Meningioma, a tumor arising from the meninges—the protective membranes enveloping the brain and spinal cord—is the most frequently diagnosed intracranial neoplasm in dogs, accounting for roughly half of all canine primary brain tumors. In humans, meningiomas represent approximately 40 percent of primary brain tumors. Despite this shared prominence, diagnostic criteria for canine meningioma have remained poorly codified, and until now no study had subjected a large cohort of canine cases to standardized review by a panel of multiple pathologists working alongside physician neuropathologists.

The CBTC board, which brought together veterinary pathologists and human neuropathologists from institutions across the United States and Europe, undertook a comprehensive evaluation of 190 cases of canine meningioma. Tumors were collected from the diagnostic archives of ten veterinary schools, including Auburn, Colorado State, Cornell, Mississippi State, Ohio State, Texas A&M, UC Davis, Illinois, Penn, and Virginia Tech. Samples came exclusively from treatment-naïve patients, prioritized when collected within the previous five years and accompanied by clinical follow-up data such as tumor location, therapy, progression, and cause of death. Histology slides were cut at four micrometers, stained with hematoxylin and eosin, and digitally scanned at 40X resolution, allowing every reviewer to examine identical digital images.

To enable direct comparison with human medicine, the board applied the 2016 World Health Organization classification and grading guidelines for human meningioma to each canine tumor. Reviewers assessed histologic subtype, mitotic count within a fixed region of 2.37 square millimeters, invasion into surrounding nervous tissue, geographic coagulative necrosis, and the atypical features used in human grading: sheeting architecture, small-cell formation, hypercellularity, and macronucleoli. The process began with a virtual meeting in October 2020 to familiarize the physician neuropathologists with canine histology, followed by additional consensus sessions to resolve difficult diagnostic calls before a final independent assessment of all cases by October 2021.

The results demonstrated that canine meningiomas mirror the morphologic diversity of the human disease. The overwhelming majority of tumors—140 of 190, or roughly 74 percent—were classified as meningothelial, with transitional, microcystic, psammomatous, rhabdoid, fibrous, metaplastic, clear cell, and chordoid subtypes making up the remainder. Most cases, 109 tumors or 57 percent, were assigned grade 2 under the human WHO scheme, while 79 were grade 1 and only two reached grade 3. Roughly 60 percent of tumors with assessable adjacent brain or spinal cord tissue showed invasion into the nervous system, and features such as necrosis, sheeting, and hypercellularity were commonly observed, closely paralleling the histologic picture of atypical human meningioma.

Yet the clinical correlation told a more complicated story. Among the subset of patients with detailed progression and cause-of-death information, and again in a larger cohort restricted to live/dead status, there was no statistically significant difference in outcome between grade 1 and grade 2 canine tumors. Relative risk ratios for death at one, two, and three years after diagnosis—0.75, 0.93, and 1.02 respectively—were all statistically insignificant. This challenges the assumption that the human WHO grading framework, which strongly predicts recurrence and progression in people, can be transplanted wholesale to veterinary patients. Several features that signal higher grade in humans, notably macronucleoli and small-cell formation, appeared frequently even in grade 1 canine tumors, and medical pathologists on the board repeatedly observed that macronucleoli occur more often in canine tumors regardless of grade.

One feature did emerge as potentially meaningful: necrosis. Although many progressing tumors lacked necrosis, every case in the outcome-linked subset that did exhibit necrosis went on to show clinical progression, compared with 57 percent of cases lacking it. The authors suggest that necrosis, when present, may be a significant indicator of more aggressive behavior and a critical feature for future prognostic studies. Brain tumors were also significantly more likely than spinal tumors to show necrosis. Notably, the study echoes a shifting paradigm in human medicine, where tumors showing brain invasion without other atypical features—so-called brain-invasive, otherwise benign tumors—now benefit from additional molecular testing, suggesting that molecular characterization could likewise improve prognostication in dogs.

The review also shed light on the reproducibility of diagnosis across specialists. Interobserver agreement, measured by intraclass correlation coefficients, was generally low for most histologic features, with the highest agreement—0.44 for both—achieved for necrosis and CNS invasion, the same features that command the highest concordance in human meningioma review. Concordance exceeded 70 percent for most histologic subtypes, especially those with distinctive appearances such as clear cell and microcystic tumors, while mitotic counting proved the least reliable. Interestingly, veterinary pathologists agreed with one another significantly more often than physician neuropathologists on histologic subtype, hypercellularity, and macronucleoli, suggesting that species-specific experience is critical for diagnostic consistency.

Clinically, the cohort reflected established patterns of canine disease. The median patient age was ten years, and mixed-breed dogs, Golden Retrievers, Labrador Retrievers, Boxers, and West Highland Terriers were the most commonly represented breeds. Most tumors arose over the brain, particularly the olfactory and frontal lobes, with a smaller proportion in the cervical spinal cord. Surgery remained the mainstay of treatment, with a median survival of 437 days for dogs treated surgically, while dogs receiving surgery combined with radiation or other adjuvant therapies survived longer on average, at 28 to 55 months, consistent with previously reported ranges.

The CBTC board concluded that while canine and human meningioma share important histologic features, a revised grading framework specific to dogs is needed, distinct from the human WHO scheme. The consortium recommends that future studies include review of all slides by at least three pathologists, systematic evaluation of location, subtype, mitotic count, invasion, necrosis, and other atypical features, and enrollment limited to cases with complete clinical follow-up. The authors also call for the kind of large-scale, shared cancer databases in veterinary medicine that exist in human oncology, and note that molecular characterization, transcriptional profiling, and immune landscape studies of related canine tumor collections are already underway. If successful, these efforts could position the canine patient as a genuinely translational model—accelerating biomarker discovery and therapeutic development for both dogs and the humans who love them.

Subject of Research: Comparative pathology of canine and human meningioma and the validation of dogs as a naturally occurring model for human meningioma research

Article Title: A comparative evaluation of canine meningioma supporting the canine patient as a naturally occurring animal model for human meningioma: a report from the NCI Comparative Brain Tumor Consortium (CBTC) meningioma pathology board

Article References: Church, M. E., Rissi, D. R., Koehler, J. W., Miller, A. D., Beck, J. A., Belluco, S., Bitar, M., Chkheidze, R., Corps, K. N., Matiasek, K., Phillips, J. J., Rajan, S., Stemmer-Rachamimov, A., Yip, S., Shih, J. H., Mazcko, C., & LeBlanc, A. (2026). A comparative evaluation of canine meningioma supporting the canine patient as a naturally occurring animal model for human meningioma: a report from the NCI Comparative Brain Tumor Consortium (CBTC) meningioma pathology board. Veterinary Oncology, 3(1), Article 16. https://doi.org/10.1186/s44356-026-00068-1

Image Credits: AI Generated

DOI: 10.1186/s44356-026-00068-1

Keywords: meningioma, canine, comparative oncology, brain tumor, WHO grading, pathology, NCI Comparative Brain Tumor Consortium, veterinary oncology, CNS invasion, tumor necrosis, animal model, One Health

The scientific question underlying the study is deceptively simple: what happens inside the fetal brain when a pregnant mother experiences chronic stress? Epidemiological work in humans has long suggested that children born to mothers who endure significant stress during pregnancy face elevated risks of cognitive difficulties, anxiety, and other neuropsychiatric conditions. Animal models have replicated these observations, but the molecular choreography connecting maternal stress hormones to lasting changes in brain function has remained only partially mapped. The new research homes in on one specific player in that choreography: the resident immune cells of the brain, called microglia, and a protein they produce known as Galectin-3, or Gal-3.

Microglia are the brain’s frontline surveillance cells, constantly scanning their environment and responding to injury or infection. When activated, they change shape, engulf debris, and release inflammatory signaling molecules called cytokines. In moderation, this response is protective and essential for healthy brain development, since microglia help prune and remodel neural circuits during critical developmental windows. But when microglial activation becomes excessive or prolonged, the resulting neuroinflammation can damage neurons and disrupt the formation of the very circuits that support learning and memory. Galectin-3 has emerged in recent years as a marker and possible driver of this harmful activation, and it has been implicated in neurodegenerative and inflammatory brain disorders, making it a compelling candidate for explaining how prenatal stress translates into adult cognitive dysfunction.

To test this idea, the research team turned to a well-established rodent model. Twelve pregnant Sprague-Dawley rats were randomly divided into two groups. From gestational day 15 to day 21, the final week before birth, six of the dams were subjected to restraint stress, a standard and ethically controlled way of inducing psychological stress in laboratory animals. The remaining six dams experienced no intervention and served as controls. Once the offspring reached adulthood, the researchers put them through a battery of behavioral assessments designed to probe different dimensions of brain function: the open-field test and elevated plus maze for anxiety-like behavior and exploratory activity, the novel object recognition test for declarative memory, and the Y-maze test for working memory and spatial navigation.

The behavioral results were unambiguous. Compared with offspring of unstressed mothers, the prenatal stress group showed significant impairments across all four tests, indicating disruptions in both emotional regulation and core cognitive domains. The team then measured the hormonal footprint of stress by using enzyme-linked immunosorbent assays to quantify corticotropin-releasing hormone and corticosterone, two central components of the hypothalamic-pituitary-adrenal axis, in the peripheral blood of both mothers and offspring. Levels of both hormones rose significantly in stressed dams, confirming that the manipulation worked, and, strikingly, they were also elevated in the adult offspring, with the strongest statistical differences appearing in the young animals whose mothers had endured the restraint protocol.

With the behavioral and hormonal phenotypes established, the researchers turned to the molecular evidence. Assays of peripheral blood serum and of tissue from two brain regions critically involved in cognition, the hippocampus and the prefrontal cortex, revealed significantly increased expression of the inflammatory cytokines interleukin-6, interleukin-1 beta, and tumor necrosis factor-alpha in the prenatally stressed offspring. These molecules are classic signatures of an immune system in overdrive. Their presence in both blood and brain tissue suggested that maternal stress had ignited inflammatory pathways that persisted long after the initial stressor had ended, effectively leaving the adult brain in a chronically inflamed state.

Immunofluorescence staining then allowed the team to visualize what was happening to microglia at the cellular level. In the stressed offspring, Iba1-positive microglia displayed activation-associated morphological changes, shifting toward the amoeboid, hypertrophic appearance characteristic of cells engaged in an inflammatory response. The number of cells double-positive for Iba1 and CD68, a marker of phagocytic activity, increased significantly in both the hippocampus and prefrontal cortex. Most importantly for the study’s central hypothesis, the number of cells co-expressing Iba1 and Galectin-3 also rose markedly, indicating that the upregulated Gal-3 signal was coming specifically from activated microglia rather than from other cell types. Quantitative PCR and Western blotting confirmed the story at the transcript and protein levels: Galectin-3 expression was significantly upregulated in both brain regions, total NF-kappa-B p65 protein, a central transcriptional regulator of inflammation, was increased, and NeuN, a marker of mature neurons, was decreased, all pointing to a process in which microglial inflammation coincides with neuronal loss or dysfunction.

Taken together, the data sketch a coherent mechanistic narrative. Maternal restraint stress during late gestation elevates stress hormones, which appear to program the fetal immune system in a way that persists into adulthood. The programmed microglia become chronically activated, produce Galectin-3, and drive expression of pro-inflammatory cytokines through pathways involving NF-kappa-B signaling. The resulting neuroinflammation in the hippocampus and prefrontal cortex, two regions essential for memory formation and executive function, is accompanied by reduced neuronal marker expression and manifests behaviorally as impaired learning, memory, and anxiety regulation. While the study is correlational in design and does not prove that Galectin-3 causally drives the cognitive deficits, the tight association across behavioral, hormonal, cellular, and molecular layers of evidence makes the protein a strong candidate for future intervention studies.

The clinical implications are significant. If the same biology operates in humans, Galectin-3 could serve as a biomarker for identifying children at risk of stress-related cognitive impairment, potentially allowing earlier intervention. More ambitiously, drugs that inhibit Galectin-3 or dampen microglial activation are already under investigation for other neurological conditions, and the new findings provide a rationale for testing whether such approaches could protect the brains of offspring exposed to prenatal adversity. The researchers caution that their model used restraint stress in rats and that direct extrapolation to human pregnancy requires further work, but the convergence of evidence strengthens a growing consensus in neuroscience: the prenatal environment is not merely a backdrop for development but an active sculptor of the brain’s immune architecture, with consequences that can echo for a lifetime.

The timing of the stress exposure in this model is worth noting. Gestational days 15 through 21 in the rat correspond to a late gestational window during which fetal brain development is particularly sensitive to glucocorticoid exposure, as the hippocampal formation and cortical circuits are actively being organized. Restraining the dams during this period therefore represents a targeted challenge to a developmental phase in which stress hormones can plausibly shape the trajectory of immune and neural maturation.

The choice of markers in the study reflects established conventions in neuroimmunology research. Iba1 is a constitutive marker that labels microglia regardless of their activation state, while CD68 identifies lysosomal and phagocytic activity, so the increase in cells double-positive for both proteins indicates not merely more microglia but microglia shifted toward an active, phagocytic phenotype. Galectin-3 itself is a beta-galactoside-binding lectin that has been linked to Toll-like receptor 4 signaling and NF-kappa-B pathway activation in prior work, which is consistent with the elevated NF-kappa-B p65 protein levels observed here alongside increased Gal-3 expression.

The reduction in NeuN, a marker expressed by mature neurons, is a particularly consequential observation, because it suggests that the inflammatory changes are not simply parallel to neuronal health but may reflect actual neuronal compromise in the hippocampus and prefrontal cortex. However, the study design is cross-sectional and correlational, so it cannot distinguish whether Gal-3 upregulation drives neuronal dysfunction, results from it, or both arise from a shared upstream mechanism such as sustained HPA axis activation. Future experiments using Gal-3 inhibitors or genetic approaches in this prenatal stress paradigm would be needed to establish causality and to determine whether blocking this pathway can rescue the behavioral deficits observed in adult offspring.

Subject of Research: Microglial Galectin-3 expression linked to prenatal stress-induced cognitive dysfunction in adult offspring

Article Title: Microglia-associated Galectin-3 expression in prenatal stress-induced cognitive dysfunction in adult offspring

Article References: Wang, Q., Luo, H., Fan, F., Zhao, Z., Liu, D., Liao, L., & Bai, S. (2026). Microglia-associated Galectin-3 expression in prenatal stress-induced cognitive dysfunction in adult offspring. BMC Neuroscience. https://doi.org/10.1186/s12868-026-01048-9

Image Credits: AI Generated

DOI: 10.1186/s12868-026-01048-9

Keywords: prenatal stress, microglia, Galectin-3, neuroinflammation, cognitive impairment, hippocampus, prefrontal cortex, cytokines, HPA axis, neurodevelopment, BMC Neuroscience, animal model