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1.
Neuroscience ; 310: 342-53, 2015 Dec 03.
Article in English | MEDLINE | ID: mdl-26386295

ABSTRACT

Ambulatory instability and falls are a major source of morbidity in the elderly. Age-related loss of tendon reflexes is a major contributing factor to this morbidity, and deterioration of the afferent limb of the stretch reflex is a potential contributing factor to such age-dependent loss of tendon reflexes. To evaluate this, we assessed the number and distribution of muscle spindle afferent fibers in human sacral spinal ganglia (S1) and tibial nerve samples obtained at autopsy, using immunohistochemical staining for the α3 isoform of Na(+), K(+)-ATPase (α3NKA), a marker of muscle spindle afferents. Across all age groups, an average of 26 ± 4% of myelinated fibers of tibial nerve and 17 ± 2% of ganglion neuronal profiles were α3NKA-positive (n = 8 per group). Subject age explained 85% of the variability in these counts. The relative frequency of α3NKA-labeled fibers/neurons starts to decline during the 5th decade of life, approaching half that of young adult values in 65-year-old subjects. At all ages, α3NKA-positive neurons were among the largest of spinal ganglia neurons. However, as compared to younger subjects, the population of α3NKA-positive neurons from advanced-age subjects showed diminished numbers of large (both moderately and strongly labeled), and medium-sized (strongly labeled) profiles. Considering the critical significance of ion transport by NKA for neuronal activity, our data suggest that functional impairment and, also, most likely atrophy and/or degeneration of muscle spindle afferents, are mechanisms underlying loss of tendon reflexes with age. The larger and more strongly α3NKA-expressing spindle afferents appear to be proportionally more vulnerable.


Subject(s)
Aging , Ganglia, Spinal/enzymology , Muscle Spindles/enzymology , Neurons/enzymology , Sodium-Potassium-Exchanging ATPase/metabolism , Tibial Nerve/enzymology , Adult , Aged , Aged, 80 and over , Axons/enzymology , Cell Membrane/enzymology , Female , Humans , Isoenzymes , Male , Middle Aged , Young Adult
2.
Exp Neurol ; 225(1): 173-82, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20599980

ABSTRACT

Peripheral nerve grafts (PNG) into the rat spinal cord support axon regeneration after acute or chronic injury, with synaptic reconnection across the lesion site and some level of behavioral recovery. Here, we grafted a peripheral nerve into the injured spinal cord of cats as a preclinical treatment approach to promote regeneration for eventual translational use. Adult female cats received a partial hemisection lesion at the cervical level (C7) and immediate apposition of an autologous tibial nerve segment to the lesion site. Five weeks later, a dorsal quadrant lesion was performed caudally (T1), the lesion site treated with chondroitinase ABC 2 days later to digest growth inhibiting extracellular matrix molecules, and the distal end of the PNG apposed to the injury site. After 4-20 weeks, the grafts survived in 10/12 animals with several thousand myelinated axons present in each graft. The distal end of 9/10 grafts was well apposed to the spinal cord and numerous axons extended beyond the lesion site. Intraspinal stimulation evoked compound action potentials in the graft with an appropriate latency illustrating normal axonal conduction of the regenerated axons. Although stimulation of the PNG failed to elicit responses in the spinal cord distal to the lesion site, the presence of c-Fos immunoreactive neurons close to the distal apposition site indicates that regenerated axons formed functional synapses with host neurons. This study demonstrates the successful application of a nerve grafting approach to promote regeneration after spinal cord injury in a non-rodent, large animal model.


Subject(s)
Peripheral Nerves/transplantation , Spinal Cord Injuries/surgery , Spinal Cord/surgery , Animals , Axons/enzymology , Axons/physiology , Axons/transplantation , Cats , Chondroitin ABC Lyase/therapeutic use , Disease Models, Animal , Female , Nerve Regeneration/physiology , Peripheral Nerves/enzymology , Spinal Cord/enzymology , Spinal Cord Injuries/enzymology , Spinal Cord Injuries/physiopathology , Synaptic Transmission/physiology , Tibial Nerve/cytology , Tibial Nerve/enzymology , Tibial Nerve/transplantation
4.
Neurosci Lett ; 228(2): 71-4, 1997 Jun 06.
Article in English | MEDLINE | ID: mdl-9209101

ABSTRACT

We tested the hypothesis that inhibition of nitric oxide synthase (NOS) following transection of the sciatic nerve in the mouse would adversely influence regeneration of myelinated fibers from the proximal stump. NOS was inhibited by N(omega)-nitro-L-arginine-methyl ester (L-NAME; 10 mg/kg i.p.), a broad spectrum NOS inhibitor given twice daily for the first 10 days following nerve transection in Swiss mice. Controls received the inactive enantiomer N(omega)-nitro-D-arginine methyl ester (D-NAME). Regeneration was assessed by serial recordings of the M potential from interosseous muscles of the foot innervated by sciatic-tibial motor fibers and morphometric analysis of myelinated fibers distal to the injury site. Contrary to expectation, M potentials reappeared earlier in the mice treated with L-NAME and were higher in amplitude (reflecting the number of reinnervating motor fibers) at 10 weeks after the injury. In the L-NAME treated mice, the mean axonal diameter of regenerating tibial myelinated fibers was larger and the fiber size histogram was shifted to larger fibers. Inhibition of NOS in a transected peripheral nerve is associated with enhanced regeneration of myelinated fibers. Local elaboration of NO may be toxic to regenerating axons.


Subject(s)
Nerve Regeneration/physiology , Nitric Oxide Synthase/antagonists & inhibitors , Tibial Nerve/enzymology , Animals , Denervation , Electrophysiology , Enzyme Inhibitors/pharmacology , Male , Mice , NG-Nitroarginine Methyl Ester/pharmacology , Nerve Fibers, Myelinated/drug effects , Nerve Fibers, Myelinated/pathology , Nerve Fibers, Myelinated/physiology , Nerve Regeneration/drug effects , Tibial Nerve/surgery , Tibial Nerve/ultrastructure
5.
J Toxicol Environ Health ; 42(3): 331-42, 1994 Jul.
Article in English | MEDLINE | ID: mdl-8021966

ABSTRACT

In previous studies on rat peripheral nerve, we showed that acrylamide (ACR) exposure was associated with alterations in axonal and Schwann cell elemental composition that were consistent with decreased Na-K ATPase activity. In the present corollary study, the effects of ACR exposure on Na-K ATPase activity were determined in sciatic and tibial nerves. Subacute ACR treatment (50 mg/kg/d x 10 d, ip) significantly (p < .05) decreased Na-K ATPase activity by 45% in sciatic nerve but did not affect this activity in tibial nerve. Subchronic ACR treatment (2.8 mM in drinking water for 30 d) significantly decreased (p < .05) Na-K ATPase activities by 19% and 35% in sciatic and tibial nerves, respectively. Na-K ATPase activity was not altered in sciatic nerve homogenates exposed to 1.0 mM ACR in vitro. Since protein kinase C (PKC) has been proposed to play a role in the modulation of membrane Na-K ATPase function, PKC activity was also measured in sciatic nerve homogenates and subcellular fractions prepared from control and ACR-treated rats. Regardless of the ACR treatment protocol, PKC activity was elevated in nerve cytosol, but not in a particulate fraction. The results of this study suggest that decreased Na-K ATPase activity is involved in ACR-induced perturbation of axoplasmic and Schwann cell elemental composition in rat peripheral nerves and that loss of activity is not due to direct chemical inhibition of the enzyme. The role of PKC in ACR neurotoxicity requires further elucidation.


Subject(s)
Acrylamides/toxicity , Peripheral Nerves/drug effects , Peripheral Nerves/enzymology , Protein Kinase C/drug effects , Sodium-Potassium-Exchanging ATPase/antagonists & inhibitors , Acrylamide , Acrylamides/administration & dosage , Analysis of Variance , Animals , Biological Assay , Male , Rats , Rats, Sprague-Dawley , Sciatic Nerve/drug effects , Sciatic Nerve/enzymology , Tibial Nerve/drug effects , Tibial Nerve/enzymology
6.
Nihon Seikeigeka Gakkai Zasshi ; 66(10): 1059-72, 1992 Oct.
Article in Japanese | MEDLINE | ID: mdl-1460377

ABSTRACT

The functional recovery of the newly formed endplates in the muscle reinnervated by direct neurotization was studied grossly, electrophysiologically and histologically in the anterior tibialis muscle of rats. The proximal stump of the tibial nerve was severed at the ankle level and was embedded at the level of distal one fifth of the muscle where no endplates were detected just after denervation of the muscle. Histologically, the accumulations of acetylcholinesterase activity were detected 4 weeks after neurotization. Electrophysiological study using a multi-channel electrode revealed the two-directional propagation of action potentials 8 weeks after neurotization, and the propagation started from no other sites than the nerve-implantation. The muscle tension revealed 42% of the contralateral muscle 52 weeks after neurotization. These results concluded that the function of the newly formed endplates spread throughout the muscle and it was lasting.


Subject(s)
Motor Endplate/physiology , Muscles/surgery , Nerve Regeneration , Tibial Nerve/transplantation , Action Potentials , Animals , Cholinesterases/metabolism , Male , Muscle Contraction , Muscle Denervation , Muscles/innervation , Muscles/physiology , Rats , Rats, Sprague-Dawley , Tibial Nerve/enzymology , Tibial Nerve/physiology
7.
Br J Cancer ; 45(4): 582-7, 1982 Apr.
Article in English | MEDLINE | ID: mdl-7073948

ABSTRACT

A quantitative, cytochemical assay for measuring lysosomal enzymes in the peripheral nerves of mice has been developed. That the time course of lysosomal enzyme changes after misonidazole (MISO) treatment reflects the degree of neurotoxicity of this agent in the mouse, has been confirmed by the use of two known neurotoxic compounds: methyl mercury and acrylamide. This effect is specific to the peripheral nerves and was not found in liver, kidney, heart or cerebral cortex. Enzyme activities varied with mouse strain and sex, as did the response to MISO treatment. Of the mice studied, female C57 gave the greatest increase in beta-glucuronidase activity. With the MISO dose of 0.6 mg/g/dose the increased enzyme activity was independent of the route of administration and appeared to approach a plateau after 5 daily doses.


Subject(s)
Glucuronidase/metabolism , Misonidazole/pharmacology , Nitroimidazoles/pharmacology , Tibial Nerve/drug effects , Acrylamide , Acrylamides/pharmacology , Animals , Female , Male , Methylmercury Compounds/pharmacology , Mice , Mice, Inbred Strains , Misonidazole/administration & dosage , Sex Factors , Tibial Nerve/enzymology
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