Fibulin-2 is an extracellular matrix inhibitor of oligodendrocytes relevant to multiple sclerosis.

Impairment of oligodendrocytes and myelin contributes to neurological disorders including multiple sclerosis (MS), stroke and Alzheimer's disease. Regeneration of myelin (remyelination) decreases the vulnerability of demyelinated axons, but this repair process commonly fails with disease progression. A contributor to inefficient remyelination is the altered extracellular matrix (ECM) in lesions that remains to be better defined. We have identified fibulin-2 (FBLN2) as a highly upregulated ECM component in lesions of MS and stroke, and in proteome databases of Alzheimer's disease and traumatic brain injury. Focusing on MS, the inhibitory role of FBLN2 was suggested in the experimental autoimmune encephalomyelitis (EAE) model in which genetic FBLN2 deficiency improved behavioral recovery by promoting the maturation of oligodendrocytes and enhancing remyelination. Mechanistically, when oligodendrocyte progenitors were cultured in differentiation media, FBLN2 impeded their maturation into oligodendrocytes by engaging the Notch pathway, leading to cell death. Adeno-associated virus-deletion of FBLN2 in astrocytes improved oligodendrocyte numbers and functional recovery in EAE and generated new myelin profiles after lysolecithin-induced demyelination. Collectively, our findings implicate FBLN2 as a hitherto unrecognized injury-elevated ECM, and a therapeutic target, that impairs oligodendrocyte maturation and myelin repair.

Sophocarpine attenuates doxorubicin-induced heart injury through inhibition of fibrosis.

BACKGROUND: Doxorubicin (DOX) is a potent anti-cancer medication that is associated with numerous adverse effects, particularly concerning damage to the heart. METHODS: This study aimed to investigate the impact of sophocarpine (SOP) on DOX-induced heart injury through both in vivo and in vitro experiments. The experimental techniques employed encompassed echocardiography, hematoxylin/eosin (H&E) staining, Masson staining, immunohistochemical staining, western blotting, and so on. RESULTS: Echocardiography showed that SOP alleviated DOX-induced cardiac dysfunction, as evidenced by the improvements in both left ventricle ejection fraction and left ventricle fractional shortening. DOX caused upregulations of creatine kinase-MB and lactate dehydrogenase, while SOP decreased these indices. Staining methods such as H&E and Masson showed that SOP reversed the pathological changes induced by DOX. DOX elevated the expression levels of fibrosis-associated proteins such as Collagen I, Collagen III, α-SMA, Fibronectin, MMP-2, and MMP-9. However, SOP reversed these changes. Moreover, the study further revealed that SOP inhibited the TGF-ß1/Smad3 signaling pathway. CONCLUSIONS: These findings imply that SOP has the potential to mitigate DOX-induced heart injury by suppressing fibrosis. The underlying molecular mechanism may involve the inhibition of the TGF-ß1/Smad3 signaling pathway.

The role of payment sources in the continuation of rehabilitation therapy in tertiary hospitals for patients with traumatic spinal cord injury: a study in Southwest China.

Medical security support for rehabilitation therapy in China is different from that in other countries. We investigated whether the discharge plan to continue rehabilitation therapy in tertiary hospitals for patients after traumatic spinal cord injury (TSCI) was influenced by payment sources or other conditions. This was a cross-sectional, observational study. Information was collected on the general condition, caregiver, types of payment sources for continued rehabilitation, American Spinal Injury Association Impairment Scale (AIS) scores, and discharge plans. In total, 135 patients with TSCI (107 male, mean age 41.00 ± 13.73 years, mean spinal cord injury duration 238.43 ± 345.54 days) were enrolled. Medical insurance (43%) and out-of-pocket payments (27.4%) were the primary payment sources. Although most patients were beyond the acute phase, 40% continued rehabilitation therapy at other tertiary hospitals. The caregiver, payment sources, injury level, AIS level, and complete urinary tract infection (UTI) were different due to discharge plans (p > .05). Patients seemingly consider a higher AIS level and co-UTI as the requirement for tertiary hospital therapy. In non-medical insurance payment source patients, the discharge plan also differed due to the AIS level and co-UTI (p > .05). However, in medical insurance patients, the discharge plan differed only in terms of TSCI duration (p > .05). The restricted duration of medical coverage restricted the continuation of rehabilitation therapy and influenced the discharge plan of most patients with TSCI.

The role of the sensory input intervention in recovery of the motor function in hypoxic ischemic encephalopathy rat model.

Motor disturbances predominantly characterize hypoxic-ischemic encephalopathy (HIE). Among its intervention methods, environmental enrichment (EE) is strictly considered a form of sensory intervention. However, limited research uses EE as a single sensory input intervention to validate outcomes postintervention. A Sprague-Dawley rat model subjected to left common carotid artery ligation and exposure to oxygen-hypoxic conditions is used in this study. EE was achieved by enhancing the recreational and stress-relief items within the cage, increasing the duration of sunlight, colorful items exposure, and introducing background music. JZL184 (JZL) was administered as neuroprotective drugs. EE was performed 21 days postoperatively and the rats were randomly assigned to the standard environment and EE groups, the two groups were redivided into control, JZL, and vehicle injection subgroups. The Western blotting and behavior test indicated that EE and JZL injections were efficacious in promoting cognitive function in rats following HIE. In addition, the motor function performance in the EE-alone intervention group and the JZL-alone group after HIE was significantly improved compared with the control group. The combined EE and JZL intervention group exhibited even more pronounced improvements in these performances. EE may enhance motor function through sensory input different from the direct neuroprotective effect of pharmacological treatment.NEW & NOTEWORTHY Rarely does literature assess motor function, even though it is common after hypoxia ischemic encephalopathy (HIE). Previously used environmental enrichment (EE) components have not been solely used as sensory inputs. Physical factors were minimized in our study to observe the effects of purely sensory inputs.

Choosing the optimal target area for repeated transcranial magnetic stimulation in treating neuropathic pain in spinal cord injury patients: a comparative analysis.

Objective: The specific target area of repeated transcranial magnetic stimulation (rTMS) in treating neuropathic pain resulting from spinal cord injury (SCI-NP) remains uncertain. Methods: Thirty-four participants with SCI-NP were allocated into three groups, namely, the motor cortex (M1, A) group, the left dorsolateral prefrontal cortex (LDLPFC, B) group, and the control (sham stimulation, C) group. The intervention was administered totally 10 times. Outcome measures assessed pre-(T0) and post-(T1)intervention, including Numerical Rating scale (NRS), anxiety (SAS), depression (SDS), sleep quality (PSQI), brief pain inventory (BPI), and impression of change. Results: All outcomes in groups A and B significantly changed after intervention (p < 0.05), and the delta value (T1-T0) also significantly changed than group C (p < 0.05). The delta value of SDS in the group B was better than the group A, and the change of pain degree in the group B was moderately correlated with the change in PSQI (r = 0.575, p < 0.05). Both patients in the groups A and B showed significant impression of change about their received therapy (p < 0.05). Conclusion: Both targets are effective, but LDLPFC is more effective in reducing depression in SCI-NP. Healthcare providers might select the suitable area according to the specific attributes of their patients.

Inhibition Effect of Pancreatic Exocrine Insufficiency on Immune Checkpoint Inhibitor Treatment in Pancreatic Cancer: A Retrospective Study.

Introduction: Chemotherapy combined with immune checkpoint inhibitors (ChIM) is used to treat advanced pancreatic ductal adenocarcinoma (PDAC). However, the efficacy of ChIM is similar to that of chemotherapy alone. Methods: To assess potential factors affecting the effectiveness of ChIM, we analyzed the clinical data of 359 patients with PDAC who visited the hospital during June 2017 to December 2022. Results: Surgical resection, diabetes, and ChIM were risk factors for pancreatic exocrine insufficiency (PEI). The adjusted odds ratio of ChIM was 2.63 (95% confidence interval (CI) 1.492-4.626) (P = 0.001). The incidence of PEI in the ChIM group (76.9%) was significantly higher than that of the chemotherapy group (60.2%) (P = 0.004). Survival analysis showed that ChIM did not improve the survival rate of patients with PDAC (hazard ratio (HR) 0.92, 0.707-1.197) (P = 0.534) in comparison with that of the chemotherapy group. However, in patients without PEI, those receiving ChIM showed a higher 1-year overall survival (OS) rate of 70.8% (two-sided, P = 0.045) and a median OS of 22.0 months (95% CI 11.5-32.5). Moreover, pancreatic enzyme replacement therapy significantly improved the OS of patients with PDAC (HR = 0.73, 95% CI = 0.561-0.956) (P = 0.022). Conclusion: Immune checkpoint inhibitors (ICIs) increased the incidence of PEI in patients with PDAC. The OS was not different between patients receiving chemotherapy and ChIM due to irregular PERT treatment. The finding show that pancreatic enzyme replacement therapy may improve the response rate of patients with PDAC to ICIs.

Emerging role of galectin 3 in neuroinflammation and neurodegeneration.

Neuroinflammation and neurodegeneration are key processes that mediate the development and progression of neurological diseases. However, the mechanisms modulating these processes in different diseases remain incompletely understood. Advances in single cell based multi-omic analyses have helped to identify distinct molecular signatures such as Lgals3 that is associated with neuroinflammation and neurodegeneration in the central nervous system (CNS). Lgals3 encodes galectin-3 (Gal3), a ß-galactoside and glycan binding glycoprotein that is frequently upregulated by reactive microglia/macrophages in the CNS during various neurological diseases. While Gal3 has previously been associated with non-CNS inflammatory and fibrotic diseases, recent studies highlight Gal3 as a prominent regulator of inflammation and neuroaxonal damage in the CNS during diseases such as multiple sclerosis, Alzheimer's disease, and Parkinson's disease. In this review, we summarize the pleiotropic functions of Gal3 and discuss evidence that demonstrates its detrimental role in neuroinflammation and neurodegeneration during different neurological diseases. We also consider the challenges of translating preclinical observations into targeting Gal3 in the human CNS.

Sophocarpine alleviates doxorubicin-induced heart injury by suppressing oxidative stress and apoptosis.

Doxorubicin (DOX) is an effective anti-tumor drug accompanied with many side effects, especially heart injury. To explore what effects of sophocarpine (SOP) on DOX-induced heart injury, this study conducted in vivo experiment and in vitro experiment, and the C57BL/6J mice and the H9C2 cells were used. The experimental methods used included echocardiography, enzyme-linked immunosorbent assay (ELISA), dihydroethidium (DHE) staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, western blotting and so on. Echocardiography showed that SOP alleviated DOX-induced cardiac dysfunction, as evidenced by the improvements of left ventricle ejection fraction and left ventricle fractional shortening. DOX caused upregulations of creatine kinase (CK), creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH), while SOP reduced these indices. The relevant stainings showed that SOP reversed the increases of total superoxide level induced by DOX. DOX also contribute to a higher level of MDA and lower levels of SOD and GSH, but these changes were suppressed by SOP. DOX increased the pro-oxidative protein level of NOX-4 while decreased the anti-oxidative protein level of SOD-2, but SOP reversed these effects. In addition, this study further discovered that SOP inhibited the decreases of Nrf2 and HO-1 levels induced by DOX. The TUNEL staining revealed that SOP reduced the high degree of apoptosis induced by DOX. Besides, pro-apoptosis proteins like Bax, cleaved-caspase-3 and cytochrome-c upregulated while anti-apoptosis protein like Bcl-2 downregulated when challenged by DOX, but them were suppressed by SOP. These findings suggested that SOP could alleviate DOX-induced heart injury by suppressing oxidative stress and apoptosis, with molecular mechanism activating of the Nrf2/HO-1 signaling pathway.

Inositol-requiring enzyme 1α and c-Jun N-terminal kinase axis activation contributes to intracellular lipid accumulation in calf hepatocytes.

During the perinatal period, dairy cows undergo negative energy balance, resulting in elevated circulating levels of nonesterified fatty acids (NEFA). Although increased blood NEFA concentrations are a physiological adaptation of early lactation, excessive NEFA in dairy cows is a major cause of fatty liver. Aberrant lipid metabolism leads to hepatic lipid accumulation and subsequently the development of fatty liver. Both inositol-requiring enzyme 1α (IRE1α) and c-Jun N-terminal kinase (JNK) have been validated for their association with hepatic lipid accumulation, including their regulatory functions in calf hepatocyte insulin resistance, oxidative stress, and apoptosis. Meanwhile, both IRE1α and JNK are involved in lipid metabolism in nonruminants. Therefore, the aim of this study was to investigate how IRE1α and JNK regulate lipid metabolism in bovine hepatocytes. An experiment was conducted on randomly selected 10 healthy cows (hepatic triglyceride [TG] content <1%) and 10 cows with fatty liver (hepatic TG content >5%). Liver tissue and blood samples were collected from experimental cows. Serum concentrations of NEFA and ß-hydroxybutyrate (BHB) were greater, whereas serum concentrations of glucose and milk production were lower in cows with fatty liver. The western blot results revealed that dairy cows with fatty liver had higher phosphorylation levels of JNK, c-Jun, and IRE1α in the liver tissue. Three in vitro experiments were conducted using primary calf hepatocytes isolated from 5 healthy calves (body weight: 30-40 kg; 1 d old). First, hepatocytes were treated with NEFA (1.2 mM) for 0.5, 1, 2, 3, 5, 7, 9, or 12 h, which showed that the phosphorylated levels of JNK, c-Jun, and IRE1α increased in both linear and quadratic effects. In the second experiment, hepatocytes were treated with high concentrations of NEFA (1.2 mM) for 12 h with or without SP600125, a canonical inhibitor of JNK. Western blot results showed that SP600125 treatment could decrease the expression of lipogenesis-associated proteins (PPARγ and SREBP-1c) and increase the expression of fatty acid oxidation (FAO)-associated proteins (CPT1A and PPARα) in NEFA-treated hepatocytes. The perturbed expression of lipogenesis-associated genes (FASN, ACACA, and CD36) and FAO-associated gene ACOX1 were also recovered by JNK inhibition, indicating that JNK reduced excessive NEFA-induced lipogenesis and FAO dysregulation in calf hepatocytes. Third, short hairpin RNA targeting IRE1α (sh-IRE1α) was transfected into calf hepatocytes to silence IRE1α, and KIRA6 was used to inhibit the kinase activity of IRE1α. The blockage of IRE1α could at least partially suppressed NEFA-induced JNK activation. Moreover, the blockage of IRE1α downregulated the expression of lipogenesis genes and upregulated the expression of FAO genes in NEFA-treated hepatocytes. In conclusion, these findings indicate that targeting the IRE1α-JNK axis can reduce NEFA-induced lipid accumulation in bovine hepatocytes by modulating lipogenesis and FAO. This may offer a prospective therapeutic target for fatty liver in dairy cows.

The impact of superselective adrenal artery embolization on renal function in patients with primary aldosteronism: a prospective cohort study.

Superselective adrenal artery embolization (SAAE) is an effective treatment for patients with primary aldosteronism (PA). However, the impact of SAAE on renal function in the PA population remains uncertain. We investigated the estimated glomerular filtration rate (eGFR) and age, sex, body mass index, and diabetes-specific percentiles of eGFR residuals in 182 PA patients treated with SAAE in a prospective cohort from Nanchang SAAE in treating PA registry study. Data suggest that SAAE caused a significant decrease in eGFR from 91.9 ± 26.1 to 88.7 ± 24.1 ml/min/1.73 m2 (p < 0.05) after a median follow-up of 8 months in PA patients. Patients experienced a significant decrease in eGFR from 110.6 ± 18.9 to 103.8 ± 18.2 ml/min/1.73 m2 (p < 0.001) and a very slight increase from 71.1 ± 14.8 to 71.8 ± 17.8 ml/min/1.73 m2 (p = 0.770) with baseline eGFR ≥90 and <90 ml/min/1.73 m2, respectively. Patients with high eGFR residuals (glomerular hyperfiltration) experienced a significant decrease in their eGFR levels from 123.1 ± 22.6 to 105.0 ± 18.6 ml/min/1.73 m2 (p < 0.001). In contrast, there was no significant impact of SAAE on the eGFR of patients with normal or low eGFR residuals. The very early eGFR changes (24 h after SAAE) best predicted the effect of SAAE on eGFR changes after median of eight months in PA patients. On the whole, SAAE seems to have a beneficial impact on renal function in patients with PA, the results of which vary depending on the patient's baseline eGFR and glomerular hyperfiltration status.

The left adrenal vein: An important direction for right adrenal venous sampling.

This study aimed to evaluate the guiding role of left adrenal vein (LAV) for right adrenal venous sampling (AVS). A total of 347 patients who were diagnosed with primary aldosteronism (PA) and underwent successful AVS procedures from January 2020 to July 2021 were retrospectively analyzed. According to the different quadrant position of the orifice of right adrenal vein (RAV), the area where the orifice of RAV is located is divided into three areas: A, B, and C and the area A is further subdivided into A1, A2, and A3 areas. By counting the area where the orifice of RAV is located, the guiding role of the LAV on the RAV is determined. Most of the orifice of RAV are located in area A, and the proportions of areas A, B, and C was 96.8%, 1.4%, and 1.7%, respectively. In area A, areas A1, A2, and A3 account for 80.9%, 17.0%, and 2.1%, respectively. High body mass index, female and smaller the angle between the LAV and horizontal line was associated with the closer positional relationship between the LAV on the RAV. These findings suggest that most of the horizontal position of the RAV orifice is close to the horizontal position of the most distal end of the LAV, which indicate that the LAV location can play an important role on the guiding for right AVS. Additionally, body mass index, sex, and the angle of the LAV was largely related to location of the orifice of the RAV.

NEK8 regulates colorectal cancer progression via phosphorylating MYC.

Radiotherapy and chemotherapy remain the mainstay of treatment for colorectal cancer (CRC), although their efficacy is limited. A detailed understanding of the molecular mechanisms underlying CRC progression could lead to the development of new therapeutic strategies. Although it has been established that MYC signaling is dysregulated in various human cancers, direct targeting MYC remains challenging due to its "undruggable" protein structure. Post-translational modification of proteins can affect their stability, activation, and subcellular localization. Hence, targeting the post-translational modification of MYC represents a promising approach to disrupting MYC signaling. Herein, we revealed that NEK8 positively regulates CRC progression by phosphorylating c-MYC protein at serine 405, which exhibited enhanced stability via polyubiquitination. Our findings shed light on the role of NEK8/MYC signaling in CRC progression, offering a novel and helpful target for colorectal cancer treatment. Video Abstract.

New bisabolane-type sesquiterpenoid from Aspergillus sydowii BTBU20213012.

A new bisabolane-type sesquiterpenoid, named (+)-8-dehydroxylaustrosene (1), along with ten known compounds, penicibisabolanes E (2) and G (3), (+)-austrosene (4), (S)-(+)-11-dehydrosydonic acid (5), sydonic acid (6), (7S,11S)-(+)-12-hydroxysydonic acid (7), (-)-(R)-hydroxysydonic acid (8), pseudaboydin A (9), (-)-(7 R,10R)-iso-10-hydroxysydowic acid (10), lumichrome (11), were identified from the fungus Aspergillus sydowii BTBU20213012 isolated from a marine sediment sample from the Western Pacific. The structures of the compounds were identified by HRESIMS and NMR data analysis. Compound 11 showed weak antimicrobial activity against Staphylococcus aureus with MIC value of 200 µg/mL.

Adrenal Venous Sampling Via an Antecubital Approach in Primary Aldosteronism: A Multicenter Study.

CONTEXT: Adrenal venous sampling (AVS) is considered the gold standard for differentiating unilateral and bilateral forms of primary aldosteronism. Currently, almost all AVS procedures are performed via femoral vein access. OBJECTIVE: The aim of this study was to evaluate the success rate and safety of AVS via an antecubital approach. METHODS: In a retrospective multicenter study involving 7 Chinese medical centers, patients with primary aldosteronism who underwent AVS via an antecubital approach between January 2012 and December 2018 were analyzed. Successful sampling was determined by a selectivity index (cortisol in the adrenal vein/cortisol in inferior vena cava) greater than 2. RESULTS: A total of 1226 participants (mean age, 47.1 years; 57.9% male) were included. The puncture site was right and left antecubital vein in 1211 (98.8%), and 15 (1.2%) patients. The access of 6 patients (0.5%) was changed to right femoral vein due to the failure of antecubital vein cannulation or anatomic variation of adrenal vein. The success rate of bilateral, right, and left sampling was 91.5%, 94.9%, and 95.1%, respectively. The success rate of bilateral, right, and left sampling increased from 82.9%, 87.1%, and 88.6% during the initial 70 cases (total of initial 10 cases at each center) to 92.0% (P = .012), 95.3% (P = .008), and 95.5% (P = .018) with subsequent cases. Adrenal vein rupture occurred in 5 patients (0.41%), with no sequelae. CONCLUSION: This multicenter study demonstrates that AVS via an antecubital approach is safe and feasible, with a high rate of successful sampling, which may be an alternative to the femoral vein access method.

The Correlation Between Aldosterone and Leukocyte-Related Inflammation: A Comparison Between Patients with Primary Aldosteronism and Essential Hypertension.

Background: Hypertension patients with primary aldosteronism (PA) have a higher risk of cardiovascular complications than blood pressure-matched essential hypertension (EH) patients. The cause may be closely related to inflammation. We explored the correlations between leukocyte-related inflammation parameters and plasma aldosterone concentration (PAC) in PA patients and clinical characteristics-matched EH patients. Methods: A total of 346 PA and 346 sex, age and 24-h blood pressure-matched EH patients at the 2nd Affiliated Hospital of Nanchang University from January 2020 to June 2021 were enrolled in this study. The differences and correlations of aldosterone and leukocyte parameters between the two groups were analyzed. Results: Compared with EH patients, the lymphocyte count was significantly lower (P = 0.004), the neutrophil-lymphocyte ratio (NLR) (P = 0.023) and the monocyte-lymphocyte ratio (MLR) (P = 0.037) were significantly higher in PA patients. Linear regression analysis and multivariate regression analysis identified that lymphocyte count, NLR and MLR were significantly and independently correlated with PAC in PA patients, and the correlations were stronger with increasing levels of aldosterone. However, in EH patients, only NLR maintained an independent correlation with PAC. Conclusion: Leukocyte-related inflammation parameters, including lymphocyte count, NLR, and MLR, were significantly and independently correlated with PAC in PA patients. The correlations were stronger with increasing levels of aldosterone. However, the above correlations were not always present in patients with EH matched for clinical characteristics.

Corn Silk Flavonoids Ameliorate Hyperuricemia via PI3K/AKT/NF-κB Pathway.

Hyperuricemia (HUA) is a widespread metabolic disease marked by an elevated level of uric acid, and is a risk factor for premature death. The protective effect of corn silk flavonoids (CSF) against HUA and its potential mechanisms were explored. Five important apoptosis and inflammation-related signaling pathways were identified by network pharmacological analysis. The CSF exhibited significant uric acid (UA)-lowering activity in vitro by decreasing xanthine oxidase (XOD) and increasing hypoxanthine-guanine phosphoribosyl transferase levels. In a potassium oxonate-induced HUA in vivo, CSF treatment effectively inhibited XOD activity and promoted UA excretion. Furthermore, it decreased the levels of TNF-α and IL-6 and restored pathological damage. In summary, CSF is a functional food component to improve HUA by reducing inflammation and apoptosis through the down-regulating PI3K/AKT/NF-κB pathway.

NA-OR: A path optimization method for manipulators via node attraction and obstacle repulsion.

This paper is concerned with the issue of path optimization for manipulators in multi-obstacle environments. Aimed at overcoming the deficiencies of the sampling-based path planning algorithm with high path curvature and low safety margin, a path optimization method, named NA-OR, is proposed for manipulators, where the NA (node attraction) and OR (obstacle repulsion) functions are developed to refine the path by iterations. In the iterations of path optimization, the node attraction function is designed to pull the path nodes toward the center of their neighbor nodes, thereby reducing the path curvature and improving the smoothness. Also, the obstacle repulsion function is developed to push the path nodes out of the potentially unsafe region by generating a repulsive torque on the path nodes, thus improving the safety margin of the motion. By introducing the effect of NA-OR, the optimized path has a significant improvement in path curvature and safety margin compared with the initial path planned by Bi-RRT, which meaningfully enhances the operation ability of manipulators for the applications that give a strong emphasis on security. Experimental results on a 6-DOF manipulator in 4 scenarios demonstrate the effectiveness and superiority of the proposed method in terms of the path cost, safety margin, and path smoothness.

Elevated Galectin-3 Is Associated with Aging, Multiple Sclerosis, and Oxidized Phosphatidylcholine-Induced Neurodegeneration.

Aging is a significant risk factor associated with the progression of CNS neurodegenerative diseases including multiple sclerosis (MS). Microglia, the resident macrophages of the CNS parenchyma, are a major population of immune cells that accumulate in MS lesions. While they normally regulate tissue homeostasis and facilitate the clearance of neurotoxic molecules including oxidized phosphatidylcholines (OxPCs), their transcriptome and neuroprotective functions are reprogrammed by aging. Thus, determining the factors that instigate aging associated microglia dysfunction can lead to new insights for promoting CNS repair and for halting MS disease progression. Through single-cell RNA sequencing (scRNAseq), we identified Lgals3, which encodes for galectin-3 (Gal3), as an age upregulated gene by microglia responding to OxPC. Consistently, excess Gal3 accumulated in OxPC and lysolecithin-induced focal spinal cord white matter (SCWM) lesions of middle-aged mice compared with young mice. Gal3 was also elevated in mouse experimental autoimmune encephalomyelitis (EAE) lesions and more importantly in MS brain lesions from two male and one female individuals. While Gal3 delivery alone into the mouse spinal cord did not induce damage, its co-delivery with OxPC increased cleaved caspase 3 and IL-1ß within white matter lesions and exacerbated OxPC-induced injury. Conversely, OxPC-mediated neurodegeneration was reduced in Gal3-/- mice compared with Gal3+/+ mice. Thus, Gal3 is associated with increased neuroinflammation and neurodegeneration and its overexpression by microglia/macrophages may be detrimental for lesions within the aging CNS.SIGNIFICANCE STATEMENT Aging accelerates the progression of neurodegenerative diseases such as multiple sclerosis (MS). Understanding the molecular mechanisms of aging that increases the susceptibility of the CNS to damage could lead to new strategies to manage MS progression. Here, we highlight that microglia/macrophage-associated galectin-3 (Gal3) was upregulated with age exacerbated neurodegeneration in the mouse spinal cord white matter (SCWM) and in MS lesions. More importantly, co-injection of Gal3 with oxidized phosphatidylcholines (OxPCs), which are neurotoxic lipids found in MS lesions, caused greater neurodegeneration compared with injection of OxPC alone, whereas genetic loss of Gal3 reduced OxPC damage. These results demonstrate that Gal3 overexpression is detrimental to CNS lesions and suggest its deposition in MS lesions may contribute to neurodegeneration.