Brain Pathology最新文献

{"title":"Clinico-sero-pathological characteristics of anti-Ha antisynthetase syndrome.","authors":"Bing Zhao, Ying Hou, Kai Shao, XiaoTian Ma, YaPing Yan, Jian-Qiang Lu, Wei Li, ChuanZhu Yan, LiNing Zhang, TingJun Dai","doi":"10.1111/bpa.13319","DOIUrl":"10.1111/bpa.13319","url":null,"abstract":"<p><p>To define the clinical, serological, and muscle histopathological characteristics, as well as treatment outcomes, of patients with anti-Ha antibody. We performed a retrospective analysis of clinical, serological, and pathological data and long-term treatment outcomes of anti-Ha patients between January 2005 and July 2023 at our center. Anti-Ha antibody was identified by immunoblot and reconfirmed by immunoprecipitation. Of the 570 patients with idiopathic inflammatory myopathies, 17 (3.0%) were found to be anti-Ha positive, of whom 5 (29.4%) were also positive for another myositis-specific antibody (MSA). All patients with anti-Ha antibody as the single MSA (12/17, 70.6%) had clinical and histopathological evidence of muscle damage. Skin lesions were identified in nine of them (75%), while both interstitial lung disease and Raynaud's phenomenon were only seen in four patients. A necrotizing myopathy without a perifascicular pattern was the most common pathological manifestation (50%). Perifascicular necrosis (PFN) and myofiber major histocompatibility complex class-II expression were observed only in one and four patients, respectively. Muscle weakness relapse was reported in five patients, and skin rashes worsening were observed in one patient. Most of the anti-Ha patients (66.7%) finally achieved a favorable outcome at last follow-up. Anti-Ha antibody might not be as rare as previously thought and may coexist with other MSAs. Muscle damage is the most common manifestation in anti-Ha patients, while extra-muscular symptoms except for the cutaneous manifestations are unusual. The histopathological features varied with a predominance of necrotizing myopathy without PFN. These patients often finally had favorable outcomes, although relapses often occur.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e13319"},"PeriodicalIF":5.8,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667324","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":"The prevalence of chronic traumatic encephalopathy in a historical epilepsy post-mortem collection.","authors":"Maritchka Ryniejska, Hanaa El-Hachami, Alicja Mrzyglod, Joan Liu, Maria Thom","doi":"10.1111/bpa.13317","DOIUrl":"https://doi.org/10.1111/bpa.13317","url":null,"abstract":"<p><p>Previous post-mortem epilepsy series showed phosphorylated tau (pTau) accumulation in relation to traumatic brain injury (TBI) rather than driven by seizure frequency. The Corsellis Epilepsy Collection, established in the mid-20th century, represents brain samples collected from patients living with a range of epilepsies from the 1880s to 1990s. Our aim was to interrogate this historical archive to explore relationships between epilepsy, trauma and tau pathology. AT8 immunohistochemistry for pTau was carried out in 102 cases (55% male, with mean age at death of 62 years) on frontal, temporal, amygdala, hippocampal and lesional cortical regions and evaluated using current NINDS criteria for chronic traumatic encephalopathy (CTE) and Braak staging with beta-amyloid, AT8-GFAP and other pTau markers (CP13, PHF1, AT100, AT180) in selected cases. CTE-neuropathologic change (CTE-NC) was identified in 15.7% and was associated with the presence of astroglial tau, a younger age of onset of epilepsy, evidence of TBI and institutionalisation for epilepsy compared to cases without CTE-NC, but not for seizure type or frequency. Memory impairment was noted in 43% of cases with CTE-NC, and a significantly younger age of death; more frequent reports of sudden and unexpected death (p <0.05-0.001) were noted in cases with CTE-NC. In contrast, a higher Braak stage was associated with late-onset epilepsy and cognitive decline. Of note, 9% of cases showed no pTau, including cases with long epilepsy duration, poor seizure control and a history of prior TBI. In summary, this cohort includes patients with more severe and diverse forms of epilepsy, with CTE-NC observed more frequently than reported in non-epilepsy community-based studies (0%-8%) but lower than published series from contact sports participants (32%-87%). Although the literature does not report increased epilepsy occurring in CTE syndrome, our findings support an increased risk of CTE in epilepsy syndromes, likely primarily related to increased TBI.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e13317"},"PeriodicalIF":5.8,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615258","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":"Altered immune response is associated with sex difference in vulnerability to Alzheimer's disease in human prefrontal cortex.","authors":"Huiying Wen, Youzhe He, Yuanchun Tang, Langjian Zhu, Quyuan Tao, Bufan Jin, Ting Luo, Yujie Peng, Yanrong Wei, Junjie Lei, Lifang Wang, Fan Wang, Fei Ling, Yue Gao, Lei Han","doi":"10.1111/bpa.13318","DOIUrl":"https://doi.org/10.1111/bpa.13318","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a neurodegenerative disorder with a higher risk incidence in females than in males, and there are also differences in AD pathophysiology between sexes. The role of sex in the pathogenesis of AD may be crucial, yet the cellular and molecular basis remains unclear. Here, we performed a comprehensive analysis using four public transcriptome datasets of AD patients and age-matched control individuals in prefrontal cortex, including bulk transcriptome (295 females and 402 males) and single-nucleus RNA sequencing (snRNA-seq) data (224 females and 219 males). We found that the transcriptomic profile in female control was similar to those in AD. To characterize the key features associated with both the pathogenesis of AD and sex difference, we identified a co-expressed gene module that positively correlated with AD, sex, and aging, and was also enriched with immune-associated pathways. Using snRNA-seq datasets, we found that microglia (MG), a resident immune cell in the brain, demonstrated substantial differences in several aspects between sexes, such as an elevated proportion of activated MG, altered transcriptomic profile and cell-cell interaction between MG and other brain cell types in female control. Additionally, genes upregulated in female MG, such as TLR2, MERTK, SPP1, SLA, ACSL1, and FKBP5, had high confidence to be identified as biomarkers to distinguish AD status, and these genes also interacted with some approved drugs for treatment of AD. These findings underscore the altered immune response in female is associated with sex difference in susceptibility to AD, and the necessity of considering sex factors when developing AD biomarkers and therapeutic strategies, providing a scientific basis for further in-depth studies on sex differences in AD.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e13318"},"PeriodicalIF":5.8,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574909","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":"A pineal region mass in a 55-year-old female.","authors":"Aaron McConeghey, Zied Abdullaev, Kenneth Aldape, Steven A Moore, Osorio Lopes Abath Neto","doi":"10.1111/bpa.13315","DOIUrl":"https://doi.org/10.1111/bpa.13315","url":null,"abstract":"","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e13315"},"PeriodicalIF":5.8,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567582","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":"Somatostatin receptors in pituitary somatotroph adenomas as predictors of response to somatostatin receptor ligands: A pathologist's perspective.","authors":"Laura Botelho, Rômulo Sperduto Dezonne, Luiz Eduardo Wildemberg, Renan Lyra Miranda, Mônica R Gadelha, Felipe Andreiuolo","doi":"10.1111/bpa.13313","DOIUrl":"https://doi.org/10.1111/bpa.13313","url":null,"abstract":"<p><p>There are five subtypes of somatostatin receptors (SST1-5), which are expressed in several types of solid neoplasms, neuroendocrine tumors, and pituitary adenomas. Most commonly, SST2 and SST5, are of interest regarding diagnostic, treatment, and prognostic purposes. In this article the basic biological characteristics of SST are briefly reviewed, and focus given to the immunohistochemical evaluation of SST2 and SST5 in growth hormone (GH)-secreting pituitary tumors, and their quantification as predictors of response to treatment with somatostatin receptor ligands (SRL), the mainstay of the pharmacological therapy available for these tumors. Although many different scoring systems for SST2 immunohistochemistry showing correlation with SRL response have been reported, among which the immunoreactivity score (IRS) has been the most consistently used, a universally validated immunohistochemical technique and scoring scheme is lacking. Efforts should be made on collaborative multicenter studies aiming at validating homogeneous immunostaining protocols and a scoring system for SST2 and SST5 expression, to help clinicians to define the optimal therapeutic strategy for the patients with somatotroph tumors.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e13313"},"PeriodicalIF":5.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543849","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":"The molecular history of IDH-mutant astrocytomas without adjuvant treatment.","authors":"Zhi-Feng Shi, Kay Ka-Wai Li, Johnny Sheung-Him Kwan, Nellie Yuk-Fei Chung, Sze-Ching Wong, Abby Wai-Yan Chu, Hong Chen, Danny Tat-Ming Chan, Ying Mao, Ho-Keung Ng","doi":"10.1111/bpa.13300","DOIUrl":"https://doi.org/10.1111/bpa.13300","url":null,"abstract":"<p><p>Hypermutation and malignant transformation are potential complications arising from temozolomide treatment of IDH-mutant gliomas. However, the natural history of IDH-mutant low-grade gliomas without temozolomide treatment is actually under-studied. We retrieved retrospectively from our hospitals paired tumors from 19 patients with IDH-mutant, 1p19q non-codeleted Grade 2 astrocytomas where no interim adjuvant treatment with either temozolomide or radiotherapy was given between primary resections and first recurrences. Tissues from multiple recurrences were available from two patients and radiotherapy but not temozolomide was given before the last specimens were resected. We studied the natural molecular history of these low-grade IDH-mutant astrocytomas without pressure of temozolomide with DNA methylation profiling and copy number variation (CNV) analyses, targeted DNA sequencing, TERTp sequencing, FISH for ALT and selected biomarkers. Recurrences were mostly higher grades (15/19 patients) and characterized by new CNVs not present in the primary tumors (17/19 cases). Few novel mutations were identified in recurrences. Tumors from 17/19 (89.5%) patients showed either CDKN2A homozygous deletion, MYC or PDGFRA focal and non-focal gains at recurrences. There was no case of hypermutation. Phylogenetic trees constructed for tumors for the two patients with multiple recurrences suggested a lack of subclone development in their evolution when under no pressure from temozolomide. In summary, our studies demonstrated, in contrast to the phenomenon of temozolomide-induced hypermutation, IDH-mutant, 1p19q non-codeleted Grade 2 astrocytomas which had not been treated by temozolomide, acquired new CNVs at tumor recurrences. These findings improve our understanding of the molecular life history of IDH-mutant astrocytomas.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e13300"},"PeriodicalIF":5.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543850","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":"Subcortical plaques and inflammation reflect cortical and meningeal pathologies in progressive multiple sclerosis.","authors":"Betül Okutan, Jette L Frederiksen, Gunnar Houen, Finn Sellebjerg, Cecilie Kyllesbech, Melinda Magyari, Manuela Paunovic, Per S Sørensen, Christina Jacobsen, Hans Lassmann, Stephan Bramow","doi":"10.1111/bpa.13314","DOIUrl":"https://doi.org/10.1111/bpa.13314","url":null,"abstract":"<p><p>It remains elusive whether lesions and inflammation in the sub/juxtacortical white matter reflect cortical and/or meningeal pathologies. Elucidating this could have implications for MRI monitoring as sub/juxtacortical lesions are detectable by routine MRI, while cortical lesions and meningeal inflammation are not. By large-area microscopy, we quantified total and mixed active plaque loads along with densities and sizes of perivascular mononuclear infiltrates (infiltrates) in the sub/juxtacortical white matter ≤2 mm from the cortex, intra-cortically and in the meninges. Data were related to ante-mortem clinical parameters in a false discovery rate-corrected analysis. We compared 12 patients with primary progressive multiple sclerosis (PPMS) and 15 with secondary progressive MS to 22 controls. Fifteen patients and 11 controls contributed with hemispheric sections. Sections were stained with haematoxylin-eosin, for myelin and for microglia/macrophages. B cells and T cells were confirmed in a subset. Immunoglobulin G depositions in selected cortical plaques resembled depositions described before in \"slowly expanding\" plaques in the white matter. We quantified plaque activity by measuring microglia-dominated and macrophage-dominated areas. Sub/juxtacortical plaques (load and activity) reflected plaque activity in the cerebral cortex. Plaque activity and infiltrates were more pronounced in the sub/juxtacortical white matter than in the cerebral cortex while conversely, the total plaque load was highest in the cortex. Infiltrates correlated trans-cortically and sub/juxtacortical plaque activity reflected cortical and meningeal infiltrates. Sub/juxtacortical infiltrate sizes correlated with shorter survival after progression onset. Two patients with PPMS and putatively fatal brain stem lesions argue against incidental findings. Trans-cortical inflammatory flares and plaque activity may be pathogenic in progressive MS. We suggest emphasis on sub/juxtacortical MRI lesions as plausible surrogates for cortical and meningeal pathologies and, when present, as indicators for cognitive testing.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e13314"},"PeriodicalIF":5.8,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495536","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":"Aerobic exercise improves astrocyte mitochondrial quality and transfer to neurons in a mouse model of Alzheimer's disease.","authors":"Jiachen Cai, Yan Chen, Yuzhu She, Xiaoxin He, Hu Feng, Huaiqing Sun, Mengmei Yin, Junying Gao, Chengyu Sheng, Qian Li, Ming Xiao","doi":"10.1111/bpa.13316","DOIUrl":"https://doi.org/10.1111/bpa.13316","url":null,"abstract":"<p><p>Mitochondrial dysfunction is a well-established hallmark of Alzheimer's disease (AD). Despite recent documentation of transcellular mitochondrial transfer, its role in the pathogenesis of AD remains unclear. In this study, we report an impairment of mitochondrial quality within the astrocytes and neurons of adult 5 × FAD mice. Following treatment with mitochondria isolated from aged astrocytes induced by exposure to amyloid protein or extended cultivation, cultured neurons exhibited an excessive generation of reactive oxygen species and underwent neurite atrophy. Notably, aerobic exercise enhanced mitochondrial quality by upregulating CD38 within hippocampal astrocytes of 5 × FAD mice. Conversely, the knockdown of CD38 diminished astrocytic-neuronal mitochondrial transfer, thereby abolishing the ameliorative effects of aerobic exercise on neuronal oxidative stress, β-amyloid plaque deposition, and cognitive dysfunction in 5 × FAD mice. These findings unveil an unexpected mechanism through which aerobic exercise facilitates the transference of healthy mitochondria from astrocytes to neurons, thus countering the AD-like progression.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e13316"},"PeriodicalIF":5.8,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495533","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":"CIC/ATXN1-rearranged tumors in the central nervous system are mainly represented by sarcomas: A comprehensive clinicopathological and epigenetic series.","authors":"Arnault Tauziède-Espariat, Azadeh Ebrahimi, Nathalie Boddaert, Torsten Pietsch, Wieslawa Grajkowska, Tobias Blau, Arend Koch, Philipp Sievers, Delphine Guillemot, Gaëlle Pierron, Emmanuelle Uro-Coste, Yvan Nicaise, Aurore Siegfried, Adam Gilles, Franck Bielle, Karima Mokhtari, Dominique Cazals-Hatem, Gueorgui Iakovlev, Benoît Lhermitte, Natacha Entz-Werle, Marie Csanyi, Claude-Alain Maurage, Victor Legrand, Jean Boutonnat, Catherine Godfraind, Anne McLeer, Lauren Hasty, Alice Métais, Oumaima Aboubakr, Thomas Blauwblomme, Kévin Beccaria, Volodia Dangouloff-Ros, Pascale Varlet","doi":"10.1111/bpa.13303","DOIUrl":"https://doi.org/10.1111/bpa.13303","url":null,"abstract":"<p><p>CIC fusions have been described in two different central nervous system (CNS) tumor entities. On one hand, fusions of CIC or ATXN1 genes belonging to the same complex of transcriptional repressors, were reported in the CIC-rearranged, sarcoma (SARC-CIC). The diagnosis of this tumor type, which was recently added to the World Health Organization (WHO) Classification of CNS tumors, is difficult mainly because the data concerning its histopathology (as compared to its soft tissue counterpart), immunoprofile, and clinical as well as radiological characteristics are scarce in the literature. On the other hand, a recent study, based on DNA-methylation profiling, has identified a novel high-grade neuroepithelial tumor characterized by recurrent CIC fusions (HGNET-CIC). The aim of this multicentric study was to characterize a cohort of 15 primary CNS tumors harboring a CIC or ATXN1 fusion in terms of clinical, radiological, histopathological, immunophenotypical, and epigenetic characteristics. According to the integrated diagnoses, 14/15 tumors corresponded to SARC-CIC, and only one to HGNET-CIC. The tumors showed similar clinical (mainly pediatric), radiological (mostly supratentorial, cystic, and contrast enhancing), immunophenotypical (common expression of glioneuronal markers), and genetic (similar spectrum of fusions) profiles but their histopathological appearance was clearly distinct. Moreover, we found a novel fusion transcript (CIC::EWSR1) in a SARC-CIC. Most DNA methylation profiles using the Heidelberg Brain Tumor Classifier (v12.8) annotated the samples to the methylation class \"SARC-CIC\" (9/14 tumors with available data). By using uniform manifold approximation and projection analysis, four other samples were classified as SARC-CIC and another clustered within the methylation class of HGNET-CIC. Our findings confirm that CNS CIC-fused tumors do not represent a single molecular tumor entity. Further analyses are needed to characterize HGNET-CIC in more detail. These results may help to refine the essential diagnostic criteria for SARC-CIC and their terminology (with a suggested consensual name of sarcoma, CIC/ATXN1-complex rearranged).</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e13303"},"PeriodicalIF":5.8,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495534","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":"Nicorandil treatment improves survival and spatial learning in aged granulin knockout mice.","authors":"Dana M Niedowicz, Wang-Xia Wang, Paresh Prajapati, Yu Zhong, Shuling Fister, Colin B Rogers, Pradoldej Sompol, David K Powell, Indumati Patel, Christopher M Norris, Kathryn E Saatman, Peter T Nelson","doi":"10.1111/bpa.13312","DOIUrl":"https://doi.org/10.1111/bpa.13312","url":null,"abstract":"<p><p>Mutations in the human granulin (GRN) gene are associated with multiple diseases, including dementia disorders such as frontotemporal dementia (FTD) and limbic-predominant age-related TDP-43 encephalopathy (LATE). We studied a Grn knockout (Grn-KO) mouse model in order to evaluate a potential therapeutic strategy for these diseases using nicorandil, a commercially available agonist for the ABCC9/Abcc9-encoded regulatory subunit of the \"K⁺ATP\" channel that is well-tolerated in humans. Aged (13 months) Grn-KO and wild-type (WT) mice were treated as controls or with nicorandil (15 mg/kg/day) in drinking water for 7 months, then tested for neurobehavioral performance, neuropathology, and gene expression. Mortality was significantly higher for aged Grn-KO mice (particularly females), but there was a conspicuous improvement in survival for both sexes treated with nicorandil. Grn-KO mice performed worse on some cognitive tests than WT mice, but Morris Water Maze performance was improved with nicorandil treatment. Neuropathologically, Grn-KO mice had significantly increased levels of glial fibrillary acidic protein (GFAP)-immunoreactive astrocytosis but not ionized calcium binding adaptor molecule 1 (IBA-1)-immunoreactive microgliosis, indicating cell-specific inflammation in the brain. Expression of several astrocyte-enriched genes, including Gfap, were also elevated in the Grn-KO brain. Nicorandil treatment was associated with a subtle shift in a subset of detected brain transcript levels, mostly related to attenuated inflammatory markers. Nicorandil treatment improved survival outcomes, cognition, and inflammation in aged Grn-KO mice.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e13312"},"PeriodicalIF":5.8,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495535","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}