Selective Separation of U(VI) from Pu(IV) by 2,9-Diamide-1,10-phenanthroline Ligands at High Acidity: Extraction and Coordination Chemistry.

During the PUREX process, the separation between U(VI) and Pu(IV) is achieved by reducing Pu(IV) to Pu(III), which is complicated and energy-consuming. To address this issue, we report here the first case of separation of U(VI) from Pu(IV) by o-phenanthroline diamide ligands under high acidity. Two new o-phenanthroline diamide ligands (1,10-phenanthroline-2,9-diyl)bis(indolin-1-ylmethanone) (L1) and (1,10-phenanthroline-2,9-diyl)bis((2-methylindolin-1-yl)methanone) (L2) were synthesized, which can effectively separate U(VI) from Pu(IV) even at 4 mol/L HNO3. The highest separation factor of U(VI) and Pu(IV) can reach over 1000, setting a new record for the separation of U(VI) from Pu(IV) under high acidity. Furthermore, extracted U(VI) can be easily recovered with water or dilute nitric acid, and the extraction performance remains stable even after 150 kGy gamma irradiation, which provides solid experimental support for potential engineering applications. The results of UV-vis titration and single-crystal X-ray diffraction measurements show that the 1:1 complex formed by L1 with U(VI) is more stable than all of the previously reported phenanthroline ligands, which reasonably reveals that the ligand L1 designed in this work has excellent affinity for U(VI). The findings of this work promise to contribute to the facilitation of the PUREX process by avoiding the use of reducing agents. It also provides new clues for designing ligands to achieve efficient separation between U(VI) and Pu(IV) at high acidity.

Digital phenotyping: An equal opportunity approach to reducing disparities in Alzheimer's disease and related dementia research.

A rapidly aging world population is fueling a concomitant increase in Alzheimer's disease (AD) and related dementias (ADRD). Scientific inquiry, however, has largely focused on White populations in Australia, the European Union, and North America. As such, there is an incomplete understanding of AD in other populations. In this perspective, we describe research efforts and challenges of cohort studies from three regions of the world: Central America, East Africa, and East Asia. These cohorts are engaging with the Davos Alzheimer's Collaborative (DAC), a global partnership that brings together cohorts from around the world to advance understanding of AD. Each cohort is poised to leverage the widespread use of mobile devices to integrate digital phenotyping into current methodologies and mitigate the lack of representativeness in AD research of racial and ethnic minorities across the globe. In addition to methods that these three cohorts are already using, DAC has developed a digital phenotyping protocol that can collect ADRD-related data remotely via smartphone and/or in clinic via a tablet to generate a common data elements digital dataset that can be harmonized with additional clinical and molecular data being collected at each cohort site and when combined across cohorts and made accessible can provide a global data resource that is more racially/ethnically represented of the world population.

Association of Low Arousal Threshold Obstructive Sleep Apnea Manifestations with Body Fat and Water Distribution.

Obstructive sleep apnea (OSA) with a low arousal threshold (low-ArTH) phenotype can cause minor respiratory events that exacerbate sleep fragmentation. Although anthropometric features may affect the risk of low-ArTH OSA, the associations and underlying mechanisms require further investigation. This study investigated the relationships of body fat and water distribution with polysomnography parameters by using data from a sleep center database. The derived data were classified as those for low-ArTH in accordance with criteria that considered oximetry and the frequency and type fraction of respiratory events and analyzed using mean comparison and regression approaches. The low-ArTH group members (n = 1850) were significantly older and had a higher visceral fat level, body fat percentage, trunk-to-limb fat ratio, and extracellular-to-intracellular (E-I) water ratio compared with the non-OSA group members (n = 368). Significant associations of body fat percentage (odds ratio [OR]: 1.58, 95% confident interval [CI]: 1.08 to 2.3, p < 0.05), trunk-to-limb fat ratio (OR: 1.22, 95% CI: 1.04 to 1.43, p < 0.05), and E-I water ratio (OR: 1.32, 95% CI: 1.08 to 1.62, p < 0.01) with the risk of low-ArTH OSA were noted after adjustments for sex, age, and body mass index. These observations suggest that increased truncal adiposity and extracellular water are associated with a higher risk of low-ArTH OSA.

Risk factor identification and prediction models for prolonged length of stay in hospital after acute ischemic stroke using artificial neural networks.

Background: Accurate estimation of prolonged length of hospital stay after acute ischemic stroke provides crucial information on medical expenditure and subsequent disposition. This study used artificial neural networks to identify risk factors and build prediction models for a prolonged length of stay based on parameters at the time of hospitalization. Methods: We retrieved the medical records of patients who received acute ischemic stroke diagnoses and were treated at a stroke center between January 2016 and June 2020, and a retrospective analysis of these data was performed. Prolonged length of stay was defined as a hospital stay longer than the median number of days. We applied artificial neural networks to derive prediction models using parameters associated with the length of stay that was collected at admission, and a sensitivity analysis was performed to assess the effect of each predictor. We applied 5-fold cross-validation and used the validation set to evaluate the classification performance of the artificial neural network models. Results: Overall, 2,240 patients were enrolled in this study. The median length of hospital stay was 9 days. A total of 1,101 patients (49.2%) had a prolonged hospital stay. A prolonged length of stay is associated with worse neurological outcomes at discharge. Univariate analysis identified 14 baseline parameters associated with prolonged length of stay, and with these parameters as input, the artificial neural network model achieved training and validation areas under the curve of 0.808 and 0.788, respectively. The mean accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of prediction models were 74.5, 74.9, 74.2, 75.2, and 73.9%, respectively. The key factors associated with prolonged length of stay were National Institutes of Health Stroke Scale scores at admission, atrial fibrillation, receiving thrombolytic therapy, history of hypertension, diabetes, and previous stroke. Conclusion: The artificial neural network model achieved adequate discriminative power for predicting prolonged length of stay after acute ischemic stroke and identified crucial factors associated with a prolonged hospital stay. The proposed model can assist in clinically assessing the risk of prolonged hospitalization, informing decision-making, and developing individualized medical care plans for patients with acute ischemic stroke.

Left Atrial Appendage Thrombosis and Oral Anticoagulants: A Meta-Analysis of Risk and Treatment Response.

Background: Left atrial appendage thrombus (LAAT) is the main cause of cardioembolism in patients with nonvalvular atrial fibrillation (AF). Emerging evidence indicates that direct oral anticoagulants (DOACs) may be a preferred, safer choice for patients with LAAT. However, current guidelines indicate vitamin K antagonist (VKA) as the preferred treatment for LAAT. We conducted a meta-analysis to compare the efficacy of VKA and DOAC for the treatment of LAAT. Methods: The search was conducted in the PubMed, Embase, Google Scholar, and Cochrane Library databases from inception to July 2022, with the language restricted to English. A first analysis was conducted to evaluate the risk of LAAT under VKA or DOAC treatment. A second analysis was conducted to compare the resolution of LAAT under VKA and DOAC treatment. Results: In 13 studies comparing LAAT incidence rates under VKA and DOAC treatment, significant superiority of DOAC was detected (pooled RR = 0.65, 95% CI = 0.47-0.90, p = 0.009) with moderate heterogeneity being identified in the pooled studies. In 13 studies comparing LAAT resolution under VKA and DOAC use, treatment with DOAC exhibited a significantly increased probability of LAAT resolution compared with VKA (pooled odds ratio = 1.52, 95% CI = 1.02-2.26, p = 0.040). Conclusions: This meta-analysis suggests a superiority of DOAC over VKA with respect to LAAT incidence in people with AF and the likelihood of LAAT resolution. Due to their established safety profile, DOAC is a preferable choice for anticoagulation, although further randomized controlled studies are warranted to provide further evidence of their suitability as a new recommended treatment.

Validation of the Taiwanese Version of ACE-III (T-ACE-III) to Detect Dementia in a Memory Clinic.

OBJECTIVE: The Addenbrooke's Cognitive Examination III (ACE-III) is a 100-points cognitive test used in detecting dementia in many countries. There has been no validation study of the ACE-III in patients with suspected dementia in a Taiwanese population, where the language is traditional Chinese. We aimed to culturally adapt and validate the ACE-III as a cognitive assessment tool for differentiating between people with and without dementia presenting to healthcare professionals in Taiwan with possible dementia. METHODS: We culturally adapted the ACE-III for Taiwan (T-ACE-III) and tested it with consenting patients with suspected dementia in northern Taiwan who had been through the diagnostic process. We calculated receiver operating characteristic (ROC) curves to test the ability of the T-ACE-III to differentiate between dementia and non-dementia cases using clinician diagnosis as the gold standard. We generated the Youden Index to determine the best cut-off score. RESULTS: We recruited 90 Taiwanese individuals aged 49-93 years: 24 males and 33 females had dementia and 12 males and 21 females did not. The area under the ROC curve was 0.99 for distinguishing dementia from non-dementia. The T-ACE-III had a sensitivity of 100% and specificity of 78.8% when the cut-off score was 86/87. With a cut-off value of 73/74, the specificity was 100.0%, and sensitivity 89.5%. The highest Youden Index was 0.895, indicating the best overall cut-off point to be 73/74. CONCLUSIONS: The T-ACE-III is an acceptable cognitive test with excellent psychometric properties for discriminating dementia from non-dementia in Taiwanese populations in memory clinic settings.

The neurocognitive profiles of justice involved people with foetal alcohol spectrum disorder: A systematic review.

Foetal alcohol spectrum disorder (FASD) is highly prevalent in criminal justice settings. Despite increased awareness of the neurocognitive deficits among justice-involved individuals with FASD, no systematic evaluation of the literature in the field has been conducted to date. We aimed to conduct a systematic review of the literature on the neurocognitive profiles of justice-involved individuals with FASD, by searching five key electronic databases, dissertations database, and Google scholar, up to January 2021. The findings indicate that when contrasted with comparison groups, justice-involved individuals with FASD display significant impairment in a greater number of neurocognitive domains including intellectual capacity, executive function, language, academic achievements, motor skills, and adaptive living skills. The relatively small number of the studies included in the review, along with the confounding effects of comorbidities among study participants, precludes drawing firm conclusions about the true extent and implications of neurocognitive deficits in this population. To advance the field further, there is an urgent need to conduct robust studies involving larger samples of justice-involved individuals with FASD and suitable comparison groups. Advancing knowledge in the field can have important implications for understanding of the antecedents of offending behaviour in this population, and informing strategies for early identification and intervention.

Transcranial direct current stimulation for empathy: A systematic review and meta-analysis.

Transcranial Direct Current Stimulation (tDCS) has been used to modulate empathy, but no studies have meta-analyzed the evidence base for its efficacy. This study aimed to determine the efficacy of tDCS at modulating empathy. We conducted a systematic review and meta-analysis of randomized controlled trials involving anodal or cathodal versus sham tDCS to modulate empathy in healthy adults and clinical populations. Random-effects modelling was applied to pooling overall efficacy estimates using standardized mean differences (Hedge's g) and 95% confidence intervals. Outcome measures for tasks designed to measure empathy were reaction time and accuracy. Anodal tDCS appears to improve lab-based computerized measures of cognitive empathy in healthy adult volunteers. While the evidence provided by this review may be of relevance to individuals with impaired empathic capabilities, the generalizability of our findings is geared towards nonclinical populations given the preponderance of healthy volunteers in our review. Hence, it is not clear if moderate improvements in speed and accuracy on lab-based computerized empathy measures would lead to meaningful clinical improvements. Future studies should consider the use of tDCS to modulate empathy in clinical populations.

High molecular weight form of hyaluronic acid reduces neuroinflammatory response in injured sciatic nerve via the intracellular domain of CD44.

Inflammatory response after peripheral nerve injury is required for clearance of tissue debris and effective regeneration. Studies have revealed that hyaluronic acid (HA) may exert different properties depending on their molecular size. High molecular weight HA (>>1,000 kDa; HMW-HA) displays immunosuppressive properties, whereas low molecular weight HA (<800 kDa; LMW-HA) induces proinflammatory responses. The role of HMW-HA interaction with CD44, a major HA receptor, in neuroinflammatory responses has not been fully elucidated. The purpose of this experimental study was to investigate the effects of topical applications of HMW-HA on the sciatic nerve injury in an adult rat model. At the crush site on the sciatic nerve, the recordings of compound muscle action potential (CMAP) and the levels of several proteins related to inflammatory response were assessed at time intervals of 2, 4, and 6 weeks postsurgery. Here, we show that the recovery effect of HMW-HA treatment had significantly shortened latency and increased amplitude of CMAP compared with crushed alone, crushed plus γ-secretase inhibitor with or without HA treatment at 6 weeks after surgery. Our data reveal that HMW-HA could downregulate the expression of IL1-ß, TLR4, and MMP-9, whereas these proteins expression were increased when the CD44-ICD activity was inhibited using γ-secretase inhibitor. Our findings demonstrated a novel role of CD44-ICD in HA-mediated recovery of peripheral nerve injury. Clinical relevance: an alternative for the regeneration of peripheral nerve injury.

The Effects of Non-invasive Brain Stimulation on Impulsivity in People with Mental Disorders: a Systematic Review and Explanatory Meta-Analysis.

Impulsivity is a multi-faceted construct that underpins various mental health disorders. Impulsive behavior exacts a substantial health and economic burden, hence the importance of developing specific interventions to target impulsivity. Two forms of non-invasive brain stimulation, namely transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS), have been used to modulate impulsivity. To date, no reviews have systematically examined their effects on modulating impulsivity in people with mental health disorders. We conducted a systematic review and meta-analysis of the literature from AMED, Embase, Medline and PsycINFO databases on the use of rTMS and tDCS to modulate impulsivity in people with mental health disorders. Results from 11 tDCS and 18 rTMS studies indicate that tDCS has a significant, albeit small, effect on modulating impulsivity (g = 0.29; 95% CI, 0.09 to 0.48; p = .004) whereas rTMS has no significant effect on impulsivity (g = -0.08; 95% Cl, -0.35 to 0.19; p = .550). Subgroup analyses identified the key parameters required to enhance the effects of tDCS and rTMS on impulsivity. Gender and stimulation intensity acted as significant moderators for effects of rTMS on impulsivity. There is insufficient evidence to support the use of tDCS or rTMS in clinical practice to reduce impulsivity in people with mental health disorders. The use of standardized non-invasive brain stimulation protocols and outcome measures in patients with the same diagnosis is advised to minimize methodological heterogeneity.

Hydrolyzed Chicken Extract (ProBeptigen®) on Cognitive Function in Healthy Middle-Aged People: A Randomized Double-Blind Trial.

Cognitive decline is an important issue of global public health. Cognitive aging might begin at middle adulthood, the period particularly vulnerable to stress in lifespan. Essence of chicken (EOC) has consistently demonstrated its beneficial effects on various cognitive domains as nutritional supplementation. This study primarily aimed to examine the cognitive enhancement effects of ProBeptigen® (previously named CMI-168), hydrolyzed peptides extracted from EOC, in healthy middle-aged people under mild stress. Ninety healthy subjects were randomly assigned into the ProBeptigen® or placebo group for eight weeks. Neurocognitive assessment, event-related potentials (ERPs), and blood tests were conducted before, during, and after the treatment. The ProBeptigen® group outperformed placebo group on Logical Memory subtests of Wechsler Memory Scale-third edition (WMS-III) and Spatial Working Memory task in the Cambridge Neuropsychological Test Automated Battery (CANTAB). The anti-inflammatory effects of ProBeptigen® in humans were also confirmed, with progressively declining high-sensitivity C-reactive protein (hs-CRP) levels. Regular dietary supplementation of ProBeptigen® is suggested to improve verbal short- and long-term memory as well as spatial working memory, and reduce inflammation in middle-aged healthy individuals with stress. The effects of ProBeptigen® on cognition warrant further investigation. (NCT03612752).

Presynaptic SNAP-25 regulates retinal waves and retinogeniculate projection via phosphorylation.

Patterned spontaneous activity periodically displays in developing retinas termed retinal waves, essential for visual circuit refinement. In neonatal rodents, retinal waves initiate in starburst amacrine cells (SACs), propagating across retinal ganglion cells (RGCs), further through visual centers. Although these waves are shown temporally synchronized with transiently high PKA activity, the downstream PKA target important for regulating the transmission from SACs remains unidentified. A t-SNARE, synaptosome-associated protein of 25 kDa (SNAP-25/SN25), serves as a PKA substrate, implying a potential role of SN25 in regulating retinal development. Here, we examined whether SN25 in SACs could regulate wave properties and retinogeniculate projection during development. In developing SACs, overexpression of wild-type SN25b, but not the PKA-phosphodeficient mutant (SN25b-T138A), decreased the frequency and spatial correlation of wave-associated calcium transients. Overexpressing SN25b, but not SN25b-T138A, in SACs dampened spontaneous, wave-associated, postsynaptic currents in RGCs and decreased the SAC release upon augmenting the cAMP-PKA signaling. These results suggest that SN25b overexpression may inhibit the strength of transmission from SACs via PKA-mediated phosphorylation at T138. Moreover, knockdown of endogenous SN25b increased the frequency of wave-associated calcium transients, supporting the role of SN25 in restraining wave periodicity. Finally, the eye-specific segregation of retinogeniculate projection was impaired by in vivo overexpression of SN25b, but not SN25b-T138A, in SACs. These results suggest that SN25 in developing SACs dampens the spatiotemporal properties of retinal waves and limits visual circuit refinement by phosphorylation at T138. Therefore, SN25 in SACs plays a profound role in regulating visual circuit refinement.

Effects of intermittent theta burst stimulation applied to the left dorsolateral prefrontal cortex on empathy and impulsivity in healthy adult males.

Impulsivity and empathy are clinically relevant multi-dimensional concepts. Existing evidence suggests the left dorsolateral prefrontal cortex (LDLPFC) plays a crucial role in impulsivity and empathy. However, the neuromodulation effect of excitatory repetitive transcranial magnetic stimulation at the LDLPFC is insufficiently explored in the current literature. To address this important gap in the literature, we aimed to examine the effects of intermittent theta burst stimulation (iTBS) at the LDLPFC on impulsivity and empathy. A single-blind sham-controlled randomised crossover trial involving twenty-three healthy male adults was conducted. The iTBS protocol delivered 1800 pulses to the LDLPFC at 80% of the motor threshold in each condition. Trait impulsivity and empathy were measured at baseline using the Barrett Impulsiveness Scale and UPPS-P Impulsiveness Scale. The Reading the Mind in the Eyes Test, Information Sampling Task, and Adjusting Amount Task serving as behavioural measures of empathy, cognitive and temporal impulsivity respectively were administered before and after iTBS sessions. No significant changes were found on any of the measures after iTBS at the LDLPFC compared to the sham stimulation. Neuromodulation at the LDLPFC using iTBS may not alter cognitive empathy and temporal and cognitive impulsivity. Further research is required using amended protocols in a large-scaled sample.

The Effects of rTMS on Impulsivity in Normal Adults: a Systematic Review and Meta-Analysis.

Impulsivity is a multi-dimensional construct that is regarded as a symptom of many psychiatric disorders. Harm resulting from impulsive behaviour can be substantial for the individuals concerned, for their social network, and for wider society. Therefore, the importance of developing therapeutic interventions to target impulsivity is paramount. We conducted a systematic review and meta-analysis of the literature from AMED, Embase, Medline, and PsycINFO databases on the use of repetitive transcranial magnetic stimulation (rTMS) in healthy adults to modulate different subdomains (motor, temporal and reflection) of impulsivity. The results indicated that rTMS has distinct effects on different impulsivity subdomains. It has a significant, albeit small, effect on modulating motor impulsivity (g = 0.30, 95% CI, 0.17 to 0.43, p < .001) and a moderate effect on temporal impulsivity (g = 0.59, 95% CI, 0.32 to 0.86, p < .001). Subgroup analyses (e.g., excitatory vs. inhibitory rTMS, conventional rTMS vs. theta burst stimulation, analyses by stimulation sites, and type of outcome measure used) identified key parameters associated with the effects of rTMS on motor and temporal impulsivity. Age, sex, stimulation intensity and the number of pulses were not significant moderators for effects of rTMS on motor impulsivity. Due to lack of sufficient data to inform a meta-analysis, it has not been possible to assess the effects of rTMS on reflection impulsivity. The present findings provide preliminary evidence that rTMS can be used to modulate motor and temporal impulsivity in healthy individuals. Further studies are required to extend the use of rTMS to modulate impulsivity in those at most risk of engaging in harmful behaviour as a result of impulsivity, such as patients with offending histories and those with a history of self-harming behaviour.

Schwann-Cell Autophagy, Functional Recovery, and Scar Reduction After Peripheral Nerve Repair.

The functional outcome after peripheral nerve repair is often unpredictable for many reasons, e.g., the severity of neuronal death and scarring. Axonal degeneration significantly affects outcomes. Post-injury axonal degeneration in peripheral nerves is accompanied by myelin degradation initiated by Schwann cells (SCs), which activate autophagy, a ubiquitous cytoprotective process essential for degrading and recycling cellular constituents. Scar formation occurs concomitantly with nerve insult and axonal degeneration. The association between SC autophagy and the mechanisms of nerve scar formation is still unknown. A rat model of peripheral nerve lesions induced by sciatic nerve transection injuries was used to examine the function of autophagy in fibrosis reduction during the early phase of nerve repair. Rats were treated with rapamycin (autophagy inducer) or 3-methyladenine (autophagy inhibitor). One week after the nerve damage, fibrosis was potently inhibited in rapamycin-treated rats and, based on gait analysis, yielded a better functional outcome. Immunohistochemistry showed that the autophagic activity of SCs and the accumulation of neurofilaments were upregulated in rapamycin-treated rats. A deficiency of SC autophagic activity might be an early event in nerve scar formation, and modulating autophagy might be a powerful pharmacological approach for improving functional outcomes.

Excitatory repetitive transcranial magnetic stimulation applied to the right inferior frontal gyrus has no effect on motor or cognitive impulsivity in healthy adults.

BACKGROUND: Impulsivity is a multi-faceted concept. It is a crucial feature of many neuropsychiatric disorders. Three subtypes of impulsivity have been identified: motor, temporal, and cognitive impulsivity. Existing evidence suggests that the right inferior frontal gyrus (rIFG) plays a crucial role in impulsivity, and such a role has been elucidated using inhibitory repetitive transcranial magnetic stimulation (rTMS). There is a dearth of studies using excitatory rTMS at the rIFG, an important gap in the literature this study aimed to address. METHODS: Twenty healthy male adults completed a single-blind sham-controlled randomised crossover study aimed at assessing the efficacy of rTMS in the neuromodulation of impulsivity. This involved delivering 10-Hz excitatory rTMS to the rIFG at the intensity of 100% motor threshold with 900 pulses per session. Trait impulsivity was measured at baseline using the Barrett Impulsiveness Scale and UPPS-P Impulsiveness Scale. The Stop Signal Task (SST) and Information Sampling Task (IST), administered before and after rTMS sessions, were used as behavioural measures of impulsivity. RESULTS: No significant changes on any measures from either SST or IST after active rTMS at the rIFG compared to the sham-controlled condition were found. CONCLUSIONS: Excitatory rTMS applied to the rIFG did not have a statistically significant effect on response inhibition and reflective/cognitive impulsivity. Further research is required before drawing firm conclusions. This may involve a larger sample of highly impulsive individuals, a different stimulation site or a different TMS modality such as theta burst stimulation.

The effect of molecular weight and concentration of hyaluronan on the recovery of the rat sciatic nerve sustaining acute traumatic injury.

Acute traumatic peripheral nerve injury remains a significant clinical issue affecting mostly young individuals and their productivity in spite of advances in current medicine. Hyaluronan has been explored in this scenario for its anti-adhesive and high biocompatibility properties for decades. The molecular weight and concentration of the locally applied hyaluronan has been overlooked and not optimized. We used different molecular weights and concentrations of hyaluronan in a rat sciatic nerve crush injury model and found better overall outcomes with high molecular weight (3000 kDa) hyaluronan. The anti-inflammatory effect of the higher molecular weight hyaluronan may have a more favorable effect. We conclude that the optimization of hyaluronan is necessary when incorporating hyaluronan in the engineering of biomaterials for use in acute traumatic peripheral nerve injury.

Effects of decompression on behavioral, electrophysiologic, and histomorphologic recovery in a chronic sciatic nerve compression model of streptozotocin-induced diabetic rats.

PURPOSE: To determine susceptibility to decompression surgery in diabetic and nondiabetic peripheral neuropathy using a chronic compression neuropathy model. MATERIALS AND METHODS: Twenty-four streptozotocin-induced diabetic rats were randomly divided into three groups: group I, chronic compression of the left sciatic nerve for 4 weeks with decompression; group II, similar without decompression; and group III, sham exposing the sciatic nerve only. The other 24 nondiabetic rats were assigned to groups IV-VI, which received compression-decompression, compression, and the sham operation, respectively. Mixed-nerve-elicited somatosensory evoked potentials (M-SSEPs) and compound muscle action potentials (CMAPs) were measured to verify the compression neuropathy in the posttreatment follow-up. Behavioral observations in thermal hyperalgesia tests were quantified before electrophysiologic examinations. Treated and contralateral nerves were harvested for histomorphologic analysis. RESULTS: Chronic compression of sciatic nerve induced significant reduction of amplitude and increment of latency of M-SSEP and CMAP in both diabetic and nondiabetic rats. Diabetic group changes were more susceptible. Decompression surgery significantly improved both sensory and motor conduction, thermal hyperalgesia, and the mean myelin diameter of the rat sciatic nerve in both diabetic and nondiabetic groups. Near full recovery of motor and sensory function occurred in the nondiabetic rats, but not in the diabetic rats 8 weeks postdecompression. CONCLUSION: Behavioral, electrophysiologic, and histomorphologic findings indicate that decompression surgery is effective in both diabetic and nondiabetic peripheral neuropathy.

Caffeine treatment aggravates secondary degeneration after spinal cord injury.

Spinal cord injury (SCI) often results in some form of paralysis. Recently, SCI therapy has been focused on preventing secondary injury to reduce both neuroinflammation and lesion size so that functional outcome after an SCI may be improved. Previous studies have shown that adenosine receptors (AR) are a major regulator of inflammation after an SCI. The current study was performed to examine the effect of caffeine, a pan-AR blocker, on spontaneous functional recovery after an SCI. Animals were assigned into 3 groups randomly, including sham, PBS and caffeine groups. The rat SCI was generated by an NYU impactor with a 10 g rod dropped from a 25 mm height at thoracic 9 spinal cord level. Caffeine and PBS were injected daily during the experiment period. Hind limb motor function was evaluated by the Basso, Beattie, Bresnahan (BBB) locomotor rating scale at 1 week and 4 weeks after the SCI. Spinal cord segments were collected after final behavior evaluation for morphological analysis. The tissue sparing was evaluated by luxol fast blue staining. Immunofluorescence stain was employed to assess astrocyte activation and neurofilament positioning, while microglia activation was examined by immunohistochemistry stain.The results showed that spontaneous functional recovery was blocked after the animals were subjected caffeine daily. Moreover, caffeine administration increased the demyelination area, promoted astrocyte and microglia activation and decreased the quantity of neurofilaments. These findings suggest that the neurotoxicity effect of caffeine may be associated with the inhibition of neural repair and the promotion of neuroinflammation.

Significance of the mass-compression effect of postlaminectomy/laminotomy fibrosis on histological changes on the dura mater and nerve root of the cauda equina: an experimental study in rats.

PURPOSE: The precise mechanism and pathological role of postlaminectomy/laminotomy fibrosis (PLF) in postoperative neurological deficits have not been established. Many studies use magnetic resonance imaging (MRI) to prove that there is no consistent correlation between PLF and postoperative neurological deficits and back pain (PNDBP). Therefore, we assumed that the direct-compression effect may not be the only factor but that other neurological deficits associated with pathological mechanisms should exist and need more investigation. The purpose of this study was to compare over time the differences and changes in histopathological properties of PLF in rats. METHODS: We used a rat model with walking-track analysis for neurologic evaluation, grading scale to evaluate PLF, histomorphometric measurements of dura sac diameter, and histological tissue reactions (dura mater and spinal rootlets) juxtaposed to the postlaminectomy/laminotomy defect. The 54 adult Sprague-Dawley rats were divided into laminotomy (n = 18), laminectomy (n = 18), and sham-operation groups (n = 18). All groups were subdivided into three equal subgroups based on different postoperative time points (1, 2, and 3 months). All sections of vertebral column were stained with hematoxylin and eosin and with Masson's trichrome. RESULTS: The results showed that only a slight compression effect reflected by nonsignificant changes in the maximum anterior-posterior diameters within the dura sac, in the walking tract test, and increased grades of PLF over time. In addition, significant pathological inflammatory changes, such as thickening of the dura mater, axonal swelling, and neovascularization, were found in the post-laminectomy/laminotomy groups at each time point. CONCLUSION: Laminectomy-/laminotomy-related inflammation may lead to PLF, and these pathological changes may be the main cause of postoperative neurological deficits. These findings show that research on preventing PLF should include perioperative modulation of inflammatory reactions induced by laminectomy/laminotomy.