permeability coefficients of the three ionic tracers but did not affect their permeability ratios. The flux ratio of 22Na/[14C]sucrose, however, was decreased by hypertonic treatment. It is concluded that there is no evidence of active Na or K transport across the perineurium and that the paracellular path in the perineurium exhibits size-dependent permselectivity properties. In addition, the low rates of transperineurial permeation of ions and water-soluble non-electrolytes (e.g. sucrose) are comparable to those in epithelia with tight junctions. These permeability coefficients provide quantitative estimates of the diffusion barrier properties of the perineurium.

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Interaction between primary afferent nerves in the elicitation of reflex swallowing.

In adult cats anesthetized with urethan, a number of observations were made that support the concept that some control over the rate of reflexly induced swallowing occurs in the intermediate network at the level of the nucleus of the solitary tract. It was shown that different nerves, e.g., the two superior laryngeal and glossopharyngeal nerves, when activated in sequence interact in such a manner as to facilitate reflex swallowing. It was also shown that the decrement in the reflex response observed to continuous stimulation of a primary afferent nerve, e.g., one superior laryngeal, can be reversed by switching the stimulation to another nerve either on the same or contralateral side. And finally, following discrete medullary lesions, it was observed that that portion of the nucleus of the solitary tract located 2 mm or more rostral to the rostralmost point of the dorsal medial sulcus appears to contain an integral component of the intermediate network that governs reflexly induced swallowing, whereas lesions restricted to the ventrolateral portion of the nucleus of the solitary tract have no effect on the reflex response.

Action Potentials↗

Basal forebrain facilitation of reflex swallowing in the cat.

In adult cats anaesthetized with urethane, electrical and chemical stimulation of the basal forebrain facilitated reflex swallowing elicited by electrical stimulation of the superior laryngeal nerve. A systematic stereotaxic mapping study using electrical stimulation revealed that the facilitatory sites were distributed along the course of the ansa peduncularis, specifically its rostral forebrain and hypothalamic components associated with the anterior amygdalar area, substantia innominata, lateral preoptic area, anterior hypothalamus and nucleus accumbens. By means of acute discrete radiofrequency lesions, the descending pathways mediating facilitatory influences from the nucleus accumbens and the amygdala to the brain stem were found to traverse the lateral hypothalamus. Ventral tegmental facilitatory sites in the midbrain are likely to be associated with these descending pathways; however, there is evidence for independent participation of this region of the brain in the control of swallowing. Chemical stimulation by means of microinjections of dopamine and apomorphine into the amygdala and nucleus accumbens also enhanced reflex swallowing. It is concluded that the results of this investigation implicate the basal forebrain as a site of integration of viscero-olfacto-gustatory information needed for the enactment of ingestive behaviour.

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Modification of permeability of frog perineurium to [14C]-sucrose by stretch and hypertonicity.

An in vitro method has been developed to determine quantitatively the permeability of the perineurium to radiotracers at room temperature. The permeability to [14C]sucrose of the isolated perineurium of the sciatic nerve of the frog, Rana pipiens, was measured at rest length, when the perineurium was stretched and after the perineurium had been subjected to hypertonic treatment. Mean permeability at rest length was calculated to be 5.6 +/- 0.27 (S.E.M., n = 45) X 10(-7) cm/sec, and both stretch and hypertonic treatment increased the permeability. A 10% stretch increased permeability reversibly, whereas a 20% stretch or immersion of the perineurium in a hypertonic bath increased permeability irreversibly. Altered permeability under these conditions might be related to changes in the ultrastruct of tight junctions in the perineurium.

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