Does electrical stimulation of denervated muscle,continued after reinnervation,influence recovery of contractile function?

The study was conducted to determine if daily electrical stimulation of denervated muscle, initiated the day following crush denervation and continued for 8 weeks (i.e., 5 weeks after presumptive reinnervation), would influence denervation-associated alterations in muscle size and in situ contractile properties of rat gastrocnemius. A stimulation protocol of brief, strong, isometric contractions was designed to maximize the beneficial effects as described by previous authors. By 8 weeks after crush, unstimulated muscles were still significantly lighter in wet weight, were tetanically weaker, and showed slower isometric contractile responses in situ than controls. Denervated muscles which had been stimulated daily were heavier and tetanically stronger (the latter not different from controls) than those in the nonstimulated group. Muscle weights from groups of animals killed at 2 or 4 weeks after nerve crush indicated the major benefit of stimulation occurred during this initial 4-week period. In situ fatigue properties were unaffected by denervation or stimulation. A protocol of electrical stimulation-evoked strong contractions, initiated soon after denervation and continued after reinnervation, was effective in attenuating the strength-related, but not speed-related, changes in neuromuscular function resulting from denervation. These latter changes are presumably the result of loss of “neurotrophic influence” and/or continuous low-tension muscle activity lost as a result of denervation.     

Hypothalamus and Brown Fat: White and Brown Adipose Tissue Lipolysis in Weanling Rats with Dorsomedial Hypothalamic Lesions

Weanling male Sprague-Dawley rats received bilateral electrolytic lesions in the dorsomedial hypothalamic nuclei (DMN); sham-operated animals served as controls. The animals were fed lab chow and given tap water ad libitum. Fourteen days after the hypothalamic operation they were weighed and measured to assess ponderal and linear growth gains and Lee Index and were sacrificed on the following day. Body weight, body weight gain over two weeks, nose-tail length and gain in nose-tail length, and food intake were all highly significantly reduced in DMNL rats in comparison with controls. Lee Index and efficiency of food utilization were normal, however. Epididymal fat pads weighed less in both absolute and relative (percentage body weight) terms than in controls. Basal lipolysis was increased and epinephrine-stimulated lipolysis was decreased in DMNL rats, as was the protein content of the epididymal fat pads. Lipid content was normal, however. Interscapular brown adipose tissue (BAT) was significantly lighter in DMNL rats than in controls in absolute terms, but all other parameters measured were normal, as were plasma glucose, glycerol, and free fatty acids. Comparison with results from rats that received ventromedial hypothalamic lesions shortly after weaning indicates a differential effect in most epididymal fat pad parameters but similarities to changes in BAT. These data add to previous demonstrations of normal responses to homeostatic challenges in the growth-retarded, hypophagic-hypodipsic rat with lesions in the dorsomedial hypothalamic nucleus.     

Intact brown adipose tissue thermogenesis is required for restorative sleep responses after sleep loss

Metabolic signals related to feeding and body temperature regulation have profound effects on vigilance. Brown adipose tissue (BAT) is a key effector organ in the regulation of metabolism in several species, including rats and mice. Significant amounts of active BAT are also present throughout adulthood in humans. The metabolic activity of BAT is due to the tissue‐specific presence of the uncoupling protein‐1 (UCP‐1). To test the involvement of BAT thermogenesis in sleep regulation, we investigated the effects of two sleep‐promoting stimuli in UCP‐1‐deficient mice. Sleep deprivation by gentle handling increased UCP‐1 mRNA expression in BAT and elicited rebound increases in non‐rapid‐eye‐movement sleep and rapid‐eye‐movement sleep accompanied by elevated slow‐wave activity of the electroencephalogram. The rebound sleep increases were significantly attenuated, by ~ 35–45%, in UCP‐1‐knockout (KO) mice. Wild‐type (WT) mice with capsaicin‐induced sensory denervation of the interscapular BAT pads showed similar impairments in restorative sleep responses after sleep deprivation, suggesting a role of neuronal sleep‐promoting signaling from the BAT. Exposure of WT mice to 35 °C ambient temperature for 5 days led to increased sleep and body temperature and suppressed feeding and energy expenditure. Sleep increases in the warm environment were significantly suppressed, by ~ 50%, in UCP‐1‐KO animals while their food intake and energy expenditure did not differ from those of the WTs. These results suggest that the metabolic activity of the BAT plays a role in generating a metabolic environment that is permissive for optimal sleep. Impaired BAT function may be a common underlying cause of sleep insufficiency and metabolic disorders.     

An expanded cortical representation for hand movement after peripheral motor denervation

OBJECTIVES: Functional reorganisation of the motor or sensory cortex has been demonstrated in animals after section of mixed peripheral nerves. Here functional changes in the motor cortex specifically after peripheral motor denervation in humans are investigated. METHODS: Functional MRI (fMRI) was used to study brain activation during a finger flexion-extension task in patients with a late onset, acquired pure motor neuropathy (n=6), contrasting results with those from patients with pure sensory neuropathies (n=4) or healthy controls (n=7). RESULTS: Increases in the extent of activation in the motor cortex both ipsilateral and contralateral to the hand moved were found in the patients with motor neuropathy. The neuroanatomical localisation of the mixed contralateral sensorimotor cortex activation volume was more posterior for the patients with motor neuropathy than for the healthy controls (mean difference, 12 mm, p<0.05). The pure sensory neuropathy group by contrast showed no change in the extent of activation relative to healthy controls and a trend for more anterior primary sensorimotor cortex activation (p<0.06). To test whether the increased activation volumes found in patients with motor neuropathy were a result simply of factors such as increased effort with movement rather than the motor denervation, patients with hand weakness from inclusion body myositis (n=4) were studied while making similar hand movements. No differences in either the numbers of significantly activated voxels or in their localisation were found relative to healthy controls (n=10). CONCLUSIONS: These results provide a novel demonstration that peripheral denervation (as distinguished from factors related to weakness) leads to functional reorganisation of the sensorimotor cortex in the adult brain. This suggests that adaptive responses to motor denervation involve the central as well as the peripheral nervous system.     

Hypothalamic control of brown adipose tissue in Zucker lean and obese rats. Effect of electrical stimulation of the ventromedial nucleus and other hypothalamic centres

Electrophysiological stimulation of the hypothalamic ventromedial nucleus (VMN) resulted in an increase in interscapular brown adipose tissue (BAT) temperature in both lean and obese (fa/fa) rats. Graded stimulations resulted in progressively larger temperature increases in both lean and obese (fa/fa) groups. Both intraperitoneal injection of propranolol and surgical denervation (but not sham denervation) abolished the increase in BAT temperature following VMN stimulation, in both lean and obese (fa/fa) groups. Electrical stimulation of the supraoptic region, and certain anterior hypothalamic regions also resulted in increases in BAT temperature of lean and obese (fa/fa) rats, but stimulation of the dorsomedial nucleus and regions of the lateral hypothalamus did not affect BAT temperature. All hypothalamic regions capable of activating BAT gave a similar maximum rise in temperature for a given stimulus in lean and obese (fa/fa) rats. These results suggest that the efferent sympathetic pathway from the VMN and other hypothalamic regions of BAT is normal in the obese (fa/fa) rat.     

Impact of renal denervation on renal content of GLUT1, albuminuria and urinary TGF-beta1 in streptozotocin-induced diabetic rats

In long-term diabetes mellitus, the progression of nephropathy has been related to the occurrence of autonomic neuropathy. This study was designed to evaluate the effects of bilateral denervation of the kidneys of streptozotocin-diabetic rats, an experimental model that presents diabetic nephropathy with increased abundance of cortical GLUT1 in the kidney and increased urinary excretion of albumin and transforming growth factor-beta1 (TGF-beta1). Twenty-four-hour urinary TGF-beta1 (ELISA), urinary albumin (electroimmunoassay) and GLUT1 protein levels (Western blotting) in the renal cortex and medulla were evaluated in diabetic (n=13) and control (n=13) rats 45 days after streptozotocin injection, submitted or not to surgical renal denervation. Evaluations were performed 15 days after the surgery. The effects of renal denervation were confirmed by intra-renal decrease of norepinephrine levels. Mean arterial pressure did not differ between diabetic and control rats, whether they underwent renal denervation or not. Renal denervation increased cortical (6905+/-287, 3506+/-193, 4144+/-246 and 5204+/-516 AU in renal-denervated controls, controls, renal-denervated diabetics and diabetics, respectively) and medullar GLUT1 protein in control rats, but reverted the cortical GLUT1 protein rise determined by diabetes. Although kidney denervation in diabetic rats induced a decrease in cortical GLUT1 abundance toward normal levels, these levels did not reach those of normal animals. However, renal denervation did not determine any changes in urinary albumin and urinary TGF-beta1 in both diabetic (127.3+/-12 microg/24 h and 111.8+/-24 ng mg(-1) creatinine, respectively) and control rats (45.9+/-3 microg/24 h and 13.4+/-4 ng mg(-1) creatinine, respectively). In conclusion, early-phase renal denervation in streptozotocin-diabetic rats produces a normalisation of previously elevated cortical GLUT1 protein content, but is not enough for reverting the increased urinary TGF-beta1 and albuminuria of diabetes.     

Differential effects of antiepileptic drugs on sexual function and reproductive hormones in men with epilepsy: interim analysis of a comparison between lamotrigine and enzyme-inducing antiepileptic drugs

PURPOSE: We compared sexual function and reproductive hormone levels among men with localization-related epilepsy (LRE) taking various antiepileptic drugs (AEDs) and normal controls (NC). METHODS: Subjects were 63 men with LRE [enzyme-inducing (EI) AEDs, 36; lamotrigine (LTG), 18; no AEDs, 9] and 18 NC. Sexual interest and function (S-score), hormone levels [bioactive testosterone (BAT) and estradiol (BAE)], hormone ratios [BAT/BAE], and gonadal efficiency [BAT/luteinizing hormone (LH)] were compared among the groups. RESULTS: S-scores, BAT levels, BAT/BAE, and BAT/LH were significantly lower in the EIAED group than in NC or LTG groups. Sex hormone-binding globulin (SHBG) was significantly higher in the EIAED group than in all other groups. Of men with LRE, 23.8% had abnormally low S-scores: 33.3% taking EIAEDs, 5.5% taking LTG, and 22.2% taking no AEDs (p < 0.01). BAT was low in 55.6% taking EIAEDs as compared with 33.3% taking LTG and 33.3% taking no AEDs (p < 0.05). Among men with low S-scores, 86.7% had low BAT as compared with 33.3% of men with normal scores (p < 0.01). BAT decline with age was greater among men with LRE than in controls (3.75 vs. 1.80 ng/dl/yr). The slope showed no significant difference among LRE groups. However, 89% of 40- to 50-year-old men taking EIAEDs had low BAT as compared with 33% taking LTG and 33% taking no AED (p < 0.01). CONCLUSIONS: Sexual function, BAT levels, BAT/BAE, and gonadal efficiency are greater with LTG than with EIAED. Abnormally low BAT levels are reached at an earlier age with EIAEDs than with LTG.     

Impaired diet-induced thermogenesis in brown adipose tissue from rats made obese with parasagittal hypothalamic knife-cuts

Two experiments were performed to determine if bilateral parasagittal hypothalamic knife-cuts (KCs), which produce long-term overeating and obesity, after biochemical indices of brown adipose tissue (BAT) reactivity to thermogenic stimuli. In the first study, responses to environmental cold were tested. Four weeks after surgery, KC rats had gained 4-5 times more weight than controls and were obese (increased Lee Obesity Index and weight of gonadal white fat). Before being sacrificed, groups of KC and control rats were exposed to 4 degrees C for 21 hr or remained at 28 degrees C. Interscapular BAT weighed 300% more in KC rats, due largely to increased white fat content. Functional indices of BAT thermogenic capacity (protein content, DNA content, cytochrome oxidase activity and mitochondrial guanosine diphosphate (GDP) binding) were normal at 28 degrees C. Exposure to 4 degrees C produced greatly enhanced responses but these were equivalent for both groups. This suggested an intact capacity for non-shivering thermogenesis in obese KC rats. In the second study, the same BAT responses were examined in other rats fed a palatable "cafeteria" diet (CAFE). One week after surgery, KC and control rats were subdivided into groups that received chow alone or chow plus four different palatable foods daily. Before sacrificing 4-5 weeks later, KC rats had gained 3-4 times more weight than controls and were obese. Interscapular BAT weighed 200-300% more in KC rats. CAFE feeding produced larger increments in all variables for KC vs. control rats. Most importantly, GDP binding was reduced in both KC groups, and significantly more so after CAFE feeding.(ABSTRACT TRUNCATED AT 250 WORDS)     

Quantification of extrajunctional acetylcholine receptors in human muscle biopsies

Extrajunctional acetylcholine receptors were quantified in human muscle biopsies by in vitro autoradiography with 3H-alpha-bungarotoxin (alpha-Btx). Specific alpha-Btx binding was found in seven of eight biopsies with histological and/or histochemical signs of denervation. The highest binding (21 fmol/mg) was seen in the biopsy with the most pronounced signs of denervation. The specimens with co-existing signs of innervation had generally lower binding levels. Four of the control biopsies showed low binding (less than or equal to 1 fmol/mg) while no specific binding could be detected in the other six controls. The findings suggest that this method cannot only be used to demonstrate denervation in muscle biopsy specimens, but also to give a quantitative measure of the changes.     

Effect of Maternal Dexamethasone Treatment and Ambient Temperature on Prolactin Receptor Abundance in Brown Adipose and Hepatic Tissue in the Foetus and New-born Lamb

We investigated the influence of maternal dexamethasone treatment and ambient temperature on prolactin receptor (PRLR) abundance in brown adipose tissue (BAT) and hepatic tissue from foetuses and 6-h-old lambs delivered by caesarean section. Lambs were either delivered into a warm (30 degrees C; WD) or cool (15 degrees C; CD) ambient temperature at 140 days gestation, 2 days after dexamethasone treatment, or at 146 days gestation for controls. Uncoupling protein-1 (UCP1) content of BAT was higher in dexamethasone-treated groups compared to controls. A range of tissue-specific PRLR isoforms was detected. For the long form of PRLR in BAT these isoforms had molecular weights of 66, 54, 34 and 19 kD compared with 88, 76, 66, 58, 54 and 48 kD in liver. In BAT, isoforms of the short form of PRLR had molecular weights of 66, 62, 54, 48, 33 and 31 kD compared with 82, 66, 56, 54, 48, 40 and 33 kD in liver. Dexamethasone treatment in CD lambs resulted in higher abundance of the 54 kD isoform of the short form of PRLR in liver, whilst in BAT dexamethasone resulted in a greater abundance of the 48 kD isoform of the short form, and lower abundance of the 66 kD isoform of the long form of PRLR, compared to controls. A negative correlation (r2 = 0.52) was observed between abundance of 66 kD isoform for the long form of PRLR and UCP1, compared with positive correlations (r2 = 0.58-0.60) for the abundance of the 54 and 48 kD isoforms for the short form of PRLR and UCP1. In conclusion, maternal dexamethasone treatment 1 week before term alters the abundance of PRLR isoforms in a tissue-specific manner. This response is dependent on ambient temperature after birth and may provide a critical endocrine signal for maximising non-shivering thermogenesis.     

Early changes of protein-kinase (glycogen-synthetase kinase) in denervated muscle

After denervation, muscle glycogen decreases in simultaneously with glycogen synthetase I activity (the physiologically active form of this enzyme). The present experiment was performed to determine the changes, if any, in the enzymes that convert glycogen synthetase from the inactive D form to the active I (glycogen synthetase phosphatase) as well as the opposite reaction (glycogen synthetase kinase or protein kinase). Enzyme activities were assayed by testing the capability of muscle extracts to cause conversion of purified glycogen synthetase D (in the case of phosphatase determinations) or of purified glycogen synthetase I (kinase assays) in the presence of the required cofactors and activators. No changes of glycogensynthetase phosphatase were observed. However, there was a marked increase of both the cAMP independent and the total kinase activities 1 day after denervation. This fact can account for the changes in glycogen synthetase I levels and in glycogen metabolism after denervation. Also, it might be relevant to understand the early changes in RNA and protein metabolism after denervation, owing to the supposed regulatory effect of protein kinase on nuclear activity.     

Apoptosis in young and old denervated rat skeletal muscle

Introduction: We investigated the apoptotic response to different degrees of denervation in young and older rats randomized into control (C), partial (PD), and complete denervation (CD) of muscles innervated by the sciatic nerve. Methods: Muscle wet weight to body weight (MWW/BW), myosin heavy chain (MHC) isoforms, and fiber cross‐sectional area were determined in gastrocnemius and soleus muscles. Apoptotic responses were determined by changes in myonuclei and expression of Bcl‐2 and BAX. Results: PD and CD resulted in significant reductions in MWW/BW and FCSA in both young and older rats. Older controls had greater apoptotic responses than young controls. Apoptotic responses were greater in PD and CD than in C in both age groups. No statistical interaction between denervation and age group was seen. Conclusions: Older age was associated with increased level of apoptosis, but older muscle was not more vulnerable to the effect of denervation. Muscle Nerve 55 : 262–269, 2017     

Astrocyte responses to dopaminergic denervations by 6-hydroxydopamine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine as evidenced by glial fibrillary acidic protein immunohistochemistry

Astrocytic responses to dopaminergic denervation by two widely used dopamine neurotoxins, 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were monitored using immunofluorescence with antibodies against glial fibrillary acidic protein (GFA) while neurofilament (NF) antibodies were used to monitor neuronal disturbances. Following stereotaxic injection of 6-OHDA into the nigrostriatal dopamine bundle in rats, an increased amount of GFA-immunoreactivity in striatum was detectable after 24 hours and remained after one month. Retrograde degeneration of nigral neurons led to gliosis in the cell body area. At the site of injection, astrocytes were destroyed and NF-immunoreactivity increased. New astrocytes invaded the injection area during the first month after injection. MPTP given systemically to mice in a dose that causes marked dopaminergic denervation of striatum also caused marked increases of GFA-immunoreactivity in striatum. These changes were larger in C57 BL/6 mice, known to be more sensitive to MPTP, than in N.M.R.I. mice, which are less sensitive to MPTP. The glial responses to MPTP-induced dopaminergic denervation did not occur when the dopamine neurotoxic effects were prevented by pretreatment with nomifensine or pargyline. It is concluded that dopaminergic denervation by neurotoxins causes rapid and profound changes in striatal astrocytes characterized by increased GFA-immunoreactivity. These changes remained up to a month after denervation and should be taken into account when functional consequences of dopaminergic denervations are discussed.     

Apelin-13 microinjection into the paraventricular nucleus increased sympathetic nerve activity innervating brown adipose tissue in rats

The aim of present study is to clarify the role of apelin in regulating energy homeostasis in brown adipose tissue (BAT). We examined the central effects of apelin-13 on the brain c-fos like immunoreactivity (c-FLI), BAT temperature and the activity of the sympathetic nerve activity innervating BAT in rats. In the hypothalamus, central infusion into the third cerebral ventricle (i3vt) of apelin-13 caused induction of c-FLI in the paraventricular nucleus (PVN) compared with the controls (PBS-treated) group. In addition, microinjection of apelin-13 into the PVN produced significant increases in BAT temperature. Furthermore, microinjection of apelin-13 treatment increased BAT sympathetic nerve activity compared with controls. We conclude that apelin-13 microinjection into PVN increases sympathetic nerve activity innervating BAT.     

Re-innervation of submucosal arterioles by myenteric neurones following extrinsic denervation.

We used a combination of selective lesions, immunohistochemistry and video monitoring of arteriolar diameter to determine the source of the changes in vasodilator innervation to guinea pig ileal submucosal arterioles which occur following removal of their extrinsic sympathetic and sensory nerve fibre input. A non-cholinergic neurogenic vasodilation appeared in arterioles in which extrinsic denervation was performed 50-90 days previously. The non-cholinergic innervation did not result from regrowth of extrinsic fibres because the neurogenic response was not altered by combining long-term denervation with capsaicin treatment or re-denervation 7 days prior to examination. However, non-cholinergic neurogenic vasodilations were not observed in arterioles which had been subjected to long-term denervation combined with a myectomy 7 days prior to examination. Immunohistochemical co-localization of SP and CGRP in these vessels confirmed previous findings that a prominent SP perivascular nerve plexus appeared after long-term denervation. Perivascular SP-containing fibres that appeared after long-term denervation were unaffected by capsaicin or re-denervation but were absent from preparations in which long-term denervation and myectomy were performed. These results demonstrate that myenteric neurones are the source of the non-cholinergic innervation which appears after extrinsic denervation and support our previous conclusion that SP is the neurotransmitter responsible for this non-cholinergic vasodilation in submucosal arterioles of the small intestine.     

Long-term effects of partial denervation on sprouting and muscle fiber area in rat plantaris.

The long-term effects of partial denervation on the muscle fiber cross-sectional area, degree of axonal sprouting, and end-plate morphology were examined 1, 3, 6, 9, and 12 months postsurgery in rat plantaris muscle. After 1 month of partial denervation, mean cross-sectional areas of type I and type II myofibers were significantly lower than that of sham-operated controls; fiber atrophy and hypertrophy was observed. After 3 months, we found no statistical difference in the mean cross-sectional fiber area between the two experimental groups. After 6 months, the fiber areas were now significantly larger than controls, possibly the result of compensatory work hypertrophy, due to the overuse of remaining hyperexpanded motor units. Preterminal, intranodal, and intraterminal sprouting were found to significantly increase from 1 to 6 months following partial denervation. While sprouting was enhanced, the number of terminal branch points per end plate did not change. Following 9 months of partial denervation and overuse, the mean fiber areas significantly decreased as compared to controls. The former muscles were found to contain angulated fibers, group atrophy, and increased levels of axonal sprouting. The number of terminal branches per end plate was now significantly increased over control values, possibly a compensatory response to reduced synthesis of neurotrophic factor(s) and/or transmitter-related components. At 12 months, fiber areas, axonal sprouting, and the number of terminal branches per end plate have all decreased. Degenerating end plates, denervated myofibers, angulated fibers, and group atrophy were observed. It would appear that aging-like changes are occurring earlier in chronically stressed, partially denervated muscles.     

Functional activity of zona incerta neurons is altered after nigrostriatal denervation in hemiparkinsonian rats

The cellular expression of cytochrome oxidase subunit I (COI) mRNA as a metabolic marker for neuronal activity has recently been used to examine the effects of nigrostriatal denervation on the functioning of the basal ganglia. However, this technique also allows functional changes to be detected in other cerebral structures in parkinsonian syndromes. Since the zona incerta has been implicated in locomotor activity and has been the site of stereotactic surgery in Parkinson's disease, the aim of our study was to determine whether changes in neuronal activity are observed in this structure during parkinsonism. Using in situ hybridization, we analyzed the expression of COI mRNA in rats with 6-hydroxydopamine unilateral lesion of the substantia nigra and sham-operated animals. A quantitative analysis showed that COI mRNA expression was increased in the zona incerta ipsilateral to the lesion 24 h and 3 days after lesion, but by day 14 had returned almost to the level observed in controls. The hyperactivity of zona incerta neurons was confirmed by single-unit electrophysiological recordings. In contrast to the COI mRNA expression, the increase in electric neuronal activity was still observed 1 month after the lesion. This increase in zona incerta neuronal activity after nigrostriatal denervation might be related to the pathophysiology of parkinsonism, at least in the early stages, in agreement with previous reports suggesting an involvement of the zona incerta in motor functions.     

The time course of functional and morphological changes of the guinea-pig colon after “a frigore” denervation of the periarterial sympathetic nerves

Summary After sympathetic denervation of the guinea-pig distal colon the time course and the relationship between morphological and functional changes were studied, by using the fluorescence method and by evaluating the response of longitudinal muscle to periarterial nerve stimulation.The inhibitory response to sympathetic nerve stimulation was completely abolished 48 h after denervation. Tissue catecholamines can no longer be detected in either the intramural vessels or in the intramural plexuses 96 h after denervation, and in no preparation could they be observed again until 24 days after denervation.After 30 days catecholamines stores slowly began to reappear and were completely restored only 100–120 days after denervation. During the whole period of reinnervation the response to periarterial nerve stimulation was lacking.The inhibitory effect could be elicited only 130 days after denervation and before the morphological pattern had been completely restored.Some of the results were communicated at the 33rd Congress of the German Pharmacological Society—Heidelberg 27–30 September 1970 and appeared earlier in Arch. Pharmak.269, n. 2-4, 387 (1971).Suported by a grant of the Consiglio Nazionale delle Richerche (Roma).     

Effect of denervation during development upon membrane potential and intracellular potassium and sodium activities of skeletal muscle of the rat

Potassium and sodium ion-selective microelectrodes were used in vitro to investigate the effect of denervation of fast-twitch skeletal muscle (extensor digitorum longus) at 5 days of age upon subsequent development of the resting membrane potential. Normally, during the first 3 weeks of life the balance of intracellular potassium and sodium changed to elevate potassium and to lower sodium. These changes were reflected in the development of a more hyperpolarized resting membrane. Periods of denervation delayed, or prevented, the changes in ion activities and membrane hyperpolarization from occurring. The results are compared with those found after denervation of adult skeletal muscle.     

Muscle magnetic resonance imaging of denervation and reinnervation: correlation with electrophysiology and histology

A signal increase in denervated muscle on magnetic resonance imaging (MRI) has been described in several clinical and experimental studies. Here, we studied the time course of T2-relaxation time changes in denervation and subsequent reinnervation in a rat model and correlated the findings with electrophysiology and quantitative histology. A prolongation of the T2 relaxation time in muscles was present 48 h after denervation, which was paralleled by spontaneous activity on electromyography (EMG). Histologically, there was a marked enlargement of the capillaries at that time point, indicating increased blood volume. The relaxation time changes peaked 3 weeks after beginning of nerve regeneration identified by EMG. Subsequently, the T2 prolongation normalized until 10 weeks after beginning of regeneration which was associated with a histological regression of the capillary enlargement. MRI closely mirrors the electrophysiological changes following denervation and reinnervation and may thus be used as adjunct to electrophysiology. The pathophysiological basis for the MR relaxation time changes is predominantly the enlargement of the capillary bed.