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Biomedical subjects

M C Brown

Publications and source records attributed to M C Brown.

At least 163 records · Page 9Linked to original sources

Absence of postnatal death among motoneurones supplying the inferior gluteal nerve of the rat.

Motoneurones innervating the caudal part of the gluteus maximus muscle of 0-2 day, 10-12 day and 2-3-month-old rats were labelled by a half-hour application of a solution of 30% horseradish peroxidase (HRP) and 2% lysophatidylcholine delivered by suction electrode to the cut inferior gluteal nerves. The numbers of motoneurones labelled 24-48 h later were not significantly different in the 3 age groups (mean = 58.75, 54.0, 57.5, respectively). When a simple 30% HRP solution was used in adult rats, the number of motoneurones labelled was significantly less (mean = 48.75). In contrast, application of 0.5 microliter of HRP in a pledget of gelfoam to either the cut or uncut inferior gluteal nerve of neonates labelled large numbers of motoneurones, presumably by diffusion into nearby muscles. It is concluded that no death of motoneurones innervating the gluteus maximus muscle occurs postnatally, and that spread of HRP to neighbouring muscles can give rise to spuriously high motoneurone counts in neonates, and that incomplete uptake or transport of HRP in adults can lead to incorrectly low counts.

Age Factors↗

Potential use of ultrasound in place of X-ray fluoroscopy in urodynamics.

A moving picture can be obtained using an ultrasonic scanning probe in the rectum to provide information about the bladder and urethra in the same projection as for lateral cystography. The method has potential as a substitute for cinecystography but there are a number of problems still to be overcome.

Cough↗

Muscles of adult rats and mice express the Thy-1 glycoprotein on denervation.

Adult-skeletal muscles when denervated undergo extensive changes in biochemical and physiological properties. Many of these changes, for example the appearance of acetylcholine receptors along the length of the fibres, are characterized by a reacquisition of features normally found in developing muscles. This generalization can now be extended to the surface glycoprotein, Thy-1, which is expressed in myoblasts and transiently in newly fused myotubes in culture, for we have found that denervation leads to extensive production of Thy-1 in hindlimb muscles of adult rats and mice where its expression is normally very low. In addition, there is a slight transient rise in Thy-1 in muscles contralateral to the denervation.

Animals↗

Comparison of single and multichannel cystometry in diagnosing bladder instability.

The abilities of single channel cystometry and standard multichannel cystometry to diagnose bladder instability were compared in 100 women taking part in a single blind crossover trial. In 93 of the women both tests yielded the same result. The single channel system detected every case of detrusor instability but in seven women suggested detrusor contractions that were not evident on multichannel cystometry. These were probably due to changes in abdominal pressure. It is concluded that single channel cystometry when used in conjunction with simple urethral tests can provide most of the information that is obtained in specialist centres investigating bladder function.

Abdomen↗

Efferent control of cochlear inner hair cell responses in the guinea-pig.

The efferent crossed olivocochlear bundle (c.o.c.b.) was electrically stimulated during intracellular recordings from cochlear inner hair cells in anaesthetized guinea-pigs. The effect of c.o.c.b. stimulation was to decrease the magnitude of the inner hair cell depolarizing component (d.c.) and alternating component (a.c.) receptor potentials evoked by tone bursts at the characteristic frequency. At low sound pressure levels, the decrease in receptor potentials caused by c.o.c.b. stimulation was equivalent to decreasing the sound intensity by 9-24 dB. C.o.c.b. stimulation usually had a similar effect on the compound action potential of the auditory nerve. The change in inner hair cell membrane resistance during moderate-level sound was measured for sound alone and when sound was accompanied by c.o.c.b. stimulation. Sound alone produced a greater membrane resistance change than sound with c.o.c.b. stimulation, in proportion to the d.c. receptor potential during the same conditions. The time course of the c.o.c.b. effect was slow, with 50-250 ms required for a full effect and for recovery. The effects of varying the frequency and voltage of electrical stimulation were similar for the d.c. receptor potential and for the compound action potential. For sounds of high level and for frequencies well below the characteristic frequency, c.o.c.b. stimulation was less effective in reducing receptor potentials. Frequency tuning curves for the d.c. receptor potential taken during intervals of continuous c.o.c.b. stimulation showed decreases in sensitivity primarily in the tip segment of the tuning curve. When no sound stimulus was present, the resting membrane potential was relatively unaltered during c.o.c.b. stimulation. The resting membrane resistance did not change during c.o.c.b. stimulation. Since the c.o.c.b. innervates mainly the outer hair cells, these results strongly suggest that changes in outer hair cell activity can influence the receptor potentials of inner hair cells and thus alter the transmission of acoustic responses to the central nervous system.

Animals↗

Intracellular recordings from cochlear inner hair cells: effects of stimulation of the crossed olivocochlear efferents.

Intracellular recordings were obtained from inner hair cells located in the lower basal turn of the guinea pig cochlea. At low sound pressure levels the inner hair cells were highly frequency selective, producing receptor potentials only in response to sound frequencies between about 16 and 24 kilohertz. Electrical stimulation of efferent nerves in the crossed olivocochlear bundle markedly reduced these receptor potentials while causing little change in the resting membrane potential. At high sound levels, where cells responded to an increasingly wider range of sound frequencies, stimulation was less effective in reducing receptor potentials. Since the crossed olivocochlear bundle primarily innervates outer hair cells, these results support an outer hair cell contribution to the most sensitive response region of inner hair cells.

Afferent Pathways↗

Segregation of motor nerves on a segmental basis during synapse elimination in neonatal muscles.

The distribution of motor axons from segmental roots L4 and L5 entering the gluteus muscle of neonatal rats via the inferior gluteal nerve was determined by visual inspection of contractions when the muscle was pinned out in vitro. In both 0-2-day-old rats and in rats older than 11 days, there was overlap in the distribution. But in rats older than 11 days there was a clear tendency for the L4 root to avoid the muscle's posterior margin and for the L5 to avoid the anterior portion of the muscle innervated by the inferior gluteal nerve. This segregation was less sharp in 0-2-day-old rats. Hence synapse elimination does not occur randomly, but by a process which favours particular root distributions.

Animals↗

Sprouting of mammalian motor neurones at nodes of Ranvier: the role of the denervated motor endplate.

Treatment of the mouse gluteus maximus with the organophosphorus anticholinesterase ecothiopate, 4-aminopyridine and caffeine caused necrosis of the endplate region of the muscle fibres. When these drugs were given 12 h prior to partial denervation of the muscle there was a significant reduction in the amount of nodal sprouting seen 48 h after nerve section. No such reduction was seen if the drugs were given immediately after nerve section. In the former case both innervated and denervated fibres are necrotic; in the latter, only innervated fibres are necrotic. The amount of terminal sprouting was significantly increased in the former group, showing that the drug treatment and necrosis were not directly inhibitory to nerve growth. The reduction of nodal sprouting is therefore likely to be due to necrosis of denervated fibres; this supports the hypothesis that the denervated endplate is the source of a stimulus to nodal sprouting of motoneurones.

Animals↗

Cochlear inner hair cells: effects of transient asphyxia on intracellular potentials.

Intracellular potentials were recorded from inner hair cells in the guinea pig cochlea. Transient asphyxia was induced by interrupting respiration for brief periods. Asphyxia caused a hyperpolarization of the resting membrane potential (resting Em). The hyperpolarization averaged 2.9 mV for 30 s asphyxias and 5.7 mV for 45 s asphyxias. The membrane potential recovered quickly after normal ventilation was resumed. Asphyxia also induced a rapid and profound decrease of the d.c. receptor potential in response to moderate intensity tone bursts at the characteristic frequency of the inner hair cell. At maximal depression, the receptor potential was reduced about 60% for a 30 s asphyxia and 100% for a 45 s asphyxia. The receptor potential recovered slowly after normal ventilation was resumed. A similar percent reduction and time course of recovery were observed for the a.c. receptor potential. In recordings from the same animals, the round window compound action potential (CAP) was as severely depressed by asphyxia as the hair cell receptor potentials. The time course of recovery for the CAP was similar to the slow recovery of the d.c. receptor potential. In contrast, the round window cochlear microphonics (CM) and the endolymphatic potential (EP) were affected less by asphyxia and recovered quickly after ventilation was resumed. Frequency tuning curves (FTCs) for the d.c. receptor potential were measured during the period of maximal receptor potential depression. These FTCs showed decreased tip sensitivity and a decrease in sharpness of tuning, as measured by the Q10. These changes were fully reversible. Low frequency (tail) segments of the FTCs were much less affected by asphyxia. The inner hair cell FTC changes during asphyxia were compared with neural FTC changes reported by other investigators. The similarities lead us to the conclusion that the inner hair cell and the auditory neural response to sound are equally sensitive to asphyxia.

Animals↗

Anesthesia and surgical trauma: their influence on the guinea pig compound action potential.

A chronic implant consisting of a fine thermocouple placed on the round window permitted measurement of temperature and of the compound action potential (CAP) of the cochlear nerve in guinea pigs. Thresholds and latencies of the CAP, in response to tone bursts (2-40 kHz), were measured when the animal was awake and unrestrained, and again after several hours of anesthesia. The CAP remained unchanged with a variety of common anesthetics when precise control of round window temperature was maintained. However, when anesthesia was accompanied by several hours of slight cochlear cooling, thresholds were elevated for CAPs evoked by frequencies above 24 kHz and latencies were increased for CAPs evoked by all frequencies tested. The effects of surgery on CAP threshold and latency were also examined. Guinea pigs were tested while still anesthetized at the conclusion of the implantation procedure, and then again several days later while awake. Thresholds and latencies were unchanged. In two anesthetized guinea pigs already implanted with thermocouples, ventral and post-auricular surgery to expose the middle ear had no effect on the CAP, when low-speed drilling was used to open the auditory bulla. However, when small portions of the bulla were broken away with forceps, the CAP in response to high-frequency tone bursts immediately showed elevated thresholds. This alteration of the CAP was clearly different from that produced by lowered temperature, since the latencies at threshold were significantly decreased.

Action Potentials↗

The temperature dependency of neural and hair cell responses evoked by high frequencies.

A fine thermocouple, placed on the round window of the guinea pig cochlea, was used to measure temperature and electrical potentials. In acute experiments, rectal temperature was held constant at 38 degrees C while cochlear temperature was varied between 38 degrees C and 31.5 degrees C. Cochlear cooling to 36 degrees C caused elevated thresholds for the compound action potential (CAP) in response to tone bursts with frequencies above 24 kHz. CAP latencies increased for all frequencies tested (2 to 40 kHz). Cooling to lower temperatures produced larger latency increases and greater threshold shifts which extended to CAPs evoked by frequencies as low as 16 kHz. These CAP changes were fully reversible after a cochlear temperature of 38 degrees C was restored. In an attempt to create more uniform cooling of the cochlea, experiments were also conducted with round window thermo-couples chronically implanted in guinea pigs. After cooling the entire anesthetized animal to 36 degrees C, CAP thresholds were again elevated only for frequencies above 24 kHz. In other acute experiments, extracellular dc receptor potentials were recorded from the organ of Corti with micropipettes. Cooling caused a decreased sensitivity to tones at the characteristic frequency of the recording location (20 kHz) and had less effect on responses to lower frequencies. The receptor potential usually recovered after rewarming the cochlea. These data emphasize that temperature is an important parameter when electrophysiological measurements are being made. They also suggest an explanation for the reported discrepancy between behavioral and electrophysiological thresholds at high frequencies.

Action Potentials↗

Importance of pathway formation for nodal sprout production in partly denervated muscles.

Experiments were carried out to investigate possible factors controlling nodal sprout growth in partly denervated mouse gluteal muscles. Pretreatment of the muscle with botulinum toxin for up to 20 days, which produces denervation-like change and elicits terminal and nodal sprouting, increased reinnervation by terminal sprouting after partial denervation but did not alter the rate of reinnervation by nodal sprouts. This implies that nodal sprout growth is not limited by the development of an adequate growth stimulus from denervated muscle. A disto-proximal gradient of degeneration was observed in denervated intramuscular nerves in the electron microscope, suggesting that nodal sprout growth may be modulated by the availability of endoneurial pathways sufficiently degenerated to permit reinnervation by nodal sprouts, although the initial outgrowths from nodes of Ranvier may appear in response to a growth stimulus from denervated muscle.

Animals↗

The distribution of nodal sprouts in a paralysed or partly denervated mouse muscle.

The right gluteus maximus muscles of young adult mice were paralysed with botulinum toxin for up to 21 days or partly denervated by spinal root section for up to 63 days; the intramuscular and extramuscular nerves were then examined in the electron microscope in thin sections of tissue fixed conventionally or stained with zinc iodide-osmium tetroxide. Contralateral muscles were also examined as controls. The distribution of nodal sprouts in the nerves of the paralysed or partly denervated muscles was determined by calculating the mean ratios of unmyelinated to myelinated axons in nerve profiles containing different numbers of myelinated axons (intact or degenerating) and comparing these with control ratios. In paralysed muscles there was a significantly higher proportion of nerve profiles containing one or two unmyelinated axons alongside a single myelinated axon. Nerve profiles containing two or more myelinated axons did not show any increase in the proportion of unmyelinated axons. Thus, there is probably nodal sprouting in paralysed muscles which is restricted to the most distal nodes of the intramuscular nerves. In muscles partly denervated for 8 days there were significant increases in the proportion of unmyelinated axons in nerve profiles which had contained up to 5-10 myelinated axons. After 21 days of partial denervation, similar increases may have occurred in the larger intramuscular nerve profiles and after 63 days there were large increases in the proportion of unmyelinated axons in the main intramuscular nerve branches and in the extramuscular nerve. Nodal sprouting in response to partial denervation is therefore localised initially to the smaller, more distal nerve branches; at later times, some sprouts probably grow slowly in a disto-proximal direction along denervated Schwann cell pathways. The existence of nodal sprouts in paralysed muscles and their restricted distribution in paralysed and partly denervated muscles suggest that the nodal sprouting stimulus is produced by the muscle and acts only at distal nodes.

Animals↗

Comparison of effects of denervation and botulinum toxin paralysis on muscle properties in mice.

1. The properties of denervated and fully innervated but paralysed soleus and extensor digitorum longus (e.d.l.) muscles were compared in mice.2. Muscles were paralysed by single or repeated injections of botulinum toxin into the right lower leg. Contralateral muscles were denervated at the same time by sciatic nerve section. Muscles were excised 3-20 days later and direct and indirect isometric twitch and tetanic tensions measured in vitro. ACh sensitivity was assessed from isometric contractions to various concentrations of bath-applied ACh perchlorate.3. Denervated muscles as expected from the work of others developed sensitivity to ACh earlier and more rapidly than paralysed muscles. A transient peak of sensitivity was reached after 7 days of denervation in soleus and after 8 days in e.d.l. However 2 days later the sensitivity of muscles fully paralysed to nerve twitch and tetanic stimuli was not significantly different from that of denervated muscles.4. In both e.d.l. and soleus the direct tetanus/twitch ratios declined in paralysed and denervated muscles. The decline was initially more rapid in denervated than paralysed soleus, but the ratios for paralysed and denervated muscles were not significantly different after 10 days in either muscle. By this time there were no differences in the absolute strengths of the paralysed and denervated muscles.5. It is concluded that the ACh sensitivity and dynamic properties of fully paralysed mouse muscles become equal to those of denervated muscles once the acute effects associated with nerve degeneration are past. This result is consistent with the idea that normal neuronal control of extrajunctional mammalian skeletal muscle properties is mediated solely by means of activity.

Acetylcholine↗