Experimental Neurology最新文献

{"title":"Chronic moderate-intensity noise exposure leads to less severe hearing loss but comparable prolonged cognitive impairment compared with acute high-intensity noise exposure","authors":"Kejun Liu ,&nbsp;Qian Li ,&nbsp;Congli Sun ,&nbsp;Guangliang Cao ,&nbsp;Ziyu Liang ,&nbsp;Huishan Zhu ,&nbsp;Shengqiu Liu ,&nbsp;Lijie Liu","doi":"10.1016/j.expneurol.2025.115428","DOIUrl":"10.1016/j.expneurol.2025.115428","url":null,"abstract":"<div><div>Noise can induce stress responses and even result in noise-induced hearing loss (NIHL), which is a common form of acquired peripheral hearing loss (HL). Acquired peripheral HL in midlife is the most common modifiable risk factor for dementia, and the underlying mechanism of this relationship deserves more attention due to the increasing prevalence of unsafe listening practices among young people. This study aimed to investigate the effects of different noise exposure paradigms on cognition, hippocampal neurogenesis and hippocampal microglial status, and to analyze the potential roles of stress responses and HL in these effects. Adult C57BL/6 J mice were randomly allocated into a control group or one of two noise groups: Na123 (animals underwent a single 2-h session of acute noise exposure at 123 dB SPL) and Nc100 (animals subjected to chronic noise exposure at 100 dB SPL for 4 h/day for a continuous 28 days). The results revealed a short-term transient stress response after noise exposure in both noise groups with early-stage cognitive impairments observed only in Nc100 mice. Although the Nc100 mice developed less severe HL than the Na123 mice, they exhibited comparable cognitive impairment and hippocampal neurogenesis deficiency accompanied by similar microglial morphological disturbance in the late stage after noise exposure. These findings indicate that both the HL and stress response might collectively and synergistically contribute to the cognitive impairment following noise exposure, and this relationship may be mediated by the hippocampal neurogenesis deficiency and microglial morphological disturbance. Furthermore, these results revealed the detrimental and insidious nature of long-term but moderate-intensity noise exposure.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"394 ","pages":"Article 115428"},"PeriodicalIF":4.2,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pain after traumatic brain injury (TBI) fosters hemorrhage at the site of injury","authors":"Paris A. Bean ,&nbsp;Grace A. Giddings ,&nbsp;Megan M. Tarbet ,&nbsp;D. Travis Johnston ,&nbsp;Jacob A. Davis ,&nbsp;Emerson T. Lout ,&nbsp;Melissa K. Henwood ,&nbsp;Hannah L. Borland ,&nbsp;James W. Grau","doi":"10.1016/j.expneurol.2025.115422","DOIUrl":"10.1016/j.expneurol.2025.115422","url":null,"abstract":"<div><div>Traumatic brain injury (TBI) is a major cause of death and disability in the United States. In many cases, TBI is accompanied by additional tissue damage (polytrauma) that will engage pain (nociceptive) sensory fibers. Prior work using an animal model (rats) has shown that nociceptive stimulation after a spinal cord injury (SCI) fosters hemorrhage at the site of injury and amplifies secondary tissue loss. The current study explores whether noxious stimulation fosters hemorrhage after a TBI. Anesthetized rats were given a cortical impact of the frontal region. Nociceptive fibers that express the transient receptor potential vanilloid 1 (TRPV1) receptor were engaged by applying capsaicin to one hind paw a day after injury. Brain tissue was collected three hours later. Capsaicin applied contralateral, but not ipsilateral, to injury increased the area of hemorrhage in both male and female animals. Noxious stimulation fostered capillary fragmentation in the area of injury and increased infiltration of Evan's blue, implying a breakdown of the blood-brain barrier. Inducing a coma-like state with pentobarbital blocked capsaicin-induced hemorrhage after TBI. Systemic morphine also had a protective effect. Engaging pain fibers with electrical stimulation applied to the tail increased the area of hemorrhage and this effect too was blocked by systemic morphine. The results suggest that pain after TBI fosters hemorrhage, which increases the area of secondary tissue loss.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"394 ","pages":"Article 115422"},"PeriodicalIF":4.2,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurodevelopmental abnormalities underlying behavioral deficits in a model of pediatric obstructive sleep apnea","authors":"Arvind Chandrakantan ,&nbsp;Michael R. Williamson ,&nbsp;Vaishnav Krishnan ,&nbsp;Mahyar J. Hedaytpour ,&nbsp;Adam C. Adler ,&nbsp;Nandani Adyapak ,&nbsp;Chris S. Ward ,&nbsp;Russell Ray ,&nbsp;David Durgan ,&nbsp;Farrah Kheradmand ,&nbsp;Benjamin Deneen","doi":"10.1016/j.expneurol.2025.115418","DOIUrl":"10.1016/j.expneurol.2025.115418","url":null,"abstract":"<div><h3>Rationale</h3><div>Pediatric Obstructive Sleep Apnea (POSA) is a relatively common childhood sleep disorder whose neurodevelopmental phenotype includes deficits in learning and memory, olfaction, and fine motor abilities.</div></div><div><h3>Objectives</h3><div>To date, there has not been a validated preclinical model of POSA, hampering efforts in understanding how nocturnal episodes of intermittent hypoxia disrupt neurodevelopmental trajectories. The objective of this study was to create a faithful sculpting of the human condition in a preclinical murine model.</div></div><div><h3>Methods</h3><div>We used clinical data from children with POSA to develop and validate a mouse model of POSA that faithfully recapitulates several behavioral deficits seen in the human condition. We then studied synapses, and cellular constituents of neurogenic niches to interrogate the behavioral deficits.</div></div><div><h3>Measurements and main results</h3><div>POSA mice showed deficits in postnatal neurogenesis in both the subventricular zone and hippocampus. Specifically, we discovered fewer neural stem cells, neuroblasts, and newborn neurons in POSA mice.</div></div><div><h3>Conclusions</h3><div>This reduction in developmental neurogenesis was coupled with impaired functional integration of post exposure born neurons in the hippocampus and olfactory bulb. Taken together, our findings from this preclinical model based on human data indicate that POSA disrupts developmental neurogenesis and neuronal maturation, resulting in deficits in learning, memory, olfactory, and fine motor abilities</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"393 ","pages":"Article 115418"},"PeriodicalIF":4.2,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144840840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective striatal pathological changes in a novel human HTT exon 1 knock-in mouse model of Huntington's disease","authors":"Tengteng Wu ,&nbsp;Yu Zhang ,&nbsp;Yongchao Li ,&nbsp;Lishan Lin ,&nbsp;Jinfeng Gao ,&nbsp;Wenzheng Hu ,&nbsp;Di Hu ,&nbsp;Xiaofeng Yu ,&nbsp;Nicole Déglon ,&nbsp;Jean-Marc Burgunder ,&nbsp;Zhong Pei ,&nbsp;Xinling Yang ,&nbsp;Xiang Chen ,&nbsp;Pingyi Xu","doi":"10.1016/j.expneurol.2025.115423","DOIUrl":"10.1016/j.expneurol.2025.115423","url":null,"abstract":"<div><div>Huntington's disease (HD) is an autosomal-dominant neurodegenerative disorder characterized by progressive motor deficits, cognitive decline, and psychiatric disturbances caused by expanded CAG repeats in the huntingtin gene (<em>HTT</em>). Despite the development of various animal models, achieving a comprehensive model that closely replicates the biological mechanisms in order to test therapeutic modalities remains a challenge. Here, we describe a novel human <em>HTT</em> exon 1 knock-in (HEKI-150Q) mouse model that incorporates a 3.465-kb human <em>HTT</em> sequence with 150 polyglutamine and successfully mimics key aspects of HD. Behavioral analysis revealed motor dysfunction, hyperactivity, and cognitive deficits similar to those observed in a human HD clinical manifestation. HEKI-150Q mice exhibited age-dependent motor impairment progression with significant phenotypic changes observed starting at six months of age. Histopathological analysis demonstrated the accumulation of mutant huntingtin aggregates, selective striatal neuronal dysfunction, and increased gliosis, further confirming the model's validity for HD research. HEKI-150Q mice thus provide a valuable tool for studying the pathogenic mechanisms of HD and testing potential therapeutic strategies, particularly those targeting human <em>HTT</em> exon 1.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"394 ","pages":"Article 115423"},"PeriodicalIF":4.2,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Widespread induction of SINE-RNA expression in the mouse brain following transient focal ischemia","authors":"Sarra Limam ,&nbsp;Ankit Patel ,&nbsp;Dhanashri Satav ,&nbsp;Sandeep Miryala ,&nbsp;Ashutosh Dharap","doi":"10.1016/j.expneurol.2025.115424","DOIUrl":"10.1016/j.expneurol.2025.115424","url":null,"abstract":"<div><div>Ischemic stroke triggers rapid transcriptional changes in the brain, including the induction of noncoding RNAs, which are well-established regulators of post-stroke pathophysiology. Among the numerous classes of noncoding RNAs, short interspersed nuclear element RNAs (SINE-RNAs) are transcribed by Pol III and reported to be upregulated in various paradigms of cellular stress. In the ischemic brain, Pol III-driven gene expression is not well-studied and the expression of SINE-RNAs is virtually unmapped. In the current study, we used a mouse model of transient focal ischemia to evaluate for the first time post-stroke SINE-RNA expression in the cerebral cortex on a genome-wide scale. We observed SINE-RNA induction as early as 0 to 3 h of reperfusion and peak expression at 6 h of reperfusion, with 335 SINE-RNAs induced at this timepoint as compared to sham controls. Many of these transcripts remained induced through later timepoints during the acute phase of reperfusion (24 h). Fluorescence in situ hybridization against the SINE-RNAs, combined with immunohistochemistry for cell-type markers, revealed that these RNAs are localized to the nuclei of post-ischemic neurons and microglia in the ipsilateral cortex and hippocampus in both males and females. Further, we found that SINE-RNA expression was recapitulated in vitro following oxygen-glucose deprivation in HT22 hippocampal neurons, showing that they are reproducibly expressed in neurons in both in vivo and in vitro models of ischemia. Together, this is the first study to map genome-wide SINE-RNA expression in the post-ischemic brain and reveals a new layer of the noncoding transcriptome that may play a role in the post-stroke pathophysiology.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"394 ","pages":"Article 115424"},"PeriodicalIF":4.2,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Experimental analysis of blast shock wave-induced injuries in rats: Neurobehavioral and tissue damage assessments","authors":"Boya Yu,&nbsp;Hong Wang,&nbsp;Xiaolin Fan,&nbsp;Liang Li,&nbsp;Xiao Li,&nbsp;Yuhao Zhang,&nbsp;Jinxuan Ma,&nbsp;Ning Ma,&nbsp;Qi Wang,&nbsp;Qing Lu,&nbsp;Junhong Gao","doi":"10.1016/j.expneurol.2025.115427","DOIUrl":"10.1016/j.expneurol.2025.115427","url":null,"abstract":"<div><div>To investigate the dynamic response characteristics of personnel injuries caused by blast shock waves under actual working conditions, experimental studies on blast-induced injuries in rats, behavioral experiments post-injury, and pathological examinations were conducted, followed by injury assessments. The results showed that all rats died when the peak overpressure was 0.427 MPa. At a peak overpressure of 0.192 MPa, the rats were assessed as moderately injured. Behavioral tests at 7 and 28 days revealed reduced motor ability and decreased autonomous exploration, with statistically significant results (<em>P</em> &lt; 0.05). Pathological examinations indicated gradual recovery of brain and lung tissues, with only minor residual damage by day 28. At a peak overpressure of 0.125 MPa, the rats were classified as mildly injured. Statistically significant behavioral differences were observed only on day 7 (<em>P</em> &lt; 0.05), and pathological results demonstrated complete recovery of brain and lung tissues by day 28. These findings provide valuable references for future personnel injury assessments and engineering applications.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"394 ","pages":"Article 115427"},"PeriodicalIF":4.2,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low-intensity pulsed ultrasound enhances microglial-mediated Aβ clearance and synaptic preservation in an APP transgenic mouse model of Alzheimer's disease","authors":"Wei-Shen Su ,&nbsp;Meng-Ting Wu ,&nbsp;Irene Han-Juo Cheng ,&nbsp;Feng-Yi Yang","doi":"10.1016/j.expneurol.2025.115420","DOIUrl":"10.1016/j.expneurol.2025.115420","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is characterized by amyloid-β (Aβ) plaque accumulation and neurofibrillary tangles, leading to neuroinflammation, synaptic dysfunction, and cognitive decline. Despite extensive research, current therapies for AD show limited efficacy. Low-intensity pulsed ultrasound (LIPUS) has emerged as a promising non-invasive therapeutic approach due to its neuroprotective and immunomodulatory properties. This study investigates the effects of LIPUS on Aβ pathology, neuroinflammation, and cognitive deficits in a transgenic AD mouse model. Twelve-month-old J20 transgenic mice expressing human amyloid precursor protein (APP) were used to model middle-to-late-stage AD. LIPUS was administered for 30 days, targeting the bilateral hippocampus. Spatial memory was assessed via the Morris water maze (MWM). Aβ plaque burden and synaptic integrity were quantified using immunofluorescence and Thioflavin-S staining. Western blot analysis evaluated neurotrophic factors, inflammatory markers, and synaptic proteins (PSD95). LIPUS treatment significantly improved spatial learning and memory deficits in APP transgenic mice, as evidenced by reduced escape latency and increased platform crossings in the MWM test. LIPUS significantly reduced hippocampal amyloid plaque burden and promoted microglial recruitment to Aβ plaques. Importantly, LIPUS downregulated TNF-α expression without affecting IL-6 levels, suggesting enhanced Aβ clearance without inducing neuroinflammation. Furthermore, LIPUS increased synaptophysin expression in the CA3-mossy fiber and dentate gyrus (DG) regions, while PSD95 levels remained unchanged. Our findings demonstrate that LIPUS enhances microglial-mediated Aβ clearance, preserves synaptic integrity, and improves cognitive function in a transgenic AD model. As a non-invasive modality capable of targeting deep brain structures, LIPUS holds promise as a potential therapeutic strategy for AD.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"394 ","pages":"Article 115420"},"PeriodicalIF":4.2,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multifunctional roles of MicroRNAs in regulating cell death during cerebral ischemic injury","authors":"Qiuyue Yang,&nbsp;Hongfa Cheng,&nbsp;Qiuxia Zhang","doi":"10.1016/j.expneurol.2025.115421","DOIUrl":"10.1016/j.expneurol.2025.115421","url":null,"abstract":"<div><div>Ischemic stroke is characterized by cerebral ischemic injury, in which multiple forms of cell death-including apoptosis, pyroptosis, autophagy-dependent cell death, and ferroptosis- contribute significantly to severe pathological outcomes. MicroRNAs (miRNAs), as key post-transcriptional regulators of gene expression, play a pivotal role in modulating cell death mechanisms induced by cerebral ischemic injury. Using ‘cerebral ischemia’ and ‘microRNA’ as keywords, we conducted a literature search on the PubMed database. This review systematically summarizes research from the past five years on the multifunctional roles, clinical significance, and therapeutic applications of miRNAs in cell death associated with cerebral ischemic injury. Moreover, this review briefly discusses alterations in miRNA expression in clinical settings and their implications, as well as summarizes pharmacological interventions that mitigate cerebral ischemic injury through miRNA regulation.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"394 ","pages":"Article 115421"},"PeriodicalIF":4.2,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ketogenic diet and quercetin promote the recovery of motor function in rats with spinal cord injury","authors":"Xuhua Liu ,&nbsp;Xinfang Liu ,&nbsp;Jinbo Lin ,&nbsp;Jinsong Wei ,&nbsp;Kaiting Chen ,&nbsp;Sidong Luo ,&nbsp;Xu Wang ,&nbsp;Kaifan Li ,&nbsp;Pengqing Qiu ,&nbsp;Yongsheng Li ,&nbsp;Sheng Luo ,&nbsp;Yeyang Wang","doi":"10.1016/j.expneurol.2025.115415","DOIUrl":"10.1016/j.expneurol.2025.115415","url":null,"abstract":"<div><div>Spinal cord injury (SCI) is a devastating neurological disorder, and currently, there are no effective therapeutic options to promote the recovery of motor function. Therefore, exploring safe and effective post-SCI repair strategies is crucial. In our study, we investigated the therapeutic effects of ketogenic diet (KD) and quercetin, both separately and in combination, on the recovery of motor and neurological functions in rats with SCI. Female Sprague-Dawley rats were randomly assigned to five groups: (i) sham-operated surgery (sham), (ii) spinal cord injury (injury), (iii) ketogenic diet (KD), (iv) quercetin (Que), and (v) ketogenic diet+quercetin (KD + Que). We used thoracic cord clamp compression to create the SCI model and studied the potential synergistic effects of quercetin and KD on functional restoration. The Basso, Beattie, and Bresnahan (BBB) tests were conducted to assess motor performance, while motor-evoked potentials (MEPs) were used to evaluate neurophysiological function. 4 weeks post-SCI, magnetic resonance imaging (MRI), histological examination, immunofluorescence staining, and western blotting were performed to investigate the mechanisms underlying the synergistic repair effects. Our findings revealed that the combined treatment significantly decreased cavity volume, reduced glial scarring, attenuated local inflammatory infiltration, and enhanced neurite structural preservation and myelin integrity compared to either the KD or quercetin alone. Additionally, the synergistic effect of the KD and quercetin on SCI recovery may be mediated through the NF-κB/NLRP3 pathway. In conclusion, a KD in conjunction with quercetin can facilitate the regaining of motor function following SCI by inhibiting the NF-κB/NLRP3 pathway.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"394 ","pages":"Article 115415"},"PeriodicalIF":4.2,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144811991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating sensitive motor tasks with histopathology detects sex differences in recovery after spinal cord injury","authors":"Emily A. Swarts ,&nbsp;Ashley I. Munro ,&nbsp;Courtney A. Bannerman ,&nbsp;Julie R. Zielonka ,&nbsp;Colleen E. Tordoff ,&nbsp;Nader Ghasemlou ,&nbsp;Faith H. Brennan","doi":"10.1016/j.expneurol.2025.115417","DOIUrl":"10.1016/j.expneurol.2025.115417","url":null,"abstract":"<div><div>Biological sex governs a myriad of molecular, cellular, and physiological features of the intact and injured nervous system. In traumatic spinal cord injury (SCI), biological sex is thought to influence functional recovery and tissue pathology. However, the open-field Basso Mouse Scale (BMS) used to track experimental SCI recovery relies on observer-based non-parametric scoring, which may not be sensitive enough to detect sex differences in motor behavior. Here, we tested whether two additional behavioral tasks – the infrared activity box and advanced dynamic weight bearing (ADWB) – identify any sex differences in motor recovery in male and female mice following a 70 kilodyne contusion SCI or sham (laminectomy) surgery. We then integrated data from these tasks with BMS scores, lesion area, myelin sparing, fibrosis, macrophage presence, and astrogliosis, using principal component analysis (PCA). BMS data were not different between sexes. However, the infrared activity box detected sex differences in both sham and SCI groups, with male mice spending more time making ambulatory bouts, and female mice spending more time performing stereotypic behaviors (e.g., grooming, sniffing). ADWB also detected sex differences in SCI, with male mice placing more weight on their hind end and abdomen, and females placing more weight on their fore paws. Histological analysis showed that male SCI lesions have more myelin loss than female SCI lesions, though several other readouts did not reach statistical significance. However, reducing multivariate behavioral and histopathological data into principal components stratified mice based on their surgical group and sex, with females scoring higher on the PCA-generated “Stereotypy, front paw weight-bearing and tissue preservation” index. Together, these data show that integrating multiple quantitative and observer-independent behavioral tasks with histopathology data increases sensitivity to detect sex differences in SCI.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"394 ","pages":"Article 115417"},"PeriodicalIF":4.2,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144811990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}