Role of Dectin-1 in peripheral nerve injury

Dectin-1, a C-type lectin receptor, plays a role in nerve injury in the central nervous system. However, whether it plays a role in the peripheral nervous system is not well understood. Our study showed the expression of Dectin-1 on the membrane of macrophages. We also used a sciatic nerve crushing injury model to demonstrate that there was a delay in nerve degeneration-related processes such as breakdown of injured myelinated nerve fibers and formation of myelin ovoid in groups injected with whole glucan particle soluble (WGPS), a Dectin-1 antagonist. There were also fewer intraneural blood vessels in the Dectin-1 antagonist treated group. Our study suggested inhibiting Dectin-1 delayed debris clearance, nerve degeneration, and angiogenesis after peripheral nerve injury

Neuroanatomy- and Pathology-Based Functional Examinations of Experimental Stroke in Rats: Development and Validation of a New Behavioral Scoring System

In experimental stroke studies, a neuroanatomy-based functional examination of behaviors is critical to predict the pathological extent of infarcts because brain-imaging studies are not always available. However, there is a lack of systematic studies to examine the efficiency of a behavioral test for this purpose. Our work aimed to design a new score for this goal in stroke rats, by simplifying the Garcia score (with subscore 1–6) and adding circling as subscore 7. MRI and 2,3,5-triphenyltetrazolium chloride staining were used to determine the pathological extent after transient middle cerebral artery occlusion. The modified summations of subscores were designed according to the predictability of each subscore for locations and sizes of infarcts in one group of stroke rats, and were validated in another group. The original Garcia score was able to predict the pathological extent of edema-adjusted infarct size ≥30%, and the summation of subscore 4, 6, and 7 (4: climbing, 6: vibrissae sensation, 7: circling) also could predict it well. The original Garcia score failed to predict infarct at the primary motor cortex, while the summation of subscore 4, 6, and 7 potentially could predict not only the primary motor cortex, but also the forelimb, hindlimb, and barrel field regions of the primary sensory cortex. Accordingly, this neuroanatomy-correlated functional assessment system composed of subscore 4, 6, and 7 was proposed, with less examination time and better inter-rater reliability than the original Garcia score. In summary, this new scoring system, summation (4,6,7) score, examined motor and sensory functions based on neuroanatomical involvement, having the potential to predict the pathological extent and specific relevant brain areas of infarcts, respectively

Pathophysiology of Neuropathic Pain in Type 2 Diabetes: Skin denervation and contact heat–evoked potentials

OBJECTIVE: Neuropathic pain due to small-fiber sensory neuropathy in type 2 diabetes can be diagnosed by skin biopsy with quantification of intra- epidermal nerve fiber ( IENF) density. There is, however, a lack of noninvasive physiological assessment. Contact heat-evoked potential ( CHEP ) is a newly developed approach to record cerebral responses of A fiber- mediated thermonociceptive stimuli. We investigated the diagnostic role of CHEP. RESEARCH DESIGN AND METHODS: From 2006 to 2009, there were 32 type 2 diabetic patients (20 males and 12 females, aged 51.63 10.93 years) with skin denervation and neuropathic pain. CHEPs were recorded with heat stimulations at the distal leg, where skin biopsy was performed. RESULTS: CHEP amplitude was reduced in patients compared with age- and sex-matched control subjects (14.8 15.6 vs. 33.7 10.1 V, P < 0.001). Abnormal CHEP patterns ( reduced amplitude or prolonged latency) were noted in 81.3 % of these patients. The CHEP amplitude was the most significant parameter correlated with IENF density (P = 0. 003) and pain perception to contact heat stimuli (P = 0.019) on multiple linear regression models. An excitability index was derived by calculating the ratio of the CHEP amplitude over the IENF density. This excitability index was higher in diabetic patients than in control subjects (P = 0.023), indicating enhanced brain activities in neuropathic pain. Among different neuropathic pain symptoms, the subgroup with evoked pain had higher CHEP amplitudes than the subgroup without evoked pain (P = 0.011). CONCLUSIONS: CHEP offers a noninvasive approach to evaluate the degeneration of thermonociceptive nerves in diabetic neuropathy by providing physiological correlates of skin denervation and neuropathic pain

Effective gene expression in the rat dorsal root ganglia with a non-viral vector delivered via spinal nerve injection

Delivering gene constructs into the dorsal root ganglia (DRG) is a powerful but challenging therapeutic strategy for sensory disorders affecting the DRG and their peripheral processes. The current delivery methods of direct intra-DRG injection and intrathecal injection have several disadvantages, including potential injury to DRG neurons and low transfection efficiency, respectively. This study aimed to develop a spinal nerve injection strategy to deliver polyethylenimine mixed with plasmid (PEI/DNA polyplexes) containing green fluorescent protein (GFP). Using this spinal nerve injection approach, PEI/DNA polyplexes were delivered to DRG neurons without nerve injury. Within one week of the delivery, GFP expression was detected in 82.8% ± 1.70% of DRG neurons, comparable to the levels obtained by intra-DRG injection (81.3% ± 5.1%, p = 0.82) but much higher than those obtained by intrathecal injection. The degree of GFP expression by neurofilament(+) and peripherin(+) DRG neurons was similar. The safety of this approach was documented by the absence of injury marker expression, including activation transcription factor 3 and ionized calcium binding adaptor molecule 1 for neurons and glia, respectively, as well as the absence of behavioral changes. These results demonstrated the efficacy and safety of delivering PEI/DNA polyplexes to DRG neurons via spinal nerve injection.National Science Council of Taiwan (100-2321-B-002-007)National Science Council of Taiwan (100-2320-B-002-083-MY3)Taiwan. Ministry of Science and Technology (104-2300-B-002-019-MY3)National Taiwan University. College of Medicine (Translational Medicine Project)National Taiwan University Hospital (101C101-201

Role of acid-sensing ion channel 3 in sub-acute-phase inflammation

<p>Abstract</p> <p>Background</p> <p>Inflammation-mediated hyperalgesia involves tissue acidosis and sensitization of nociceptors. Many studies have reported increased expression of acid-sensing ion channel 3 (ASIC3) in inflammation and enhanced ASIC3 channel activity with pro-inflammatory mediators. However, the role of ASIC3 in inflammation remains inconclusive because of conflicting results generated from studies of <it>ASIC3 </it>knockout (<it>ASIC3</it>^-/-) or dominant-negative mutant mice, which have shown normal, decreased or increased hyperalgesia during inflammation.</p> <p>Results</p> <p>Here, we tested whether ASIC3 plays an important role in inflammation of subcutaneous tissue of paw and muscle in <it>ASIC3</it>^-/-mice induced by complete Freund's adjuvant (CFA) or carrageenan by investigating behavioral and pathological responses, as well as the expression profile of ion channels. Compared with the <it>ASIC3</it>^+/+controls, <it>ASIC3</it>^-/-mice showed normal thermal and mechanical hyperalgesia with acute (4-h) intraplantar CFA- or carrageenan-induced inflammation, but the hyperalgesic effects in the sub-acute phase (1–2 days) were milder in all paradigms except for thermal hyperalgesia with CFA-induced inflammation. Interestingly, carrageenan-induced primary hyperalgesia was accompanied by an <it>ASIC3</it>-dependent <it>Nav1.9 </it>up-regulation and increase of tetrodotoxin (TTX)-resistant sodium currents. CFA-inflamed muscle did not evoke hyperalgesia in <it>ASIC3</it>^-/-or <it>ASIC3</it>^+/+mice, whereas carrageenan-induced inflammation in muscle abolished mechanical hyperalgesia in <it>ASIC3</it>^-/-mice, as previously described. However, <it>ASIC3</it>^-/-mice showed attenuated pathological features such as less CFA-induced granulomas and milder carrageenan-evoked vasculitis as compared with <it>ASIC3</it>^+/+mice.</p> <p>Conclusion</p> <p>We provide a novel finding that ASIC3 participates in the maintenance of sub-acute-phase primary hyperalgesia in subcutaneous inflammation and mediates the process of granuloma formation and vasculitis in intramuscular inflammation.</p

Mobile-cloud assisted video summarization framework for efficient management of remote sensing data generated by wireless capsule sensors

YesWireless capsule endoscopy (WCE) has great advantages over traditional endoscopy because it is portable and easy to use, especially in remote monitoring health-services. However, during the WCE process, the large amount of captured video data demands a significant deal of computation to analyze and retrieve informative video frames. In order to facilitate efficient WCE data collection and browsing task, we present a resource- and bandwidth-aware WCE video summarization framework that extracts the representative keyframes of the WCE video contents by removing redundant and non-informative frames. For redundancy elimination, we use Jeffrey-divergence between color histograms and inter-frame Boolean series-based correlation of color channels. To remove non-informative frames, multi-fractal texture features are extracted to assist the classification using an ensemble-based classifier. Owing to the limited WCE resources, it is impossible for the WCE system to perform computationally intensive video summarization tasks. To resolve computational challenges, mobile-cloud architecture is incorporated, which provides resizable computing capacities by adaptively offloading video summarization tasks between the client and the cloud server. The qualitative and quantitative results are encouraging and show that the proposed framework saves information transmission cost and bandwidth, as well as the valuable time of data analysts in browsing remote sensing data.Supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2013R1A1A2012904)

免疫型神經病變 的診斷與治療

免疫型神經病變(immune-mediated neuropathy)或稱為發炎型神經病變( inflammatory neuropathy)是指因免疫系統異常，導致神經軸突、髓鞘或細胞本體受 傷所造成的神經病變：病理學上通常伴隨有發炎細胞如淋巴球、巨噬細胞筆的浸潤。 病理生理學上，分成免疫傷害( immune injury)與結構傷害(structural injury)兩 期，造成髓鞘及神經軸突的損傷。狹義的免疫型神經病變依病程分為急性神經根炎( Guillain-Barr&eacute; syndrome，GBS)與慢性脫髓鞘性神經炎(chronic inflammatory demyelinating polyneuropathy，CIDP)。臨床上，GBS及CIDP主要都 是以進行性的運動及感覺障礙為主要表現，神經的受犯範圍則有甚大差異。於神經傳 導檢查，GBS以遠端潛時延長及F-wave潛時延長為主：CIDP的遠端潛時延長、F-wave 潛時延長及神經傳導速度下降。病理機制的研究，發現某些對抗醣脂質抗體(anti- ganglioside antibodies)與免疫型神經病變的亞型有關。於GBS，積極的免疫治療可 以縮短病患病程、減少併發症與日後的殘存運動障礙：靜脈注射免疫球蛋白( intravenous immunoglobulin，IVIG)與血漿交換有相同的療效，高劑量類固醇對GBS 的治療無益。對於CIDP的治療，血漿交換及IVIG兩者皆可減輕神經學缺失，因為CIDP 的免疫障礙是持續性的，必需使用類固醇保持療效。免疫型神經病變的診治是神經科 醫師的挑戰，然而病人有極佳回復正常生活的契機：不論GBS或CIDP都是症候群，而 非單一疾病，實驗室檢查僅能作為臨床評估的參考，不能以此主導臨床診治，詳細的 臨床觀察及判斷是診斷免疫型神經病變的唯一依據。 Immune-mediate neuropathies, or inflammatory neuropathies are neuropathies due to the dysregulation of the immune system. The injury to peripheral nerves can be divided into two phases: an early stage of immune injury, and a later stage of structural damage. The overall effects are axonal degeneration or demyelination depending on the target of immunological attacks. According to time course, there are two major types: Guillain-Barreacute; syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP). Clinical manifestations of both diseases include progressive motor weakness and sensory disturbance with some variations among different patients. The major findings of nerve conduction studies on GBS patients are prolonged distal motor latencies and minimal F-wave latencies with variable reduction of nerve conduction velocities. In CIDP patients, slowed nerve conduction velocities are the usual findings in addition to prolongation of distal motor latencies and minimal F-wave latencies. Certain subtypes of immune-mediated neuropathies are associated with high titers of anti-gangliosdie antibodies. Patients with GBS and CIDP can benefit from immunotherapy. For GBS, plasma exchange and intravenous immunoglobulin (IVIG) are equally effective in reducing complications and neurological disability. Steroid of high dose is, however, harmful to GBS. Plasma exchange and IVIG can alleviate neurological deficits of CIDP with steroid to maintain the effects of plasma exchange and IVIG. In conclusion, careful clinical observations and judgment are the most important issue to manage patients with immune- mediated neuropathies

Pathology of Nerve Terminal Degeneration in the Skin

To characterize the pathology of epidermal nerve degeneration and regeneration, we investigated temporal and spatial changes in skin innervation of the mouse footpad. Within 24 hours after sciatic nerve axotomy, terminals of epidermal nerves appeared swollen and there was a mild reduction in epidermal nerve density (5.7 +/- 2.8 vs 12.7 +/- 2.2 fibers/mm, p < 0.04). Epidermal nerves completely disappeared by 48 hours (0.2 +/- 0.2 vs 14.2 +/- 0.9 fibers/mm, p < 0.001). Concomitant with the disappearance of epidermal nerves, the immunocytochemical pattern of the subepidermal nerve plexus became fragmented. At the electron microscopic level, the axoplasm of degenerating dermal nerves was distended with organelles and later became amorphous. Beginning from day 28 after axotomy, collateral sprouts from the adjacent saphenous nerve territory extended into the denervated area with a beaded appearance. They never penetrated the epidermal-dermal junction to innervate the epidermis. In contrast, 3 months after nerve crushing, the epidermis on the surgery side resumed a normal innervation pattern as the epidermis on the control side (10.3 +/- 3.9 vs 10.6 +/- 1.5 fibers/mm, p = 0.1). This study demonstrates the characteristics of degenerating and regenerating nerves, and suggests that successful reinnervation mainly originates from regenerating nerves of the original nerve trunks. All these findings provide qualitative and quantitative information for interpreting the pathology of cutaneous nerves