Implications of regional identity for neural stem and progenitor cell transplantation in the injured or diseased nervous system

Neural stem and progenitor cell(NSPC)transpla ntation has emerged as a promising therapeutic strategy for replacing lost neuronal populations and repairing damaged neural circuits following nervous system injury and disease.A great deal of experimental work has investigated the biology of NSPC grafting in preclinical animal models;more recently.

Nucleoside modified mRNA-lipid nanoparticles as a new delivery platform for the repair of the injured spinal cord

Spinal cord injury and treatment opportunities:The adult mammalian spinal cord has a very limited capacity for spontaneous regeneration due to various intrinsic molecular and cellular factors.Although the spinal cord neurons have the capacity to regenerate their axons,the expression of growth inhibitory factors,lack or suppression of proper guidance cues,and profound inflammatory responses do not permit successful regeneration(Khyeam et al.,2021).

Clinical efficacy and safety of kyphoplasty for the treatment of osteoporotic vertebral compression fractures at different surgical timings based on the theory of“dynamic-static integration”

Objective:To investigate the clinical efficacy and safety of percutaneous kyphoplasty at different surgical timings in the treatment of osteoporotic vertebral compression fracture(OVCF)based on the theory of“dynamic-static integration”.Methods:Patients with OVCF who underwent percutaneous kyphoplasty in our hospital were selected and divided into Groups A,B,and C for those undergoing surgery within 7,7—21,and>21 days of fracture occurrence.The variations in the amount of bone cement injected,pre-and post-operative pain levels,functional activity,deformity correction of the injured vertebrae,bone cement leakage,and vertebral body height loss were compared among the three groups.Results:Regarding pain relief and functional activity,the postoperative Visual Analog Scale and Oswestry Disability Index scores of the three groups significantly improved.Furthermore,the deformities of the injured vertebrae in the three groups were significantly corrected,with Groups A and B exhibiting superior correction compared to Group C.Moreover,the bone cement leakage rates in groups A and C were higher than that in Group B.At the 3-month follow-up,the loss of vertebral height in Group C was significantly higher than those in groups A and B.Conclusion:Kyphoplasty is effective for OVCF treatment.Early surgery can effectively restore the vertebral height of the injured vertebra,reduce kyphosis,and reduce height loss of the injured vertebra after surgery;nevertheless,treatment within 1—3 weeks of the fracture can reduce the occurrence of bone cement leakage,making the surgery safer.Therefore,surgical treatment within 1—3 weeks of fracture is safer and can achieve satisfactory therapeutic effects.From the perspective of traditional Chinese medicine,PKP surgery can transform the fracture end from a micromotion state to a fixed state,which fully embodies the theory of“dynamic-static integration”.

How Dangerous!

This morning I came across something dangerous on my way to school,which nearly injured me or even made me lose my life.

Towards simulation of germinal matrix hemorrhage as a complication of premature birth

The germinal matrix being an accumulation of immature blood vessels in the premature infant brain is known to be the main cause of the intracranial hemorrhage. To investigate the injuring mechanism to the blood vessels of the germinal matrix, a modeling scenario that consists of three basic steps is proposed. First, the cerebral blood flow that depends on autoregulation, CO2 reactivity, and variations of intracranial pressure is modeled. Second, the chaotic blood vessel network of the germinal matrix is generated, and blood pressures in the vessels of this network are computed dependent on the outcome of the first step. In the third step, the pressures computed on the second step are used in finite element simulations of separate blood vessels of the germinal matrix to detect critical values for vessels impairment.

腹腔镜胆囊切除术中胆道损伤原因及处理的探讨（附4例报告）

自2005年4月～2006年6月，笔者在苏州大学附属第一医院进修期间，参加了腹腔镜胆囊切除术（LC）200余例，发生胆道损伤（bile duetinjure）4例，印象极为深刻，现根据临床资料就LC中并发BDI的原因及处理结合文献浅作探讨。

MRS and diffusion tensor image in mild traumatic brain injuries

Objective:To analyze characters of magnetic resonance spectroscopy(MRS) and diffusion tensor imaging(DTI) in the diagnosis of mild trauma brain injuries(MTBI) in frontal lobe and to compare with conventional magnetic resonance imaging(MRI).Methods:A total of 21 patients were selected,who all aged 12-51 years old and had injury within 24 hours.Computer tomography (CT) and the Glasgow Coma Scale were used to evaluate the degree of injury.All patients were diagnosed as MTBI,and 19 had conventional MRI,MRS and DTI.The major parameters of MRS were Probe-P sequence,TE= 144 or 35 ms,and both single voxel spectrum and chemical shift imging were included.The major parameters of DTI were diffusion directions =15,b value = 1000 s/mm^2. Frational anisotropic(FA) map and average ADC map were obtained to evaluate DTI result. Positive deletion ratio was observed and the imaging changes were compared between injured side and normal side.Results:All 21 patients had CT scan and Glasgow scale.A total of 19 patients had conventional MRI.DTI and MRS.Results of CT and conventional MRI showed no significant abnormality in lobe,and Glasgow scale showed mild type.MRS result showed significant decrease in N-acetyl aspartate(NAA) and NAA/creatine(Cr) in 13 cases(68.4%) (P【0.001),and increase in lactic acid(Lac) in 7 cases(36.8%).FA mapping of the frontal lobe displayed significant changes in 7 cases(36.8%),with 5 out of the 7 cases having increase in FA value.And there was no significant difference in average ADC.Conclusions:MRS and DTI might be more sensible than other methods,such as CT and conventional MRI in diagnosis of MTBI.The particular changes were reduced NAA and increased Lac for MRS.and increased FA values for DTI.

Bridging the injured spinal cord with neural stem cells

Spinal cord injury （SCI） damages not only the gray matter neurons, but also the white matter axonal tracts that carry signals to and from the brain, re- suiting in permanent loss of function below injury. Neural stem cells （NSCs） have high therapeutic potential for reconstruction of the injured spinal cord since they can potentially fnrm neuronal relays to bridge functional con-nectivity between separated spinal cord segments. This requires host axonal regeneration into and connectivity with donor neurons, and axonal growth and connectivity of donor neurons to host central nervous system （CNS） circuitry. In this mini-review, we will discuss key studies that explore novel neuronal relay formation by grafting NSCs in models of SCI, with emphasis on long-distance axonal growth and connectivity of NSCs grafted into in-jured spinal cord.

Beneficial effects of BV2 cell on proliferation and neuron-differentiating of mesenchymal stem cells in the circumstance of injured PC12 cell supernatant

Objective The microglias is the representative of immune cells in the brain. It plays dual roles of both repairing and damaging in injured nervous system, and works as an inevitable component of the circumstance of injured neurons. This study was aiming at the effects of the microglias on the biological activities of mesenchymal stem cells （MSCs） in the circumstance of injured neurons. Methods MSCs were obtained by primary culture. We adopted PC12 cells （PC12） and BV2 cells （BV2） to substitute for neurons and microglias, respectively. PC12 were injured by aged Aβ1-40 and the supernatant of the injured PC12 was used to set up the circumstance of injured neurons. Transwells were used for co-culture of BV2 and MSCs, which allowed the independent detection of cells after co-culture. Immunofluorescence was used to identify MSCs and neuron-differentiating cells with CD44 and neuron specific enolase （NSE） staining, respectively. MTT assay was adopted to measure the proliferation. Results In the circumstance of both BV2 presence and injured PC 12 supernatant incubation, either the proliferation or the differentiation of MSCs reached the highest, which seemed to be contradictory, but we gave our explanations. With the BV2 co-culture, the proliferation of MSCs tend to be higher, but the neuron-differentiating MSCs were similar to those incubated without BV2 co-culture either in normal or injured in PC12 supernatant. With the incubation of injured PC12 supernatant, the neuron-differentiating cells were significantly higher than that of control （P 〈 0.05）. Conclusion In the circumstance of injured neurons, microlgias tend to promote the MSCs proliferation. Although not helpful in neuron-differentiating, microglias did not exert any negative effect either.

Neurosurgical procedures in patients with liver cirrhosis: A review

Liver cirrhosis, a devastating liver fibrosis caused by hepatitis/inflammation or tumors, is a major comorbid factor in known surgery fields, such as cardiovascular and abdominal surgeries. It is important to review possible comorbid results in neurosurgical procedures in cirrhotic patients. In the reviewed literature, ChildPugh and model for end-stage liver disease scores are commonly used in the assessment of surgical risks for cirrhotic patients undergoing abdominal, cardiovascular or neurosurgical procedures. The major categories of neurosurgery are traumatic brain injury(TBI), spontaneous intracranial hemorrhage(SICH), brain tumors, and spinal instrumentation procedures. TBI was reported with surgical mortality as high as 34.5% and a complication rate of 87.2%. For SICH, mortality ranged from 22.7% to 47.0%, while complications were reported to be 43.2%. Less is discussed in brain tumor patients; still the postoperative hemorrhage rate approached 26.7%. In spinal fusion instrumentation procedures, the complication rate was as high as 41.0%. Preoperative assessment and correction could possibly decrease complications such as hemorrhage, wound infection and other cirrhosis-related complications(renal, pulmonary, ascites and encephalopathy). In this study, we reviewed the neurosurgical-related literature with regard to liver cirrhosis as a prognostic factor influencing neurosurgical outcomes.

Neural cell injury microenvironment induces neural differentiation of human umbilical cord mesenchymal stem cells

This study aimed to investigate the neural differentiation of human umbilical cord mesenchymal stem cells （hUCMSCs） under the induction of injured neural cells. After in vitro isolation and culture, passage 5 hUCMSCs were used for experimentation, hUCMSCs were co-cultured with normal or AI31.4o-injured PC12 cells, PC12 cell supernatant or PC12 cell lysate in a Transwell co-culture system. Western blot analysis and flow cytometry results showed that choline acetyltransferase and microtubule-associated protein 2, a specific marker for neural cells, were expressed in hUCMSCs under various culture conditions, and highest expression was observed in the hUCMSCs co-cultured with injured PC12 cells. Choline acetyltransferase and microtubule-associated protein 2 were not expressed in hUCMSCs cultured alone （no treatment）. Cell Counting Kit-8 assay results showed that hUCMSCs under co-culture conditions promoted the proliferation of injured PC12 cells. These findings suggest that the microenvironment during neural tissue injury can effectively induce neural cell differentiation of hUCMSCs. These differentiated hUCMSCs likely accelerate the repair of injured neural ceils.

Mechanisms of electroacupuncture effects on acute cerebral ischemia/reperfusion injury:possible association with upregulation of transforming growth factor beta 1

Electroacupuncture at the head acupoints Baihui（GV20） and Shuigou（GV26） improves recovery of neurological function following ischemic cerebrovascular events,but its mechanism remains incompletely understood.We hypothesized that the action of electroacupuncture at these acupoints is associated with elevated serum levels of transforming growth factor beta 1（TGF-β1）.To test this,we established a rat model of cerebral ischemia by middle cerebral artery occlusion.Electroacupuncture was performed at Baihui and Shuigou with a “dispersedense” wave at an alternating frequency of 2 and 150 Hz,and at a constant intensity of 3 m A.Each electroacupuncture session lasted 30 minutes and was performed every 12 hours for 3 days.Neurological severity scores were lower in injured rats after acupuncture than in those not subjected to treatment.Furthermore,serum level of TGF-β1 was greater after electroacupuncture than after no treatment.Our results indicate that electroacupuncture at Baihui and Shuigou increases the serum level of TGF-β1 in rats with acute cerebral ischemia/reperfusion injury,and exerts neuroprotective effects.

Transplanting neural progenitors to build a neuronal relay across the injured spinal cord

Cellular transplantation for repair of spinal cord injury is a prom- ising therapeutic strategy that includes the use of a variety of neural and non-neural cells isolated or derived from embryonic and adult tissue as well as embryonic stem cells and induced plu- ripotent stem cells. In particular, transplants of neural progenitor cells （NPCs） have been shown to limit secondary injury and scar formation and create a permissive environment in the injured spinal cord through the provision of neurotrophic molecules and growth supporting matrices that promote growth of injured host axons. Importantly, transplants of NPC are unique in their poten- tial to replace lost neural cells - including neurons, astrocytes,

Protective effects of ginsenoside Rg1 against hydrogen peroxide-induced injury in human neuroblastoma cells

The active ingredient of ginseng,ginsenosides Rg1,has been shown to scavenge free radicals and improve antioxidant capacity.This study hypothesized that ginsenosides Rg1 has a protective role in human neuroblastoma cells injured by H2O2.Ginsenosides Rg1 at different concentrations（50 and 100 μM） was used to treat H2O2（150 μM）-injured SH-SY5 Y cells.Results demonstrated that ginsenoside Rg1 elevated the survival rate of SH-SY5 Y cells injured by H2O2,diminished the amount of leaked lactate dehydrogenase,and increased superoxide dismutase activity.Ginsenoside Rg1 effectively suppressed caspase-3 immunoreactivity,and contributed to heat shock protein 70 gene expression,in a dose-dependent manner.These results indicate that ginsenoside Rg1 has protective effects on SH-SY5 Y cells injured by H2O2 and that its mechanism of action is associated with anti-oxidation and the inhibition of apoptosis.

Mechanisms underlying the promotion of functional recovery by deferoxamine after spinal cord injury in rats

Deferoxamine, a clinically safe drug used for treating iron overload, also repairs spinal cord injury although the mechanism for this action remains unknown. Here, we determined whether deferoxamine was therapeutic in a rat model of spinal cord injury and explored potential mechanisms for this effect. Spinal cord injury was induced by impacting the spinal cord at the thoracic T10 vertebra level. One group of injured rats received deferoxamine, a second injured group received saline, and a third group was sham operated. Both 2 days and 2 weeks after spinal cord injury, total iron ion levels and protein expression levels of the proinflammatory cytokines tumor necrosis factor-α and interleukin-1β and the pro-apoptotic protein caspase-3 in the spinal cords of the injured deferoxamine-treated rats were significantly lower than those in the injured saline-treated group. The percentage of the area positive for glial fibrillary acidic protein immunoreactivity and the number of terminal deoxynucleotidyl transferase d UTP nick end labeling-positive cells were also significantly decreased both 2 days and 2 weeks post injury, while the number of Neu N-positive cells and the percentage of the area positive for the oligodendrocyte marker CNPase were increased in the injured deferoxamine-treated rats. At 14–56 days post injury, hind limb motor function in the deferoxamine-treated rats was superior to that in the saline-treated rats. These results suggest that deferoxamine decreases total iron ion, tumor necrosis factor-α, interleukin-1β, and caspase-3 expression levels after spinal cord injury and inhibits apoptosis and glial scar formation to promote motor function recovery.

ACUPUNCTURE TREATMENT FOR SPRAINS OF THE ANKLE JOINT IN 354 CASES

Sprains of the ankle joint is one of themost common soft tissue injuries,which isusually caused by a violent twisting.Thismovement can lacerate the interarticular lig-aments and the tendon insertions aroundthe ankle joint.We treated 354 cases of thistype of injury with acupuncture,yielding aninspiring therapeutic result.CLINICAL MATERIALSOf the 354 cases in this series,291 caseswere injured for the first time,and 63

Application and implications of polyethylene glycol-fusion as a novel technology to repair injured spinal cords

Conventional vs. polyethylene glycol （PEG）-fusion tech- nologies to repair severed spinal axons： Most spinal cord injuries （SCIs） involve cutor crush-severance of spinal tract axons in the central nervous system （CNS）. Clinical out- comes after CNS axonal severance is very poor because proximal segments of CNS axons lack a suitable environment for outgrowth （Kakulas, 1999; Fitch and Silver, 2008; Rowland et al., 2008; Kwon et al., 2010） and therefore do not naturally regenerate （Ramon y Caial, 1928）. Current strategies to try to increase behavioral recovery after SCI are focused on en- hancing the environment for axonal outgrowth.

Brain injury in combination with tacrolimus promotes the regeneration of injured peripheral nerves

Both brain injury and tacrolimus have been reported to promote the regeneration of injured peripheral nerves. In this study, before transection of rat sciatic nerve, moderate brain contusion was（or was not） induced. After sciatic nerve injury, tacrolimus, an immunosuppressant, was（or was not） intraperitoneally administered. At 4, 8 and 12 weeks after surgery, Masson＇s trichrome, hematoxylin-eosin, and toluidine blue staining results revealed that brain injury or tacrolimus alone or their combination alleviated gastrocnemius muscle atrophy and sciatic nerve fiber impairment on the experimental side, simultaneously improved sciatic nerve function, and increased gastrocnemius muscle wet weight on the experimental side. At 8 and 12 weeks after surgery, brain injury induction and/or tacrolimus treatment increased action potential amplitude in the sciatic nerve trunk. Horseradish peroxidase retrograde tracing revealed that the number of horseradish peroxidase-positive neurons in the anterior horn of the spinal cord was greatly increased. Brain injury in combination with tacrolimus exhibited better effects on repair of injured peripheral nerves than brain injury or tacrolimus alone. This result suggests that brain injury in combination with tacrolimus promotes repair of peripheral nerve injury.

Physical interactions between activated microglia and injured axons:do all contacts lead to phagocytosis?

Axonal injury is a pathological hallmark of both head injury and inflammatory-mediated neurological disorders,including multiple sclerosis（Schirmer et al.,2013）.Such axonal disruptions and/or disconnections typically result in proximal axonal segments that remain in continuity with the neuronal somawhile losing contact with their distal targets.

Recovery of multiply injured ascending reticular activating systems in a stroke patient

Consciousness is controlled by ular activating system （ARAS）. lower and upper parts between activation of the ascending retic- The ARAS consists mainly of the the thalamus and cerebral cortex （Edlow et al., 2012; Yeo et al., 2013; Jang et al., 2014）. Because the ARAS is composed of several neuronal circuits connecting the brainstem to the cortex. These neuronal connections begin from the reticular formation （RF） of the brainstem and the intralaminar nucleus of thalamus to the cerebral cortex （Gosseroes et al., 2011）. In addition, the ARAS system also includes several brainstem nuclei （such as dorsal raphe, locus coeruleus, pedun-culopontine nucleus, median raphe and parabrachial nucleus）, non-specific thalamic nuclei, hypothalamus, and basal forebrain （Fuller et al., 2011）.