Free neuropathology最新文献

{"title":"Evaluating ultrastructural preservation quality in banked brain tissue.","authors":"Macy Garrood, Alicia Keberle, Allison Sowa, William Janssen, Emma L Thorn, Claudia De Sanctis, Kurt Farrell, John F Crary, Andrew T McKenzie","doi":"10.17879/freeneuropathology-2025-6763","DOIUrl":"10.17879/freeneuropathology-2025-6763","url":null,"abstract":"<p><p>The ultrastructural analysis of postmortem brain tissue can provide important insights into cellular architecture and disease-related changes. For example, connectomics studies offer a powerful emerging approach for understanding neural circuit organization. However, electron microscopy (EM) data is difficult to interpret when the preservation quality is imperfect, which is common in brain banking and may render it unsuitable for certain research applications. One common issue is that EM images of postmortem brain tissue can have an expansion of regions that appear to be made up of extracellular space and / or degraded cellular material, which we call ambiguous interstitial zones. In this study, we report a method to assess whether EM images have ambiguous interstitial zone artifacts in a cohort of 10 postmortem brains with samples from each of the cortex and thalamus. Next, in matched samples from the contralateral hemisphere of the same brains, we evaluate the structural preservation quality of light microscopy images, including immunostaining for cytoskeletal proteins. Through this analysis, we show that on light microscopy, cell membrane morphology can be largely maintained, and neurite trajectory visualized over micrometer distances, even in specimens for which there are ambiguous interstitial zone artifacts on EM. Additionally, we demonstrate that synaptic structures can be successfully traced across serial EM sections in some postmortem samples, indicating the potential for connectivity studies in banked human brain tissue when appropriate preservation and visualization protocols are employed. Taken together, our analysis may assist in maximizing the usefulness of donated brain tissue by informing tissue selection and preparation protocols for various research goals.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"6 ","pages":"13"},"PeriodicalIF":0.0,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12189018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144499693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Applying machine learning to assist in the morphometric assessment of brain arteriolosclerosis through automation.","authors":"Jerry J Lou, Peter Chang, Kiana D Nava, Chanon Chantaduly, Hsin-Pei Wang, William H Yong, Viharkumar Patel, Ajinkya J Chaudhari, La Rissa Vasquez, Edwin Monuki, Elizabeth Head, Harry V Vinters, Shino Magaki, Danielle J Harvey, Chen-Nee Chuah, Charles S DeCarli, Christopher K Williams, Michael Keiser, Brittany N Dugger","doi":"10.17879/freeneuropathology-2025-6387","DOIUrl":"10.17879/freeneuropathology-2025-6387","url":null,"abstract":"<p><p>Objective quantification of brain arteriolosclerosis remains an area of ongoing refinement in neuropathology, with current methods primarily utilizing semi-quantitative scales completed through manual histological examination. These approaches offer modest inter-rater reliability and do not provide precise quantitative metrics. To address this gap, we present a prototype end-to-end machine learning (ML)-based algorithm, Arteriolosclerosis Segmentation (ArtSeg), followed by Vascular Morphometry (VasMorph) - to assist persons in the morphometric analysis of arteriolosclerotic vessels on whole slide images (WSIs). We digitized hematoxylin and eosin-stained glass slides (13 participants, total 42 WSIs) of human brain frontal or occipital lobe cortical and/or periventricular white matter collected from three brain banks (University of California, Davis, Irvine, and Los Angeles Alzheimer's Disease Research Centers). ArtSeg comprises three ML models for blood vessel detection, arteriolosclerosis classification, and segmentation of arteriolosclerotic vessel walls and lumens. For blood vessel detection, ArtSeg achieved area under the receiver operating characteristic curve (AUC-ROC) values of 0.79 (internal hold-out testing) and 0.77 (external testing), Dice scores of 0.56 (internal hold-out) and 0.74 (external), and Hausdorff distances of 2.53 (internal hold-out) and 2.15 (external). Arteriolosclerosis classification demonstrated accuracies of 0.94 (mean, 3-fold cross-validation), 0.86 (internal hold-out), and 0.77 (external), alongside AUC-ROC values of 0.69 (mean, 3-fold cross-validation), 0.87 (internal hold-out), and 0.83 (external). For arteriolosclerotic vessel segmentation, ArtSeg yielded Dice scores of 0.68 (mean, 3-fold cross-validation), 0.73 (internal hold-out), and 0.71 (external); Hausdorff distances of 7.63 (mean, 3-fold cross-validation), 6.93 (internal hold-out), and 7.80 (external); and AUC-ROC values of 0.90 (mean, 3-fold cross-validation), 0.92 (internal hold-out), and 0.87 (external). VasMorph successfully derived sclerotic indices, vessel wall thicknesses, and vessel wall to lumen area ratios from ArtSeg-segmented vessels, producing results comparable to expert assessment. This integrated approach shows promise as an assistive tool to enhance current neuropathological evaluation of brain arteriolosclerosis, offering potential for improved inter-rater reliability and quantification.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"6 ","pages":"12"},"PeriodicalIF":0.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12159543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144287431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective cellular and regional vulnerability in frontotemporal lobar degeneration: a scoping review.","authors":"Kashif Ravasia, Veronica Hirsch-Reinshagen","doi":"10.17879/freeneuropathology-2025-5812","DOIUrl":"https://doi.org/10.17879/freeneuropathology-2025-5812","url":null,"abstract":"<p><p>The three main types of frontotemporal lobar degeneration (FTLD) are characterized by the accumulation of abnormal proteins, namely tau, TDP-43 and FUS. The distribution of these proteins within different human brain regions is well known, as is the range of morphological variability of the cellular inclusions they form. Compared to the extensive knowledge that exists about distinct protein aggregates in FTLD, surprisingly little is known about the specific cell (sub)types that these inclusions affect. Even less is known about disease-specific abnormalities other than protein inclusions in affected and unaffected areas. These are non-trivial knowledge gaps. First, knowing which cell subtypes are vulnerable or resilient to the development of pathological protein inclusions is crucial to understand the cellular disease mechanisms. Second, mounting evidence suggests that non-cell autonomous mechanisms may play important roles in neurodegenerative conditions. For example, astrocytic tau pathology is associated with synaptic loss in corticobasal degeneration but not in progressive supranuclear palsy. Furthermore, changes that are more difficult and time-consuming to quantify, for example loss of a specific neuronal subtype that does not develop pathological inclusions, remain virtually unexplored and their relevance for disease progression are unknown. This scoping review is an attempt to collate all histological evidence from human studies that address the question of cell-specific vulnerability in the most common FTLD subtypes. By taking a systematic approach including various brain cell types such as neurons and their subtypes as well as astrocytes, microglia and oligodendrocytes and the entire central nervous system with its affected and unaffected regions, this review summarizes the current status in the field and highlights important knowledge gaps.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"6 ","pages":"11"},"PeriodicalIF":0.0,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11980436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144059740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurooncology: 2025 update.","authors":"Michel Mittelbronn","doi":"10.17879/freeneuropathology-2025-6316","DOIUrl":"10.17879/freeneuropathology-2025-6316","url":null,"abstract":"<p><p>This collection of studies highlights groundbreaking advancements in brain tumor research, particularly primary CNS tumors and brain metastasis. One major focus is the tumor microenvironment, where alterations in cerebral microcirculation and hypoxic-ischemic conditions have been shown to influence metastatic progression. In glioblastoma, recurrent tumors exhibit distinct DNA methylation profiles, and global DNA methylation has emerged as an independent diagnostic marker for IDH-wildtype glioblastoma. A whole-tumor perspective further emphasizes the extensive intratumoral heterogeneity driving glioblastoma evolution. The immune landscape of glioblastoma is another key area of research. Cranioencephalic functional lymphoid units have been implicated in tumor progression, while time-dependent single-cell phenotyping offers novel insights into immune cell dynamics within glioblastoma. Additionally, histone serotonylation has been identified as a critical epigenetic regulator in ependymoma tumorigenesis. Diagnostic and prognostic innovations are paving the way for improved patient care. Histomorphological features provide enhanced prognosis prediction for glioblastoma patients. Confocal laser microscopy enables real-time intraoperative histopathological diagnostics, and sequencing of cerebrospinal fluid-derived cell-free DNA presents a promising non-invasive diagnostic approach. Together, these top studies of 2024 underscore the complexity of brain tumor biology and the integration of epigenetics, immune interactions, and advanced diagnostics into clinical practice. These insights mark significant progress toward personalized treatment strategies and improved outcomes in neurooncology.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"6 ","pages":"10"},"PeriodicalIF":0.0,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11960715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143766058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Morphological substrate of chronic schizophrenia in elderly patients: a clinicopathological study.","authors":"Kurt A Jellinger","doi":"10.17879/freeneuropathology-2025-6135","DOIUrl":"10.17879/freeneuropathology-2025-6135","url":null,"abstract":"<p><p><b>Objective:</b> Patients with schizophrenia are at a higher risk of developing dementia, but the basis of cognitive impairment is a matter of discussion. Conflicting results regarding the association of schizophrenia with Alzheimer disease (AD) may partly be attributable to the inclusion of non-AD lesions, which few clinicopathological studies have considered. Therefore, a re-evaluation of an autopsy cohort of elderly schizophrenics published previously [1] was performed. <b>Material & methods:</b> Among 99 consecutive autopsy cases of patients who met the DSM-5 and ICD.10 criteria for schizophrenia (mean age 69.5 ± 8.25 years), 56 showed moderate to severe dementia. All brains were blindly examined using the current criteria for AD and looking for concomitant lesions. They were compared with the frequency of AD in an autopsy series of 1.750 aged demented individuals <b>Results:</b> Four cases revealed the features of definite AD, five probable AD, and three aged 82-89 years were classified as primary age-related tauopathy (PART). Two cases were a cortical type of dementia with Lewy bodies (DLB), one Lewy body disease of brainstem type; six showed hippocampal sclerosis, 14 argyrophilic grain disease (AGD), and one progressive supranuclear palsy (PSP). Other co-pathologies were frequent lacunes in basal ganglia, moderate cerebral amyloid angiopathy, minor development anomalies in the entorhinal cortex, Fahr's disease, metastatic tumors, and acute or old cerebral infarctions (n = 4 each). Definite AD was seen in 48 % of the age-matched demented control group. <b>Conclusions:</b> In this cohort of elderly schizophrenic patients, only 7.6 % fulfilled the neuropathological criteria of definite or probable AD and 3.6 % of PART compared to 6 % to 13.7 % typical and atypical AD in the literature, whereas a considerable number of cases showed non-AD co-pathologies. This is in line with other studies showing that the frequency of AD in elderly schizophrenics may be equal to or less than in age-matched controls. Further studies are needed to elucidate the mechanisms of cognitive decline in schizophrenia.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"6 ","pages":"9"},"PeriodicalIF":0.0,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11911938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143652471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Depletion of nuclear cytoophidia in Alzheimer's disease.","authors":"Alyona Ivanova, David G Munoz, John Woulfe","doi":"10.17879/freeneuropathology-2025-6282","DOIUrl":"10.17879/freeneuropathology-2025-6282","url":null,"abstract":"<p><p>There is considerable evidence for a role for metabolic dysregulation, including disordered purine nucleotide metabolism, in the pathogenesis of Alzheimer's disease (AD). Purine nucleotide synthesis in the brain is regulated with high fidelity to co-ordinate supply with demand. The assembly of some purine biosynthetic enzymes into linear filamentous aggregates called \"cytoophidia\" (Gk. Cellular \"snakes\") represents one post-translational mechanism to regulate enzyme activity. Cytoophidia comprised of the nucleotide biosynthetic enzymes inosine monophosphate dehydrogenase (IMPDH) and phosphoribosyl pyrophosphate synthetase (PRPS) have been described in neuronal nuclei (nuclear cytoophidia; NCs). In light of the involvement of purine nucleotide dysmetabolism in AD, the rationale for this study was to determine whether there are disease-specific qualitative or quantitative alterations in PRPS cytoophidia in the AD brain. Double fluorescence immunostaining for PRPS and the neuronal marker MAP2 was performed on tissue microarrays of cores of temporal cortex extracted from post-mortem tissue blocks from a large cohort of participants with neuropathologically confirmed AD, Lewy body disease (LBD), progressive supranuclear palsy, and corticobasal degeneration, as well as age-matched cognitively unimpaired control participants. The latter group included individuals with substantial beta-amyloid deposition. NCs were significantly reduced in frequency in AD samples relative to those from controls, including those with a high beta-amyloid load, or participants with LBD or 4 repeat tauopathies. Moreover, double staining for PRPS and hyperphosphorylated tau revealed evidence for an association between NCs and neurofibrillary tangles. The results of this study contribute to our understanding of metabolic contributions to AD pathogenesis and provide a novel avenue for future studies. Moreover, because PRPS filamentation is responsive to a variety of drugs and metabolites, they may have implications for the development of biologically rational therapies.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"6 ","pages":"8"},"PeriodicalIF":0.0,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11894473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143607339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased frontocortical microvascular raspberry density in frontotemporal lobar degeneration compared to Lewy body disease and control cases: a neuropathological study.","authors":"Henric Ek Olofsson, Elisabet Englund","doi":"10.17879/freeneuropathology-2025-6178","DOIUrl":"10.17879/freeneuropathology-2025-6178","url":null,"abstract":"<p><p><b>Background:</b> Brain raspberries are histologically defined microvascular entities that are highly prevalent in the neocortex. Increased cortical raspberry density occurs in vascular dementia, but also with advancing age. Here, we examined the raspberry density in two neurodegenerative diseases, wherein vascular alterations distinct from conventional vascular risk factors have been indicated: frontotemporal lobar degeneration (FTLD) and Lewy body disease (LBD). <b>Methods:</b> This retrospective study included 283 clinically autopsied individuals: 105 control cases without neurodegenerative disease, 98 FTLD cases (mainly FTLD-tau and FTLD-TDP), and 80 LBD cases (mainly neocortical). The raspberry density was quantified on haematoxylin-eosin-stained tissue sections from the frontal cortex, and the frontocortical atrophy was ranked 0-3. <b>Results:</b> There was a higher raspberry density in the FTLD group compared to both other groups (<i>P</i> ≤ 0.001; Games-Howell post hoc test). The difference between the FTLD and LBD groups remained significant in multiple linear regression models that included age, sex, and either brain weight (<i>P</i> = 0.034) or cortical atrophy (<i>P</i> = 0.012). The difference between the FTLD and control groups remained significant when including age, sex, and brain weight in the model (<i>P</i> = 0.004), while a trend towards significance was demonstrated when including age, sex, and cortical atrophy (<i>P</i> = 0.054). Further analyses of the FTLD group revealed a trend towards a positive correlation between raspberry density and cortical atrophy (<i>P</i> = 0.062; Spearman rank correlation). Comparisons of FTLD subgroups were inconclusive. <b>Conclusion:</b> The frontocortical raspberry density is increased in FTLD. An examination of the raspberry density in relation to a quantitative measure of cortical atrophy is motivated to validate the results. Future studies are needed to determine whether increased raspberry density in FTLD could function as a marker for more widespread vascular alterations, and to elucidate the relation between microvascular alterations and neurodegenerative disease.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"6 ","pages":"7"},"PeriodicalIF":0.0,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11884261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Capillary basal lamina in human brain and spinal cord has fibrillar collagen type I and type III: Ignorance may not be bliss.","authors":"Wen-Lang Lin, Dennis W Dickson","doi":"10.17879/freeneuropathology-2025-6159","DOIUrl":"10.17879/freeneuropathology-2025-6159","url":null,"abstract":"<p><p>The capillary basal lamina (BL) located between the endothelial cell, pericyte and perivascular astrocyte plays important roles in normal and diseased central nervous system (CNS). Using immunohistochemistry (IHC), electron microscopy (EM) and post-embedding immunogold EM (IEM), we studied capillary BL in biopsy and autopsy tissues of human CNS from cases with and without significant brain pathology and aged from 4 days to 49 years. In all cases, IHC showed, in the BL of microvessels, immunoreactivity for collagen types I, III, IV, VI and fibronectin. EM revealed fusion of the BL of capillary endothelial cells or pericyte with perivascular astrocyte BL, which was focally split, resulting in expanded spaces bordered by BL and containing striated fibrils. There was no significant thickening of fused or split BL. IEM showed localization of collagen I and III to banded fibrils, and of collagen IV to split and fused BL. These characteristic ultrastructural findings in human capillary BL were not found in normal or transgenic mice. Our observations of fibrillar collagen in young individuals complement previous observations of similar findings in older individuals. This raises the possibility that fibrillar collagen in human vascular BL plays a significant role in CNS capillary physiology and pathophysiology. The species-specific differences in capillary morphology between humans and mice might have relevance to poor correlations between benefits of immunotherapy and drug treatment in mice compared with human.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"6 ","pages":"6"},"PeriodicalIF":0.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11862662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143517622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel KDM2A::YAP1 fusion in a pediatric supratentorial CNS neoplasm resembling a tumor with BCOR internal tandem duplication.","authors":"Arnault Tauziède-Espariat, Alice Métais, Dorian Bochaton, Euphrasie Servant, Guillaume Chotard, Mégane Le Quang, Benjamin Bonhomme, Nathalène Truffaux, Volodia Dangouloff-Ros, Nathalie Boddaert, Lauren Hasty, Edouard Gimbert, Pascale Varlet","doi":"10.17879/freeneuropathology-2025-6152","DOIUrl":"10.17879/freeneuropathology-2025-6152","url":null,"abstract":"","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"6 ","pages":"5"},"PeriodicalIF":0.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11862909/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143517620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preservation of cellular structure via immersion fixation in brain banking.","authors":"Macy Garrood, Emma L Thorn, Adam Goldstein, Allison Sowa, William Janssen, Alyssa Wilson, Claudia S López, Raakhee Shankar, Erin S Stempinski, Kurt Farrell, John F Crary, Andrew T McKenzie","doi":"10.17879/freeneuropathology-2025-6104","DOIUrl":"10.17879/freeneuropathology-2025-6104","url":null,"abstract":"<p><p>Immersing the brain in a solution containing formaldehyde is a commonly used method for preserving the structure of human brain tissue in brain banking. However, there are questions about the quality of preservation using this method, as formaldehyde takes a relatively long period of time to penetrate a large organ such as the human brain. As a result, there is a critical need to determine whether immersion fixation is an adequate initial preservation method. To address this, we present exploratory histologic findings from our brain bank following the immersion fixation of hemi-sectioned brain specimens under refrigeration. Using light microscopy, we found that there was no significant change in the size of pericellular or perivascular rarefaction areas based on the postmortem interval (PMI) or on the progression from the outer (frontal cortex) to the inner (striatum) brain regions. Additionally, we did not identify any significant number of ghost cells - a state of late-stage cellular necrosis - in the light micrographs analyzed. Using transmission electron microscopy of tissue from the frontal cortex, we found that synapses could still be visualized, but there was vacuolization and variable degrees of myelin disbanding identified. Using serial section transmission electron microscopy, we found that identified synapses could be traced from one section to the next. Using serial block face scanning electron microscopy, we also found that myelinated axons on 2D images can be traced with high fidelity from one image to the next, even at PMIs of up to 27 hours. Collectively, our data corroborate previous findings that immersion fixation is effective for prevention of cellular necrosis and for visualizing many ultrastructural features in at least the surface areas of the brain. However, how structural preservation quality should best be assessed in brain banking is an open question that depends on the intended research applications.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"6 ","pages":"4"},"PeriodicalIF":0.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11795511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}