Phase Of Degeneration Research Articles

A Transcriptional Program for Arbuscule Degeneration during AM Symbiosis Is Regulated by MYB1

During the endosymbiosis formed between plants and arbuscular mycorrhizal (AM) fungi, the root cortical cells are colonized by branched hyphae called arbuscules, which function in nutrient exchange with the plant [1]. Despite their positive function, arbuscules are ephemeral structures, and their development is followed by a degeneration phase, in which the arbuscule and surrounding periarbuscular membrane and matrix gradually disappear from the root cell [2, 3]. Currently, the root cell's role in this process and the underlying regulatory mechanisms are unknown. Here, by using a Medicago truncatula pt4 mutant in which arbuscules degenerate prematurely[4], we identified arbuscule degeneration-associated genes, of which 38% are predicted to encode secreted hydrolases, suggesting a role in disassembly of the arbuscule and interface. Through RNAi and analysis of an insertion mutant, we identified a symbiosis-specific MYB-like transcription factor (MYB1) that suppresses arbuscule degeneration in mtpt4. In myb1, expression of several degeneration-associated genes is reduced. Conversely, in roots constitutively overexpressing MYB1, expression of degeneration-associated genes is increased and subsequent development of symbiosis is impaired. MYB1-regulated gene expression is enhanced by DELLA proteins and is dependent on NSP1 [5], but not NSP2 [6]. Furthermore, MYB1 interacts with DELLA and NSP1. Our data identify a transcriptional program for arbuscule degeneration and reveal that its regulators include MYB1 in association with two transcriptional regulators, NSP1 and DELLA, both of which function in preceding phases of the symbiosis. We propose that the combinatorial use of transcription factors enables the sequential expression of transcriptional programs for arbuscule development and degeneration.

Altered Synapse Stability in the Early Stages of Tauopathy

SummarySynapse loss is a key feature of dementia, but it is unclear whether synaptic dysfunction precedes degenerative phases of the disease. Here, we show that even before any decrease in synapse density, there is abnormal turnover of cortical axonal boutons and dendritic spines in a mouse model of tauopathy-associated dementia. Strikingly, tauopathy drives a mismatch in synapse turnover; postsynaptic spines turn over more rapidly, whereas presynaptic boutons are stabilized. This imbalance between pre- and post-synaptic stability coincides with reduced synaptically driven neuronal activity in pre-degenerative stages of the disease.

Synaptic Dysfunction in Alzheimer's Disease and Glaucoma: From Common Degenerative Mechanisms Toward Neuroprotection.

Alzheimer’s disease (AD) and glaucoma are two distinct multifactorial neurodegenerative diseases, primarily affecting the elderly. Common pathophysiological mechanisms have been elucidated in the past decades. First of all both diseases are progressive, with AD leading to dementia and glaucoma inducing blindness. Pathologically, they all feature synaptic dysfunction with changes of neuronal circuitry, progressive accumulation of protein aggregates such as the beta amyloid (Aβ) and intracellular microtubule inclusions containing hyperphosphorylated tau, which belongs to microtubule associated protein family. During an early phase of degeneration, both diseases are characterized by synaptic dysfunction and changes of mitogen-activated protein kinases (MAPK). Common degenerative mechanisms underlying both diseases are discussed here, along with recent results on the potential use of the visual system as a biomarker for diagnosis and progression of AD. Common neuropathological changes and mechanisms in AD and glaucoma have facilitated the transfer of therapeutic strategies between diseases. In particular, we discuss past and present evidence for neuroprotective effects of brain-derived neurotrophic factor (BDNF).

Multimodal MRI Imaging of Apoptosis-Triggered Microstructural Alterations in the Postnatal Cerebral Cortex.

Prematurely born children often develop neurodevelopmental delay that has been correlated with reduced growth and microstructural alterations in the cerebral cortex. Much research has focused on apoptotic neuronal cell death as a key neuropathological features following preterm brain injuries. How scattered apoptotic death of neurons may contribute to microstructural alterations remains unknown. The present study investigated in a rat model the effects of targeted neuronal apoptosis on cortical microstructure using in vivo MRI imaging combined with neuronal reconstruction and histological analysis. We describe that mild, targeted death of layer IV neurons in the developing rat cortex induces MRI-defined metabolic and microstructural alterations including increased cortical fractional anisotropy. Delayed architectural modifications in cortical gray matter and myelin abnormalities in the subcortical white matter such as hypomyelination and microglia activation follow the acute phase of neuronal death and axonal degeneration. These results establish the link between mild cortical apoptosis and MRI-defined microstructure changes that are reminiscent to those previously observed in preterm babies.

LENGTH- WEIGHT RELATIONSHIP (LWR) AND CONDITION FACTOR OF Amblyceps apangi NATH & DEY FROM ARUNACHAL PRADESH, INDIA

Length-weight relationship of Amblyceps apangi had been carried out from streams of Dikrong River Arunachal Pradesh, during January 2014 to December 2015 . The co-efficient of regression (b) was recorded as 2.213 (males); 2.376 (females); 2.312 in pooled (both sexes). The result reveals that females have better growth than males and both sexes signify a negative allometric growth pattern . The highest Condition factor ‘K’ value (0.82 ±0.24) for male was found in November and minimum (0.45 ± 0.12) was observed in July. In case of female, the highest value (0.95 ± 0.11) was recorded in November and lowest (0.50 ± 0.09) was noticed in June. Again, the highest K values (0.83 ± 0.16) of male was found in 61-70 mm while in females the highest (0.86 ± 0.13) was in 51-60 mm. The lowest values for both male (0.38 ± 0.07) and female (0.36 ± 0.03) were observed in 141-150 mm. The Relative Condition factor (Kn) value did not show any variation with respect to monthly and size grouping. The result indicates that both the sex was found in a good condition. Moreover, the K values were encountered with GSI values during the quiescent and degenerative phases of the reproductive cycle but minimum K values coincides with the increased GSI during the recrudescent phases both the sexes. Coefficient of correlation (r) shows more or less similar trend in all male, female and pooled. The correlation coefficient ‘r’ was found to be 0.906 (males); 0.949 (females) and 0.934 (pooled). This result indicates that there was a good correlation between length and weight of the fish.

Dynamic activation of basilar membrane macrophages in response to chronic sensory cell degeneration in aging mouse cochleae

In the sensory epithelium, macrophages have been identified on the scala tympani side of the basilar membrane. These basilar membrane macrophages are the spatially closest immune cells to sensory cells and are able to directly respond to and influence sensory cell pathogenesis. While basilar membrane macrophages have been studied in acute cochlear stresses, their behavior in response to chronic sensory cell degeneration is largely unknown. Here we report a systematic observation of the variance in phenotypes, the changes in morphology and distribution of basilar membrane tissue macrophages in different age groups of C57BL/6J mice, a mouse model of age-related sensory cell degeneration. This study reveals that mature, fully differentiated tissue macrophages, not recently infiltrated monocytes, are the major macrophage population for immune responses to chronic sensory cell death. These macrophages display dynamic changes in their numbers and morphologies as age increases, and the changes are related to the phases of sensory cell degeneration. Notably, macrophage activation precedes sensory cell pathogenesis, and strong macrophage activity is maintained until sensory cell degradation is complete. Collectively, these findings suggest that mature tissue macrophages on the basilar membrane are a dynamic group of cells that are capable of vigorous adaptation to changes in the local sensory epithelium environment influenced by sensory cell status.

Diffusion restriction in the corticospinal tracts and the corpus callosum in neonates after cerebral insult

BackgroundIn neonatal brains diffusion restriction, which is not limited to the region of insult, but is also found in distant locations from it seems to be a frequent finding, called pre-Wallerian degeneration. ObjectivesThe purpose of this study was to describe these findings and to estimate the frequency of their occurrence with an attempt to determine their clinical significance. Methods125 brain MRI examinations of neonates with confirmed brain damage performed or consulted in our Institute were retrospectively reviewed, focusing on the presence of restricted diffusion in corticospinal tracts (CST) and corpus callosum (CC). Apparent diffusion coefficients (ADC) were measured in callosal splenium and compared to normal neonatal brains. ResultsRestricted diffusion was found in 21 newborns (16.8%): in 4 in CST (3.2%), in 5 in CC (4.0%), in 12 in both (9.6%). Mean ADC value in CC was 0.638, standard deviation (SD): 0.211μm2/s and in the control group 0.995, SD: 0.162μm2/s (p=0,001). ConclusionsNeonatal brain MRI should be searched for DWI abnormalities which are not rare and require careful studying of ADC maps. Diffusion restriction in the corpus callosum and/or corticospinal tracts below the region of insult should not be mistaken for acute ischemia as it most likely reflects early phase of secondary neuronal degeneration called pre-Wallerian degeneration. This finding helps in prognostication and guides the management of the affected neonates.

Native DIGE proteomic analysis of mitochondria from substantia nigra and striatum during neuronal degeneration and its compensation in an animal model of early Parkinson’s disease

Cause of Parkinson’s disease (PD) is still not understood. Motor symptoms are not observed at early stages of disease due to compensatory processes. Dysfunction of mitochondria was indicated already at preclinical PD. Selective toxin 6-OHDA was applied to kill dopaminergic neurons in substantia nigra and disturb neuronal transmission in striatum. Early phase of active degeneration and later stage, when surviving cells adapted to function normally, were analysed. 2D BN/SDS difference gel electrophoresis (DIGE) of mitochondrial proteome enabled to point out crucial processes involved at both time-points in dopaminergic structures. Marker proteins such as DPYSL2, HSP60, ATP1A3, EAAT2 indicated structural remodelling, cytoskeleton rearrangement, organelle trafficking, axon outgrowth and regeneration. Adaptations in dopaminergic and glutamatergic neurotransmission, recycling of synaptic vesicles, along with enlargement of mitochondria mass were proposed as causative for compensation. Changed expression of carbohydrates metabolism and oxidative phosphorylation proteins were described, including their protein–protein interactions and supercomplex assembly.

Regulation of striatal astrocytic receptor for advanced glycation end-products variants in an early stage of experimental Parkinson's disease.

Convincing evidence indicates that advanced glycation end-products and danger-associated protein S100B play a role in Parkinson's disease (PD). These agents operate through the receptor for advanced glycation end-products (RAGE), which displays distinct isoforms playing protective/deleterious effects. However, the nature of RAGE variants has been overlooked in PD studies. Hence, we attempted to characterize RAGE regulation in early stages of PD striatal pathology. A neurotoxin-based rodent model of PD was used in this study, through administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to C57BL/6 mice. Animals were killed 6h post-MPTP to assess S100B/RAGE contents (RT-qPCR, ELISA) and RAGE isoform density (WB) and cellular distribution (immunohistochemistry). Dopaminergic and gliotic status were also mapped (HPLC-ED, WB, immunohistochemistry). At this preliminary stage of MPTP-induced PD in mice, RAGE inhibitory isoforms were increased whereas full-length RAGE was not affected. This putative cytoprotective RAGE phenotype paired an inflammatory and pro-oxidant setting fueling DAergic denervation. Increased RAGE inhibitory variants occur in astrocytes showing higher S100B density but no overt signs of hypertrophy or NF-κB activation, a canonical effector of RAGE. These findings expand our understanding of the toxic effect of MPTP on striatum and offer first invivo evidence of RAGE being a responder in early stages of astrogliosis dynamics, supporting a protective rather tissue-destructive phenotype of RAGE in the initial phase of PD degeneration. These data lay the groundwork for future studies on the relevance of astrocytic RAGE in DAergic neuroprotection strategies. We report increased antagonistic RAGE variants paralleling S100B up-regulation in early stages of MPTP-induced astrogliosis dynamics . We propose that selective RAGE regulation reflects a self-protective mechanism to maintain low levels of RAGE ligands , preventing long-term inflammation and oxidative stress arising from sustained ligands/flRAGE activation . Understanding loss of RAGE protective response to stress may provide new therapeutic options to halt or slow down dopaminergic axonopathy and, ultimately, neuronal death .

Cav1.4 L-Type Calcium Channels Contribute to Calpain Activation in Degenerating Photoreceptors of rd1 Mice.

Retinitis pigmentosa is an inherited blinding disorder characterized by progressive degeneration and loss of photoreceptors. The exact mechanism of degeneration and cell death of photoreceptors is not known, but is thought to involve disturbed Ca2+—signaling. Ca2+ can enter the photoreceptor cell via outer segment cyclic nucleotide-gated (CNG) channels or synaptic Cav1.4 L-type voltage-gated calcium channels (VGCC). Previously, we have shown that genetic ablation of the Cngb1 gene encoding the B subunit of the rod CNG channel delays the fast progressing degeneration in the rd1 mutant mouse model of retinitis pigmentosa. In this study, we crossbred rd1 mice with the Cacna1f-deficient mouse lacking the Cav1.4 α1 subunit of the L-type VGCC. Longitudinal in vivo examinations of photoreceptor layer thickness by optical coherence tomography revealed a significant, but not sustained delay of retinal degeneration in Cacna1f x rd1 double mutant mice compared to rd1 mice. This was accompanied by a reduction of TUNEL positive cells in the early phase of rod degeneration. Remarkably, Cacna1f x rd1 double mutant mice displayed a strong decrease in the activation of the Ca2+-dependent protease calpain during photoreceptor loss. Our results show that genetic deletion of the synaptic Cav1.4 L-type VGCCs impairs calpain activation and leads to a short-term preservation of photoreceptors in the rd1 mouse.

Molecular mechanisms in the initiation phase of Wallerian degeneration.

Axonal degeneration is an early hallmark of nerve injury and many neurodegenerative diseases. The discovery of the Wallerian degeneration slow mutant mouse, in which axonal degeneration is delayed, revealed that Wallerian degeneration is an active progress and thereby illuminated the mechanisms underlying axonal degeneration. Nicotinamide mononucleotide adenylyltransferase 2 and sterile alpha and armadillo motif-containing protein 1 play essential roles in the maintenance of axon integrity by regulating the level of nicotinamide adenine dinucleotide, which seems to be the key molecule involved in the maintenance of axonal health. However, the function of nicotinamide mononucleotide remains debatable, and we discuss two apparently conflicting roles of nicotinamide mononucleotide in Wallerian degeneration. In this article, we focus on the roles of these molecules in the initiation phase of Wallerian degeneration to improve our understanding of the mechanisms underpinning this phenomenon.

GluD2 Endows Parallel Fiber-Purkinje Cell Synapses with a High Regenerative Capacity.

Although injured axons usually do not regenerate in the adult CNS, parallel fibers (PFs) regenerate synaptic connections onto cerebellar Purkinje cells (PCs). In this study, we investigated the role of GluD2 in this regenerative process after PF transection using GluD2-knock-out (KO) mice. All dendritic spines on distal dendrites were innervated by PFs in sham-operated wild-type controls, whereas one-third were devoid of innervation in GluD2-KO mice. In both genotypes, a steep drop in the number of PF synapses occurred with a reciprocal surge in the number of free spines on postlesion day 1, when the PF territory aberrantly expanded toward the proximal dendrites. In wild-type mice, the territory and number of PF synapses were nearly fully restored to normal on postlesion day 7, although PF density remained low. Moreover, presynaptic and postsynaptic elements were markedly enlarged, and the PF terminal-to-PC spine contact ratio increased from 1:1 to 1:2 at most synapses. On postlesion day 30, the size and contact ratio of PF synapses returned to sham-operated control values and PF density recovered through the sprouting and elongation of PF collaterals. However, GluD2-KO mice showed neither a hypertrophic response nor territorial restoration 7 d postlesion, nor the recovery of PF axons or synapses on postlesion day 30. This suggests that PF wiring regenerates initially by inducing hypertrophic responses in surviving synaptic elements (hypertrophic phase), followed by collateral formation by PF axons and retraction of PF synapses (remodeling phase). Without GluD2, no transition to these regenerative phases occurs. The glutamate receptor GluD2 expressed at parallel fiber (PF)-Purkinje cell (PC) synapses regulates the formation and maintenance of the synapses. To investigate the role of GluD2 in their extraordinarily high regenerative capacity, the process after surgical transection of PFs was compared between wild-type and GluD2-knock-out mice. We discovered that, in wild-type mice, PF synapses regenerate initially by inducing hypertrophic responses in surviving synaptic elements, and then by sprouting and elongation of PF collaterals. Subsequently, hypertrophied PF synapses remodel into compact synapses. In GluD2-knock-out mice, PF wiring remains in the degenerative phase, showing neither a hypertrophic response nor recovery of PF axons or synapses. Our finding thus highlights that synaptic connection in the adult brain can regenerate with aid of GluD2.

Influence of Botulinumtoxin A on the Expression of Adult MyHC Isoforms in the Masticatory Muscles in Dystrophin-Deficient Mice (Mdx-Mice).

The most widespread animal model to investigate Duchenne muscular dystrophy is the mdx-mouse. In contrast to humans, phases of muscle degeneration are replaced by regeneration processes; hence there is only a restricted time slot for research. The aim of the study was to investigate if an intramuscular injection of BTX-A is able to break down muscle regeneration and has direct implications on the gene expression of myosin heavy chains in the corresponding treated and untreated muscles. Therefore, paralysis of the right masseter muscle was induced in adult healthy and dystrophic mice by a specific intramuscular injection of BTX-A. After 21 days the mRNA expression and protein content of MyHC isoforms of the right and left masseter, temporal, and the tongue muscle were determined using quantitative RT-PCR and Western blot technique. MyHC-IIa and MyHC-I-mRNA expression significantly increased in the paralyzed masseter muscle of control-mice, whereas MyHC-IIb and MyHC-IIx/d-mRNA were decreased. In dystrophic muscles no effect of BTX-A could be detected at the level of MyHC. This study suggests that BTX-A injection is a suitable method to simulate DMD-pathogenesis in healthy mice but further investigations are necessary to fully analyse the BTX-A effect and to generate sustained muscular atrophy in mdx-mice.

Spatiotemporal Cadence of Macrophage Polarisation in a Model of Light-Induced Retinal Degeneration.

BackgroundThe recruitment of macrophages accompanies almost every pathogenic state of the retina, and their excessive activation in the subretinal space is thought to contribute to the progression of diseases including age-related macular degeneration. Previously, we have shown that macrophages aggregate in the outer retina following damage elicited by photo-oxidative stress, and that inhibition of their recruitment reduces photoreceptor death. Here, we look for functional insight into macrophage activity in this model through the spatiotemporal interplay of macrophage polarisation over the course of degeneration.MethodsRats were exposed to 1000 lux light damage (LD) for 24hrs, with some left to recover for 3 and 7 days post-exposure. Expression and localisation of M1- and M2- macrophage markers was investigated in light-damaged retinas using qPCR, ELISA, flow cytometry, and immunohistochemistry.ResultsExpression of M1- (Ccl3, Il-6, Il-12, Il-1β, TNFα) and M2- (CD206, Arg1, Igf1, Lyve1, Clec7a) related markers followed discrete profiles following light damage; up-regulation of M1 genes peaked at the early phase of cell death, while M2 genes generally exhibited more prolonged increases during the chronic phase. Moreover, Il-1β and CD206 labelled accumulations of microglia/macrophages which differed in their morphological, temporal, and spatial characteristics following light damage.ConclusionsThe data illustrate a dynamic shift in macrophage polarisation following light damage through a broad swathe of M1 and M2 markers. Pro-inflammatory M1 activation appears to dominate the early phase of degeneration while M2 responses appear to more heavily mark the chronic post-exposure period. While M1/M2 polarisation represents two extremes amongst a spectrum of macrophage activity, knowledge of their predominance offers insight into functional consequences of macrophage activity over the course of damage, which may inform the spatiotemporal employment of therapeutics in retinal disease.

Surgical treatment of early knee osteoarthritis with a cell-free osteochondral scaffold: results at 24 months of follow-up.

"Early Osteoarthritis (EOA)" has been defined combining clinical, imaging and surgical parameters, with the aim to identify patients in early degenerative phases, who might benefit from the use of available regenerative procedures. Aim of this first clinical trial is to prospectively evaluate the results obtained in a group of patients meeting the inclusion criteria of "EOA" as proposed by the ESSKA Cartilage Committee, and surgically treated with the implantation of a multi-phasic osteochondral scaffold. 23 patients were prospectively evaluated at 12 and 24 months of follow-up. Etiology of the chondral or osteochondral defect was rated as microtraumatic or degenerative in 18 cases, and traumatic in 5 cases. Patients included were complaining of clinical symptoms like knee pain and affected by chondral and osteochondral lesions located at the femoral condyles or trochlea and MRI findings demonstrating articular cartilage degeneration and/or meniscal degeneration and/or subchondral bone marrow lesions. All patients increased significantly in any clinical score adopted. The IKDC subjective score increased from 42.8 ± 13.8 at basal evaluation to 74.3 ± 17.4 at 12 months' (p < 0.0005), being stable (74.9 ± 20.4) up to the final follow-up of 24 months. Tegner score showed a statistically significant improvement in sports activity from 3.3 ± 2.7 pre-operative to 4.6 ± 2.2 at 12 months (p < 0.005), with a slight improvement to the final evaluation (4.7 ± 2.1; n.s.). However, the activity level was significantly lower than the pre-injury one (6.1 ± 2.6; p = 0.004). A significant difference was shown between patients younger versus older than 40 years, with younger patients had better clinical improvement (76.0 ± 18.6 vs 45.1 ± 38.8 respectively, p = 0.037). The implantation of a multi-phasic osteochondral scaffold represents a good option after failure of conservative management for Early OA patients, where younger age represent an important factor for a better outcome. Longer follow-up is needed to evaluate the benefit over time. IV, case series.

Autophagy in osteoarthritis

Degradation of the articular cartilage is at the centre of the pathogenesis of osteoarthritis (OA), for which age is the major risk factor. Maintaining the chondrocytes in a healthy condition appears to be an important factor for preservation of the entire cartilage and preventing its degeneration. Autophagy, which is an essential cellular homeostatic mechanism for the removal of dysfunctional cellular organelles and macromolecules, is increased by catabolic and nutritional stresses. Autophagy is increased in OA chondrocytes and cartilage, particularly during the initial degenerative phase, to regulate changes in OA-like gene expression through modulation of apoptosis and reactive oxygen species (ROS). In this way, autophagy acts as an adaptive response to protect chondrocytes from various environmental changes, while with gradual cartilage degradation, decreased autophagy is linked with cell death. Rapamycin, which is a specific inhibitor of the mTOR signaling pathway, enhances expression of autophagy regulators and prevents chondrocyte death. In the future, pharmacological activation of autophagy may be an effective therapeutic approach for OA.

Interpretation of Flood-Illuminated Adaptive Optics Images in Subjects with Retinitis Pigmentosa.

The purpose of this study was to correlate features on flood-illuminated adaptive optics (AO) images with color fundus, fundus autofluorescence (FAF) and spectral domain optical coherence tomography (SD-OCT) images in patients with retinitis pigmentosa (RP). We imaged 39 subjects diagnosed with RP using the rtx1™ flood-illuminated AO camera from Imagine Eyes (Orsay, France). We observed a correlation between hyper-autofluoresence changes on FAF, disruption of the interdigitation zone (IZ) on SD-OCT and loss of reflective cone profiles on AO. Four main patterns of cone-reflectivity were seen on AO: presumed healthy cone mosaics, hypo-reflective blurred cone-like structures, higher frequency disorganized hyper-reflective spots, and lower frequency hypo-reflective spots. These regions were correlated to progressive phases of cone photoreceptor degeneration observed using SD-OCT and FAF. These results help provide interpretation of en face images obtained by flood-illuminated AO in subjects with RP. However, significant ambiguity remains as to what truly constitutes a cone, especially in areas of degeneration. With further refinements in technology, flood illuminated AO imaging has the potential to provide rapid, standardized, longitudinal and lower cost imaging in patients with retinal degeneration.

A Review of Preventive Health Care in Geriatrics through Ayurveda

Ayurveda is basically the science of life and longevity. Ageing is a process of physical, psychological and social change in multi dimensional aspects. According to the Ayurveda, ageing is outcome of kala or parinama. Vata dosha is the most important factor in the pathophysiology of ageing obviously because of its natural predominance at that stage of life. Ayurveda advocates an excellent approach for promotion of health, prevention of diseases and delaying the process of ageing with number of measures mentioned in svastha chatushka and rasayanadhyaya of charakasamhita, time to time panchakarma and various herbal drugs. Jarachikitsa or Rasayana in Ayurveda is a unique therapeutic methodology to delay ageing and to minimize the intensity of problems occuring in this degenerative phase of one's life. Prevention and management of health problems could help the elderly to improve quality of life and remain self dependant for their daily activities to maximum possible extent.

Pedosphere Degradation due to Seasonal Water Logging in Southwestern Punjab

Introduction of irrigated agriculture has turned some basin lands seasonally waterlogged. Seasonally waterlogged soils remain poorly understood particularly in relation to the changes in pedosphere and pedogenic pathways. Present investigation evaluated changes in the pedosphere and its implications in pedogenic pathways of these seasonal waterlogged soils. Five soil profiles along the central transit of the waterlogged area of the southwestern Punjab (74°30′–74°45′E longitude and 30°03′75″–30°33′07″N latitude) were studied. On seasonal water logging, the present land depicts shift of matrix colour from yellowish brown to olive brown, decay in the thickness and strength of structured B-horizons, increase in exchangeable Na and soluble salts in the surface horizons, fall of exchangeable divalent cations to exchangeable-Na ratio and an increase in the mobility of citrate–bicarbonate–dithionite extractable free Fe and Mn. Seasonal water logging resulted in two phases of degeneration, deterioration of structured B-horizon and the dispersion of clays and soluble salts and their inconsistent downward movements with water table front. The operating soil process is incipient hydromorphism.

Dexamethasone as adjuvant to bupivacaine prolongs the duration of thermal antinociception and prevents bupivacaine-induced rebound hyperalgesia via regional mechanism in a mouse sciatic nerve block model.

BackgroundDexamethasone has been studied as an effective adjuvant to prolong the analgesia duration of local anesthetics in peripheral nerve block. However, the route of action for dexamethasone and its potential neurotoxicity are still unclear.MethodsA mouse sciatic nerve block model was used. The sciatic nerve was injected with 60ul of combinations of various medications, including dexamethasone and/or bupivacaine. Neurobehavioral changes were observed for 2 days prior to injection, and then continuously for up to 7 days after injection. In addition, the sciatic nerves were harvested at either 2 days or 7 days after injection. Toluidine blue dyeing and immunohistochemistry test were performed to study the short-term and long-term histopathological changes of the sciatic nerves. There were six study groups: normal saline control, bupivacaine (10mg/kg) only, dexamethasone (0.5mg/kg) only, bupivacaine (10mg/kg) combined with low-dose (0.14mg/kg) dexamethasone, bupivacaine (10mg/kg) combined with high-dose (0.5mg/kg) dexamethasone, and bupivacaine (10mg/kg) combined with intramuscular dexamethasone (0.5mg/kg).ResultsHigh-dose perineural dexamethasone, but not systemic dexamethasone, combined with bupivacaine prolonged the duration of both sensory and motor block of mouse sciatic nerve. There was no significant difference on the onset time of the sciatic nerve block. There was “rebound hyperalgesia” to thermal stimulus after the resolution of plain bupivacaine sciatic nerve block. Interestingly, both low and high dose perineural dexamethasone prevented bupivacaine-induced hyperalgesia. There was an early phase of axon degeneration and Schwann cell response as represented by S-100 expression as well as the percentage of demyelinated axon and nucleus in the plain bupivacaine group compared with the bupivacaine plus dexamethasone groups on post-injection day 2, which resolved on post-injection day 7. Furthermore, we demonstrated that perineural dexamethasone, but not systemic dexamethasone, could prevent axon degeneration and demyelination. There was no significant caspase-dependent apoptosis process in the mouse sciatic nerve among all study groups during our study period.ConclusionsPerineural, not systemic, dexamethasone added to a clinical concentration of bupivacaine may not only prolong the duration of sensory and motor blockade of sciatic nerve, but also prevent the bupivacaine-induced reversible neurotoxicity and short-term “rebound hyperalgesia” after the resolution of nerve block.