Brain Research Bulletin[JOURNAL]
Sun
200 papers
White matter microstructure and cognitive decline in subacute ischemic stroke: Insights from free water imaging and glymphatic dysfunction.
Qin Y, Li X, Wang L … +6 more , Qiao Y, Liu L, Tian J, Jin D, Zhu Y, Zhang M
Brain Res Bull · 2026 Apr · PMID 41794270 · Publisher ↗
OBJECTIVE: This study aimed to investigate white matter microstructural changes and their relationship with cognitive function in patients with subacute ischemic stroke (IS) using free water diffusion tensor imaging (FW-...
OBJECTIVE: This study aimed to investigate white matter microstructural changes and their relationship with cognitive function in patients with subacute ischemic stroke (IS) using free water diffusion tensor imaging (FW-DTI) and tract-based spatial statistics (TBSS). METHODS: Thirty-nine patients with subacute IS (31 males, age 59.2 ± 11.2 years) and 39 well-matched healthy controls (HC, 30 males, age 58.5 ± 7.7 years) underwent diffusion spectrum imaging. FW, fractional anisotropy (FA), mean diffusivity (MD), and FW-corrected DTI metrics (FA and MD) were analyzed using TBSS. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). Group differences and correlations in these metrics, as well as their correlations with cognitive performance and clinical variables, were examined. RESULTS: Compared with the HCs, IS patients showed significantly higher FW in both the whole-brain (t = -3.03, p = 0.003) and white matter skeleton (t = -3.20, p = 0.002), and reduced white matter skeleton FA (t = 3.81, p < 0.001) and FA (t = 3.60, p = 0.006). After adjusting for alcohol and smoking, MoCA scores were negatively correlated with whole-brain (ρ = -0.49, p = 0.032) and white matter skeleton FW (ρ = -0.48, p = 0.039) in the IS group. White matter skeleton FW was positively associated with time since stroke onset (ρ = 0.48, p = 0.039). Age was negatively correlated with white matter skeleton FA (r = -0.35, p = 0.030) and FA (r = -0.38, p = 0.018), but positively with whole-brain FW (r = 0.59, p < 0.001) and white matter skeleton MD (r = 0.38, p = 0.018). CONCLUSIONS: FW-DTI reveals widespread microstructural disruption in patients with subacute IS, which may reflect glymphatic dysfunction and vasogenic edema. Elevated FW is associated with cognitive decline, highlighting its potential as a biomarker for post-stroke cognitive impairment.
Effect of perioperative preemptive analgesia on hippocampal GABAA receptor α1/α5 balance in aged mild cognitive impairment rats.
Ren H, Zhang L, Yang C … +3 more , Wang X, Liu X, Wang H
Brain Res Bull · 2026 Apr · PMID 41794269 · Publisher ↗
BACKGROUND: Postoperative cognitive dysfunction (POCD) is a frequent complication in elderly patients that delays recovery and increases long-term health risks. Preemptive analgesia may alleviate surgery-induced inflamma...
BACKGROUND: Postoperative cognitive dysfunction (POCD) is a frequent complication in elderly patients that delays recovery and increases long-term health risks. Preemptive analgesia may alleviate surgery-induced inflammation and central sensitization, but its role in improving postoperative neurocognitive disorder (PND) through modulation of hippocampal Gamma-aminobutyric acid type A (GABAA) receptor α1/α5 subunits in aged rats with mild cognitive impairment (MCI) remains unclear. METHODS: Twenty-two-month-old male Sprague-Dawley (SD) rats were used to establish the MCI model via severe bilateral common carotid artery stenosis. After successful modeling, rats were randomly divided into five groups: Control (Con, only tibial exposure and suturing), Surgery (intravenous 0.9% normal saline), Nalbuphine (Nal, 10 mg/kg), Dezocine (Dez, 10 mg/kg), and Sufentanil (Suf, 10 μg/kg). Drugs were administered 1 h preoperatively. Anesthesia was induced with a subanesthetic regimen (0.7 MAC sevoflurane + 1.2 μg/ml propofol, validated previously), followed by tibial fracture open reduction and internal fixation (ORIF). Postoperative evaluations included pain indicators (paw withdrawal latency [PWL], paw withdrawal threshold [PWT]), cognitive function, and hippocampal GABAA α1/α5 and PSD95 expression levels. RESULTS: This study examined preemptive analgesia's effects on postoperative outcomes in aged MCI rats. Behavioral tests (PWL, PWT) showed it alleviated postoperative pain, while Y-maze and novel object recognition tests improved anesthesia/surgery-related cognitive decline on postoperative days 1, 3, 7. Western blot revealed ORIF model rats had reduced hippocampal GABAA α1/α5 ratio on postoperative days 1, partial recovery on postoperative days 3, 7, abnormal balance on postoperative days 7, and sustained PSD95 downregulation. Preemptive nalbuphine, dezocine, or sufentanil prevented GABAA α1/α5 imbalance and attenuated PSD95 reduction. HE staining indicated mitigated hippocampal neutrophil infiltration and structural damage induced by anesthesia/surgery. CONCLUSION: Perioperative preemptive analgesia effectively reduces postoperative pain and improves neurocognitive function in aged MCI rats, via a mechanism linked to maintaining hippocampal GABAA receptor α1/α5 subunit balance and ameliorating hippocampal neural dysfunction. This study provides foundational evidence for clinical postoperative pain management and cognitive protection in elderly MCI patients.
Neuronal phenotypic alterations and the therapeutic potential of Anxa2 in traumatic brain injury recovery.
Hu H, Zhang Y, Jin Y … +5 more , Zhao J, Xing W, Wang Z, Liu J, Zhang B
Brain Res Bull · 2026 Apr · PMID 41785976 · Publisher ↗
BACKGROUND: Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. After TBI, neurons undergo various phenotypic changes in response to multiple stimuli, and these changes may either facilitat...
BACKGROUND: Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. After TBI, neurons undergo various phenotypic changes in response to multiple stimuli, and these changes may either facilitate recovery or exacerbate neuronal damage. Our study aimed to explore the potential impact of such phenotypic alterations on TBI outcomes. METHODS: We obtained publicly available single-cell and bulk RNA-sequencing datasets of mouse cortical tissue from the GEO database. These datasets were used to identify genes associated with neuronal phenotypic changes following TBI. Using stereotactic intracranial injections of AAV vectors, we modulated the expression of candidate genes in neurons and evaluated their biological functions in TBI recovery through behavioral tests, including the modified Garcia score, rotarod test, and balance beam test. Finally, we employed molecular docking analyses to assess the binding capacity of various small-molecule compounds to the identified target gene. RESULTS: Our scRNA-Seq analyses identified a population of neurons that displayed significant mRNA expression changes after TBI. Enrichment analyses, pseudotime trajectory studies, and cell-to-cell pathway communication analyses highlighted distinct gene expression and signaling pathway alterations within this neuronal cluster post-TBI. Among these genes, Anxa2 emerged as a potentially important factor in neuronal repair following injury. Behavioral experiments indicated that overexpression of Anxa2 led to improved outcomes, whereas Anxa2 knockdown worsened recovery. Furthermore, molecular docking analysis revealed several small-molecule compounds that may interact with Anxa2, suggesting potential therapeutic candidates for TBI treatment. CONCLUSIONS: Neurons exhibit extensive gene expression and signaling pathway modifications after TBI, and neuronal Anxa2 plays a beneficial role in behavioral recovery. Moreover, our findings suggest that multiple small-molecule compounds may serve as potential therapeutic agents targeting Anxa2, providing new insights for the development of TBI therapeutics.
Mesencephalic astrocyte-derived neurotrophic factor attenuates sepsis-associated encephalopathy by inhibiting oxidative stress and pyroptosis.
Gao J, Wang LX, Zhou LY … +8 more , Tang YC, Ning JW, Wang C, Liu J, Zhuo EB, Zhou YN, Shen YJ, Shen QY
Brain Res Bull · 2026 Apr · PMID 41785975 · Publisher ↗
BACKGROUND: Sepsis-associated encephalopathy (SAE) is a diffuse form of brain dysfunction, and the mechanism of SAE remains unclear. Mesencephalic astrocyte-derived neurotrophic factor (MANF) has been reported to play ke...
BACKGROUND: Sepsis-associated encephalopathy (SAE) is a diffuse form of brain dysfunction, and the mechanism of SAE remains unclear. Mesencephalic astrocyte-derived neurotrophic factor (MANF) has been reported to play key roles in inhibiting the inflammatory response, but the specific role of MANF in SAE remains to be fully elucidated. METHODS: We compared the MANF content between healthy individuals and septic individuals. We established an SAE model in wild-type (WT) and mono-macrophage specific MANF knockout (MKO) mice and detected MANF expression in SAE mice. The rhMANF protein was used to observe the effect and mechanism of MANF on SAE-associated behavioral changes, inflammatory biomarkers and microglial activation, polarization and pyroptosis in SAE mice. RESULTS: MANF levels were significantly elevated in the serum and circulating monocytes of septic individuals. LPS-induced SAE increased the expression of MANF in the prefrontal cortex, monocytes and macrophages, whereas MKO aggravated peripheral neuropathy and neuroinflammation in SAE mice. rhMANF treatment alleviated SAE-associated delirium-like behavioral changes and reduced the production of proinflammatory cytokines in the prefrontal cortex and serum of SAE mice. Additionally, rhMANF inhibited microglial activation, oxidative stress and Caspase 11-GSDMD-dependent microglial pyroptosis both in vivo and in vitro. CONCLUSION: The results of the present study indicate that MANF alleviates SAE, likely by inhibiting ROS-GSDMD-dependent microglial pyroptosis.
Rapamycin improves memory and blood pressure stability in asymmetrical cortico-brainstem connectivity following stroke.
Hsu Y, Sung PS, Lin CC … +2 more , Wu WL, Chang AYW
Brain Res Bull · 2026 Apr · PMID 41785974 · Publisher ↗
Emerging reports suggest that patients with ischemic stroke involving the insular cortex (IC), particularly in the right hemisphere, may lead to paradoxical reduction in blood pressure-a condition associated with worse o...
Emerging reports suggest that patients with ischemic stroke involving the insular cortex (IC), particularly in the right hemisphere, may lead to paradoxical reduction in blood pressure-a condition associated with worse outcomes, including increased mortality and cognitive decline-whereas elevated blood pressure is more commonly observed during the acute phase of stroke. To investigate this lateralized effect and its underlying mechanisms, we established focal ischemic stroke models targeting either the left or right IC in male rats. In this study, we demonstrated that infarction of the right insular cortex results in sustained reductions in systemic blood pressure, changes in blood pressure variability consistent with reduced rostral ventrolateral medulla (RVLM) neurogenic activity, and bilateral impairment of autophagy-related signaling pathways. By contrast, left-sided IC infarction induced no significant changes, indicating a lateralized effect of IC stroke on autonomic regulation. These alterations in the right-sided IC stroke were accompanied by significant memory deficits. Retrograde tracing confirmed direct neuronal projections from the IC to the RVLM, suggesting a cortico-brainstem pathway through which cortical stroke may impair systemic autonomic regulation. Notably, pharmacological activation of autophagy with rapamycin restored RVLM activity, normalized blood pressure, and improved cognitive performance. These findings identify a novel lateralized insula-RVLM autonomic pathway involving autophagy that contributes to post-stroke hypotension and memory impairment, and suggest that modulation of this pathway may offer a therapeutic strategy for stroke patients with autonomic dysfunction beyond the hypotensive presentation.
The activation of p66shc in the prelimbic cortex contributes to the development of neuropathic pain.
Wang R, He T, Li C … +3 more , Du R, Lin Q, Wang Y
Brain Res Bull · 2026 Apr · PMID 41780698 · Publisher ↗
This study investigated the role of the adaptor protein p66shc in the prelimbic cortex (PrL) in neuropathic pain development in rats. Results showed that activated p66shc and reactive oxygen species (ROS) were elevated i...
This study investigated the role of the adaptor protein p66shc in the prelimbic cortex (PrL) in neuropathic pain development in rats. Results showed that activated p66shc and reactive oxygen species (ROS) were elevated in the PrL following peripheral nerve injury. Intra-PrL administration of p66shc siRNA significantly alleviated mechanical allodynia and reduced ROS levels, without impairing locomotor activity. Electrophysiological analysis revealed that neuropathic pain enhanced the excitability of PrL layer 2/3 pyramidal neurons, an effect reversed by p66shc inhibition. Furthermore, spared nerve injury (SNI) shifted synaptic transmission in these neurons, increasing miniature excitatory postsynaptic current (mEPSC) frequency and decreasing miniature inhibitory postsynaptic current (mIPSC) frequency. Both synaptic alterations were normalized by p66shc siRNA. Collectively, these findings indicate that p66shc in the PrL plays a crucial role in neuropathic pain pathogenesis and may represent a novel therapeutic target.
Refined model of common peroneal nerve injury and regeneration: A neurophysiological, morphometric, and functional analysis in the adult rat.
Supper P, Schmoll M, Wiesner P … +13 more , Brettlecker S, Dena A, Semmler L, Millesi F, Haertinger M, Wolf S, Rad Anda C, Borger A, Mero S, Unger E, Bijak M, Lanmüller H, Radtke C
Brain Res Bull · 2026 Apr · PMID 41780697 · Publisher ↗
The common peroneal nerve lesion induces a specific peripheral nerve injury, characterized by a specific motor deficit with little animal burden. Although, it has been described in the 1980s, there is a lack of consisten...
The common peroneal nerve lesion induces a specific peripheral nerve injury, characterized by a specific motor deficit with little animal burden. Although, it has been described in the 1980s, there is a lack of consistent outcome measurements in the literature. This study presents a refined common peroneal nerve injury model in Sprague Dawley rats with crush or transection injury. It introduces a morphometric muscle analysis, a refined videometric gait analysis and isometric force measurement, as well as testing the validity of outcome measures. The tibialis anterior muscle exhibited the largest physiological cross-sectional area, the highest muscle volume and wet weight. Crush injury showed significantly higher gait regeneration, a stronger twitch force and greater muscle masses compared to nerve transection. The introduced model offers shorter regeneration time, muscle-sparing access, and a high test validity for muscle mass, joint angle analysis, and isometric twitch force.
Calycosin exerts anti-glioblastoma effects by inhibiting GPX-4 to promote oxidative stress.
Wei Q, Yang K, Liu Z … +6 more , Kong D, Pang W, Qiu R, Fan H, Li Y, Zhang X
Brain Res Bull · 2026 Apr · PMID 41771447 · Publisher ↗
Temozolomide (TMZ) is a first-line drug for treating glioblastoma (GBM), but its efficacy has been greatly limited by the development of resistance. Calycosin (CAL), an isoflavone, has demonstrated efficacy in anti-tumor...
Temozolomide (TMZ) is a first-line drug for treating glioblastoma (GBM), but its efficacy has been greatly limited by the development of resistance. Calycosin (CAL), an isoflavone, has demonstrated efficacy in anti-tumor therapy. However, its effect on TMZ-resistant GBM cells remains unclear. This study explored the effects of CAL on the parental and TMZ-resistant GBM cells in vitro and in vivo experiments. The results showed that CAL could significantly inhibit the proliferation, migration, and invasion of both parental and TMZ-resistant GBM cells and promote their apoptosis, and could exert anti-GBM effects in vivo. Furthermore, by detecting the changes in oxidative stress-related indicators and glutathione peroxidase 4 (GPX-4) protein in the resistant cells and tissues after CAL treatment, it was found that the level of reactive oxygen species (ROS) increased, while the levels of glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) decreased, and the expression of GPX-4 was lowered. It indicates that the effect of CAL on drug-resistant GBM is related to the inhibition of GPX-4 expression, thereby promoting the occurrence of oxidative stress. In conclusion, CAL has potential clinical application value in the treatment of TMZ-resistant GBM and provides a new approach for the treatment of drug-resistant GBM.
Pituitary height and clivus-mesencephalic angle in combination with Bern Score in the diagnosis of spontaneous intracranial hypotension.
Zhou Z, Chi F, Zhang J … +5 more , Ding J, Jia H, Xi Z, Teng J, Li X
Brain Res Bull · 2026 Apr · PMID 41763586 · Publisher ↗
BACKGROUND AND OBJECTIVES: There is a lack of reliable spontaneous intracranial hypotension (SIH) diagnosing tools. The commonly used Bern Score, which integrates six established imaging signs, has proven reliable in dis...
BACKGROUND AND OBJECTIVES: There is a lack of reliable spontaneous intracranial hypotension (SIH) diagnosing tools. The commonly used Bern Score, which integrates six established imaging signs, has proven reliable in discriminating spinal cerebrospinal fluid (CSF) leaks. However, this score does not include several commonly observed imaging features, and new signs have been reported recently. This study aimed to identify additional reliable imaging signs in order to develop a new scoring system for the diagnosis of SIH. METHODS: In this case-control study, brain MR images from consecutive SIH patients and control participants at our institution were retrospectively and independently reviewed by 3 blinded readers. 3 qualitative and 9 quantitative imaging signs were evaluated. Firth's regression was performed and a diagnostic scoring system composed of reliable imaging signs was developed. The performance of this new scoring system was validated in an external retrospective patient cohort and compared with that of the Bern Score. RESULTS: Our derivation cohort comprised 20 SIH patients and 20 age- and gender- matched control participants, while the validation cohort included 55 SIH patients and 55 controls. We identified pituitary height (ICC=0.873) and the clivus-mesencephalic angle (ICC=0.897) as two additional reliable and practicable imaging features. All six imaging signs in the original Bern Score showed good inter-observer and inter-study agreement (except for prepontine cistern size, which was smaller in the present study). We then developed a new scoring system, the PS-Bern score (PS denoting pituitary and skull base). It incorporates pituitary height (2 points), clivus-mesencephalic angle (1 point) and the full Bern Score (prepontine cistern size [≤4 mm]). In the validation cohort, the PS-Bern score outperformed the Bern score. For ruling in SIH (cutoff ≥5 vs Bern ≥4), the PS-Bern score had a sensitivity of 89.1% and specificity of 98.2%, compared to 85.5% and 94.6% for the Bern score. For ruling out SIH (cutoff ≤3 vs Bern ≤2), its sensitivity and specificity were 89.1% and 92.7%, respectively, superior to the Bern score's values of 65.5% and 90.9%. DISCUSSION: Pituitary height and clivus-mesencephalic angle are useful imaging biomarkers and the PS-Bern score including these two signs may aid in the timely and accurate diagnosis of SIH. The small sample size requires that the results be validated in larger cohorts.
Evaluation of cerebral cannabinoid type 2 receptors using [C]RSR-056 PET in a rat model of epilepsy.
Zeng C, Tang G, Jiang Y … +12 more , Dong C, Wei H, Hou L, Liao K, Tan Z, Wu H, Wu B, Ye W, Zhu H, Gong J, Xu H, Ling X
Brain Res Bull · 2026 Apr · PMID 41763585 · Publisher ↗
PURPOSE: Cannabinoid receptor type 2 (CB2R) plays a critical yet mechanistically undefined role in epileptogenesis. This study employed a CB2R-targeting PET probe to visualize spatiotemporal alterations in cerebral CB2R...
PURPOSE: Cannabinoid receptor type 2 (CB2R) plays a critical yet mechanistically undefined role in epileptogenesis. This study employed a CB2R-targeting PET probe to visualize spatiotemporal alterations in cerebral CB2R expression in epileptic rats, elucidating its potential role in epileptogenesis. METHODS: The CB2R-targeting PET probe [C]RSR-056 underwent automated radiosynthesis. A lithium chloride-pilocarpine-induced epileptic rat model was utilized, and [C]RSR-056 PET/CT imaging was performed in controls and status epilepticus (SE) groups (1 d, 1 w, 1 m and 2 m post SE). Image analysis using PMOD software yielded data expressed as standard uptake value (SUV) and the percentage of injected dose per gram of tissue (%ID/g). Immunofluorescence was performed on brain tissue from all groups. RESULTS: [C]RSR-056 PET/CT imaging revealed higher SUV in the hippocampus, thalamus, hypothalamus, and cerebellum of epileptic rats at 1 w post SE, and significantly higher %ID/g in the cortex, hippocampus, striatum, thalamus, hypothalamus, and cerebellum at both 1 d and 1 w post SE, compared with the control group (all P < 0.05). Immunofluorescence confirmed CB2R co-localization in both microglia and neurons. Relative to controls, the 1 w post SE group showed a significant increase in the mean CB2R immunofluorescence intensity within the hippocampal CA1 region (P < 0.05). CONCLUSION: CB2R-targeted PET probe [C]RSR-056 enables non-invasive visualization of spatiotemporal changes in brain CB2R expression of living epileptic rats. CB2R expression elevated at 1 d post SE, peaked at 1 w post SE, and declined to baseline at 1 m and 2 m post SE. Elevated CB2R expression was associated not only with microglia but also with neurons.
Edaravone dexborneol promotes oligodendrocyte precursor cell proliferation and differentiation to repair white matter and improve long-term outcomes after ischemic stroke.
Han W, Duan T, Xu J … +6 more , Jin G, Wei H, Jiang J, Zhu Y, Yu M, Xu Y
Brain Res Bull · 2026 Apr · PMID 41763584 · Publisher ↗
BACKGROUND: White matter repair after ischemic stroke is critical for long-term recovery. Edaravone dexborneol (EDB) has antioxidative and anti-inflammatory properties, but its role in white matter integrity remains uncl...
BACKGROUND: White matter repair after ischemic stroke is critical for long-term recovery. Edaravone dexborneol (EDB) has antioxidative and anti-inflammatory properties, but its role in white matter integrity remains unclear. METHODS: We enrolled 73 patients with first-ever left basal ganglia infarction, including the conventional treatment group (n = 33) and the EDB treatment group (n = 40). In addition, 32 healthy individuals were recruited as a control group. After 3 months, MRI (T1WI and DTI) was performed to assess FA values of 8 major tracts and rich-club network organization. In parallel, middle cerebral artery occlusion (MCAO) was induced in mice. Behavioral tests, histology, immunofluorescence, and Western blot were conducted to evaluate functional recovery, white matter injury, OPC proliferation/differentiation, and Akt/mTOR signaling. Primary OPC cultures were used to validate mechanisms in vitro. RESULTS: Clinically, the conventional group showed reduced FA values and weakened rich-club connectivity, whereas both metrics were significantly improved in the EDB group. In MCAO mice, EDB alleviated brain atrophy and white matter injury, promoted sensorimotor and cognitive recovery, and enhanced OPC proliferation and differentiation via Akt/mTOR activation. In vitro, EDB stimulated OPC proliferation/differentiation, while Akt/mTOR inhibition abolished these effects. CONCLUSION: EDB treatment was associated with improved local tract integrity and global network connectivity in stroke patients. In experimental models, EDB promoted OPC proliferation and differentiation via Akt/mTOR signaling, potentially contributing to remyelination and white matter repair, accompanied by improved long-term functional outcomes. These findings suggest that EDB may represent a promising strategy for post-stroke white matter repair.
Retigabine ameliorates CRS-induced depressive-like behaviors and cognitive impairment by inhibiting endoplasmic reticulum stress-mediated apoptosis.
Zhang J, Li YH, Zhang JJ … +4 more , Chen SB, Zhan JQ, Wei B, Hu J
Brain Res Bull · 2026 Apr · PMID 41763583 · Publisher ↗
BACKGROUND: Retigabine (RTG) shows notable neuroprotective efficacy in multiple brain injury models; however, its interplay with endoplasmic reticulum stress (ERS) is poorly understood. This study was designed to explore...
BACKGROUND: Retigabine (RTG) shows notable neuroprotective efficacy in multiple brain injury models; however, its interplay with endoplasmic reticulum stress (ERS) is poorly understood. This study was designed to explore the therapeutic potential of RTG against CRS-induced depression-like behaviors and cognitive deficits in mice and to uncover the associated molecular mechanisms. METHODS: A depression-like and cognitive impairment model was established in C57BL/6 male mice using chronic restraint stress (CRS). Six-week-old C57BL/6 male mice were randomly assigned to the following groups: control (Con), model (CRS), RTG (10 mg/kg), XE-991 (2 mg/kg) or tunicamycin (Tm, 2 mg/kg). Behavioral tests were conducted to assess depression-like behaviors and cognitive function. Hippocampal neuronal morphology was examined by H&E and immunofluorescence staining, while changes in endoplasmic reticulum stress (ERS)-related signaling pathways were analyzed by Western blot. RESULTS: Retigabine treatment reduced hippocampal neuronal damage and the expression of ERS-related factors (GRP78, CHOP) and the pro-apoptotic factor BAX in CRS-induced mice, while it increased the levels of BDNF. These effects were antagonized by XE-991 and the ERS agonist tunicamycin (Tm). CONCLUSIONS: Retigabine may alleviate CRS-induced depressive-like behaviors and cognitive impairment by inhibiting ERS-mediated apoptosis, suggesting its potential as a novel therapeutic strategy for depression.
Research progress of miRNA in post-stroke cognitive impairment.
Weng Y, Xue C, Guo H … +2 more , Zhang L, Tang X
Brain Res Bull · 2026 Apr · PMID 41763582 · Publisher ↗
Post-stroke cognitive impairment (PSCI) is a common and severe complication of stroke, significantly reducing patients' quality of life and life expectancy while imposing a heavy burden on families and society. MicroRNAs...
Post-stroke cognitive impairment (PSCI) is a common and severe complication of stroke, significantly reducing patients' quality of life and life expectancy while imposing a heavy burden on families and society. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the post-transcriptional level and play critical roles in the development, plasticity, and repair of the central nervous system. Recent studies have revealed that multiple miRNAs are aberrantly expressed after cerebral ischemia and contribute to PSCI progression by modulating key processes such as oxidative stress，cell death，neuroinflammation, blood-brain barrier，myelin repair. This review summarizes recent advances in understanding the roles, target genes, and signaling pathways of miRNAs in PSCI, and discusses their potential as early diagnostic biomarkers and therapeutic targets, aiming to provide a theoretical basis and research direction for the precision management of PSCI.
Vagus nerve stimulation enhances memory and long-term potentiation via the hippocampal NE/β-AR signaling pathway in pilocarpine rats.
Qi R, Wang J, Pei H … +7 more , Zhang M, Shen J, Chen X, Chen Y, Yu H, Li J, Wei J
Brain Res Bull · 2026 Apr · PMID 41759686 · Publisher ↗
BACKGROUND: Memory deficits in temporal lobe epilepsy severely impair quality of life, yet effective therapeutic strategies remain limited. Vagus nerve stimulation (VNS), an FDA approved treatment for drug resistant epil...
BACKGROUND: Memory deficits in temporal lobe epilepsy severely impair quality of life, yet effective therapeutic strategies remain limited. Vagus nerve stimulation (VNS), an FDA approved treatment for drug resistant epilepsy, has demonstrated beneficial effects on cognition, but the underlying mechanisms are unclear. VNS activates the locus coeruleus norepinephrine (NE) system, and hippocampal β-adrenergic receptors (β-AR) are critical for memory formation and synaptic plasticity. In this study, we used a pilocarpine (PILO) induced memory impaired rodent model to investigate whether VNS improves memory and hippocampal synaptic plasticity via NE/β-AR signaling. METHODS: Memory impairment was induced in rats using PILO. VNS was administered to PILO-treated rats for 2 weeks via electrodes implanted on the left cervical vagus nerve (parameters: 1 mA, 30 Hz, 250 µs pulse width; 2 h daily). Following VNS treatment, rats underwent contextual fear conditioning (CFC) and long-term potentiation (LTP) testing. Protein expression of NE, β-AR, and downstream signaling molecules (protein kinase A and CaMKII) was quantified. To verify pathway specificity, the β-AR antagonist propranolol (PR) was administered RESULTS: PILO-treated rats exhibited significant memory deficits and impaired LTP compared to controls. VNS treatment markedly improved CFC performance and restored hippocampal LTP in PILO rats. Molecular analysis revealed VNS increased hippocampal NE release and upregulated β-AR and downstream signaling molecules PKA expression. Administration of β-AR antagonist PR prior to VNS abolished these enhancements in memory and synaptic plasticity. CONCLUSION: The enhancement of hippocampal LTP and memory by VNS is associated with the hippocampal NE/β-AR signaling pathway, indicating a potential therapeutic mechanism for VNS in memory related disorders.
A high-performance SSVEP-BCI system based on high-frequency flickers in the peripheral visual field.
Pang Z, Li Z, Zhang R … +4 more , Dong Q, Cheng Z, Cui H, Chen X
Brain Res Bull · 2026 Apr · PMID 41759685 · Publisher ↗
BACKGROUND: The existing steady-state visual evoked potential (SSVEP)-based brain-computer interfaces (BCIs) primarily use central visual field flickers with a stimulus frequency of 8-20 Hz, which is prone to exhibit str...
BACKGROUND: The existing steady-state visual evoked potential (SSVEP)-based brain-computer interfaces (BCIs) primarily use central visual field flickers with a stimulus frequency of 8-20 Hz, which is prone to exhibit strong flicker perception in users. Considering that, this study aims to develop an SSVEP-based BCI system which is both high-performance and low-flicker-perception by employing high-density electrodes and high-frequency flickers in the peripheral visual field. METHODS: A custom-made electroencephalogram (EEG) cap with high-density electrodes was used to acquire more EEG data. To alleviate flicker perception, this study combined high-frequency visual stimulation with peripheral visual field stimulation. The proposed system encoded 40 targets using annuli with an angular range in 2.1°-4.1° and high-frequency flickers in the range of 32.00-36.68 Hz. For signal decoding, the task-discriminant component analysis (TDCA) was first applied to the peripheral visual field SSVEP-based BCI system with weak response. RESULTS: Through online experiments, the feasibility of this system was verified. It achieved an average classification accuracy of 83.22 ± 11.95% and an information transfer rate (ITR) of 178.21 ± 43.84 bits/min. Moreover, the role of high-density electrodes to obtain more useful EEG information and thus improving the classification accuracy has been proved. COMPARISON WITH EXISTING METHODS: The online ITR of this system was the highest for current peripheral visual field SSVEP-based BCIs. CONCLUSION: The proposed system not only provides novel ideas for the design of BCI systems with weak flicker, but also provides reference value for the future application of high-density electrodes in SSVEP-based BCIs.
Predicting long-term prognosis in comatose patients through brain network analysis under name-evoked stimulation.
Ye J, Xu M, Hu J … +6 more , Yu H, Zhang S, Jiang L, Li F, Xu P, Dai A
Brain Res Bull · 2026 Apr · PMID 41759684 · Publisher ↗
Accurate prognosis assessment of comatose patients remains a significant challenge in neurocritical care. Growing evidence indicates that brain connectivity is integral to the maintenance of consciousness and may be link...
Accurate prognosis assessment of comatose patients remains a significant challenge in neurocritical care. Growing evidence indicates that brain connectivity is integral to the maintenance of consciousness and may be linked to its recovery. In this study, we recorded bedside electroencephalography (EEG) from comatose patients during an auditory oddball name-calling task to investigate task-related dynamic causal modeling (DCM) connectivity and to examine whether connectivity strengths correlated with patients' functional recovery. Our findings reveal that a bidirectional model, incorporating reciprocal connectivity among the superior frontal gyri, superior parietal lobules, and primary auditory cortices, was significantly associated with the neural processing of name-calling stimuli in comatose patients. Furthermore, the strength of these DCM connections demonstrated a capacity to predict long-term prognostic outcomes, as evaluated via the Glasgow Outcome Scale-Extended scale. Together, these results provide evidence supporting the potential of DCM-derived biomarkers in evaluating functional prognosis in comatose patients. (ChiCTR2000033586).
The cortical Morphometric Inverse Divergence in major depressive disorder is associated with neurotransmitter and genetic profiles.
Zheng S, Zhan Y, Ren Q … +6 more , Chen Y, Zheng M, Wang T, Li Q, Zu M, Wang A
Brain Res Bull · 2026 Apr · PMID 41759683 · Publisher ↗
BACKGROUND: Major depressive disorder (MDD) is a prevalent psychiatric disorder with significant global impact. Neuroimaging studies have shown cortical thickness and connectivity alterations in MDD, but the underlying m...
BACKGROUND: Major depressive disorder (MDD) is a prevalent psychiatric disorder with significant global impact. Neuroimaging studies have shown cortical thickness and connectivity alterations in MDD, but the underlying mechanisms are still unclear. The Morphometric Inverse Divergence (MIND) network, based on vertex-level morphometric features, offers a new approach to explore cortical morphometric characteristics in MDD. METHODS: Individual MIND networks were constructed from T1-weighted MRI data for 75 MDD patients and 46 healthy controls (HCs). Group comparisons identified regions with significant morphometric changes. Partial least squares (PLS) regression was used to identify MDD-associated genes, which were then analyzed for Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway enrichment analysis and protein-protein interaction (PPI) networks. Spatial correlation analyses were also conducted between MIND and neurotransmitter density maps. RESULTS: MDD patients exhibited decreased MIND in regions related to sensation and cognition, with potential epicenters in the left fusiform, postcentral, lingual, and right occipital gyri. MIND alterations in MDD were spatially correlated with genes involved in glutamatergic synapse, calcium signaling pathway, and neuroactive ligand-receptor interaction, and significantly correlated with 5-HT, glutamate, cannabinoid, and opioid receptor/transporter densities. CONCLUSION: Our study reveals abnormal morphometric similarity patterns in MDD, which are spatially coupled with specific neurotransmitter profiles and associated with a distinct transcriptomic signature.
Dynamics of hidden brain states in post-stroke cognitive impairment: Linking neural activity to neurotransmitter systems and genetic pathways.
Ma C, Wang X, Liu J … +6 more , Li Y, Sun P, Lin L, Cong F, Liu A, Liu J
Brain Res Bull · 2026 Apr · PMID 41747873 · Publisher ↗
BACKGROUND: Post-stroke cognitive impairment (PSCI) is associated with abnormal dynamic functional connectivity, yet the temporal dynamic of brain activity and their underlying molecular mechanisms remain unclear. METHOD...
BACKGROUND: Post-stroke cognitive impairment (PSCI) is associated with abnormal dynamic functional connectivity, yet the temporal dynamic of brain activity and their underlying molecular mechanisms remain unclear. METHODS: Participants were classified into two groups based on neuropsychological assessments: PSCI group (N = 67) and post-stroke with no cognitive impairment (NPSCI) group (N = 65), alongside 47 healthy controls (HCs). Dynamic brain states were analyzed using a Hidden Markov Model (HMM) with the Brainnetome Atlas, yielding metrics like fractional occupancy (FO), mean dwell time (MDT), switching rate (SR) and transition probabilities (TP) based on resting-state functional magnetic resonance imaging (rs-fMRI). Finally, we further assessed the spatial correlations between the mean activation of HMM state and neurotransmitter receptors/transporters distribution, cognitive relative term, and gene expression profiles. RESULTS: Five HMM states were identified. Compared with HCs and NPSCI group, patients with PSCI group exhibited different dynamics, including FO, MDT, SR, and TP. Additionally, we found that the mean activation maps of HMM state were associated with the neurotransmitter receptors/transporters distribution and cognitive relative term. Furthermore, our results demonstrated a spatial correlation between the mean activation maps of state 5 and gene expression patterns. Finally, enrichment analysis indicated that PLS-positive genes were enriched in pathways related to DNA/RNA metabolism, signal transduction and regulation, and immune-disease associations, whereas, PLS-negative genes were mainly enriched in lipid metabolism and insulin response, virus-cytokine interactions, and influenza response pathways. CONCLUSIONS: This study provides new insights into characterizing dynamic neural activity in PSCI. The brain network dynamics defined by HMM analysis may deepen our understanding of the neurobiological underpinnings of PSCI, indicating a linkage between neural configuration and gene expression in PSCI.
A coupling network for brain computing: E-I balanced embedding in dual-attractor dynamics systems.
Yao S, Wang Z, Zhu R … +2 more , Cheng W, Chai Y
Brain Res Bull · 2026 Apr · PMID 41747406 · Publisher ↗
As an important neural network model, the continuous attractor neural network (CANN) demonstrates unique advantages in simulating and explaining the representation and storage mechanisms of continuous variables (such as...
As an important neural network model, the continuous attractor neural network (CANN) demonstrates unique advantages in simulating and explaining the representation and storage mechanisms of continuous variables (such as position, direction, etc.) in the brain. However, in the real brain network, the connections between neurons are not only random or equal, but regulated by various factors. The coding methods and interactions of multiple neuron groups form the collective behavior of the complex brain network. To study the role of complex networks in the brain, this research proposes a selective coupling network model based on CANN, which operates under the dynamic balance between excitatory and inhibitory inputs. In this study, we have investigated the interaction between two classes of CANNs with distinct selective preferences for motion direction recognition under fast excitation and inhibition (E-I) balance. Based on simulation results and theoretical analysis, we found that the fast E-I balance located in the brain can provide indirect linking effects among multiple different networks. The indirect mutual inhibition of the coupled network through E-I balance can promote the accuracy and stability of the network response to a given position. This suggests that a dynamic system of collaborative work activity is possible between different neural networks. We hope that this work could provide insightful references for the development of multi-network coupling in brain-like computing.
Glucose metabolism drives the hierarchical propagation of gray matter atrophy from the orbitofrontal cortex in obesity.
Li W, Miao Z, Ma C … +14 more , Jia Y, Li C, Wang Y, Yu F, Kong D, Zhu W, Yuan X, Wu G, Wang J, Wang Y, Hong Z, Wang Z, Yuan M, Zhang P
Brain Res Bull · 2026 Apr · PMID 41740684 · Publisher ↗
AIMS: To characterize the directional influence among brain regions across a metabolic gradient in obesity, thereby offering insights into the neurobiological pathways linking obesity to Type 2 Diabetes Mellitus (T2DM)....
AIMS: To characterize the directional influence among brain regions across a metabolic gradient in obesity, thereby offering insights into the neurobiological pathways linking obesity to Type 2 Diabetes Mellitus (T2DM). MATERIALS AND METHODS: The study included 85 individuals with obesity and 89 healthy controls (HCs). All participants underwent structural MRI, glycemic status (normoglycemia (NGM), prediabetes, or T2DM) and other metabolic risk factors were assessed. A causal structural covariance network was constructed to investigate the directional relationships of gray matter (GM) alterations in obesity across distinct glucose metabolic states. This was achieved by applying Granger Causality Analysis (GCA) to morphometric T1-weighted MRI data that were ordered across subjects according to glycated hemoglobin (HbA1c) levels. RESULTS: Relative to HCs, the obesity with NGM displayed restricted GM atrophy localized mainly within the orbitofrontal cortex (OFC), whereas those with prediabetes or T2DM exhibited widespread GM volume reductions involving the putamen, insula, thalamus, and multiple parietal and temporal regions, as well as a broader OFC area. The results of CaSCN analysis revealed that the OFC may serve as a core region in which atrophy is anchored, exerting a positive directional influence on the frontal, parietal, temporal, and occipital regions as HbA1c levels increase. CONCLUSIONS: Our findings identify a stepwise pattern of GM atrophy in obesity, characterized by a putative hierarchical organization anchored in the OFC that appears more pronounced with worsening glucose metabolism. These results underscore the OFC as a critical nodal hub that may serve as a potential target for early neuroprotective intervention.
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