Establishment and evaluation of a rat model of complete transected spinal cord injury

BACKGROUND： The establishment of a rat model of complete transected spinal cord injury lacks technological specifications. The current models lack concordance and reliability, and the death rate of the experimental animals is high. Therefore, there is a great need for a reliable model to apply clinical applications of therapy. OBJECTIVE： To construct a rat model of complete transected spinal cord injury characterized by stability, reproducibility, and a high animal survival rate. DESIGN： Completely randomized controlled study. SETTING： Department of Neurosurgery, Xiangya Hospital of Central South University. MATERIALS： Fifty-five healthy specific pathogen free grade adult female Sprague Dawley rats were provided by the Experimental Animal Department, Xiangya Medical College, Central South University. Olympus BX51 imaging collecting analytic system was provided by Olympus Company, Japan; and SEN-7203 Nihon-Kohden electrical stimulator by Nihon Kohden, Japan. METHODS： This study was performed at the Laboratory of Neurosurgery, Xiangya Hospital of Central South University from April to June 2006. Experimental grouping： 55 rats were randomly divided into model group （n = 40） and sham surgery group （n = 15）. In the model group, a self-made sliver hook was passed through the ventral side to support the spinal cord at the T12 segment and to shear it off. A complete transected spinal cord, 2 mm in length, was resected. In the sham surgery group, the spinal cord was identically exposed. The dura mater of the spinal cord was cut open, but the spinal cord was not damaged. MAIN OUTCOME MEASURES： Histopathological changes after spinal cord injury at L2 segment were observed subsequent to hematoxylin and eosin staining under optical microscopy. Olympus BX51 imaging collecting analytic system was used to count spinal cord ventral horn neurons. Motor function of rat hindlimb was evaluated with the Basso, Beattie and Bresnahan （BBB） scale. Paraplegia was evaluated as 0 point, and complete normality as 21 points. Somatosensory-evoked potential was measured using Nihon-Kohden electric stimulator at 21 days post-operation. RESULTS： A total of 82% （33/40） rats survived longer than 30 days after modeling. Pathological changes of spinal cord tissue： degenerative and necrotic pathological changes appeared in the model group after surgery; for example, neuronal swelling, chromatinolysis, and karyopyknosis. The spinal cord in the sham surgery group displayed mild edema 24 hours after surgery, gradually recovering to normal levels. Quantification of spinal cord ventral horn neurons： the number of spinal cord ventral horn neurons in the model group was less than in the sham surgery group at 24 hours, as well as 7 and 21 days after surgery （P 〈 0.01）; while, the number at 7 and 21 days after surgery decreased compared to 24 hours after surgery （P 〈 0.01）. Motor function changes： Rats in the sham operation group moved lightly abnormally following anesthesia recovery and then moved normally 7 days after surgery. BBB scores in the model group were less than in the sham surgery group 21 days after surgery （P 〈 0.01）. BBB scores of both lower extremities increased slightly 7 days after surgery （P 〈 0.01）; however, voluntary motor function of both lower extremities was still not recovered 30 days after surgery. Changes of somatosensory-evoked potential： wave form of somatosensory-evoked potential was normal in the sham surgery group 21 days after surgery, but recovered wave form was not recorded in the model group. CONCLUSION： Results from spinal cord histopathology, cytology, motor function, and somatosensory-evoked potential suggested that the complete transected spinal cord injury model in this study was stable, reliable, and reproducible. Furthermore, the survival rate of experimental animals was high.

Expression of hippocampal corticosteroid receptors,as well as corticotrophin-releasing hormone and vasopressin in the hypothalamic paraventricular nucleus,in fornix transected rats

BACKGROUND： The hippocampus regulates the hypothalamic-pituitary-adrenal axis through negative feedback. The hypothalamic paraventricular nucleus receives neuronal input from the hippocampus via the fomix, OBJECTIVE： To explore whether the negative feedback effect of the hippocampus on the hypothalamic-pituitary-adrenal axis is contributed to the inhibitory effect of mineralocorticoid receptor （MR） and glucocorticoid receptor （GR） in the hippocampus on the paraventricular nucleus via the fornix. DESIGN, TIME AND SETTING： Randomized, controlled, animal experiment. The study was performed at the Department of Histology and Embryology, China Medical University between September 2006 and September 2008. MATERIALS： Rabbit anti-rat anti-MR and rabbit anti-rat anti-GR antibodies were purchased from Santa Cruz Biotechnology, USA. Rabbit anti-rat anti-corticotrophin releasing hormone （CRH） and rabbit anti-rat anti-arginine vasopressin antibodies were purchased from Wuhan Boster. METHODS： A total of 90 male, Wistar rats were randomly divided into model and sham-surgery groups （n = 45）. Fornix transection was performed in the model group, while the sham-surgery group underwent surgery, but no fornix transection. MAIN OUTCOME MEASURES： Immunohistochemistry was used to examine MR and GR expression in the hippocampus, as well as CRH and anti-arginine vasopressin in the paraventricular nucleus. Western blot was used to measure alterations in MR, GR, and CRH protein expression following fomix transection. RESULTS： Compared with the sham-surgery group, there were no obvious changes in MR and GR expression in the hippocampus, or CRH and anti-arginine vasopressin expression in the paraventdcular nucleus within 4 days of fornix transection. However, after 7-10 days, significantly decreased MR and GR expression in the hippocampus, and increased CRH and anti-arginine vasopmssin expression in the paraventricular nucleus were observed （P 〈 0.05-0.01）. CONCLUSION： Negative feedback from the hippocampus on the hypothalamic-pituitary-adrenal axis might be mediated through the fornix, and the corticosterene actions mediated by hippocampal corticosteroid receptors indirectly modulated the hypothalamic-pituitary-adrenal axis.

Inhibition of ciliary neurotrophic factor in a rat model of transected spinal cord

Ciliary neurotrophic factor （CNTF） dramatically increases following spinal cord injury and participates in the repair process, although some studies have shown that CNTF plays a role in promoting glial scar formation following spinal cord injury. The antibody closure model can be used to inhibit CNTF expression following spinal cord injury, thereby furthering the understanding of the role of CNTF in spinal cord injury repair. In the present experiment, spinal catheters were placed in the vertebral canal of spinal cord transected rats, and CNTF antibodies were injected following fixation of the paraspinal muscle catheter. At 24 hours after a single CNTF antibody injection, CNTF expression decreased in the thoracic and lumbar spinal cord and recovered to normal levels by 48 72 hours. CNTF antibody treatment can effectively block endogenous CNTF expression in the thoracic and lumbar spinal cord during an interval of less than 24 hours in transected rats.

Regenerative medicine strategies for chronic complete spinal cord injury

Spinal cord injury is a condition in which the parenchyma of the spinal cord is damaged by trauma or various diseases.While rapid progress has been made in regenerative medicine for spinal cord injury that was previously untreatable,most research in this field has focused on the early phase of incomplete injury.However,the majority of patients have chronic severe injuries;therefore,treatments for these situations are of fundamental importance.The reason why the treatment of complete spinal cord injury has not been studied is that,unlike in the early stage of incomplete spinal cord injury,there are various inhibitors of neural regeneration.Thus,we assumed that it is difficult to address all conditions with a single treatment in chronic complete spinal cord injury and that a combination of several treatments is essential to target severe pathologies.First,we established a combination therapy of cell transplantation and drug-releasing scaffolds,which contributes to functional recovery after chronic complete transection spinal cord injury,but we found that functional recovery was limited and still needs further investigation.Here,for the further development of the treatment of chronic complete spinal cord injury,we review the necessary approaches to the different pathologies based on our findings and the many studies that have been accumulated to date and discuss,with reference to the literature,which combination of treatments is most effective in achieving functional recovery.

EZH2-dependent myelination following sciatic nerve injury

Demyelination and remyelination have been major focal points in the study of peripheral nerve regeneration following peripheral nerve injury.Notably,the gene regulatory network of regenerated myelin differs from that of native myelin.Silencing of enhancer of zeste homolog 2(EZH2)hinders the differentiation,maturation,and myelination of Schwann cells in vitro.To further determine the role of EZH2 in myelination and recovery post-peripheral nerve injury,conditional knockout mice lacking Ezh2 in Schwann cells(Ezh2^(fl/fl);Dhh-Cre and Ezh2^(fl/fl);Mpz-Cre)were generated.Our results show that a significant proportion of axons in the sciatic nerve of Ezh2-depleted mice remain unmyelinated.This highlights the crucial role of Ezh2 in initiating Schwann cell myelination.Furthermore,we observed that 21 days after inducing a sciatic nerve crush injury in these mice,most axons had remyelinated at the injury site in the control nerve,while Ezh2^(fl/fl);Mpz-Cre mice had significantly fewer remyelinated axons compared with their wild-type littermates.This suggests that the absence of Ezh2 in Schwann cells impairs myelin formation and remyelination.In conclusion,EZH2 has emerged as a pivotal regulatory factor in the process of demyelination and myelin regeneration following peripheral nerve injury.Modulating EZH2 activity during these processes may offer a promising therapeutic target for the treatment of peripheral nerve injuries.

Transplantation of adult spinal cord grafts into spinal cord transected rats improves their locomotor function

Grafted embryonic central neural tissue pieces can recover function of hemisected spinal cord in neonatal rats and promote axonal growth in adults. However, spinal cord segments from adults have not been used as donor segments for allogeneic transplantation. Here, we utilized adult spinal cord tissue grafts(aSCGs) as donor constructs for repairing complete spinal cord injury(SCI). Moreover, to provide a favourable microenvironment for SCI treatment, a growth factor cocktail containing three growth factors(brain-derived neurotrophic factor, neurotrophin-3 and vascular endothelial growth factor), was applied to the aSCG transplants. We found that the locomotor function was significantly improved 12 weeks after transplantation of aSCGs into the spinal cord lesion site in adult rats. Transplantation of aSCGs combined with these growth factors enhanced neuron and oligodendrocyte survival and functional restoration. These encouraging results indicate that treatment of complete SCI by transplanting aSCGs, especially in the presence of growth factors, has a positive effect on motor functional recovery, and therefore could be considered as a possible therapeutic strategy for SCI.

An ultrasound-guided percutaneous electrical nerve stimulation regimen devised using finite element modeling promotes functional recovery after median nerve transection

Percutaneous electrical nerve stimulation of an injured nerve can promote and accelerate peripheral nerve regeneration and improve function.When performing acupuncture and moxibustion,locating the injured nerve using ultrasound before percutaneous nerve stimulation can help prevent further injury to an already injured nerve.However,stimulation parameters have not been standardized.In this study,we constructed a multi-layer human forearm model using finite element modeling.Taking current density and activated function as optimization indicators,the optimal percutaneous nerve stimulation parameters were established.The optimal parameters were parallel placement located 3 cm apart with the injury site at the midpoint between the needles.To validate the efficacy of this regimen,we performed a randomized controlled trial in 23 patients with median nerve transection who underwent neurorrhaphy.Patients who received conventional rehabilitation combined with percutaneous electrical nerve stimulation experienced greater improvement in sensory function,motor function,and grip strength than those who received conventional rehabilitation combined with transcutaneous electrical nerve stimulation.These findings suggest that the percutaneous electrical nerve stimulation regimen established in this study can improve global median nerve function in patients with median nerve transection.

A hyaluronic acid granular hydrogel nerve guidance conduit promotes regeneration and functional recovery of injured sciatic nerves in rats

A hyaluronic acid granular hydrogel can promote neuronal and astrocyte colony formation and axonal extension in vitro,suggesting that the hydrogel can simulate an extracellular matrix structure to promote neural regeneration.However,in vivo experiments have not been conducted.In this study,we transplanted a hyaluronic acid granular hydrogel nerve guidance conduit to repair a 10-mm long sciatic nerve gap.The Basso,Beattie,and Bresnahan locomotor rating scale,sciatic nerve compound muscle action potential recording,Fluoro-Gold retrograde tracing,growth related protein 43/S100 immunofluorescence staining,transmission electron microscopy,gastrocnemius muscle dry/wet weight ratio,and Masson’s trichrome staining results showed that the nerve guidance conduit exhibited similar regeneration of sciatic nerve axons and myelin sheath,and recovery of the electrophysiological function and motor function as autologous nerve transplantation.The conduit results were superior to those of a bulk hydrogel or silicone tube transplant.These findings suggest that tissue-engineered nerve conduits containing hyaluronic acid granular hydrogels effectively promote the morphological and functional recovery of the injured sciatic nerve.The nerve conduits have the potential as a material for repairing peripheral nerve defects.

Serum response factor promotes axon regeneration following spinal cord transection injury

Studies have snown that serum response factor is beneficaial for axonar regeneration of peripheral herves.However,Its role after central nervous system injury remains unclear. In this study,we established a rat model of T9-T10 spinal cord transection injury.We found that the expression of serum response factor in injured spinal cord gray matter neurons gradually increased with time,reached its peak on the 7^(th) day,and then gradually decreased.To investigate the role of serum response factor,we used lentivirus vecto rs to ove rexpress and silence serum response factor in spinal cord tissue.We found that overexpression of serum response factor promoted motor function recovery in rats with spinal cord injury.Qualitative observation of biotinylated dextran amine anterograde tra cing showed that ove rexpression of serum response factor increased nerve fibers in the injured spinal co rd.Additionally,transmission electron microscopy showed that axon and myelin sheath morphology was restored.Silencing serum response factor had the opposite effects of ove rexpression.These findings suggest that serum response factor plays a role in the recovery of motor function after spinal cord injury.The underlying mechanism may be related to the regulation of axonal regeneration.

Functional recovery and muscle atrophy in pre-clinical models of peripheral nerve transection and gap-grafting in mice:effects of 4-aminopyridine

We recently demonstrated a repurposing beneficial effect of 4-aminopyridine(4-AP),a potassium channel blocker,on functional recove ry and muscle atrophy after sciatic nerve crush injury in rodents.However,this effect of 4-AP is unknown in nerve transection,gap,and grafting models.To evaluate and compare the functional recovery,nerve morphology,and muscle atrophy,we used a novel stepwise nerve transection with gluing(STG),as well as 7-mm irreparable nerve gap(G-7/0)and 7-mm isografting in 5-mm gap(G-5/7)models in the absence and presence of 4-AP treatment.Following surgery,sciatic functional index was determined wee kly to evaluate the direct in vivo global motor functional recovery.After 12 weeks,nerves were processed for whole-mount immunofluorescence imaging,and tibialis anterior muscles were harvested for wet weight and quantitative histomorphological analyses for muscle fiber crosssectional area and minimal Feret's diameter.Average post-injury sciatic functional index values in STG and G-5/7 models were significantly greater than those in the G-7/0 model.4-AP did not affect the sciatic functional index recovery in any model.Compared to STG,nerve imaging revealed more misdirected axons and distorted nerve architecture with isografting.While muscle weight,cross-sectional area,and minimal Feret's diameter were significantly smaller in G-7/0 model compared with STG and G-5/7,4-AP treatment significantly increased right TA muscle mass,cross-sectional area,and minimal Feret's diameter in G-7/0 model.These findings demonstrate that functional recovery and muscle atrophy after peripheral nerve injury are directly related to the intervening nerve gap,and 4-AP exerts diffe rential effects on functional recove ry and muscle atrophy.

Quantifying Arborescent Flora Diversity in a Secondary Forest Ecosystem: A Comprehensive Assessment in Nambalan, Mayantoc, Tarlac, Philippines

Forest plays a crucial role in providing essential ecosystem services, including water supply, climate regulation, and biodiversity conservation. This study aimed to assess the current state of the forest in Barangay Nambalan, Mayantoc, Tarlac. The specific objectives were to identify tree species in the area and determine the tree diversity index, with a focus on endemism and conservation status. Two transect lines, each spanning one kilometer, were established and a total of 10 sampling quadrats were surveyed. Ecological parameters (relative frequency, relative density, relative dominance, and importance value index) and diversity indices (Shannon-Weiner index, Simpson’s index) were computed using the Paleontological Statistic Software Package for Educational Analysis (PAST 4.03). A comprehensive inventory revealed a total of 756 individuals representing 52 species, 46 genera, and 25 families. Among the recorded species, 10 (17.2%) were endemic and 11 (21.6%) were classified as threatened. The Fabaceae (20.8%), Moraceae (14.6%), and Euphorbiaceae (8.3%) were identified as the most abundant families. The computed diversity indices indicated that Barangay Nambalan retains a diverse forest cover;however, species composition was found to be relatively low. Based on the finding, this study recommends the strict enforcement of protective measures and legislation to mitigate further degradation of the remaining forest in Barangay Nambalan.

Spatio-temporal distribution of net primary productivity along the northeast China transect and its response to climatic change

An improved Carnegie Ames Stanford Approach model （CASA model） was used to estimate the net primary productivity （NPP） of the Northeast China Transect （NECT） every month from 1982 to 2000. The spatial-temporal distribution of NPP along NECT and its response to climatic change were also analyzed. Results showed that the change tendency of NPP spatial distribution in NECT is quite similar to that of precipitation and their spatial correlation coefficient is up to 0.84 （P 〈 0.01）. The inter-annual variation of NPP in NECT is mainly affected by the change of the aestival NPP every year, which accounts for 67.6% of the inter-annual increase in NPP and their spatial correlation coefficient is 0.95 （P 〈 0.01）. The NPP in NECT is mainly cumulated between May and September, which accounts for 89.8% of the annual NPP. The NPP in summer （June to August） accounts for 65.9% of the annual NPP and is the lowest in winter. Recent climate changes have enhanced plant growth in NECT. The mean NPP increased 14.3% from 1980s to 1990s. The inter-annual linear trend of NPP is 4.6 gC·m^-2·a^-1, and the relative trend is 1.17%, which owns mainly to the increasing temperature.

Spatial Characteristics and Change for Tree Species (Genera) Along Northeast China Transect (NECT)

The 16 tree species on Northeast China Transect (NECT) were analyzed from the change of geographical distribution, frequency and dominance pattern and the spatial correlation at landscape scale in 1986 and 1994. Pinus koraiensis Sieb. et Zucc. and Fraxinus rhynchophylla Hemsl. had spread rapidly towards west and east, respectively. The frontier form of species had close relation with its movement. The patch size of Pinus koraiensis , Populus davidiana Dode., Phellodendron amurense Rupr., Juglans mandshurica Maxim., Fraxinus mandshurica Rupr., Betula dahurica Pall., Picea koraiensis Nakai, Abies nephrolepis Maxim. and Larix olgeusis var. koreana Nakai decreased, however, Quercus mongolica Fisch., Betula costata Trautv., Acer mono Maxim., Tilia spp., Ulmus spp., Betula platyphylla Suk. and Fraxinus rhynchophylla increased. The frequency pattern of Populus davidiana , Betula platyphylla , Fraxinus rhynchophylla and Betula dahurica changed significantly. The dominance pattern of Populus davidiana , Tilia spp., Juglans mandshurica , Betula platyphylla , Betula dahurica and Abies nephrolepis changed significantly. The spatial correlation between Quercus mongolica and Betula dahurica , Betula costata and Picea spp., Betula costata and Abies nephrolepis , Picea spp. and Abies nephrolepis declined, however, the spatial correlation between Larix spp. and Betula platyphylla , Acer mono and Ulmus spp. increased.

A Comparative Study on Photosynthesis and Water Use Efficiency Between Clonal and Non_clonal Plant Species Along the Northeast China Transect (NECT)

Net photosynthesis ( P n ), transpiration ( E ), stomatal conductance ( g s) and water use efficiency (WUE) of more than 218 species belonging to two different reproductive functional types, i.e. clonal (115 species) and non_clonal species (103 species), along the 1 670 km Northeast China Transect (NECT) were analyzed. The results showed that P n and WUE appeared to be lower in the east and west ends of NECT, with peaks in the middle. Transpiration was found to be higher in the west end, where most temperate desert species were distributed. On the same site, most clonal species showed higher P n and related physiological variables than non_clonal species. For different growth forms over NECT, e.g. forest trees, shrubs and grasses, meadow steppe shrubs and grasses, typical steppe shrubs and grasses, the meadow steppe and typical steppe grasses, showed higher values of physiological variables than the forest or the desert species. But for the two reproductive plant functional types (PFTs), clonal species had higher physiological variables, with averages of 22%, 15%, 23% and 14% higher than the non_clonal ones for P n , E, g s, and WUE, respectively. Such differences indicated that clonal species might have advantages over non_clonal species in utilizing environmental resources such as light, CO 2, and especially water.

Peripheral nerve regeneration and intraneural revascularization

Peripheral nerves are particularly vulnerable to injuries and are involved in numerous pathologies for which specific treatments are lacking. This review summarizes the pathophysiological features of the most common traumatic nerve injury in humans and the different animal models used in nerve regeneration studies. ~Ihe current knowledge concerning Wallerian degeneration and nerve regrowth is then described. Finally, the involvement of intraneural vascularization in these processes is addressed. As intraneural vascularization has been poorly studied, histological experiments were carried out from rat sciatic nerves damaged by a glycerol injection. The results, taken together with the data from literature, suggest that revascularization plays an important role in peripheral nerve regeneration and must therefore be studied more carefully.

Comprehensive application of modern technologies in precise liver resection

BACKGROUND: Liver surgery has gone through the phases of wedge liver resection, regular resection of hepatic lobes, irregular and local resection, extracorporeal hepatectomy, hemi-extracorporeal hepatectomy and Da Vinci surgical system-assisted hepatectomy. Taking advantage of modern technologies, liver surgery is stepping into an age of precise liver resection. This review aimed to analyze the comprehensive application of modern technologies in precise liver resection. DATA SOURCE: PubMed search was carried out for English-language articles relevant to precise liver resection, liver anatomy, hepatic blood inflow blockage, parenchyma transection, and down-staging treatment. RESULTS: The 3D image system can imitate the liver operation procedures, conduct risk assessment, help to identify the operation feasibility and confirm the operation scheme. In addition, some techniques including puncture and injection of methylene blue into the target Glisson sheath help to precisely determine the resection. Alternative methods such as Pringle maneuver are helpful for hepatic blood inflow blockage in precise liver resection. Moreover, the use of exquisite equipment for liver parenchyma transection, such as cavitron ultrasonic surgical aspirator, ultrasonic scalpel, Ligasure and Tissue Link is also helpful to reduce hemorrhage in liver resection, or even operate exsanguinous liver resection without blocking hepatic blood flow. Furthermore, various down-staging therapies including transcatheter arterial chemoembolization and radio-frequency ablation were appropriate for unresectable cancer, which reverse the advanced tumor back to early phase by local or systemic treatment so that hepatectomy or liver transplantation is possible.CONCLUSIONS: Modern technologies mentioned in this paper are the key tool for achieving precise liver resection and can effectively lead to maximum preservation of anatomical structural integrity and functions of the remnant liver. In addition, large randomized trials are needed to evaluate the usefulness of these technologies in patients with hepatocellular carcinoma who have undergone precise liver resection.

Classic axon guidance molecules control correct nerve bridge tissue formation and precise axon regeneration

The peripheral nervous system has an astonishing ability to regenerate following a compression or crush injury;however,the potential for full repair following a transection injury is much less.Currently,the major clinical challenge for peripheral nerve repair come from long gaps between the proximal and distal nerve stumps,which prevent regenerating axons reaching the distal nerve.Precise axon targeting during nervous system development is controlled by families of axon guidance molecules including Netrins,Slits,Ephrins and Semaphorins.Several recent studies have indicated key roles of Netrin1,Slit3 and EphrinB2 signalling in controlling the formation of new nerve bridge tissue and precise axon regeneration after peripheral nerve transection injury.Inside the nerve bridge,nerve fibroblasts express EphrinB2 while migrating Schwann cells express the receptor EphB2.EphrinB2/EphB2 signalling between nerve fibroblasts and migrating Schwann cells is required for Sox2 upregulation in Schwann cells and the formation of Schwann cell cords within the nerve bridge to allow directional axon growth to the distal nerve stump.Macrophages in the outermost layer of the nerve bridge express Slit3 while migrating Schwann cells and regenerating axons express the receptor Robo1;within Schwann cells,Robo1 expression is also Sox2-dependent.Slit3/Robo1 signalling is required to keep migrating Schwann cells and regenerating axons inside the nerve bridge.In addition to the Slit3/Robo1 signalling system,migrating Schwann cells also express Netrin1 and regenerating axons express the DCC receptor.It appears that migrating Schwann cells could also use Netrin1 as a guidance cue to direct regenerating axons across the peripheral nerve gap.Engineered neural tissues have been suggested as promising alternatives for the repair of large peripheral nerve gaps.Therefore,understanding the function of classic axon guidance molecules in nerve bridge formation and their roles in axon regeneration could be highly beneficial in developing engineered neural tissue for more effective peripheral nerve repair.

Etomidate affects the anti-oxidant pathway to protect retinal ganglion cells after optic nerve transection

Our previous studies revealed that etomidate, a non-barbiturate intravenous anesthetic agent, has protective effects on retinal ganglion cells within 7 days after optic nerve transection. Whether this process is related to anti-oxidative stress is not clear. To reveal its mechanism, we established the optic nerve transection injury model by transecting 1 mm behind the left eyeball of adult male Sprague-Dawley rats. The rats received an intraperitoneal injection of etomidate(4 mg/kg) once per day for 7 days. The results showed that etomidate significantly enhanced the number of retinal ganglion cells retrogradely labeled with Fluorogold at 7 days after optic nerve transection. Etomidate also significantly reduced the levels of nitric oxide and malonaldehyde in the retina and increased the level of glutathione at 12 hours after optic nerve transection. Thus, etomidate can protect retinal ganglion cells after optic nerve transection in adult rats by activating an anti-oxidative stress response. The study was approved by the Animal Ethics Committee at Air Force Medical University, China(approval No. 20180305) on March 5, 2018.

Silicon limitation on primary production and its destiny in Jiaozhou Bay, China Ⅳ: Study on cross-bay transect from estuary to ocean

The authors analyzed the data collected in the Ecological Station Jiaozhou Bay from May 1991 to November 1994, including 12 seasonal investigations, to determine the characteristics, dynamic cycles and variation trends of the silicate in the bay. The results indicated that the rivers around Jiaozhou Bay provided abundant supply of silicate to the bay. The silicate concentration there depended on river flow variation. The horizontal variation of silicate concentration on the transect showed that the silicate concentration decreased with distance from shorelines. The vertical variation of it showed that silicate sank and deposited on the sea bottom by phytoplankton uptake and death, and zooplankton excretion. In this way, silicon would endlessly be transferred from terrestrial sources to the sea bottom. The silicon took up by phytoplankton and by other biogeochemical processes led to insufficient silicon supply for phytoplankton growth. In this paper, a 2D dynamic model of river flow versus silicate concentration was established by which silicate concentrations of 0.028–0.062 μmol/L in seawater was yielded by inputting certain seasonal unit river flows (m3/s), or in other words, the silicate supply rate; and when the unit river flow was set to zero, meaning no river input, the silicate concentrations were between 0.05 –0.69 μmol/L in the bay. In terms of the silicate supply rate, Jiaozhou Bay was divided into three parts. The division shows a given river flow could generate several different silicon levels in corresponding regions, so as to the silicon-limitation levels to the phytoplankton in these regions. Another dynamic model of river flow versus primary production was set up by which the phytoplankton primary production of 5.21–15.55(mgC/m2·d)/(m3/s) were obtained in our case at unit river flow values via silicate concentration or primary production conversion rate. Similarly, the values of primary production of 121.98–195.33 (mgC/m2·d) were achieved at zero unit river flow condition. A primary production conversion rate reflects the sensitivity to silicon depletion so as to different phytoplankton primary production and silicon requirements by different phytoplankton assemblages in different marine areas. In addition, the authors differentiated two equations (Eqs.1 and 2) in the models to obtain the river flow variation that determines the silicate concentration variation, and in turn, the variation of primary production. These results proved further that nutrient silicon is a limiting factor for phytoplankton growth.

A multi-channel collagen scaffold loaded with neural stem cells for the repair of spinal cord injury

Collagen scaffolds possess a three-dimensional porous structure that provides sufficient space for cell growth and proliferation,the passage of nutrients and oxygen,and the discharge of metabolites.In this study,a porous collagen scaffold with axially-aligned luminal conduits was prepared.In vitro biocompatibility analysis of the collagen scaffold revealed that it enhances the activity of neural stem cells and promotes cell extension,without affecting cell differentiation.The collagen scaffold loaded with neural stem cells improved the hindlimb motor function in the rat model of T8 complete transection and promoted nerve regeneration.The collagen scaffold was completely degraded in vivo within 5 weeks of implantation,exhibiting good biodegradability.Rectal temperature,C-reactive protein expression and CD68 staining demonstrated that rats with spinal cord injury that underwent implantation of the collagen scaffold had no notable inflammatory reaction.These findings suggest that this novel collagen scaffold is a good carrier for neural stem cell transplantation,thereby enhancing spinal cord repair following injury.This study was approved by the Animal Ethics Committee of Nanjing Drum Tower Hospital(the Affiliated Hospital of Nanjing University Medical School),China(approval No.2019AE02005)on June 15,2019.