Mechanism of spinal cord injury regeneration and the effect of human neural stem cells-secretome treatment in rat model

BACKGROUND Globally,complete neurological recovery of spinal cord injury(SCI)is still less than 1%,and 90%experience permanent disability.The key issue is that a pharmacological neuroprotective-neuroregenerative agent and SCI regeneration mechanism have not been found.The secretomes of stem cell are an emerging neurotrophic agent,but the effect of human neural stem cells(HNSCs)secretome on SCI is still unclear.AIM To investigate the regeneration mechanism of SCI and neuroprotective-neuroregenerative effects of HNSCs-secretome on subacute SCI post-laminectomy in rats.METHODS An experimental study was conducted with 45 Rattus norvegicus,divided into 15 normal,15 control(10 mL physiologic saline),and 15 treatment(30μL HNSCssecretome,intrathecal T10,three days post-traumatic).Locomotor function was evaluated weekly by blinded evaluators.Fifty-six days post-injury,specimens were collected,and spinal cord lesion,free radical oxidative stress(F2-Isoprostanes),nuclear factor-kappa B(NF-κB),matrix metallopeptidase 9(MMP9),tumor necrosis factor-alpha(TNF-α),interleukin-10(IL-10),transforming growth factor-beta(TGF-β),vascular endothelial growth factor(VEGF),B cell lymphoma-2(Bcl-2),nestin,brain-derived neurotrophic factor(BDNF),glial cell line-derived neurotrophic factor(GDNF)were analyzed.The SCI regeneration mechanism was analyzed using partial least squares structural equation modeling(PLS SEM).RESULTS HNSCs-secretome significantly improved locomotor recovery according to Basso,Beattie,Bresnahan(BBB)scores and increased neurogenesis(nestin,BDNF,and GDNF),neuroangiogenesis(VEGF),anti-apoptotic(Bcl-2),anti-inflammatory(IL-10 and TGF-β),but decreased proinflammatory(NF-κB,MMP9,TNF-α),F2-Isoprostanes,and spinal cord lesion size.The SCI regeneration mechanism is valid by analyzed outer model,inner model,and hypothesis testing in PLS SEM,started with pro-inflammation followed by anti-inflammation,anti-apoptotic,neuroangiogenesis,neurogenesis,and locomotor function.CONCLUSION HNSCs-secretome as a potential neuroprotective-neuroregenerative agent for the treatment of SCI and uncover the SCI regeneration mechanism.

Adventitious Root Regeneration:Molecular Basis and Influencing Factors

Plant regeneration is a self-repair of the plant body in response to adverse conditions or damaged structures,and root regeneration allows the plant body to better adapt to its environment by supplementing the roots’structure.Previous research has shown that adventitious roots can be made to occur from scratch in two ways.Studies that simulate adventitious root regeneration through natural conditions allow the regeneration process to be broadly divided into three stages:the perception of early signals,the massive accumulation of auxin,and the transformation of cell fate.The strength of regeneration,in turn,is influenced by wounding,stress,hormones,etc.This study mainly reviews the molecular mechanisms of de novo adventitious roots and discusses how the environment,hormones,and its own development in Arabidopsis thaliana.

Laboratory Evaluation of Performance Recovery of Aged SBS-modified Asphalt Using Regenerants with Different Base Oil Components

In this study,the regenerative effects of different regenerants on aged SBS-modified asphalt from different perspectives were investigated,including their conventional properties,viscoelastic behavior,creep-related properties,and micromorphology.Base oils composed of different proportions of aromatic and saturated hydrocarbons as well as the styrene-butadiene-styrene(SBS)restorer were used to prepare the regenerants.The results showed that the components of the base oil of the regenerant played a crucial role in determining the characteristics and performance of the recycled SBSmodified asphalt.Regenerants containing a high proportion of aromatics dissolved the hard segment in the SBS restorer,thereby delaying the effect of a reduction in the regenerants on the performance of the aged asphalts at a high temperature.Regenerants containing a high proportion of saturates dissolved the soft segment in the SBS restorer to enhance the lowtemperature performance of the recycled asphalts.In addition,the stress sensitivity of the recycled asphalts increased with the fraction of aromatics in the regenerant.As the aromatic content of the base oil components of the regenerants increased and their saturate content decreased,the state of dispersion of the SBS phase in the recycled SBS-modified asphalts improved.The optimal content of aromatics in the base oil of the regenerants should be set in the range of 33%to 47%to ensure the adequate performance of the recycled asphalts and a high efficiency of the SBS restorer.

Streptozotocin induced Alzheimer's disease like changes and the underlying neural degeneration and regeneration mechanism

Alzheimer’s disease（AD）is a neurodegenerative disorder which is remarkably characterized by pathological hallmarks that include neurofibrillary tangles,neuronal loss extracellular senile plaques containing aggregated amyloid beta（Aβ）,and neurofibrillary tangles composed of the hyperphosphorylated form of the microtubule protein tau.It is the most common form of dementia which is characterized by severe neurodegenerative changes such as loss of neurons and synapses in brain（Kamat et al.,2014）.

Diffusion and Regeneration Mechanism of Waste Composite Oils Rejuvenator in Aged Asphalt

The physical performance of recycled asphalt was used as the main evaluation index to study the optimal range of a self-made rejuvenator.Through the penetration,viscosity and gel permeation chromatography(GPC)tests,the diffusion degree of the rejuvenator under different temperatures and time process was analyzed,and the diffusion efficiency of the rejuvenator was evaluated from the macro and micro perspective.The regeneration mechanism of the rejuvenator in the aged asphalt was also analyzed using the Fourier transform infrared spectroscopy(FTIR),scanning electron microscope(SEM)and chemical composition tests.The research results showed that the optimum rejuvenator content was about 3%.Higher temperature and longer time were beneficial to improving the permeability and diffusion of the rejuvenator.During the aging process,the light components were reduced,and more macromolecular asphaltenes were generated as well as a large number of carbonyl and sulfoxide.After diffusion and regeneration,the light components in the asphalt were supplemented,the wrinkles and gullies of the aged asphalt were almost improved to the surface state of the matrix asphalt.

Extrinsic and intrinsic mechanisms of axon regeneration:the need for spinal cord injury treatment strategies to address both

Spinal cord injury（SCI）causes disturbances in motor and sensory functions leading to paralysis,the severity of which depends on the spinal level of the injury.Traumatic lesions of spinal cord axon projection tracts are untreatable in human patients,although numerous research groupsworldwide are studying putative treatment strategies.

Okadaic acid: a tool to study regulatory mechanisms for neurodegeneration and regeneration in Alzheimer's disease

Okadaic acid： Okadaic acid （OKA）, a polyether （C38 fatty acid） toxin, is a potent and selective inhibitor of protein phosphatase, PP1 and protein phosphatase 2A （PP2A）. It is mainly extracted from a black sponge Hallichondria okadaii and has been suggested to play a potent probe for studying the various molecular, cellular, biochemical and mechanism of neurotoxicity. It is known as a selective and potent in- hibitor of serine/threonine phosphatases 1 and 2A induces hyperphosphorylation of tau in vitro and in vivo. It has been reported that Alzheimer＇s disease （AD） is a complex multi- factorial neurodegenerative disorder and hyperphosphor- ylated tau protein is a major pathological hallmark of AD. The reduced activity of phosphatases like, PP2A has been implicated in the brain of AD patients. OKA also induced inhibition of protein phosphatases cause neurofibrillary tangles （NFTs） like pathological changes and tau hyperphos- phorylation seen in AD pathology. Our and others reports inferred that OKA induces neurodegeneration along with tau hyperphosphorylation, GSK3β activation, oxidative stress, neuroinflammation and neurotoxicity which are char- acteristic of AD pathology （Figure 1）.

Acetylation as a mechanism that regulates axonal regeneration

The capacity for adult axons to regenerate after injury is diminished compared with developing axons.In the case of central nervous system（CNS）axons,injury causes a total failure to regenerate.This failure is due to both the intrinsic developmental decrease in growth capacity and the extrinsic inhibitory environment formed because of the injury.

Diffusion tensor tractography studies on mechanisms of recovery of injured fornix

The fornix,which connects the medial temporal lobe and the medial diencephalon,is involved in episodic memory as an important part of the Papez circuit.The mechanisms of recovery of an injured fornix revealed by diffusion tensor tractography in the five studies are summarized as follows：1） recovery through the nerve tract from an injured fornical crus to the medial temporal lobe via the normal pathway of the fornical crus;2）recovery through the nerve tract originating from an ipsi-lesional fornical body connected to the ipsi-lesional medial temporal lobe via the splenium of the corpus callosum;3） recovery through the nerve tract from the ipsi-lesional fornical body extending to the contra-lesional medial temporal lobe via the splenium of the corpus callosum;4） recovery through the nerve tract originating from the ipsi-lesional fornical column connected to the ipsi-lesional medial temporal lobe;and 5） recovery through the nerve tract originating from the contra-lesional fornical column connected to the ipsi-lesional medial temporal lobe via the contra-lesional medial temporal lobe and the splenium of the corpus callosum.These diffusion tensor tractography studies on mechanisms of recovery of injured fornical crus appeared to provide useful information for clinicians caring for patients with brain injury,however,studies on this topic are still in the beginning stages.

Ischemic postconditioning protects against ischemic brain injury by up-regulation of acid-sensing ion channel 2a

Ischemic postconditioning renders brain tissue tolerant to brain ischemia,thereby alleviating ischemic brain injury.However,the exact mechanism of action is still unclear.In this study,a rat model of global brain ischemia was subjected to ischemic postconditioning treatment using the vessel occlusion method.After 2 hours of ischemia,the bilateral common carotid arteries were blocked immediately for 10 seconds and then perfused for 10 seconds.This procedure was repeated six times.Ischemic postconditioning was found to mitigate hippocampal CA1 neuronal damage in rats with brain ischemia,and up-regulate acid-sensing ion channel 2a expression at the m RNA and protein level.These findings suggest that ischemic postconditioning up-regulates acid-sensing ion channel 2a expression in the rat hippocampus after global brain ischemia,which promotes neuronal tolerance to ischemic brain injury.