Sleeve bridging of the rhesus monkey ulnar nerve with muscular branches of the pronator teres: multiple amplification of axonal regeneration

Multiple-bud regeneration, i.e., multiple amplification, has been shown to exist in peripheral nerve regeneration. Multiple buds grow towards the distal nerve stump during proximal nerve fiber regeneration. Our previous studies have verified the limit and validity of multiple amplification of peripheral nerve regeneration using small gap sleeve bridging of small donor nerves to repair large receptor nerves in rodents. The present study sought to observe multiple amplification of myelinated nerve fiber regeneration in the primate peripheral nerve. Rhesus monkey models of distal ulnar nerve defects were established and repaired using muscular branches of the right forearm pronator teres. Proximal muscular branches of the pronator teres were sutured into the distal ulnar nerve using the small gap sleeve bridging method. At 6 months after suture, two-finger flexion and mild wrist flexion were restored in the ulnar-sided injured limbs of rhesus monkey. Neurophysiological examination showed that motor nerve conduction velocity reached 22.63 ± 6.34 m/s on the affected side of rhesus monkey. Osmium tetroxide staining demonstrated that the number of myelinated nerve fibers was 1,657 ± 652 in the branches of pronator teres of donor, and 2,661 ± 843 in the repaired ulnar nerve. The rate of multiple amplification of regenerating myelinated nerve fibers was 1.61. These data showed that when muscular branches of the pronator teres were used to repair ulnar nerve in primates, effective regeneration was observed in regenerating nerve fibers, and functions of the injured ulnar nerve were restored to a certain extent. Moreover, multiple amplification was subsequently detected in ulnar nerve axons.     

Endogenous level of TIGAR in brain is associated with vulnerability of neurons to ischemic injury

In previous studies,we showed that TP53-induced glycolysis and apoptosis regulator(TIGAR) protects neurons against ischemic brain injury.In the present study,we investigated the developmental changes of TIGAR level in mouse brain and the correlation of TIGAR expression with the vulnerability of neurons to ischemic injury.We found that the TIGAR level was high in the embryonic stage,dropped at birth,partially recovered in the early postnatal period,and then continued to decline to a lower level in early adult and aged mice.The TIGAR expression was higher after ischemia/reperfusion in mouse brain 8and 12 weeks after birth.Four-week-old mice had smaller infarct volumes,lower neurological scores,and lower mortality rates after ischemia than 8- and12-week-old mice.TIGAR expression also increased in response to oxygen glucose deprivation(OGD)/reoxygenation insult or H_2O_2 treatment in cultured primary neurons from different embryonic stages(E16 and E20).The neurons cultured from the early embryonic period had a greater resistance to OGD and oxidative insult.Higher TIGAR levels correlated with higher pentose phosphate pathway activity and less oxidative stress.Older mice and more mature neurons had more severe DNA and mitochondrial damage than younger mice and less mature neurons in response to ischemia/reperfusion or OGD/reoxygenation insult.Supplementation of cultured neurons with nicotinamide adenine dinuclectide phosphate(NADPH) significantly reduced ischemic injury.These results suggest that TIGAR expression changes during development and its expression level may be correlated with the vulnerability of neurons to ischemic injury.     

Pain and Depression: A Neurobiological Perspective of Their Relationship

Remarkable progresses have been achieved regarding the understanding of the neurobiological bases of pain and depression. The principal role of neurotransmitters, neuromodulators, and neurohormones has been proposed in the development of pain and depression. With the progression of molecular biology, an intricate interaction among biological factors accountable to the development and management of pain and depression has been also shown in a numerous preclinical and clinical researches. This mini-review will briefly describe the current issues and future research direction for better understanding of the relationship between pain and depression.     

Longitudinal correlations between MRE,MRI-PDFF,and liver histology in patients with non-alcoholic steatohepatitis: Analysis of data from a phase II trial of selonsertib

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Comparisons of changes in the two-point discrimination test following muscle fatigue in healthy adults

[Purpose] This study aimed to examine the effects of muscle fatigue on skin sensation by looking at changes in two-point discrimination (2PD) after inducing muscle fatigue. [Subjects] Thirty-four young and healthy adults with no pathological symptoms (17 males; 17 females) participated in this study. [Methods] Continuous isometric contraction was applied to the upper and lower extremities with an intensity of 50% of the maximal muscle strength to trigger muscle fatigue, and then the 2PD test was conducted on the 3 cm medial area of the elbow and 5 cm area of the knee bone. [Results] After muscle fatigue was induced, the 2PD distance significantly increased in the upper and lower extremities of both males and females. Before triggering muscle fatigue, the 2PD distance was longer in males than females, but after causing muscle fatigue, there was no difference between males and females. The increase in 2PD distance after the experiment was more significant in females than males. [Conclusion] Muscle fatigue has an effect of reducing the skin’s sensory faculty by increasing the 2PD distance in the skin. There is a difference in the response of the skin according to body area and gender; therefore, caution is needed to avoid triggering fatigue during exercise.Key words: Muscle fatigue, Skin sensation, Two-point discrimination     

The effects of stretching exercise for upper trapezius on the asymmetric rate of bite force

[Purpose] The purpose of this study was to observe the effects of stretching the upper trapezius muscle on the asymmetric rate of bite force. [Subjects] Forty-seven female university students who had all their original teeth, had no disorders in the temporomandibular joints, and had never worn braces; participated in this study. [Methods] An occlusometer was used to measure biting forces. Subsequently, stretching exercises of the upper trapezius were performed. The subjects were divided into 3 groups at the start of the testing: the asymmetric rate of the first group was less than 10%; the asymmetric rate of the second group was between 10% and 20%; and the asymmetric rate of the third group was more than 20%. The stretching exercises were done on the dominant side of the upper trapezius. [Results] After the stretching exercises of the upper trapezius, the results showed that for the first group, whose asymmetric rate of biting force was less than 10%, there was a significant increase in asymmetric rate (from 5.1% to 10.3%). For the second group, whose asymmetric rate of biting force was measured to be between 10% and 20%, the asymmetric rate decreased from 14.7% to 14.3%, but the change was not statistically significant. For the third group, whose asymmetric rate of biting force was more than 20%, there was a significant decrease in asymmetric rate (from 27.8% to 12.6%). [Conclusion] We concluded that stretching exercises of the upper trapezius muscle had a direct effect on the asymmetric rate of biting force.Key words: Asymmetric rate of biting force, Upper trapezius, Stretching exercise     

Long-term potentiation decay and memory loss are mediated by AMPAR endocytosis

Long-term potentiation (LTP) of synaptic strength between hippocampal neurons is associated with learning and memory, and LTP dysfunction is thought to underlie memory loss. LTP can be temporally and mechanistically classified into decaying (early-phase) LTP and nondecaying (late-phase) LTP. While the nondecaying nature of LTP is thought to depend on protein synthesis and contribute to memory maintenance, little is known about the mechanisms and roles of decaying LTP. Here, we demonstrated that inhibiting endocytosis of postsynaptic α-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid receptors (AMPARs) prevents LTP decay, thereby converting it into nondecaying LTP. Conversely, restoration of AMPAR endocytosis by inhibiting protein kinase Mζ (PKMζ) converted nondecaying LTP into decaying LTP. Similarly, inhibition of AMPAR endocytosis prolonged memory retention in normal animals and reduced memory loss in a murine model of Alzheimer’s disease. These results strongly suggest that an active process that involves AMPAR endocytosis mediates the decay of LTP and that inhibition of this process can prolong the longevity of LTP as well as memory under both physiological and pathological conditions.