Brain Res. [JOURNAL]
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200 papers
Retraction notice to "Hydrogen-rich saline improves memory function in a rat model of amyloid-beta-induced Alzheimer's disease by reduction of oxidative stress" [Brain Res. 1328 (2010) 152-161].
Li J, Wang C, Zhang JH … +3 more , Cai JM, Cao YP, Sun XJ
Brain Res · 2026 May · PMID 41794636 · Publisher ↗
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Retraction notice to "Granulocyte-colony stimulating factor inhibits apoptotic neuron loss after neonatal hypoxia-ischemia in rats" [Brain Res. 1145 (2007) 227-238].
Yata K, Matchett GA, Tsubokawa T … +3 more , Tang J, Kanamaru K, Zhang JH
Brain Res · 2026 May · PMID 41791946 · Publisher ↗
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Brain-targeted Brivaracetam delivery using mannose-functionalized mesoporous silica nanoparticles for the treatment of epilepsy.
Patel S, Mansuri M, Mehta I … +1 more , Athalye M
Brain Res · 2026 Jun · PMID 41791502 · Publisher ↗
Surface-engineered mesoporous silica nanoparticles (MSN) as carrier system for controlled release of Brivaracetam (BVM) for targeted brain delivery in epilepsy were developed and evaluated. Modified sol-gel process emplo...
Surface-engineered mesoporous silica nanoparticles (MSN) as carrier system for controlled release of Brivaracetam (BVM) for targeted brain delivery in epilepsy were developed and evaluated. Modified sol-gel process employed to synthesize MSN using tetraethylorthosilicate (TEOS) as silica source and cetyltrimethylammonium bromide (CTAB) as structure-directing agent, followed by calcination. Surface functionalization was achieved by grafting aminopropyl triethoxysilane (APTES) to introduce amine groups. Surface modification was carried out by amination, followed by the conjugation of D-mannose. Physical adsorption method was used to incorporate BVM into MSN. In-vitro studies revealed that BVM solution released 96.11% of drug within 5 h, while MSN formulation extended release upto 98.13% over 24 h. 94.25% of the drug release was observed from mannose-conjugated amine MSN over 48 h, aligning with Korsmeyer-Peppas model. Maximal Electroshock seizures (MES) model used for In-vivo pharmacodynamic evaluation, indicated that untreated group experienced 16.25 ± 1.11 seizure episodes (absence of treatment). BVM loaded MSN treatment reduced to 13.25 ± 1.11 episodes (69.63% antiepileptic effect), while mannose-conjugated BVM-loaded MSN group further decreased to 12.5 ± 1.32 episodes (71.42% antiepileptic activity). These results suggest that surface functionalized MSN are promising for sustained drug delivery for improved seizure control.
BDNF relates to prefrontal cortex activity in the context of physical exercise.
Ronca F, Xu C, Kong E … +8 more , Chan D, Hamilton A, Schiavo G, Tachtsidis I, Pinti P, Tari B, Gurney T, Burgess PW
Brain Res · 2026 Jun · PMID 41791501 · Publisher ↗
Exercise has been shown to support brain health, cognitive function, and increase levels of brain-derived neurotrophic factor (BDNF). While BDNF is known to support the central nervous system through improved brain metab...
Exercise has been shown to support brain health, cognitive function, and increase levels of brain-derived neurotrophic factor (BDNF). While BDNF is known to support the central nervous system through improved brain metabolism, vasculature, neurotransmission and synaptic plasticity, the association between exercise-induced changes in BDNF concentrations and exercise-related cognitive improvements is still unclear. This study investigated the relationship between exercise-induced changes in plasma BDNF (pBDNF) and serum BDNF (sBDNF), and haemodynamic indicators of prefrontal cortex function in sedentary adults. Participants (n = 23, female = 7) were randomized into intervention (12-week cycling programme) and control groups (no intervention). Participants completed V̇O tests to assess changes in fitness. pBDNF and sBDNF were measured pre- and post-V̇O testing, and a battery of executive function and memory tasks were also conducted, alongside functional near-infrared spectroscopy (fNIRS) to assess haemodynamic changes in the prefrontal cortex activity. Changes were assessed using the correlation-based signal improvement (CBSI) method. Results indicated that participants in the exercise intervention group did not show increased levels of resting-state s/pBDNF levels at the end of the intervention; however, they did exhibit a significant exercise-induced increase in sBDNF at week 12. This increase was correlated with changes in V̇O. Higher pBDNF levels and exercise-induced sBDNF were associated with a decrease in CBSI values in the frontopolar, dorsolateral and orbitofrontal prefrontal cortex during attention and inhibition tasks, but not during the memory task. These results suggest that increasing physical fitness can enhance BDNF transcription in response to acute bouts of exercise. This might, in turn, play a part in the modulation of neural function during executive tasks after acute exercise.
Reversal of chronic restraint-induced HPA axis dysregulation and depressive-like behaviour by chronic escitalopram treatment in rats: involvement of SERT.
Shanker S, Saroj N, Manjarrez-Gutiérrez G … +2 more , López-Sánchez P, Terrón JA
Brain Res · 2026 Jun · PMID 41775329 · Publisher ↗
Chronic restraint stress (CRS) upregulates serotonin transporter (SERT) in adrenal glands and sensitizes restraint-induced corticosterone (CORT) secretion. We analysed the effect of chronic escitalopram (ECT) treatment o...
Chronic restraint stress (CRS) upregulates serotonin transporter (SERT) in adrenal glands and sensitizes restraint-induced corticosterone (CORT) secretion. We analysed the effect of chronic escitalopram (ECT) treatment on these CRS-induced changes. Rats were submitted to CRS or control conditions (CTRL) for 14 days; at day 8, animals received vehicle (VEH) or ECT treatment for 7 days. On day 15, SERT expression in adrenals was analysed by immunohistochemistry, Western blot, and RT-PCR; baseline and restraint-induced ACTH and CORT secretion was also determined. The effect of ECT on 5-HT turnover in adrenals and dorsal raphe nucleus (DRN), and on sucrose preference, was also investigated. SERT immunostaining (SERT-I) appeared in the adrenal medulla from CTRL animals and increased, apparently in the cortex, in adrenals from CRS-exposed animals; parallel increases of SERT protein and mRNA in adrenals were also observed. These CRS-induced changes were attenuated in ECT-treated animals. CRS exposure of VEH-treated animals blunted ACTH secretion at 10 min of restraint, and sensitized CORT responses at 30 min of restraint; these dysregulated responses were normalized by ECT treatment. CRS exposure increased 5-HT turnover in adrenal glands and decreased it in DRN; both effects were reversed by ECT. Finally, the depressogenic effect of CRS, as visualized by decreased sucrose preference, was reversed by ECT treatment. Data suggest that the antidepressant-like effects of ECT in CRS-exposed animals may be associated with: a) reversal of SERT expression and 5-HT turnover in the adrenals; b) reversal of decreased 5-HT turnover in DRN; and c) normalization of HPA axis activity.
An EEG evoked response protocol to assess brain function alterations post-concussion in professional and amateur rugby clubs.
Powell JL
Brain Res · 2026 Jun · PMID 41765219 · Publisher ↗
BACKGROUND: Concussion is a prevalent and high-profile injury in contact and collision sports like Rugby. Establishing objective markers of concussion is a critical priority to support safe return-to-play (RTP) decisions...
BACKGROUND: Concussion is a prevalent and high-profile injury in contact and collision sports like Rugby. Establishing objective markers of concussion is a critical priority to support safe return-to-play (RTP) decisions. Head injuries alter the spectral characteristics of electroencephalography (EEG) signals, highlighting the need for scalable EEG assessment protocols that can be implemented by Rugby clubs during post-injury evaluations. STUDY AIM: To integrate an easy to use, scalable EEG post-concussion assessment to test for P300 amplitude change associated with concussion that was accessible to both amateur and professional Rugby clubs. METHODS: The study utilised an easy to administer EEG protocol using a WAVi headset. P300 amplitude (assessed using an auditory oddball task) were quantified in 156 amateur and professional Rugby players at pre-season (baseline) and end of season (EoS; n = 112) points in three different Rugby clubs in South England. Post-concussion EEG measures were collected as events occurred (n = 23) across the season, within 24 h post-concussion, and at 10-14 days follow-up. RESULTS: The study showed significant changes to P300 amplitude in concussed players with P300 voltage decreasing significantly from baseline to post-concussion (p = 0.008). Changes in P300 μV-Peak from pre-season to End of Season (EoS) differed significantly between concussed and non-concussed players (p = 003). Professional players presented with significantly greater pre-season P300 amplitude in comparison to amateur Rugby players (p = 0.01). DISCUSSION: The data suggest significant P300 amplitude changes after concussion that are quantifiable and consistent, and which can be captured as part of routine assessment in both professional and amateur Rugby clubs. Findings are discussed in relation to the small sample sizes limiting generalisability of the findings, and protocol implementation within club practice.
Anticoagulant peptide LR from Whitmania pigra ameliorates cerebral ischemia-reperfusion injury.
Liu R, Jiang X, Wang Z … +8 more , Huang X, Ma Y, Nuermaimaiti B, Zhang X, Dong R, Zhang Y, Yuan R, Wei P
Brain Res · 2026 Jun · PMID 41765218 · Publisher ↗
BACKGROUND: Ischemic stroke (IS) is a leading cause of death and disability worldwide. Hypercoagulability and thrombus formation play critical roles in its pathogenesis. Leech-derived peptides, especially those obtained...
BACKGROUND: Ischemic stroke (IS) is a leading cause of death and disability worldwide. Hypercoagulability and thrombus formation play critical roles in its pathogenesis. Leech-derived peptides, especially those obtained from Whitmania pigra, have demonstrated potential antithrombotic and neuroprotective effects. This study aimed to investigate the therapeutic efficacy and underlying mechanisms of a leech peptide in a rat model of cerebral ischemia/reperfusion injury. METHODS: Adult male Sprague-Dawley rats were subjected to middle cerebral artery occlusion followed by reperfusion to establish the IS model. Rats received low-dose or high-dose leech peptide, edaravone as a positive control, or saline. Behavioral assessments, infarct volume measurement, laser speckle imaging for cerebral perfusion, and histopathology were performed. Hemorheology and coagulation parameters were analyzed. Additionally, thrombin levels and fibrinolytic factors were evaluated using ELISA. Biosafety was assessed through hemolysis and histological evaluation of major organs. RESULTS: Leech peptide significantly reduced infarct volume, improved neurological scores, enhanced cerebral perfusion, and preserved brain tissue structure. It modulated thrombin-related parameters, ameliorated coagulation dysfunction, and modulated fibrinolysis-associated factors, thereby contributing to the restoration of coagulation-fibrinolysis homeostasis. Low-dose treatment showed comparable or superior efficacy to the high dose with better safety. No significant toxicity or hemolysis was observed. CONCLUSIONS: Leech peptide derived from Whitmania pigra exerts neuroprotective effects in cerebral ischemia/reperfusion injury through anticoagulation and thrombolysis. These findings support its potential as a novel candidate for IS therapy. TRIAL REGISTRATION: Not applicable. This study did not involve human participants.
The glymphatic system as a brain scavenger in Alzheimer's disease: mechanisms and therapeutic implications.
Zheng M, Su W, Tian L … +1 more , Gao W
Brain Res · 2026 Jun · PMID 41763632 · Publisher ↗
Alzheimer's disease (AD), the most common neurodegenerative disorder worldwide, is increasingly recognized as a major threat to global health. Its pathogenesis remains highly complex, and effective treatments are still l...
Alzheimer's disease (AD), the most common neurodegenerative disorder worldwide, is increasingly recognized as a major threat to global health. Its pathogenesis remains highly complex, and effective treatments are still lacking. Recent research, however, has identified a crucial player in this process-the glymphatic system, which acts as a metabolic "scavenger" in the brain, responsible for clearing waste products such as amyloid-β (Aβ) and hyperphosphorylated tau protein. Impairment of this system leads to the accumulation of these toxic proteins, which are hallmark pathological features of AD. This review comprehensively examines how glymphatic dysfunction contributes to the aggregation of Aβ and tau, thereby driving AD progression. Astrocytes regulate fluid transport via aquaporin-4 (AQP4) water channels, while microglia modulate glymphatic efficiency through phagocytosis and neuroinflammatory signaling. These cells work in concert to maintain brain homeostasis. However, in AD, the loss of polarized AQP4 expression in astrocytes, obstruction of cerebrospinal-interstitial fluid exchange by Aβ and tau, and dysregulated microglial activation collectively accelerate disease pathology. Advances in diagnostic biomarkers-such as Aβ/tau PET imaging and CSF profiles of GFAP/sTREM2-offer promising avenues for early AD detection. Meanwhile, therapeutic strategies targeting glymphatic-astrocyte-microglia interactions, including AQP4 enhancers, TREM2 agonists, and anti-inflammatory agents, open new possibilities for treatment. By integrating insights from preclinical and clinical studies, this review underscores the vital role of the glymphatic system in early intervention, highlighting potential approaches to slow AD progression through enhanced waste clearance and immunomodulation.
miR-425-5p in the early diagnosis of neonatal brain injury and its involvement in the inflammatory response of brain injury via WTAP.
Yang X, Wang S, Fang J … +3 more , Sun Y, Cheng Z, Cao X
Brain Res · 2026 Jun · PMID 41759701 · Publisher ↗
OBJECTIVES: Neonatal brain injury (NBI) is one of the common acute and critical illnesses that lead to neonatal death and disability. This article aims to explore miR-425-5p in neonates with different degrees of brain in...
OBJECTIVES: Neonatal brain injury (NBI) is one of the common acute and critical illnesses that lead to neonatal death and disability. This article aims to explore miR-425-5p in neonates with different degrees of brain injury and its potential molecular mechanism. METHOD: The researchers used RT-qPCR to measure the level of miR-425-5p in NBI serum and evaluated its diagnostic and predictive capabilities for NBI severity through ROC curve and multivariate logistic regression analysis. In vitro experiments, the effect of miR-425-5p on lipopolysaccharide-induced microglial cell viability was detected using the CCK8 assay, while inflammation and oxidative stress levels were evaluated via ELISA. Finally, the relationship between miR-425-5p and wilms tumor 1-associating protein (WTAP) was verified using dual-luciferase assay and Pearson correlation analysis. RESULTS: miR-425-5p was significantly reduced in the group of neonates with moderate to severe brain injury. miR-425-5p demonstrates excellent diagnostic efficacy for the severity of brain injury (AUC = 0.842) and can serve as a potential protective factor for neonates with brain injury. In LPS-induced microglial cells, miR-425-5p-mimic enhanced cell viability, reduced the release of inflammatory factors, and attenuated oxidative stress levels. Meanwhile, WTAP is a direct target of miR-425-5p, and the two exhibit a negative correlation. CONCLUSIONS: miR-425-5p is lowly expressed in the group of moderate to severe neonatal brain injury and may participate in the inflammatory response of brain injury through WTAP.
The combination of Huangqi and Danggui alleviates cerebral ischemia/reperfusion injury by inhibiting pyroptosis via NOX4-mediated ROS accumulation in rats.
Chai C, Liu L, Wang R … +8 more , Yuan L, Hou X, Zhao W, Du S, Lu W, Yuan X, Chang L, Zhang Y
Brain Res · 2026 Jun · PMID 41759700 · Publisher ↗
BACKGROUND: Ischemiareperfusion (I/R) injury is a key contributor to poor prognosis of ischemic stroke (IS), with a lack of effective neuroprotective agents. Widely acknowledged as a classic traditional Chinese medicine...
BACKGROUND: Ischemiareperfusion (I/R) injury is a key contributor to poor prognosis of ischemic stroke (IS), with a lack of effective neuroprotective agents. Widely acknowledged as a classic traditional Chinese medicine (TCM) remedy for IS, Buyang Huanwu Decoction (BYHWD) contains Huangqi-Danggui (HQDG) as its primary bioactive components. Initial investigations have demonstrated that HQDG mitigates cerebral I/R injury, yet the mechanism by which it functions remains unclear. MATERIALS AND METHODS: Middle cerebral artery occlusion/reperfusion (MCAO/R) models were established. NADPH oxidase 4 (NOX4) and reactive oxygen species (ROS) levels in normal brain tissue, ischemic core, and penumbra were detected by western blot and flow cytometry. HQDG's effects on neurological deficits and neuronal pyroptosis were evaluated via neurological scoring, hematoxylin-eosin (HE) staining, cerebral blood flow monitoring, immunofluorescence and western blot. Adeno-associated virus (AAV)-mediated NOX4 overexpression was used to validate the mechanism, combined with 2,3,5-Triphenyltetrazolium chloride staining (TTC) staining, transmission electron microscopy (TEM) and enzyme-linked immunosorbent assay (ELISA). RESULTS: NOX4 and ROS were highly expressed in the ischemic penumbra of MCAO/R rats. Not only did HQDG notably improve neurological function, restore cerebral blood flow, and alleviate brain pathological injury, but it also reduced pyroptosis-related indicators. XST also improves neurological function in model rats, mitigates brain pathological damage, and inhibits pyroptosis in brain tissue cells, though its effects are weaker than those of HQDG. To further elucidate the mechanism of NOX4, we conducted targeted activation and inhibition via AAV-mediated NOX4 overexpression and Apocynin, respectively. The results showed that the AAV group reversed HQDG's suppression of ROS production and pyroptosis, exacerbating neuronal and cerebral pathological injury. In contrast, Apocynin recapitulated HQDG's neuroprotective effects, inhibiting NOX4-driven ROS and pyroptosis to mitigate I/R injury. CONCLUSION: Cerebral I/R injury is relieved by HQDG via the inhibition of pyroptosis, which is achieved through the suppression of NOX4- mediated ROS accumulation.
Astragalus polysaccharide ameliorates neuroinflammation in EAE mice by modulating microglial autophagy to reduce lipid droplet accumulation.
Wang X, Qiao X, Chen Y … +5 more , Lu Q, Ma J, Wang Y, Ding G, Cheng X
Brain Res · 2026 Jun · PMID 41759699 · Publisher ↗
Multiple sclerosis (MS) is an immune-mediated inflammatory demyelinating disease of the central nervous system. Emerging evidence indicates a close association between lipid metabolism disorders and MS, wherein microglia...
Multiple sclerosis (MS) is an immune-mediated inflammatory demyelinating disease of the central nervous system. Emerging evidence indicates a close association between lipid metabolism disorders and MS, wherein microglial neuroinflammation driven by aberrant lipid droplet accumulation represents a core pathological mechanism. In this study, we first performed GEO database-based differential gene enrichment analysis related to lipid metabolism and GWAS-based Mendelian randomization analysis, demonstrating that disordered lipid metabolism constitutes a key pathological feature of MS with lipid droplets playing a central role. Based on these findings and our previous work demonstrating the efficacy of APS in alleviating neuroinflammation and neurological deficits in experimental autoimmune encephalomyelitis (EAE) mice, we sought to elucidate its role and mechanism in regulating microglial lipid droplets metabolism and neuroinflammation in the EAE mice and LPS-stimulated BV2 microglia model. Results demonstrated impaired autophagic flux, increased lipid droplets accumulation, and elevated pro-inflammatory cytokine secretion in both EAE mice brain tissue and LPS-stimulated BV2 microglia model. Critically, APS intervention reversed these pathological changes. APS activated microglial autophagic flux, enhanced lipophagy function, cleared accumulated lipid droplets, and consequently suppressed pro-inflammatory factor secretion, thereby alleviating neuroinflammation. In conclusion, APS alleviates MS neuroinflammation partially by enhancing microglial lipophagy, which facilitates the elimination of lipid droplets accumulation. This finding provides a novel therapeutic strategy and lays a theoretical foundation for developing neuroprotective drugs targeting lipophagy.
Role of ventrolateral orbital cortex 5-HT receptors in formalin-induced secondary mechanical allodynia and hyperalgesia.
Zhang B, Yan X, Liu H … +5 more , Hai R, Jia H, Zhao Y, Yuan X, Huo F
Brain Res · 2026 Jun · PMID 41759698 · Publisher ↗
BACKGROUND: Formalin injection in hindpaw of rat produced acute nociceptive behaviors (flinching and licking/lifting) followed by secondary mechanical allodynia and hyperalgesia. Our previous study suggests that 5-HT rec...
BACKGROUND: Formalin injection in hindpaw of rat produced acute nociceptive behaviors (flinching and licking/lifting) followed by secondary mechanical allodynia and hyperalgesia. Our previous study suggests that 5-HT receptors in the ventrolateral orbital cortex (VLO) are involved in Formalin produced acute nociceptive behaviors, but it is not clear whether 5-HT receptors are involved in secondary mechanical allodynia and hyperalgesia. The purpose of this present study is to unveil the role of 5-HT receptors in the VLO and the underlying mechanisms in formalin-induced secondary mechanical allodynia and hyperalgesia. RESULTS: The expression level of 5-HT receptors were significantly increased in the VLO tissues at 6 days after formalin injection. Microinjection of the 5-HT receptors agonist DOI into the VLO decreases formalin-induced secondary mechanical allodynia and hyperalgesia in the ipsilateral paw, but not contralateral paw, which was antagonized by pre-treatment with 5-HT receptors antagonist Ketanserin. Furthermore, the antinociceptive effect of DOI was blocked by the phospholipase C (PLC) inhibitor U73122 and the protein kinase C (PKC) inhibitor Chelerythrine, or the non-selective glutamate receptor antagonist Kynurenic acid. respectively. And the antinociceptive effect of DOI was blocked by pre-treatment with GABA in the ventrolateral periaqueductal grey (PAG). CONCLUSIONS: These data suggest that 5-HT receptors in the VLO are involved in mediating the antinociceptive effect of formalin-induced long-lasting hypersensitivity. The possible mechanism underlying this effect is that 5-HT receptors activation regulate glutamatergic neuron transmission via the Gq-PLC-PKC pathway, leading to activation of VLO neurons projecting to the PAG. This could activate the PAG brainstem descending inhibitory system and depression of nociceptive information transmission at the spinal cord level.
Sex-specific behavioral effects of chronic opposite-sex visual contact in mice.
Ueno H, Tanaka Y, Kitano E … +7 more , Takahashi Y, Mori S, Murakami S, Wani K, Matsumoto Y, Okamoto M, Ishihara T
Brain Res · 2026 Jun · PMID 41747849 · Publisher ↗
BACKGROUND: Social environments exert profound influences on behavior and mental states. However, the impact of indirect social stimuli-specifically the visual recognition of opposite-sex conspecifics housed in adjacent...
BACKGROUND: Social environments exert profound influences on behavior and mental states. However, the impact of indirect social stimuli-specifically the visual recognition of opposite-sex conspecifics housed in adjacent cages-on mouse behavior has not been thoroughly investigated. This study aimed to comprehensively examine the sex-dependent behavioral effects of chronic opposite-sex visual exposure. METHODS: Male and female C57BL/6N mice were housed for 21 days in transparent cages placed adjacent to either opposite-sex or same-sex conspecifics. Following this period, a comprehensive behavioral test battery was conducted, including assessments of body weight, nociceptive sensitivity, aggressive behavior, anxiety-like behavior, social interaction, spatial working memory, and depression-like behavior. RESULTS: In male mice, opposite-sex exposure induced significant increases in body weight, heightened nociceptive sensitivity, enhanced aggression, and reduced depression-like behavior. In female mice, opposite-sex exposure resulted in increased aggression, reduced anxiety-like behavior in the open field test, and decreased alternation performance in the Y-maze. No significant differences were observed in social interaction measures in either sex. CONCLUSION: Chronic opposite-sex visual exposure in mice induces distinct behavioral changes in males and females. These findings highlight a novel mechanism by which non-contact social stimuli modulate behavior in a sex-dependent manner and provide insights relevant to understanding the influence of opposite-sex recognition on human psychology and behavior. Furthermore, the results emphasize the necessity of considering opposite-sex exposure when designing housing conditions and behavioral experiments in laboratory settings.
A novel plasma cell infiltration-associated prognostic signature suggests a potential role for CABP4 in glioma progression.
Wang Z, Wu H, Tan X … +5 more , Chen Z, Chang C, Zhang D, Yang Z, Zhao B
Brain Res · 2026 Jun · PMID 41747848 · Publisher ↗
BACKGROUND: Glioma is one of the most common malignant primary tumors of the central nervous system and its progression is closely associated with the tumor microenvironment (TME). However, the prognostic value and biolo...
BACKGROUND: Glioma is one of the most common malignant primary tumors of the central nervous system and its progression is closely associated with the tumor microenvironment (TME). However, the prognostic value and biological roles of the plasma cell infiltration-associated gene set (PCIG) in glioma remain poorly characterized. METHODS: We integrated transcriptomic and clinical data from lower-grade glioma (LGG) and glioblastoma (GBM) in The Cancer Genome Atlas (TCGA). Immune cell infiltration was estimated using xCell, CIBERSORT, and CIBERSORT-ABS to identify prognostically relevant immune subsets. Plasma cell infiltration-associated modules were defined as WGCNA modules significantly correlated with inferred plasma cell scores. A prognostic model was constructed using univariate Cox, LASSO, and stepwise multivariable Cox regression and independently validated in the Chinese Glioma Genome Atlas (CGGA). Immune TME features, immune functional states (cytolytic activity, checkpoint/exhaustion, and myeloid immunosuppression), genomic alterations, and pathway activities were compared between risk groups. CABP4 was further evaluated by RT-qPCR, Western blotting, CCK-8 proliferation assays, and Transwell migration/invasion assays. Subgroup analyses stratified by IDH status and 1p/19q codeletion were performed to test robustness across molecular subtypes. RESULTS: Plasma cells were consistently identified as protective immune cell subsets across all three algorithms and were associated with prolonged overall survival. A 15-gene PCIG signature demonstrated robust predictive performance in both TCGA and CGGA and remained an independent prognostic factor. The high-risk group exhibited an inflamed-but-immunosuppressed/exhausted TME, characterized by enrichment of immunosuppressive components together with upregulated checkpoint/exhaustion markers. The signature correlated with activation of pro-tumorigenic pathways, including angiogenesis and epithelial-mesenchymal transition. Notably, combined stratification by RiskScore and tumor mutational burden identified a subgroup with the poorest survival in Kaplan-Meier analyses. CABP4 knockdown significantly attenuated glioma cell proliferation, migration, and invasion in vitro. CONCLUSION: We developed and validated a novel 15-gene PCIG prognostic signature for glioma, enabling effective risk stratification and providing hypotheses for TME-oriented therapeutic strategies. Moreover, CABP4 emerged as a candidate pro-tumor regulator in vitro, warranting further mechanistic and in vivo validation.
Neuroprotective potential of Entada africana stem bark hydroalcoholic extract in sodium fluoride-induced neurobehavioral and biochemical alterations in animals.
Togbossi LA, Kantati YT, Lawson-Evi P … +1 more , Kwashie EG
Brain Res · 2026 Jun · PMID 41747847 · Publisher ↗
Fluorine is a toxic element naturally present in the environment. It crosses the blood-brain barrier and contributes to brain tissue damage. The present study aimed to evaluate the neuroprotective effect of the hydroalco...
Fluorine is a toxic element naturally present in the environment. It crosses the blood-brain barrier and contributes to brain tissue damage. The present study aimed to evaluate the neuroprotective effect of the hydroalcoholic extract of Entada africana stem bark (EAE) on neurological function and behavior alterations induced by sodium fluoride (NaF). Forced swim and Morris water maze tests were performed in Institue of Cancer Research (ICR) mice, while the open field test was conducted in Sprague Dawley rats. Both sexes of rats were administered NaF orally once daily at doses of 20 mg/kg (body weight, b.w.) for rats, and 10.5 mg/kg (b.w.) for mice over 30 days. Concurrently, they also received EAE orally once daily (250 mg/kg and 500 mg/kg), and distilled water for the control group. Hippocampus oxidative markers malondialdehyde (MDA), glutathione (GSH), nitric oxide (NO), catalase activity (CAT), and Acetylcholinesterase activity (AChEA) were assessed. Behavioral tests conducted on mice revealed that NaF significantly increased the immobility time of mice in the forced swim test. In Morris water maze test, NaF-treated animals expressed more difficulty locating the hidden platform. Open-field test on rats showed decreased the exploratory activity of NaF treated rats. EAE treatments significantly restored mice's mobility time in forced swim test, ability to locate the platform in Morris water maize test, rat's exploratory activity and reduced the time spent in the periphery of the chamber in Open-field test. Animals treated with NaF Hippocampus MDA and NO levels increase while GSH content, CAT and AChEA activity decrease. NaF also induced histological alterations in rat's hippocampus. EAE also reversed MDA, NO and GSH levels, CAT and AChEA activity, the hippocampus histological alterations induced by NaF treatments. E. africana stem bark hydroalcoholic extract exhibits its neuroprotective effect more likely through antioxidant mechanisms. Further research is required to thoroughly evaluate the neuroprotective potential of this medicinal plant.
Exogenous rGDF11 ameliorates chronic stress-induced cognitive impairment by suppressing the accumulation of endogenous formaldehyde.
Chen SJ, Liu F, Jiang JM … +5 more , Yi YL, Zhang P, Zou W, Yang SQ, Tang XQ
Brain Res · 2026 Jun · PMID 41740645 · Publisher ↗
BACKGROUND: Chronic unpredictable mild stress (CUMS) is a well-established model for studying stress-induced cognitive impairment. Emerging evidence suggests that dysregulation of endogenous formaldehyde (FA) metabolism...
BACKGROUND: Chronic unpredictable mild stress (CUMS) is a well-established model for studying stress-induced cognitive impairment. Emerging evidence suggests that dysregulation of endogenous formaldehyde (FA) metabolism in the hippocampus contributes to such impairment, yet therapeutic strategies targeting this pathway remain limited. Growth differentiation factor 11 (GDF11), a neuroprotective protein, has been implicated in synaptic regulation and cognitive function, but its direct roles in modulating chronic stress-induced cognitive impairment and FA homeostasis under chronic stress remain unknown. METHODS: Adult male Sprague-Dawley rats were subjected to CUMS for 4 weeks. During the last two weeks, rats received intracerebroventricular injections of recombinant GDF11 (rGDF11) at doses of 0.4, 1.2, or 4.0 ng/kg. Cognitive performance was assessed using the Y-maze, novel object recognition (NOR) test, and Morris water maze (MWM). Hippocampal tissue was analyzed for FA levels using a fluorescence probe, and protein expression of synaptic markers (SYN-1, PSD-95) and FA-metabolizing enzymes (SSAO, ADH5, ALDH2) was measured by Western blot. RESULTS: CUMS-exposed rats showed significant cognitive deficits across all behavioral tests, along with downregulation of synaptic proteins, elevated hippocampal FA levels, and imbalances in the expression of FA-metabolizing enzymes. Treatment with rGDF11, particularly at 4.0 ng/kg, dose-dependently restored synaptic protein expression and normalized FA metabolism by downregulating SSAO and upregulating ADH5 and ALDH2. CONCLUSION: Exogenous rGDF11 ameliorates CUMS-induced cognitive impairment by suppressing hippocampal FA accumulation and restoring synaptic integrity through regulation of FA-metabolizing enzymes. These findings identify GDF11 as a potential therapeutic target for stress-related cognitive disorders.
Examination and quantification of motor evoked potentials in the non-target resting leg.
Fraterrigo NJ, DiMaio RS, Girts RM … +2 more , Stock MS, Harmon KK
Brain Res · 2026 May · PMID 41740644 · Publisher ↗
Transcranial magnetic stimulation (TMS) is a research tool that can noninvasively assess efficiency of the nervous system. However, TMS of the lower limb presents considerable challenges. Guidelines to streamline data co...
Transcranial magnetic stimulation (TMS) is a research tool that can noninvasively assess efficiency of the nervous system. However, TMS of the lower limb presents considerable challenges. Guidelines to streamline data collection procedures are warranted. As a secondary analysis of previously published data (PMID: 37267320), this study aimed to determine to what extent motor evoked potentials (MEPs) are evident from the resting ipsilateral leg when the vertex is stimulated. A secondary aim was to provide methodological insight into how to identify MEPs in the resting ipsilateral limb when the contralateral limb is active. Thirteen males and 14 females underwent TMS of the lower limb. A double cone coil was used to deliver 20 pulses to the vertex of the scalp at both 120% and 130% active motor threshold (AMT) during submaximal contractions of the dominant leg. MEP amplitude of the rectus femoris (RF), vastus lateralis (VL), biceps femoris (BF), tibialis anterior (TA), and medial gastrocnemius (MG) were examined in the resting ipsilateral leg. MEPs were evaluated as breaking a threshold of ≥ 50 µV, ≥ double baseline electromyography (EMG) amplitude, or ≥ triple baseline EMG amplitude. Our findings indicate that 1) MEPs are apparent in the muscles of the resting ipsilateral leg, detectable from 30 ± 38% (120% AMT; BF) to 96 ± 13% (130% AMT; TA) of the time; 2) 130% AMT results in a greater percentage of MEPs, and 3) MEP identification is most apparent at the threshold of ≥ double baseline EMG. Stimulation at the vertex allowed response detection in multiple lower limb muscles.
Brain network differences between priming and non-priming intermittent theta burst stimulation: a functional near-infrared spectroscopy analysis.
Guo C, Geng A, Wu Y … +7 more , Zhu S, Wang Q, Kan C, Shen J, Hu W, Shen Y, Wang T
Brain Res · 2026 Jun · PMID 41740643 · Publisher ↗
According to the theory of bidirectional synaptic plasticity, the threshold for inducing long-term potentiation-like plasticity varies with neuronal activity. Continuous theta burst stimulation (cTBS) has been proposed a...
According to the theory of bidirectional synaptic plasticity, the threshold for inducing long-term potentiation-like plasticity varies with neuronal activity. Continuous theta burst stimulation (cTBS) has been proposed as a priming protocol that may modulate neural responses to subsequent intermittent theta burst stimulation (iTBS). This study examined differences between priming and non-priming iTBS conditions in their associations with brain network modulation, assessed at rest and during motor tasks, when targeting the left primary motor cortex. In a randomized crossover design, 26 healthy adults completed six sessions involving two stimulation conditions (priming and non-priming iTBS) and three task paradigms (hand grasping, multi-joint movement, and resting task). The order of stimulation conditions and tasks was randomized. In each session, a single task was performed, and fNIRS data were acquired immediately before and after stimulation. Analyses focused on cortical activation, functional connectivity, and graph theory. During the grasping task, the priming iTBS condition was associated with greater task-evoked activation in the left primary motor cortex and premotor cortex compared with the non-priming iTBS condition. During the multi-joint movement task, priming iTBS condition showed stronger functional connectivity between the left primary motor cortex and left primary somatosensory cortex. No significant between-condition differences were observed during the resting task. In summary, priming and non-priming iTBS conditions differed in cortical activation and sensorimotor connectivity during motor task performance, whereas resting-state network properties remained largely unchanged. These results suggest that priming-related differences in brain network responses are more evident during active motor engagement than at rest. Further studies are required to clarify the underlying mechanisms and functional significance of these effects.
Anemarrhenae rhizoma water extract (AWE) ameliorates learning and memory impairments by activating the ADAM17/Aph-1-Notch signaling axis and restoring synaptic protein loss.
Wu D, Chen S, Liu R … +1 more , Zhang J
Brain Res · 2026 Jun · PMID 41734830 · Publisher ↗
BACKGROUND: The scopolamine (SCOP)-induced memory impairment model is a classic model for cognitive research. The Notch signaling pathway is pivotal for synaptic plasticity. OBJECTIVE: To investigate whether Anemarrhenae...
BACKGROUND: The scopolamine (SCOP)-induced memory impairment model is a classic model for cognitive research. The Notch signaling pathway is pivotal for synaptic plasticity. OBJECTIVE: To investigate whether Anemarrhenae rhizoma water extract (AWE) ameliorates SCOP-induced synaptic dysfunction and memory impairment by activating the Notch pathway. METHODS: UPLC-Q-TOF-MS was employed technology to analyze the components of AWE. behavioral tests and HE staining were performed to evaluate cognitive function and hippocampal pathology in mice, and DIA mass spectrometry was performed for a comprehensive analysis of the hippocampal proteome analysis. Additionally, Western blotting was performed to measure the expression levels of proteins related to the Notch signaling pathway and synapses. In vitro, HT22 cells were treated with the γ-secretase inhibitor DAPT and the selective ADAM17 inhibitor TAPI-1 to verify the crucial role of the Notch pathway in mediating the protective effects of AWE. RESULTS: AWE primarily contains timosaponins BII, BIII, AI, AIII, neomangiferin, and mangiferin. Proteomic analysis revealed the upregulation of the key Notch pathway activators, ADAM17 and Aph-1, coupled with a significant overall enrichment of the Notch signaling pathway. Furthermore, AWE dose-dependently reversed SCOP-induced memory deficits, and pathological changes in the hippocampus and decreased expression of synaptic and Notch signaling proteins in mice. Critically, the protective effects of AWE on HT22 cells were completely abolished by DAPT and TAPI-1. CONCLUSIONS: AWE alleviates SCOP-induced synaptic protein loss and memory impairment by activating the Notch signaling pathway, providing new evidence for natural preventive strategies targeting Notch.
Harnessing estrogen's neuroprotective potential in mitigating Alzheimer's pathologies in postmenopausal women: a review.
Manasa M, Bethanagere Ramesha G, Krishna KL … +4 more , Ambika MS, Nadig APR, Pathak S, Jalawadi P
Brain Res · 2026 May · PMID 41730379 · Publisher ↗
Alzheimer's disease (AD) is a progressive disorder that affects the brain and leads to cognitive decline and memory loss, with postmenopausal women being unduly affected. Estrogen is believed to exert neuroprotective eff...
Alzheimer's disease (AD) is a progressive disorder that affects the brain and leads to cognitive decline and memory loss, with postmenopausal women being unduly affected. Estrogen is believed to exert neuroprotective effects by influencing amyloid-beta accumulation, tau hyperphosphorylation, oxidative stress, synaptic function, neuroinflammation, and brain-derived neurotrophic factor (BDNF) signalling. This review examines the role of estrogen in AD pathogenesis among postmenopausal women. A systematic literature search was conducted using PubMed, Scopus, and Web of Science. Keywords included "estrogen", "Alzheimer's disease", "neuroprotection", "amyloid-beta," and "BDNF." Inclusion criteria were peer-reviewed studies from the past 10 years focusing on estrogen's effects on AD mechanisms, neurobiology, and therapeutic relevance. Articles were screened by title and abstract. Followed by a full-text review to ensure methodological rigour and relevance. Evidence indicates that estrogen reduces amyloid beta burden, inhibits tau phosphorylation, mitigates oxidative stress, preserves synaptic connectivity, and suppresses neuroinflammation. Estrogen also modulates ApoE-linked lipid metabolism and enhances BDNF signalling, supporting neuronal survival and cognitive resilience. Declining estrogen after menopause increases vulnerability to AD. Understanding estrogen's neuroprotective mechanisms may support targeted therapeutic strategies. Hormone replacement therapy (HRT) and selective estrogen receptor modulators (SERMs) show potential, but further research is needed to optimise timing, dosage, and patient selection in postmenopausal AD prevention and management.
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