Effects of feeding conditions on sensitivity to tubocurarine of nerve-muscle preparations from the mouse

1. The effects of feeding conditions on the sensitivity to the effect of tubocurarine (dTc) in vitro were compared among various nerve-muscle preparations from mice. The mice were fed under conditions that restricted or compelled their movement for 64 days and controls were fed conventionally. 2. The sensitivity to the effect of dTc differed considerably among preparations. It was much higher in the sciatic nerve-extensor digitorum longus muscle (EDL), moderately higher in the sciatic nerve-soleus muscle (SOL) and lower in the phrenic nerve-diaphragm (DPH) in control mice. 3. The order of the sensitivity was not altered by either type of conditioning. Constant restriction of movement or compelled movement did not modify the sensitivity of DPH to the effect of dTc in vitro. 4. Compulsion facilitated the sensitivity in both SOL and EDL. Restriction selectively increased the sensitivity of EDL. Both types of conditioning selectively and significantly reduced twitch development in EDL. 5. These results indicate that the sensitivity to dTc of neuromuscular transmission reflects constant states of motor activity.     

Effect of immobilization on skeletal muscle nicotinic cholinergic receptors in the rat

The effect of 4 weeks of hind limb immobilization on nicotinic acetylcholinergic receptors (nAChRs) in the neuromuscular junction of the soleus (SOL) and tibialis anterior (TIB) muscles was studied in rats. Quantitative measurements of the receptors was performed using [3H]alpha-bungarotoxin ([3H]alpha-BTx) receptor autoradiography. Junctional and extrajunctional nAChRs were significantly increased in the SOL and TIB after 4 weeks immobilization. However, a significant decrease in fiber cross-sectional area was observed only in the SOL muscle. Remobilization for 4 weeks reversed the changes in cholinergic receptors and muscle fibers but not in bone. Our findings suggested that lack of nerve impulses are of importance for the events that take place after immobilization leading to muscle atrophy and osteoporosis.     

Motoneuronal death without expression of NADPH-diaphorase activity after sciatic nerve cut in 5-day-old mice

In BALB/c mice, the number of sciatic motoneurons lost was statistically insignificant whether the nerve was cut at one (P1) or five days (P5) of age. Although the motoneurons showed intense NADPH-d staining after sciatic nerve cut at P1, they were NADPH-d negative when the nerve was cut at P5. The present study casts doubt on a neurodestructive role of NO in the sciatic motoneurons after axotomy at P1.     

Na(+)-K+ ATPase concentration in different adult rat skeletal muscles is related to oxidative potential

To investigate the relationship among fibre type, oxidative potential, and Na(+)-K+ ATPase concentration in skeletal muscle, adult male Wistar rats weighing 259 +/- 8 g (mean +/- SE) were sacrificed and the soleus (SOL), extensor digitorum longus (EDL), red vastus lateralis (RV), and white vastus lateralis (WV) removed. These muscles were chosen as being representative of the two major fibre type populations: slow twitch (SOL) and fast twitch (EDL, RV, WV) and exhibiting either a high (SOL, EDL, RV) or low (WV) oxidative potential. Na(+)-K+ ATPase concentration (pmol.g-1 wet weight), measured by the [3H]ouabain binding technique, differed (p < 0.01) only between the WV (238 +/- 7.9) and the SOL (359 +/- 9.6), EDL (365 +/- 10), and RV (403 +/- 12). Similarly, muscle oxidative potential as measured by the maximal activity of citrate synthase was different (p < 0.01) only between the WV and the other three muscles. Citrate synthase activity (mumol.min-1.g-1 wet weight) was 4.0 +/- 0.7, 12.3 +/- 0.9, 9.1 +/- 0.7, and 11.3 +/- 1.0 in the WV, SOL, EDL, and RV, respectively. These results indicate that Na(+)-K+ ATPase concentration is not related to the speed of contraction but to the oxidative potential of the muscle. Since chronic activity is a primary determinant of oxidative potential, it would be expected that increases in Na(+)-K+ ATPase would accompany increases in muscle utilization.     

Sodium withdrawal contractures in developing and regenerating rat extensor digitorum longus muscles

During postnatal development of extensor digitorum longus (EDL) muscle, sodium withdrawal contractures were observed during the first 6 days after birth, and not after this time. In regenerating EDL muscles, zero-Na contractures were demonstrated: (1) 7 days after bupivacaine injection, but not 14 or 90 days after this injection; (2) 7, 14, and 90 days after autotransplantation; and (3) 7, 14, and 90 days after the intervention in sliced muscles. The present findings emphasize the role of the denervation in the development of zero-Na contractures in the regenerating muscles and suggest that a calcium-sodium exchange across the sarcolemma may appear in these muscles.     

Growth and development of the kidneys, heart and liver in S 5B/P1 and Osborne-Mendel rats fed high or low-fat diets

Male Osborne-Mendel (OM) and S 5B/P1 rats were overfed from birth to 24 or 105 days. The effects of feeding a diet with 44 per cent or 3 per cent (w/w) fat, supplementary feeding during the suckling period, and reduced litter size, on body weight and on the weight and cellularity of the heart, liver and kidneys were evaluated. Three overfeeding techniques were used: (1) feeding a high fat diet, (2) reducing litter size, (3) force-feeding from 1-24 days. The overfeeding technique which exerted the greatest effect on growth was feeding a high-fat diet. In comparison to OM rats that suckled dams fed the low-fat diet, body weight as well as organ weight, DNA, protein and lipid were significantly elevated in 24-day-old OM rats that suckled dams fed the high-fat diet. In comparison to OM rats not overfed, the organs of the rats fed the high-fat diet contained significantly more cells at both 24 and 105 days, except for the heart which by 105 days contained more protein, but not DNA. Liver weight and growth in S 5B/P1 rats was similar, regardless of dietary manipulation. Compared to S 5B/P1 rats that suckled dams fed the low-fat-diet, kidneys were 12 per cent larger at 24 days and 19 per cent larger at 105 days in rats that suckled dams fed the high-fat diet and were thereafter fed a high-fat diet. Hearts of the latter rats were larger than the former rats at 24 days, but not at 105 days.     

Evidence for age-dependent changes in motoneuron dendritic morphology following neonatal nerve-crush in the rat

Motoneurons supplying the extensor hallucis longus muscle of the rat were temporarily separated from the muscle by sciatic nerve-crush at five days postnatally. Such treatment permanently alters the reflex response of the affected motoneurons without the large-scale cell death associated with nerve-crush at birth. After reinnervation, the motoneurons were retrogradely labelled with cholera toxin subunit-B conjugated to horseradish peroxidase and the dendritic tree of each labelled cell was analysed. When compared to normal data, significantly higher levels of dendritic density were observed in the rostrodorsally orientated parts of the dendritic field. This was similar to that found previously for the same motor pool after nerve-crush at birth. However, in other parts of the field where a lower dendritic density was found after nerve-crush at birth, no change was seen after nerve-crush at five days. These data present evidence for the influence of sensory afferents on the development of motoneuron dendrites. Taken together with the previous findings after nerve-crush at birth, we suggest that the differential dendritic changes caused by neonatal nerve lesion contribute to an imbalance in the pattern of excitatory and inhibitory inputs to the motoneuron, which results either in cell death, or the abnormal activity seen in those motoneurons which survive.     

Fluorometric studies of recovery metabolism of rat fast- and slow-twitch muscles

Recovery metabolism of fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus (SOL) muscles of the rat has been investigated using fluorometric monitoring of reduction of nicotinamide adenine dinucleotide (NAD). In both EDL and SOL, groups of twitch contractions produced a decrease in fluorescence (oxidation of NADH) which returned to the resting base line after contraction ceased. These responses proceeded more quickly in EDL than SOL and were abolished by anoxia. A 1-s tetanus of SOL produced an initial reduction which could be abolished with iodoacetate followed by a prolonged oxidation which could be blocked by anoxia. The fluorescence of EDL was decreased immediately following a 1-s tetanus but then rapidly increased well beyond the resting level of reduction and persisted throughout the recovery period. This reduction was largely depressed by iodoacetate. The results indicate marked differences in the recovery metabolism of these muscles, consistent with predominantly mitochondrial oxidative activity in the slow-twitch muscles and predominantly glycolytic activity in the fast-twitch muscles.     

Molecular forms of acetylcholinesterase in dystrophic (mdx) mouse tissues

We analyzed the activity of acetylcholinesterase (AChE) and its molecular forms in the tissues of normal and dystrophic (mdx) mice, at different developmental stages. We studied the brain, the heart and the serum, in addition to four predominantly fast-twitch muscles (tibialis, plantaris, gastrocnemius and extensor digitorum longus (EDL)) and the slow-twitch, soleus muscle. We found no difference between mdx and control mice in the AChE activity of the brain and the heart. The skeletal muscles affected by the disease undergo active degeneration counterbalanced by regeneration between 3 and 14 weeks after birth. The distribution of AChE patches associated with neuromuscular junctions was abnormally scattered in mdx muscles, and in some cases (tibialis and soleus), the number of endplates was more than twice that of normal muscles. There were only minor differences in the concentration and pattern of AChE molecular forms during the acute phase of muscle degeneration and regeneration. After this period, however, we observed a marked deficit in the membrane-bound G4 molecular form of AChE in adult mdx tibialis, gastrocnemius and EDL but not in the plantaris or in the soleus, as compared with their normal counterparts. Whereas the amount of AChE markedly decreased in the serum of normal mice during the first weeks of life, it remained essentially unchanged in the serum of mdx mice. It is likely that this excess of AChE activity in serum originates from the muscles. A deficit in muscle G4 was also reported in other forms of muscular dystrophy in the mouse and chicken. Since it is not correlated to the acute phase of the disease in mdx and also occurs in genetically different dystrophies, it probably represents a secondary effect of the dystrophy.     

A comparison of the electrophysiological effects of two organophosphates, mipafox and ecothiopate, on mouse limb muscles

Adult male albino mice were given single subcutaneous injections of either mipafox (110 mumol/kg) or ecothiopate (0.5 mumol/kg), two organophosphorus compounds (OPs). Acetylcholinesterase activity was measured in the soleus (slow-twitch) and extensor digitorum longus (EDL; fast-twitch) muscles. At 7 and 28 days after dosing, in vitro electrophysiological measurements were carried out in the soleus and EDL. Action potentials and end-plate potentials were evoked at 30 Hz and recorded intracellularly from single muscle fibers. The amplitudes, time course, and latencies of these potentials were measured and the variability (jitter) of latencies was calculated. Recordings after mipafox were also made with 3-Hz stimulation. Acetylcholinesterase activity was inhibited by mipafox (65% in the soleus; 76% in the EDL) and ecothiopate (59% in the soleus; 42% in the EDL). Mipafox and ecothiopate both increased postjunctional (muscle action potential) jitter in the soleus and EDL at 7 days after dosing. Organophosphates caused an increase in end-plate potential amplitudes in the soleus. Mipafox caused an increase in prejunctional (end-plate potential) jitter at 28 days after dosing in both muscles. A single dose of ecothiopate also caused an increase in prejunctional jitter at 28 days in the soleus. The OP-induced increase in jitter was different at different frequencies of stimulation. The results show that there are electrophysiological changes in both muscles after administration of organophosphorus compounds. The slow-twitch soleus appears more sensitive to prejunctional changes caused by OPs than the fast-twitch EDL.     

Peripheral nervous system involvement in human and experimental chronic American trypanosomiasis

An electrophysiological and histological study of the muscle and the peripheral nervous system (PNS) was carried out in chronic human American trypanosomiasis (Chagas' disease) and in an experimental Chagas' disease (Chd) mouse model. Altogether 995 patients with chronic Chd and 261 mice, experimentally infected with RA and CA-I parasite strains, were investigated. Results were compared with matched controls. Techniques employed in humans were: clinical assessment, conventional electromyography (EMG), estimated number of motor units, motor and sensory nerve conduction velocities, repetitive nerve stimulation and muscle and sural nerve biopsies. In mice conventional EMG, sciatic nerve conduction time, sciatic nerve action potential amplitude, in vitro miniature end-plate potentials (MEPPs) and end-plate potentials (EPPs) recordings, muscle, nerve and spinal cord histology and identification of cell phenotypes within the inflammatory infiltrates were the employed procedures. Out of 511 patients submitted to clinical examination, 52 disclosed signs and symptoms of mixed peripheral neuropathy. By employing electrophysiological techniques, it could be shown that about 30% of the investigated patients had one or more of the following features: diminished interference pattern, most of the remainder motor unit potentials being (MUPs) polyphasic; reduced number of functional motor units in the thenar, hypothenar, soleus and/or edb muscles; slow sensory and motor nerve conduction velocities; low sensory action potential amplitude and impairement of neuromuscular transmission. In mice, MUPs duration and amplitude were increased at later stages of the infection, nerve conduction was slow, nerve action potentials were of low amplitude, mepps were of low amplitude and double epps were frequently found. Muscle histology in humans with chronic Chd showed type I and type II grouping, atrophic angular fibers and targetoid muscle fibers. In mice perivascular mononuclear cells infiltrates, small round fibers, muscle fibers necrosis, atrophic angular fibers, type II muscle fibers grouping and grouped muscle fibers atrophy were found. Sural nerve samples showed segmental and paranodal demyelination and axonal loss. The same features were observed in mice nerves, also in this model mononuclear cells infiltrates at the nerve, dorsal root ganglia and meninges surrounding the spinal cord were observed. Muscle and nervous tissues infiltrates were mainly composed of T lymphocytes with predominance of CD8 or CD4 subsets according to the parasites strain employed for infecting the animals. These findings suggest that the skeletal muscle and the PNS may be involved in chronic American trypanosomiasis.     

Effect of 3,4-diaminopyridine on rat extensor digitorum longus muscle paralyzed by local injection of botulinum neurotoxin

The actions of the K+ channel blocker, 3,4-diaminopyridine (3,4-DAP), were studied in the rat extensor digitorum longus (EDL) muscle following local inhibition of neuromuscular transmission by botulinum neurotoxin (BoNT). Local paralysis of the EDL muscle was induced by s.c. injections of BoNT serotypes A, B, E or F over the anterior tibialis muscle. One to 14 days later, the rats were anesthetized with urethane, and isometric twitch tensions following stimulation of the peroneal nerve were measured in situ. Muscles were paralyzed within 24 hr of administration of 5 mouse LD50 units (U) of BoNT/A and remained inhibited for the entire 14-day period of observation. Similar levels of inhibition, but of shorter duration, were observed after local injection of 20 U of BoNT/E, 10(4) U of BoNT/B or 20 U of BoNT/F. 3,4-DAP (4 mg/kg, i.v.) potentiated twitch tensions markedly in BoNT/A intoxicated muscle. The increase in tension developed rapidly (halftime = 5.81 +/- 0.6 min), persisted for approximately 1 hr, then decayed slowly with a halftime of 25.2 +/- 4.6 min. Subsequent administration of 3,4-DAP restored tensions to the original maxima, and this procedure could be repeated up to eight times with no decrement. The action of 3,4-DAP was comparable when given 1, 2, 3 or 7 days after BoNT/A and enhanced when administered 14 days after toxin injection. 3,4-DAP was less effective in reversing BoNT/E-induced muscle paralysis and nearly ineffective in antagonizing the paralytic actions of BoNT/B or BoNT/F. The results indicate that 3,4-DAP is of benefit in BoNT/A and BoNT/E intoxication, but is of marginal value after exposure to serotypes B and F.     

Inferential statistical method for analysis of nonsinusoidal hybrid time series with unequidistant observations

The axotomy reaction in motoneurons after a peripheral nerve transection in the adult animal is characterized by a robust upregulation of alpha-calcitonin gene-related peptide (CGRP) messenger RNA (mRNA) together with mRNAs encoding cytoskeletal and growth-related proteins. Here we have examined whether the nature of the lesion and the age of the animal have any impact on the mRNA regulation in severed cells. Thus, the effect of a sciatic nerve transection in the adult rat was compared with, on the one hand, ventral root avulsions in the adult animal and, on the other hand, sciatic nerve transection in the immature animal. In the two latter cases, a proportion of the lesioned cells die and overall chances of regeneration are small. In the adult animal a sciatic nerve transection induced an upregulation of alpha-CGRP mRNA from the 3rd day after surgery and throughout the first 3 weeks (the time span of the study). Also low-affinity nerve growth factor receptor (p75) and growth-associated protein-43 (GAP-43) mRNAs were upregulated during the entire 3-week period. In contrast, after ventral root avulsion, the expression of alpha-CGRP, c-jun, and p75 mRNAs were normalized within the 1st postoperative week, while GAP-43 mRNA was still upregulated at 3 weeks. Galanin message-associated peptide (GMAP) mRNA became upregulated preferentially in motoneurons subjected to ventral root avulsion, while nitric oxide synthase (NOS) mRNA was expressed exclusively after the latter type of injury. In the immature animal, alpha-CGRP mRNA was downregulated after sciatic nerve transection in rats aged 3 days or 7 days at the time of surgery; while, in contrast, an upregulation was seen in 12- or 21-day-old animals. GAP-43 and c-jun mRNAs were upregulated in lesioned motoneurons of all ages, while GMAP mRNA was upregulated preferentially in lesioned motoneurons of early postnatal animals. p75 mRNA was expressed in unlesioned immature motoneurons until the age of 7-10 days. The downregulation of p75 mRNA in intact cells at this age coincided with a developmental switch in the ability of axotomized cells to express increased levels of p75 mRNA. No expression of NOS mRNA was detectable in lesioned cells of any of the age groups. These results show that the age of the animal and the type of axonal injury are indeed to a high degree influencing the changes seen in the protein expression pattern in axotomized rat motoneurons. The different responses in these paradigms suggest differences in the trophic response from surrounding glia or the trophic responsiveness of lesioned motoneurons. Also, the results may indicate different roles for the studied substances during the regenerative response of lesioned neurons. Of the substances studied here, upregulation of alpha-CGRP and p75 mRNAs best correlated with a possibility of axon regeneration.     

Muscle adaptations to hindlimb suspension in mature and old Fischer 344 rats

We examined skeletal and cardiac muscle responses of mature (8 mo) and old (23 mo) male Fischer 344 rats to 14 days of hindlimb suspension. Hexokinase (HK) and citrate synthase (CS) activities and GLUT-4 glucose transporter protein level, which are coregulated in many instances of altered neuromuscular activity, were analyzed in soleus (Sol), plantaris (PI), tibialis anterior (TA), extensor digitorum longus (EDL), and left ventricle. Protein content was significantly (P < 0.05) lower in all four hindlimb muscles after suspension compared with controls in both mature (21-44%) and old (17-43%) rats. Old rats exhibited significantly lower CS activities than mature rats for the Sol, Pl, and TA. HK activities were significantly lower in the old rats for the Pl (19%) and TA (33%), and GLUT-4 levels were lower in the old rats for the TA (38%) and EDL (24%) compared with the mature rats. Old age was also associated with a decrease in CS activity (12%) and an increase in HK activity (14%) in cardiac muscle. CS activities were lower in the Sol (20%) and EDL (18%) muscles from mature suspended rats and in the Sol (25%), Pl (27%), and EDL (25%) muscles from old suspended rats compared with corresponding controls. However, suspension was associated with significantly higher HK activities for all four hindlimb muscles examined, in both old (16-57%) and mature (10-43%) rats, and higher GLUT-4 concentrations in the TA muscles of the old rats (68%) but not the mature rats. These results indicate that old age is associated with decreased CS and HK activities and GLUT-4 protein concentration for several rat hindlimb muscles, and these variables are not coregulated during suspension. Finally, old rat skeletal muscle appears to respond to suspension to a similar or greater degree than mature rat muscle responds.     

Typing of methicillin-resistant Staphylococcus aureus isolates from Düsseldorf by six genotypic methods

This in vivo double-blind study evaluated the effect of recombinant human glial growth factor 2 (rhGGF2), a Schwann cell mitogen, on the recovery of motor function of rat sciatic nerve following crush injury. Seventy three rats were divided into three groups. Group I (n=5), sham operated; Groups II (n=34) and III (n=34) received a 100 g crush load for 2 h over a 5 mm segment of the sciatic nerve. Group III was treated with 1 mg/kg rhGGF2, via subcutaneous injection one day before nerve crush and daily for the following four days. Group II received an equivalent volume of saline as a control. Motor functional recovery was assessed by calculating the sciatic functional index (SFI) and the recovery rate of tetanic contractile force of the extensor digitorum longus (EDL) muscle. Recovery of nerve function was evident at day 11 after crush in the rhGGF2-treated animals, whereas the nerves in controls were still paralyzed. The rhGGF2-treated animals showed a significant improvement of the SFI between days 11-21 postoperatively when compared to controls. The isometric tetanic contractile force was stronger in the rhGGF2-treated group than in controls, with a significant difference at 40 to 70 Hz stimulus frequencies on day 4. Correlation analysis showed that tetanic contractile force had a linear correlation with the SFI. Histologic assessment indicated that the rhGGF2-treated animals showed less severe degeneration and earlier robust remyelination of axons than controls. The results suggest that treatment with rhGGF2 is effective in promoting nerve regeneration as seen in measurements of functional recovery and qualitative assessment of nerve morphology. The mechanism of GGF's protective effect may be related to its direct action on Schwann cells, stimulating their mitosis as well as inducing neurotrophic factors essential to neuronal maintenance and repair.     

Increased spike-frequency adaptation and tea sensitivity in dorsal root fibers after sciatic nerve injury

Excitability of rat dorsal root axons were studied 3 weeks after injury to the sciatic nerve. Whole nerve recordings were obtained from injured and control nerves in a sucrose gap chamber. Constant current depolarization pulses (30-200 ms) applied approximately 50% above the stimulus strength required for maximal amplitude compound action potentials (CAPs) evoked a burst of action potentials in the dorsal root which displayed spike adaptation. The depolarization-induced burst response of the dorsal roots was greatly reduced after crush or transection of the sciatic nerve. However, application of the potassium channel blocker, tetraethylammonium (TEA), restored the burst discharge in injured dorsal root axons. Brief tetanic stimulation of the dorsal root also induced an afterhyperpolarization (AHP) that was twice as large in the transection group as compared to the control group, and which was blocked by TEA. There were no changes seen in the amplitude of the compound action potential, frequency-following characteristics, refractory properties, or 4-AP sensitivity in the dorsal roots after peripheral nerve injury. These results suggest that there is enhanced spike adaptation that occurs at the same time as an increase in the sensitivity to the potassium channel blocker, TEA, in axon regions proximal to the site of nerve injury and have implications for the pathophysiology of nerve injury.     

Subclinical thyroid disease in the elderly

The present study investigated the effect of NT-3, a neurotrophin expressed in nerve and skeletal muscle, on myelinated fiber disorders of galactose-fed rats. Adult, female Sprague-Dawley rats were fed diets containing complete micronutrient supplements and either 0% D-galactose (control) or 40% D-galactose. Treated controls received 20 mg/kg NT-3 and treated galactose-fed rats received 1, 5, or 20 mg/kg NT-3 three times per week by subcutaneous injections. After 2 months, sciatic and saphenous sensory nerve conduction velocity (SNCV) and sciatic motor nerve conduction velocity (MNCV) were measured and the sciatic, sural, peroneal and saphenous nerves and dorsal and ventral roots processed for light microscopy. Treatment of control animals with NT-3 had no effect on any functional or structural parameter. Compared to control values, galactose feeding induced a sensory and motor nerve conduction deficit and a reduction in axonal caliber. Treatment with 5 and 20 mg/kg NT-3 ameliorated deficits in sciatic and saphenous SNCV in galactose-fed rats but had no effect on the MNCV deficit. NT-3 treatment also attenuated the decrease in mean axonal caliber in the dorsal root and sural nerve but not in the saphenous nerve, ventral root and peroneal nerve. These observations show that NT-3 can selectively attenuate the sensory conduction deficit of galactose neuropathy in a dose-dependent manner that depends only in part on restoration of axonal caliber of large-fiber sensory neurons.     

BDNF attenuates functional and structural disorders in nerves of galactose-fed rats

Galactose intoxication of rats was used to disrupt metabolism of Schwann cells and skeletal muscle, two sites that contain the polyol-forming enzyme aldose reductase (AR). Galactose-fed rats develop a neuropathy characterized by nerve conduction deficits and axonal atrophy. To investigate the possibility that galactose metabolism by AR influences axonal function and structure by altering production of neurotrophic factors, the impact of galactose intoxication on nerve and muscle BDNF levels and the effects of exogenous BDNF treatment on galactose neuropathy were examined using biochemical, electrophysiologic and morphometric techniques. Galactose feeding increased BDNF protein in peripheral nerve and muscle. Exogenous BDNF treatment attenuated motor nerve conduction velocity deficits in the sciatic nerve of galactose-fed animals and myelin splitting of motor axons in the ventral root. In contrast, sensory nerve conduction velocity (SNCV) deficits in the sciatic nerve and myelin splitting in the central projections of sensory neurons were not prevented by BDNF treatment. BDNF treatment did not attenuate reduced axonal caliber in the sciatic nerve, but did ameliorate the diminution of the caliber of central sensory projections in the dorsal root. These findings point to the potential use of BDNF in the treatment of peripheral neuropathies.     

Isolated lesion of the medial orbital wall following endonasal surgery. Isolated fractures of the medial orbital wall

In many species the GnRH pulse generator functions early postnatally to become arrested during infancy. In rats highly variable LH levels in 15-day-old animals are suggestive that LH is being released by the pituitary in pulses whereas between day 20 after birth and puberty LH levels are low indicating that the GnRH pulse generator is arrested. In the present study we show on the basis of consecutively withdrawn blood samples in 15-day-old animals that LH pulses are indeed present at that age. The proper function of GnRH receptors in the pituitary is crucially dependent on pulsatile GnRH release from the hypothalamus. In addition, GnRH receptors have been demonstrated in the medial preoptic area and in the mediobasal hypothalamus of adult rats. In 15-day-old animals the functional GnRH pulse generator results in upregulated GnRH receptor gene expression as demonstrated by quantitative RT-PCR. It is not known what neural mechanisms are involved in turning the GnRH pulse generator off during infancy and a GABAergic brake has been discussed. Indeed, when 30-day-old animals were injected with the GABA-A receptor blocking drug bicuculline, this resulted in increased serum LH levels indicating that a tonic GABAergic inhibition is indeed operative at this age.     

Effects of beta 2-agonist administration and exercise on contractile activation of skeletal muscle fibers

Clenbuterol, a beta 2-adrenoceptor agonist, has therapeutic potential for the treatment of muscle-wasting diseases, yet its effects, especially at the single-fiber level, have not been fully characterized. Male C57BL/10 mice were allocated to three groups: Control-Treated mice were administered clenbuterol (2 mg.kg-1. day-1) via their drinking water for 15 wk; Trained-Treated mice underwent low-intensity training (unweighted swimming, 5 days/wk, 1 h/day) in addition to receiving clenbuterol; and Control mice were sedentary and untreated. Contractile characteristics were determined on membrane-permeabilized fibers from the extensor digitorum longus (EDL) and soleus muscles. Fast fibers from the EDL and soleus muscles of Treated mice exhibited decreases in Ca2+ sensitivity. Endurance exercise offset clenbuterol's effects, demonstrated by similar Ca2+ sensitivities in the Trained-Treated and Control groups. Long-term clenbuterol treatment did not affect the normalized maximal tension of fast or slow fibers but increased the proportion of fast fibers in the soleus muscle. Training increased the proportion of fibers with high and intermediate succinate dehydrogenase activity in the EDL and soleus muscles, respectively. If clenbuterol is to be used for treating muscle-wasting disorders, some form of low-intensity exercise might be encouraged such that potentially deleterious slow-to-fast fiber type transformations are minimized. Indeed, in the mouse, low-intensity exercise appears to prevent these effects.