In adults with acquired hearing loss, cortical reorganization and cross‐modal plasticity critically influence the timing and outcomes of cochlear implantation. This study examined the effects of 2 weeks of bilateral auditory deprivation—induced by intense broadband noise—on the structure and gene expression in the primary auditory (A1) and visual (V1) cortices of adult rats. The results revealed that the total neuronal counts in both the A1 and V1 remained unchanged compared to controls. Morphological analysis showed no significant change in mature dendritic spine density in either region, but immature spine density was significantly reduced in the V1 cortex. Ultrastructural examination demonstrated notable synaptic alterations in the A1 cortex, including significant reductions in postsynaptic density (PSD) length, thickness, area, and synaptic vesicle number—changes that were not observed in the V1 cortex. Transcriptomic profiling indicated a region‐specific response, with 197 differentially expressed genes (DEGs) in the A1 cortex, compared to a broader alteration of 545 DEGs in the V1 cortex, which were significantly involved in neuronal signaling and synaptic transmission. These findings demonstrate that auditory deprivation induces distinct molecular and synaptic remodeling in the A1 and V1 cortices, identifying neuronal plasticity and synaptic regulation as central mechanisms for cross‐modal reorganization in the adult brain.

BackgroundElectroacupuncture (EA) is widely used for analgesia, but its central mechanisms remain unclear. We investigated whether EA alleviates neuropathic pain by suppressing metabotropic glutamate receptor 5 (mGluR5) signaling in the anterior cingulate cortex (ACC).MethodsIn naïve mice, we manipulated ACC pyramidal neurons using adeno‐associated viral (AAV) vectors encoding calcium/calmodulin‐dependent protein kinase II (CaMKII)‐driven opsins—channelrhodopsin‐2 (ChR2) or halorhodopsin (NpHR3.0)—followed by blue‐ or yellow‐light stimulation to assess behavioral responses. In a chronic constriction injury (CCI) model, mice received EA and were evaluated for mechanical and thermal withdrawal thresholds. Western blotting (WB) and immunofluorescence (IF) quantified ACC mGluR5 expression. Then CaMKII‐targeted adeno‐associated viruses expressing chemogenetic receptors, such as hM3Dq or hM4Di, were injected into the ACC. Two weeks later, CCI was induced, and mice received either EA or intraperitoneal clozapine‐N‐oxide (CNO) while pain behaviors were monitored. Finally, proteomic profiling of ACC tissue compared CCI and EA groups.ResultsOptogenetic activation of ACC pyramidal neurons in naïve mice reduced both mechanical and thermal withdrawal thresholds, indicating a pronociceptive effect, whereas optogenetic inhibition increased thresholds. In CCI mice, EA significantly attenuated hypersensitivity and downregulated ACC mGluR5 protein levels by WB and IF. Chemogenetic inhibition of ACC pyramidal neurons similarly elevated thresholds in CCI mice, imitating EA. Notably, combining chemogenetic inhibition with EA produced no additional improvement, suggesting convergence on a common ACC mGluR5‐dependent pathway.ConclusionsEA relieves neuropathic pain in mice, at least in part, by suppressing ACC pyramidal neuron activity via inhibition of mGluR5 signaling.

Functional neuroimaging of the encephalon of humans with chronic musculoskeletal pain (CMP) has consistently demonstrated functional alterations in the neurophysiological properties of cortical and subcortical circuits. Nevertheless, the current knowledge on specific neural circuitries that may occur in different CMP subgroups is limited, which in turn limits the understanding of the encephalon mechanisms associated with persistent pain and clinical heterogeneity. This systematic review (CRD42022382309) and activation likelihood estimation (ALE) meta-analysis of observational functional magnetic resonance imaging (fMRI) studies on human encephalon aimed to characterize specific patterns of connectomic reorganization in different CMP subgroups. PubMed, Web of Science, and Scopus databases were searched. Two independent reviewers read titles and abstracts, full texts, assessed methodological quality using the Newcastle-Ottawa scale, and extracted X, Y, and Z coordinates. The data analyses were conducted using the GingerALE 3.0.2 software and complemented by frequency analyses. All neuroanatomical coordinates used in the ALE meta-analyses were standardized to the Montreal Neurological Institute 152 space. A 95% confidence interval (CI) for the family-wise error (FWE) rate was applied using an initial uncorrected voxel-level threshold of p < 0.001, together with 1000 permutation tests and a minimum cluster volume of ≥200 mm3. In total, 43 studies out of 5543 records met the inclusion criteria and none presented a very high risk of bias. The seven encephalon regions comprising the basic neural circuitry of CMP (somatosensory cortex, motor cortex, anterior cingulate cortex, insula, prefrontal cortex, thalamus, and cerebellum) correspond to an integrated connectomic hub that coordinates sensory-motor discriminative, affective-emotional, and cognitive-motivational processing. Additionally, 13 other regions are specifically recruited in distinct conditions of CMP. These parallel connections expand the processing network and add dimensions related to reward, memory, descending pain modulation, and attention. This dynamic reorganization reflects a pattern of cross-modal plasticity with maladaptive mechanisms.

Alzheimer's disease (AD) is a progressive and debilitating neurodegenerative disorder for which existing pharmacotherapies are inadequate to arrest pathological progression, highlighting the imperative to identify safe and effective nonpharmacological interventions. Exercise, as a multi-target therapeutic modality, has been shown to reverse multiple facets of AD-related neuropathology through diverse mechanisms. In this systematic review, we synthesize evidence on the effects of voluntary running, structured swimming, and modulation of the gut microbiota in transgenic murine models of AD. Exercise was found to ameliorate AD pathology by modulating amyloid precursor protein (APP) processing and β-amyloid (Aβ) production/clearance, restoring mitochondrial integrity and function, attenuating neuroinflammatory responses, enhancing synaptic plasticity, and upregulating neurotrophic factors. Moreover, exercise reshapes the intestinal microbiome and thereby modulates the gut-brain axis, further promoting neuroimmune homeostasis and cognitive resilience. Through RNA sequencing data analysis, key genes such as Tlr4, Cdc42, and F13a1 were identified, which may play significant roles in neuroimmune regulation and cognitive protection. By integrating multi-omics evidence, we propose a coordinated "exercise-microbiota-brain" mechanistic framework that offers theoretical support for personalized, exercise-based therapeutic strategies and translational applications in AD. We also emphasize the necessity of future studies combining exercise with complementary interventions to accelerate the clinical translation of multimodal therapeutic approaches.

Neuroinflammation‐induced cognitive impairment is characterized by a continued decline in memory, executive functioning, and information‐processing abilities. Although berberine (BBR) exhibits anti‐inflammatory and neuroprotective properties, its ability to mitigate cognitive deficits by regulating microglial‐mediated neuroinflammation remains incompletely understood. To investigate the potential of BBR in mitigating microglial‐mediated neuroinflammation and its detrimental effects on neuroplasticity and spatial memory, a mouse model was established through intrahippocampal microinjection of lipopolysaccharide (LPS). The results showed that BBR pretreatment significantly improved cognitive performance, suppressed microglial activation, reduced hippocampal neuronal damage, and increased the density of functional dendritic spines. Mechanistic analysis revealed that BBR treatment inhibited the phosphorylation of key proteins in the MAPK signaling pathway within microglia. These findings suggest that BBR is a promising therapeutic agent for mitigating neuroinflammation‐induced cognitive impairment and provide significant evidence for its potential application in treating inflammation‐related cognitive deficits.

Cardiac arrest (CA)-induced global cerebral ischemia (GCI) in childhood often results in learning and memory deficits. We previously demonstrated in a murine CA and cardiopulmonary resuscitation (CA/CPR) mouse model that a cellular mechanism of learning and memory, long-term potentiation (LTP), is acutely impaired in the hippocampus of juvenile males, correlating with deficits in memory tasks. However, little is known regarding plasticity impairments in juvenile females. We performed CA/CPR in juvenile (P21-25) female mice and used slice electrophysiology and hippocampal-dependent behavior to assess hippocampal function. LTP and contextual fear were impaired 7 days after GCI and endogenously recovered by 30 days. LTP remained impaired at 30 days in ovariectomized females, suggesting the surge in gonadal sex hormones during puberty mediates endogenous recovery. Unlike juvenile males, recovery of LTP in juvenile females was not associated with BDNF expression. NanoString transcriptional analysis revealed a potential role of neuroinflammatory processes, and specifically Cd68 pathways, in LTP impairment and hormone-dependent recovery. This was confirmed with staining that revealed increased Cd68 expression in microglia within the hippocampus. We were able to restore LTP in ovariectomized females with chronic and acute PPT administration, implicating estrogen receptor alpha in recovery mechanisms. This study supports a mechanism of endogenous LTP recovery after GCI in juvenile female mice, which differs mechanistically from juvenile males and does not occur in adults of either sex.

PurposeTo evaluate the efficacy and safety of platelet-rich plasma (PRP) in treating sciatic nerve injury (SNI).MethodsA prospective, randomized, single-blind, comparative trial was conducted. Thirty patients with SNI were randomized into two groups of 15, namely, the PRP and control groups. In the PRP group, patients were injected with 5 doses of 3 mL PRP combined with 12 weeks of rehabilitation training using ultrasound guidance, while the control group received 12 weeks of rehabilitation training. Motor function recovery rating table (MFRRT) and sensory function recovery rating table (SFRRT) were used as primary outcomes. The secondary outcomes included the cross-sectional area (CSA) of the sciatic nerve under ultrasound guidance and electrophysiological assessment. Evaluations were performed at baseline and 1–, 3-, and 6-month postinjection.ResultsAfter treatment, there were significant differences in the motor function recovery rating, motor conduction velocity, sensory conduction velocity, and CSA of the sciatic nerve at 1, 3, and 6 months in the PRP group (p < 0.05). There were significant differences in the motor conduction velocity of the sciatic nerve at 6 months in the control group (p < 0.05).ConclusionsPRP may be partially effective in the early repair of incomplete sciatic nerve injuries, and its efficacy could be maintained.

Objective. Electroacupuncture (Ea) is a useful complementary and alternative therapy for intracerebral hemorrhage (ICH). However, the neurobiological basis for the Ea treatment of ICH is still unclear. The primary aim of the present study was to explore whether Ea prevents brain edema, apoptosis, excitotoxicity, and neuroinflammation in rats after hemorrhagic stroke. Methods. Rats were randomly divided into Sham, Control, and Ea groups. We used modified neurological severity score (mNSS) and gait analysis to estimate neurological function in rats, and PET/CT to assess glucose uptake and the hemorrhagic focus volume. Measurement of the brain water content and TUNEL staining were used to evaluate brain edema and cell apoptosis, respectively. The serum myelin basic protein (MBP), neuron-specific enolase (NSE), calcium-binding protein B (S100B), and tumor necrosis factor-α (TNF-α) concentrations were examined with ELISA. The expression levels of the CD68, GALC, Arg-1, iNOS, NR2A, Glu2R, AQP4, MAP2, GFAP, AQP9, Bcl-2, Bax, and Glu proteins around the hematoma were detected via immunohistochemistry staining. Western blot was used to analyze the levels of the AQP4, AQP9, Bax, Bcl-2, iNOS, and Arg-1 proteins. Results. Ea treatment improved neurological function and reduced the hemorrhagic area and brain water content in rats after ICH. The serum concentrations of MBP, NSE, S100B, and TNF-α all decreased significantly in the Ea group compared with the Control group. Expression levels of the Glu, NR2A, AQP4, AQP9, Bax, GFAP, iNOS, and CD68 proteins in brain tissue surrounding the hematoma were obviously suppressed in ICH rats following Ea treatment. Moreover, Ea stimulation increased the levels of the MAP2, GALC, Glu2R, Arg-1, and Bcl-2 proteins, but reduced the number of TUNEL-positive cells in rats after ICH. Conclusion. The results of this study suggest that Ea may exert neuroprotective effects by suppressing brain edema, apoptosis, excitotoxicity, and neuroinflammation.