Sodium-dependent glucose transporter 2 inhibitors effects on myocardial function in patients with type 2 diabetes and asymptomatic heart failure

BACKGROUND Sodium-dependent glucose transporter 2 inhibitors(SGLT2i)have shown efficacy in reducing heart failure(HF)burden in a very heterogeneous groups of patients,raising doubts about some contemporary assumptions of their mechanism of action.We previously published a prospective observational study that evaluated mechanisms of action of SGLT2i in patients with type 2 diabetes who were in HF stages A and B on dual hypoglycemic therapy.Two groups of patients were included in the study:the ones receiving SGLT2i as an add-on agent to metformin and the others on dipeptidyl peptidase-4 inhibitors as an add-on to metformin due to suboptimal glycemic control.AIM To evaluate the outcomes regarding natriuretic peptide,oxidative stress,inflammation,blood pressure,heart rate,cardiac function,and body weight.METHODS The study outcomes were examined by dividing each treatment arm into two subgroups according to baseline parameters of global longitudinal strain(GLS),N-terminal pro-brain natriuretic peptide,myeloperoxidase(MPO),high-sensitivity C-reactive protein(hsCRP),and systolic and diastolic blood pressure.To evaluate the possible predictors of observed changes in the SGLT2i arm during follow-up,a rise in stroke volume index,body mass index(BMI)decrease,and lack of heart rate increase,linear regression analysis was performed.RESULTS There was a greater reduction of MPO,hsCRP,GLS,and blood pressure in the groups with higher baseline values of mentioned parameters irrespective of the therapeutic arm after 6 months of follow-up.Significant independent predictors of heart rate decrease were a reduction in early mitral inflow velocity to early diastolic mitral annular velocity at the interventricular septal annulus ratio and BMI,while the predictor of stroke volume index increase was SGLT2i therapy itself.CONCLUSION SGLT2i affect body composition,reduce cardiac load,improve diastolic/systolic function,and attenuate the sympathetic response.Glycemic control contributes to the improvement of heart function,blood pressure control,oxidative stress,and reduction in inflammation.

Change in Functional Status from Preoperative to One Year Postoperative in Patients Who Have Undergone Elective Open-Heart Surgery: A Repeated-Measures Study

Purpose: Although patient-related factors affect surgical outcomes, preoperative functional status is not measured by any cardiac risk score. Functional status can, however, be objectively measured using validated outcome tools such as the Late-Life Function and Disability Instrument (LLFDI). The purpose of this study was to determine 1) if there was a change over time in functional status, as measured by the LLFDI, in patients who underwent elective cardiac surgery, and if so, 2) what specific aspect(s) of functional status changed. Methods: A prospective longitudinal study of one year was conducted on elective cardiac surgery patients (n = 43) using the self-reported LLFDI, which measures Disability Frequency (frequency of participation in social tasks), Disability Limitation (ability to participate in social tasks) and Function Total (ease in performing routine activities). Higher scores indicate increased function and decreased disability. LLFDI scores were compared at three times (preoperative, six-week and one-year postoperative) using repeated measures ANOVA. Post hoc pairwise comparison was conducted for specific interactions. Results: Both Function Total and Disability Frequency significantly changed over time (p = 0.047 and p = 0.013, respectively). Specifically, patients’ function level was significantly higher one-year postoperative compared to preoperative (M difference = +3.48, SE = 1.48, p = 0.026). Likewise, Disability Frequency scores were significantly higher (i.e. more active) at one-year postoperative versus preoperative (M difference= +5.98, SE = 2.19, p = 0.033). Disability Limitation scores were not significantly different between any time points (p > 0.05). Conclusion: By one-year postoperative, patients demonstrated increased ease in their routine physical activities and were more participatory in social life tasks. Individuals who underwent elective cardiac surgery took more than six weeks to detect notable improvement in functional status, which was expected with a sternotomy approach. This study provides support for the use of the LLFDI as an effective tool to capture functional status in the cardiac population. These findings may assist cardiac patients in recovery timeline expectations.

Kill two birds with one stone:Hapatologist’s approach to metabolic dysfunction-associated steatotic liver disease and heart failure

Heart failure(HF)is a major global public health concern,and one of the less commonly known risk factors for HF development is metabolic dysfunction-associated steatotic liver disease(MASLD),as they share a similar pathophysio-logical background.In this article,we evaluated a recently published review article by Arriola-Montenegro et al.This article briefly summarizes the common pathophysiology of HF and MASLD development and evaluates the available therapeutic options to treat both conditions.Clinical practice guidelines highlight the importance of initiating and titrating guideline-directed medication therapy(GDMT)for patients with HF with reduced ejection fraction.GDMT is comprised of the four pillars currently proposed in most clinical practice guidelines,namely angiotensin-converting enzyme inhibitors(ACEIs),angiotensin receptor blockers(ARBs),angiotensin receptor-neprilysin inhibitors,beta-blockers,mineralocor-ticoid receptor antagonists,and sodium-glucose co-transporter 2 inhibitors(SGLT-2i).Given the similarity of pathophysiology and risk factors,recent studies for GDMT regarding ACEIs,ARBs,mineralocorticoid receptor antagonists,and SGLT-2i have shown beneficial effects on MASLD.Nonetheless,other medications for both conditions and novel therapies require more robust data and well-designed clinical studies to demonstrate their efficacies in both conditions.

Exercise as a modality to improve heart transplantation-related functional impairments: An article review

Heart transplantation(HT),the treatment choice of advanced heart failure pa-tients,is proven effective in increasing the survival and functional status of the recipients.However,compared to normal controls,functional status is lower in HT recipients.Exercise given in cardiac rehabilitation has been shown to improve exercise capacity as measured with peak oxygen uptake(VO2 peak)and muscle strength after completion of the program and cessation of exercise results in loss of exercise benefits.Several factors related to cardiac denervation and the use of immunosuppressive agents in HT recipients result in functional impairments including cardiovascular,pulmonary,exercise capacity,psychological,and qua-lity of life(QoL)problems.High-intensity interval training(HIIT)is the most common type of exercise used in HT recipients and given as a hospital-based program.Improvement of functional impairments was found to have occurred due to primarily musculoskeletal adaptations through improvement of muscle structure and aerobic capacity and cardiovascular adaptations.In general,exercise given after transplantation improved VO2 peak significantly and improvement was better in the HIIT group compared to moderate intensity continuous training or no-exercise groups.Improvement of QoL was ascribed to improve-ment of exercise capacity,symptoms,pulmonary function,physical capacity improve-ment,anxiety,and depression.

Impact of continuous care on cardiac function in patients with lung cancer complicated by coronary heart disease

BACKGROUND Despite sharing similar pathogenic factors,cancer and coronary heart disease(CHD)occur in comparable populations at similar ages and possess similar susceptibility factors.Consequently,it is increasingly commonplace for patients to experience the simultaneous occurrence of cancer and CHD,a trend that is steadily rising.AIM To determine the impacts of continuing care on lung cancer patients with CHD following percutaneous coronary intervention(PCI).METHODS There were 94 lung cancer patients with CHD following PCI who were randomly assigned to the intervention group(n=38)and the control group(n=41).In the intervention group,continuing care was provided,while in the control group,routine care was provided.An evaluation of cardiac and pulmonary function,medication compliance,a 6-min walk test,and patient quality of life was performed.RESULTS Differences between the two groups were significant in left ventricular ejection fraction,6-min walk test,oxygen uptake,quality of life and medication compliance(P<0.05).In comparison with the control group,the enhancement in the intervention group was more significant.The intervention group had more patients with high medication compliance than the control group,with a statistically significant difference(P<0.05).CONCLUSION After undergoing PCI,lung patients with CHD could benefit from continued care in terms of cardiac and pulmonary function,medications compliance,and quality of life.

Hypidone hydrochloride(YL-0919)ameliorates functional deficits after traumatic brain injury in mice by activating the sigma-1 receptor for antioxidation

Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0919),a self-developed antidepressant with selective sigma-1 receptor agonist properties,and its associated mechanisms and targets in traumatic brain injury.Behavioral experiments to assess functional deficits were followed by assessment of neuronal damage through histological analyses and examination of blood-brain barrier permeability and brain edema.Next,we investigated the antioxidative effects of YL-0919 by assessing the levels of traditional markers of oxidative stress in vivo in mice and in vitro in HT22 cells.Finally,the targeted action of YL-0919 was verified by employing a sigma-1 receptor antagonist(BD-1047).Our findings demonstrated that YL-0919 markedly improved deficits in motor function and spatial cognition on day 3 post traumatic brain injury,while also decreasing neuronal mortality and reversing blood-brain barrier disruption and brain edema.Furthermore,YL-0919 effectively combated oxidative stress both in vivo and in vitro.The protective effects of YL-0919 were partially inhibited by BD-1047.These results indicated that YL-0919 relieved impairments in motor and spatial cognition by restraining oxidative stress,a neuroprotective effect that was partially reversed by the sigma-1 receptor antagonist BD-1047.YL-0919 may have potential as a new treatment for traumatic brain injury.

Analysis of Cardiac Functional Status and Factors Influencing Adverse Pregnancy Outcomes in Pregnant Women with Combined Heart Disease

Objective:To investigate the cardiac function of pregnant women with complicated heart disease during pregnancy and the factors influencing the adverse pregnancy outcome.Methods:A total of 162 cases of pregnant women with complicated heart disease admitted to the Beijing Anzhen Hospital from October 2021 to December 2023 were selected to compare the occurrence of adverse pregnancy outcomes in pregnant women with complicated heart disease at different levels of cardiac function and to analyze the single and multi factors leading to adverse pregnancy outcomes in pregnant women with complicated heart disease.Results:Among 162 pregnant women with combined heart disease in pregnancy,the highest percentage of heart disease type was congenital heart disease(80/49.38%),and the lowest percentage was other(9/5.56%);the overall incidence of adverse pregnancy outcomes in pregnant women with combined heart disease in pregnancy with cardiac function grades of 3–4 cardiac function(30/68.18%)was higher than that in pregnant women with combined heart disease in cardiac function grades of 1–2(40/33.90%)(P=0.000);age,marital status,hypertension,and past history of all pregnant women were not statistically significant(P>0.05);gestational age,type of heart disease,and cardiac function grading were statistically significant(P<0.05),and these factors were all independent risk factors for adverse pregnancy resolution in pregnant women with combined heart disease(P<0.05).Conclusion:The overall incidence of adverse pregnancy outcomes was higher in pregnant women with heart disease than in those with heart disease grades 1–2,and the number of pregnancies,the type of heart disease,and heart function grades were all independent risk factors for adverse pregnancy outcomes in pregnant women with heart disease.

Effectiveness of Atorvastatin Combined with Trimetazidine in the Treatment of Coronary Heart Disease in the Elderly and Their Effect on Cardiac Function

Objective:To analyze the effect of atorvastatin combined with trimetazidine in the treatment of elderly coronary artery disease and the effect on patients’cardiac function.Methods:60 cases of elderly coronary artery disease patients were divided into 2 groups by randomization method,and all of them received conventional symptomatic treatment,while atorvastatin was added to the control group and trimetazidine was combined with atorvastatin in the observation group,and the clinical indexes were compared.Results:After treatment,the angina attack,cardiac function indexes,and inflammatory factor levels of the observation group were better than those of the control group(P<0.05),and the differences in adverse reactions between the two groups were not significant(P>0.05).Conclusion:Combined treatment of coronary heart disease in the elderly with atorvastatin and trimetazidine can positively reduce angina symptoms,improve cardiac function,and reduce inflammatory reactions,and the effect is definite.

Clinical Study on the Effect of Continuity of Care in CICU on Improving Cognitive Function and Psychological State in Patients with Heart Failure

Objective:To analyze the effect of continuity of care in the cardiac intensive care unit(CICU)on improving cognitive function and psychological state in patients with heart failure(HF).Methods:A total of 112 chronic HF patients admitted to the CICU of Xuzhou Traditional Chinese Medicine Hospital from July 2022 to August 2024 were selected and randomly divided into two groups using the red and blue ball method:a control group(n=56)and a study group(n=56).The control group received routine CICU nursing management,while the study group received routine CICU nursing combined with continuity of care management.Cognitive function(using the Montreal Cognitive Assessment,MoCA),psychological state(using the Self-Rating Depression Scale,SDS,and Self-Rating Anxiety Scale,SAS),and quality of life(using the Minnesota Living with Heart Failure Questionnaire,MLHFQ)were compared between the two groups.Results:After the intervention,the cognitive function scores of the study group were significantly higher than those of the control group(P<0.05).The SDS and SAS scores of the study group were significantly lower than those of the control group after the intervention(P<0.05).The quality of life in the study group was also significantly better than in the control group(P<0.05).Conclusion:CICU continuity of care can effectively improve cognitive function and psychological state in patients with HF,while also enhancing their quality of life.

Mediating function of heart failure in the causal relationship between diastolic blood pressure and hypertensive renal disease with renal failure:a mediated Mendelian randomization study

Objective:To study the causality relationship between diastolic blood pressure(DBP)and hypertensive renal disease with renal failure(HRDRF)and the mediating role of hear t failure(HF)in the causality relationship by network Mendelian randomization(MR).Methods:Genome-wide analysis of DBP,HRDRF,and HF was downloaded from the public database(Genome-Wide Analysis Study[GWAS])and was used to analyze the results and to conduct mediated MR analysis.Results:Analysis showed that DBP was positively correlated with HRDRF(OR=1.0002,95%CI:1.0001–1.0003,P=1.8076e-05)and DBP was positively correlated with HF(OR=1.0295,95%CI:1.0221–1.0370,P=2.5292e-15).HF and HRDRF had a positive causal effect(OR=1.0001,95%CI:1.0000–1.0001,P=0.0152).Mediation analysis showed that the contribution ratio of HF to the combined effect of DBP and HRDRF was 24.69%.Conclusions:DBP can increase the risk of renal disease with renal failure,and HF may play an impor tant role in mediating this causal relationship.

Emerging insights into the function of very long chain fatty acids at cerebellar synapses

Very long chain-saturated and-polyunsaturated fatty acids(VLC-SFA and VLC-PUFA, respectively) are a functionally important class of fatty acids containing 28 carbons or more in their acyl chain. They are synthesized by the elongation of very long fatty acids-4(ELOVL4) enzyme, expressed mainly in the brain, retina, skin, testes, and meibomian gland, where these fatty acids are found(Agbaga et al., 2008). Further, these organs exhibit tissuespecific VLC-PUFA and VLC-SFA biosynthesis and incorporation into complex lipids for specific functions. In the brain, skin, and Meibomian glands, the ELOVL4 mainly makes VLC-SFA, which are incorporated into complex sphingolipids. In the retina, the ELOVL4 makes VLC-PUFA that are incorporated into phosphatidylcholine, that are critical for visual function, while in testes and sperm, the VLC-PUFA are incorporated into sphingolipids that are critical for fertility(Yeboah et al., 2021).

The complex role of protocadherin-19 in brain function:a focus on the oxytocin system

Mutations in the protocadherin-19(PCDH19)gene(Xq22.1)cause the X-linked syndrome known as developmental and epileptic encephalopathy 9(DEE9,OMIM#300088)(Dibbens et al.,2008).DEE9 is characterized by early-onset clustering epilepsy associated with intellectual disability ranging from mild to profound,autism spectrum disorder,and other neuropsychiatric features including schizophrenia,anxiety,attentiondeficit/hyperactivity,and obsessive or aggressive behaviors.While seizures may become less frequent in adolescence,psychiatric comorbidities persist and often worsen with age(Dibbens et al.,2008;Kolc et al.,2020).

Neuropeptide cholecystokinin:a key neuromodulator for hippocampal functions

Spatial memory is crucial for survival within external surroundings and wild environments.The hippocampus,a critical hub for spatial learning and memory formation,has received extensive investigations on how neuromodulators shape its functions(Teixeira et al.,2018;Zhang et al.,2024).However,the landscape of neuromodulations in the hippocampal system remains poorly understood because most studies focus on classical monoamine neuromodulators,such as acetylcholine,serotonin,dopamine,and noradrenaline.The neuropeptides,comprising the most abundant neuromodulators in the central nervous system,play a pivotal role in neural information processing in the hippocampal system.Cholecystokinin(CCK),one of the most abundant neuropeptides,has been implicated in regulating various physiological and neurobiological statuses(Chen et al.,2019).CCK-A receptor(CCK-AR)and CCK-B receptors(CCK-BR)are two key receptors mediating the biological functions of CCK,both of which belong to class-A sevenfold transmembrane G protein-coupled receptors(Nishimura et al.,2015).CCK-AR preferentially reacts to sulfated CCK,whereas CCK-BR binds both CCK and gastrin with similar affinities(Ding et al.,2022).The expression patterns of CCK-AR and CCK-BR are distinct,implying that CCK has various functions in target regions.For instance,CCK-AR is widely expressed in the GI and brain subregions and is hence implicated in the control of digestive function and satiety regulation.Conversely,CCK-BR is abundantly and widely distributed in the central nervous system,which majorly regulates anxiety,learning,and memory(Ding et al.,2022).However,the roles of endogenous CCK and CCK receptors in regulating hippocampal function at electrophysiological and behavioral levels have received less attention.

Corrigendum: MicroRNA-502-3p regulates GABAergic synapse function in hippocampal neurons

There is an error in the name of the cell line in the abstract of the published paper“MicroRNA-502-3p regulates GABAergic synapse function in hippocampal neurons”published on pages 2698-2707,Issue 12,Volume 19 of Neural Regeneration Research(Sharma et al.,2024),because of oversight during final proof checking.The correct description should be“human-GABA receptor A-α1/β2/γ2L human embryonic kidney(HEK)recombinant cell line.”The authors apologize for any inconvenience this correction may cause for readers and editors of Neural Regeneration Research.

Chondroitinase ABC combined with Schwann cell transplantation enhances restoration of neural connection and functional recovery following acute and chronic spinal cord injury

Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury.A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity,and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar,thus limiting axonal reentry into the host spinal cord.Here we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord injury.We report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders,Schwann cells migrated for considerable distances in both rostral and caudal directions.Such Schwann cell migration led to enhanced axonal regrowth,including the serotonergic and dopaminergic axons originating from supraspinal regions,and promoted recovery of locomotor and urinary bladder functions.Importantly,the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury,even when treatment was delayed for 3 months to mimic chronic spinal cord injury.These findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.

Emerging role of A-kinase anchoring protein 5 signaling in reward circuit function

There is a strong evidence supporting the hypothesis of synaptic dysfunction as a major contributor to neural circuit and network disruption underlying emotional and mood dysregulation in psychiatric disorders(Simmons et al.,2024).Diverse sets of distinct molecular signaling pathways converge on the synapse to regulate synaptogenesis,synaptic function,and synaptic plasticity in brain regions and circuits through complex interactions organized by numerous multivalent protein scaffolds,including the family of proteins known as A-kinase anchoring proteins(AKAPs).

Resting-state brain network remodeling after different nerve reconstruction surgeries:a functional magnetic resonance imaging study in brachial plexus injury rats

Distinct brain remodeling has been found after different nerve reconstruction strategies,including motor representation of the affected limb.However,differences among reconstruction strategies at the brain network level have not been elucidated.This study aimed to explore intranetwork changes related to altered peripheral neural pathways after different nerve reconstruction surgeries,including nerve repair,endto-end nerve transfer,and end-to-side nerve transfer.Sprague–Dawley rats underwent complete left brachial plexus transection and were divided into four equal groups of eight:no nerve repair,grafted nerve repair,phrenic nerve end-to-end transfer,and end-to-side transfer with a graft sutured to the anterior upper trunk.Resting-state brain functional magnetic resonance imaging was obtained 7 months after surgery.The independent component analysis algorithm was utilized to identify group-level network components of interest and extract resting-state functional connectivity values of each voxel within the component.Alterations in intra-network resting-state functional connectivity were compared among the groups.Target muscle reinnervation was assessed by behavioral observation(elbow flexion)and electromyography.The results showed that alterations in the sensorimotor and interoception networks were mostly related to changes in the peripheral neural pathway.Nerve repair was related to enhanced connectivity within the sensorimotor network,while end-to-side nerve transfer might be more beneficial for restoring control over the affected limb by the original motor representation.The thalamic-cortical pathway was enhanced within the interoception network after nerve repair and end-to-end nerve transfer.Brain areas related to cognition and emotion were enhanced after end-to-side nerve transfer.Our study revealed important brain networks related to different nerve reconstructions.These networks may be potential targets for enhancing motor recovery.

Enhancement of motor functional recovery in thoracic spinal cord injury: voluntary wheel running versus forced treadmill exercise

Spinal cord injury necessitates effective rehabilitation strategies, with exercise therapies showing promise in promoting recovery. This study investigated the impact of rehabilitation exercise on functional recovery and morphological changes following thoracic contusive spinal cord injury. After a 7-day recovery period after spinal cord injury, mice were assigned to either a trained group(10 weeks of voluntary running wheel or forced treadmill exercise) or an untrained group. Bi-weekly assessments revealed that the exercise-trained group, particularly the voluntary wheel exercise subgroup, displayed significantly improved locomotor recovery, more plasticity of dopaminergic and serotonin modulation compared with the untrained group. Additionally, exercise interventions led to gait pattern restoration and enhanced transcranial magnetic motor-evoked potentials. Despite consistent injury areas across groups, exercise training promoted terminal innervation of descending axons. In summary, voluntary wheel exercise shows promise for enhancing outcomes after thoracic contusive spinal cord injury, emphasizing the role of exercise modality in promoting recovery and morphological changes in spinal cord injuries. Our findings will influence future strategies for rehabilitation exercises, restoring functional movement after spinal cord injury.

Pharmacological targeting cGAS/STING/NF-κB axis by tryptanthrin induces microglia polarization toward M2 phenotype and promotes functional recovery in a mouse model of spinal cord injury

The M1/M2 phenotypic shift of microglia after spinal cord injury plays an important role in the regulation of neuroinflammation during the secondary injury phase of spinal cord injury.Regulation of shifting microglia polarization from M1(neurotoxic and proinflammatory type)to M2(neuroprotective and anti-inflammatory type)after spinal cord injury appears to be crucial.Tryptanthrin possesses an anti-inflammatory biological function.However,its roles and the underlying molecular mechanisms in spinal cord injury remain unknown.In this study,we found that tryptanthrin inhibited microglia-derived inflammation by promoting polarization to the M2 phenotype in vitro.Tryptanthrin promoted M2 polarization through inactivating the cGAS/STING/NF-κB pathway.Additionally,we found that targeting the cGAS/STING/NF-κB pathway with tryptanthrin shifted microglia from the M1 to M2 phenotype after spinal cord injury,inhibited neuronal loss,and promoted tissue repair and functional recovery in a mouse model of spinal cord injury.Finally,using a conditional co-culture system,we found that microglia treated with tryptanthrin suppressed endoplasmic reticulum stress-related neuronal apoptosis.Taken together,these results suggest that by targeting the cGAS/STING/NF-κB axis,tryptanthrin attenuates microglia-derived neuroinflammation and promotes functional recovery after spinal cord injury through shifting microglia polarization to the M2 phenotype.

Activation of adult endogenous neurogenesis by a hyaluronic acid collagen gel containing basic fibroblast growth factor promotes remodeling and functional recovery of the injured cerebral cortex

The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate neurogenesis and reconstruct cortical layers II to VI in non-neurogenic regions,such as the cortex,remains unknown.In this study,we implanted a hyaluronic acid collagen gel loaded with basic fibroblast growth factor into the motor cortex immediately following traumatic injury.Our findings reveal that this gel effectively stimulated the proliferation and migration of endogenous neural stem/progenitor cells,as well as their differentiation into mature and functionally integrated neurons.Importantly,these new neurons reconstructed the architecture of cortical layers II to VI,integrated into the existing neural circuitry,and ultimately led to improved brain function.These findings offer novel insight into potential clinical treatments for traumatic cerebral cortex injuries.