Summary CNS injury often severs axons. Scar tissue that forms locally at the lesion site is thought to block axonal regeneration, resulting in permanent functional deficits. We report that inhibiting the generation of progeny by a subclass of pericytes led to decreased fibrosis and extracellular matrix deposition after spinal cord injury in mice. Regeneration of raphespinal and corticospinal tract axons was enhanced and sensorimotor function recovery improved following spinal cord injury in animals with attenuated pericyte-derived scarring. Using optogenetic stimulation, we demonstrate that regenerated corticospinal tract axons integrated into the local spinal cord circuitry below the lesion site. The number of regenerated axons correlated with improved sensorimotor function recovery. In conclusion, attenuation of pericyte-derived fibrosis represents a promising therapeutic approach to facilitate recovery following CNS injury.

Synchronous activity of cortical inhibitory interneurons expressing parvalbumin (PV) underlies the expression of cortical gamma rhythms. Paradoxically, deficient PV inhibition is associated with increased broadband gamma power. Increased baseline broadband gamma is also a prominent characteristic in schizophrenia, and a hallmark of network alterations induced by N-methyl-D-aspartate receptor (NMDAR) antagonists such as ketamine. It has been questioned if enhanced broadband gamma power is a true rhythm, and if rhythmic PV inhibition is involved or not. It has been suggested that asynchronous and increased firing activities underlie broadband power increases spanning the gamma band. Using mice lacking NMDAR activity specifically in PV neurons to model deficient PV inhibition, we here show that local LFP (local field potential) oscillations and neuronal activity with decreased synchronicity generate increases in prefrontal broadband gamma power. Specifically, reduced spike time precision of both local PV interneurons and wide-spiking (WS) excitatory neurons contribute to increased firing rates, and spectral leakage of spiking activity (spike “contamination”) affecting the broadband gamma band. Desynchronization was evident at multiple time scales, with reduced spike-LFP entrainment, reduced cross-frequency coupling, and fragmentation of brain states. While local application of S(+)-ketamine in wildtype mice triggered network desynchronization and increases in broadband gamma power, our investigations suggest that disparate mechanisms underlie increased power of broadband gamma caused by genetic alteration of PV interneurons, and ketamine-induced power increases in broadband gamma. Our studies, thus, confirm that broadband gamma increases can arise from asynchronous activities, and demonstrate that long-term deficiency of PV inhibition can be a contributor.

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Synchronous activity of cortical inhibitory interneurons expressing parvalbumin (PV) underlies the expression of cortical gamma rhythms. Paradoxically, deficient PV inhibition is associated with increased broadband gamma power. Increased baseline broadband gamma is also a prominent characteristic in schizophrenia, and a hallmark of network alterations induced by N-methyl-D-aspartate receptor (NMDAR) antagonists such as ketamine. It has been questioned if enhanced broadband gamma power is a true rhythm, and if rhythmic PV inhibition is involved or not. It has been suggested that asynchronous and increased firing activities underlie broadband power increases spanning the gamma band. Using mice lacking NMDAR activity specifically in PV neurons to model deficient PV inhibition, we here show that local LFP (local field potential) oscillations and neuronal activity with decreased synchronicity generate increases in prefrontal broadband gamma power. Specifically, reduced spike time precision of both local PV interneurons and wide-spiking (WS) excitatory neurons contribute to increased firing rates, and spectral leakage of spiking activity (spike "contamination") affecting the broadband gamma band. Desynchronization was evident at multiple time scales, with reduced spike-LFP entrainment, reduced cross-frequency coupling, and fragmentation of brain states. While local application of S(+)-ketamine in wildtype mice triggered network desynchronization and increases in broadband gamma power, our investigations suggest that disparate mechanisms underlie increased power of broadband gamma caused by genetic alteration of PV interneurons, and ketamine-induced power increases in broadband gamma. Our studies, thus, confirm that broadband gamma increases can arise from asynchronous activities, and demonstrate that long-term deficiency of PV inhibition can be a contributor..

Sandwich-type ordered mesoporous carbon/graphene nanocomposites were successfully synthesized using 2D ordered mesoporous silica/graphene nanocomposites as the hard template and an ionic liquid as a N-rich carbon source. We used an ionic liquid of 1-(3-cyanopropyl)-3-methylimidazolium dicyanamide containing nitrile groups (-CN) in the cation and anion as a carbon precursor for the preparation of the nanocomposites. Nitriles do not decompose under thermal treatment in an inert gas atmosphere, but leave significant amounts of N-rich carbon materials. The nanocomposites had a large surface area (1,316 m 2 ·g -1 ), an average pore diameter of 5.9 nm, and high electrical conductivity. The nanocomposite electrode showed a high specific capacitance of 190 F·g -1 at 0.5 A·g -1 in 1 M TEABF 4 /AN electrolyte and a good rate capability between 0 and 2.7 V for supercapacitor (or ultracapacitor) applications.

ObjectiveTo determine whether MRI is able to demonstrate the effect of radiation synovectomy after the intra-articular injection of holmium-166-chitosan complex for the treatment of rheumatoid arthritis of the knee.Materials and MethodsFourteen patients aged 36-59 years were treated with 10-20 mCi of holmium-166-chitosan complex. A criterion for inclusion in this study was the absence of observable improvement after 3- or more months of treatment of the knee with disease-modifying anti-rheumatic drugs. MR images were acquired both prior to and 4-months after treatment. Clinical evaluation included the use of visual analog scales to assess pain, and the circumference of the knee and its range of motion were also determined. MR evaluation included measurement of the volume of synovial enhancement and wall thickness, the amount of joint effusion, and quantifiable scoring of bone erosion, bone edema and lymph nodes.ResultsVisual analog scale readings decreased significantly after radiation synovectomy (p < 0.05). MRI showed that joint effusion decreased significantly (p < 0.05), and that the volume of synovial enhancement tended to decrease, but to an insignificant extent (p = 0.107).ConclusionThe decreased joint effusion noted at 4-month follow-up resulted from radiation synovectomy of the rheumatoid knee by means of intra-articular injection of holmium-166-chitosan complex.

BackgroundThe cold/heat questionnaire is one of the most actively developed patient diagnostic tools in traditional Korean medicine (hereafter abbreviated as TKM) because of its objectivity. Unfortunately, the existing questionnaires contain too many items to hold the respondent's attention. In the current study, we aimed to develop an optimized cold/heat questionnaire to be used as a complement to the existing questionnaires.MethodsWe developed a new cold/heat questionnaire based on a domain analysis of the existing questionnaires. The questionnaire's reliability was examined via two test–retest reliability analyses involving 1890 individuals in November 2013 and February 2014. Its validity was examined using a professional cold/heat diagnosis kappa value.ResultsThe new cold/heat questionnaire consisted of a total of seven items, which were created based on an analysis of the existing questionnaires. A reliability analysis performed using the study participants revealed a correlation coefficient of 0.609, 74.5% agreement with professional cold/heat diagnoses by TKM practitioners, and a kappa value of 0.487.ConclusionIn the current study, we developed an optimized cold/heat questionnaire. The level of agreement between the questionnaire and professional cold/heat diagnoses by TKM practitioners was significant, which indicates great potential for its widespread use as a diagnostic tool in TKM.

Studies in rats, monkeys, and humans have found action-value signals in multiple regions of the brain. These findings suggest that action-value signals encoded in these brain structures bias choices toward higher expected rewards. However, previous estimates of action-value signals might have been inflated by serial correlations in neural activity and also by activity related to other decision variables. Here, we applied several statistical tests based on permutation and surrogate data to analyze neural activity recorded from the striatum, frontal cortex, and hippocampus. The results show that previously identified action-value signals in these brain areas cannot be entirely accounted for by concurrent serial correlations in neural activity and action value. We also found that neural activity related to action value is intermixed with signals related to other decision variables. Our findings provide strong evidence for broadly distributed neural signals related to action value throughout the brain.