FSC-certified forest management benefits large mammals compared to non-FSC.

More than a quarter of the world's tropical forests are exploited for timber1. Logging impacts biodiversity in these ecosystems, primarily through the creation of forest roads that facilitate hunting for wildlife over extensive areas. Forest management certification schemes such as the Forest Stewardship Council (FSC) are expected to mitigate impacts on biodiversity, but so far very little is known about the effectiveness of FSC certification because of research design challenges, predominantly limited sample sizes2,3. Here we provide this evidence by using 1.3 million camera-trap photos of 55 mammal species in 14 logging concessions in western equatorial Africa. We observed higher mammal encounter rates in FSC-certified than in non-FSC logging concessions. The effect was most pronounced for species weighing more than 10 kg and for species of high conservation priority such as the critically endangered forest elephant and western lowland gorilla. Across the whole mammal community, non-FSC concessions contained proportionally more rodents and other small species than did FSC-certified concessions. The first priority for species protection should be to maintain unlogged forests with effective law enforcement, but for logged forests our findings provide convincing data that FSC-certified forest management is less damaging to the mammal community than is non-FSC forest management. This study provides strong evidence that FSC-certified forest management or equivalently stringent requirements and controlling mechanisms should become the norm for timber extraction to avoid half-empty forests dominated by rodents and other small species.

Substantial viral diversity in bats and rodents from East Africa: insights into evolution, recombination, and cocirculation.

BACKGROUND: Zoonotic viruses cause substantial public health and socioeconomic problems worldwide. Understanding how viruses evolve and spread within and among wildlife species is a critical step when aiming for proactive identification of viral threats to prevent future pandemics. Despite the many proposed factors influencing viral diversity, the genomic diversity and structure of viral communities in East Africa are largely unknown. RESULTS: Using 38.3 Tb of metatranscriptomic data obtained via ultradeep sequencing, we screened vertebrate-associated viromes from 844 bats and 250 rodents from Kenya and Uganda collected from the wild. The 251 vertebrate-associated viral genomes of bats (212) and rodents (39) revealed the vast diversity, host-related variability, and high geographic specificity of viruses in East Africa. Among the surveyed viral families, Coronaviridae and Circoviridae showed low host specificity, high conservation of replication-associated proteins, high divergence among viral entry proteins, and frequent recombination. Despite major dispersal limitations, recurrent mutations, cocirculation, and occasional gene flow contribute to the high local diversity of viral genomes. CONCLUSIONS: The present study not only shows the landscape of bat and rodent viromes in this zoonotic hotspot but also reveals genomic signatures driven by the evolution and dispersal of the viral community, laying solid groundwork for future proactive surveillance of emerging zoonotic pathogens in wildlife. Video Abstract.

Effects of a beaver dam on the benthic copepod assemblage of a Mediterranean river.

As known "ecosystem engineers", beavers influence river hydrology, geomorphology, biochemistry, and biological assemblages. However, there is a lack of research regarding the effects of beaver activities on freshwater meiofauna. In this study, we investigated the taxonomic and functional composition of the benthic copepod assemblage of a segment of the Tiber River (Italy) where a beaver dam, created about 7 weeks before our survey, had formed a semi-lentic habitat upstream and a lotic habitat downstream of the dam. We also analyzed the copepod assemblage before and after a flood event that destroyed the beaver dam, providing a unique opportunity to observe changes in a naturally reversing scenario. Our analyses revealed that, while the taxonomic composition and functional traits of the copepod assemblage remained largely unchanged across the recently formed semi-lentic and lotic habitats, substantial differences were evident between the dammed and undammed states. The dammed state showed lower copepod abundances, biomass, and functionality than the undammed one. These results highlight the role of beaver dams in changing the composition and functionality of meiofaunal assemblages offering insights into the dynamic interactions within aquatic ecosystems.

The prenatal use of agmatine prevents social behavior deficits in VPA-exposed mice by activating the ERK/CREB/BDNF signaling pathway.

BACKGROUND: According to reports, prenatal exposure to valproic acid can induce autism spectrum disorder (ASD)-like symptoms in both humans and rodents. However, the exact cause and therapeutic method of ASD is not fully understood. Agmatine (AGM) is known for its neuroprotective effects, and this study aims to explore whether giving agmatine hydrochloride before birth can prevent autism-like behaviors in mouse offspring exposed prenatally to valproic acid. METHODS: In this study, we investigated the effects of AGM prenatally on valproate (VPA)-exposed mice. We established a mouse model of ASD by prenatally administering VPA. From birth to weaning, we evaluated mouse behavior using the marble burying test, open-field test, and three-chamber social interaction test on male offspring. RESULTS: The results showed prenatal use of AGM relieved anxiety and hyperactivity behaviors as well as ameliorated sociability of VPA-exposed mice in the marble burying test, open-field test, and three-chamber social interaction test, and this protective effect might be attributed to the activation of the ERK/CREB/BDNF signaling pathway. CONCLUSION: Therefore, AGM can effectively reduce the likelihood of offspring developing autism to a certain extent when exposed to VPA during pregnancy, serving as a potential therapeutic drug.

Molecular epidemiological study of Scrub Typhus in residence, farm and forest habitats from Yunnan Province, China.

The number of people suffering from scrub typhus, which is not of concern, is increasing year by year, especially in Yunnan Province, China. From June 1, 2021 to August 15, 2022, a total of 505 mammalian samples were collected from farm, forest, and residential habitats with high incidence of scrub typhus in Yunnan, China, for nPCR (nested PCR) and qPCR (quantitative real-time PCR) detection of Orientia tsutsugamushi. A total of 4 orders of murine-like animals, Rodentia (87.52%, n = 442), Insectivora (10.29%, n = 52), Lagomorpha (1.79%, n = 9) and Scandentia (0.40%, n = 2) were trapped. Comparing the qPCR infection rates in the three habitats, it was no significant difference that the infection rate of residential habitat (44.44%) and that of the farm habitat (45.05%, P>0.05), which is much larger than that of the forest habitat (3.08%) (P<0.001). Three genotypes (Karp-like, Kato-like and TA763-like) of O. tsutsugamushi were found from Yunnan, China in this study.

Directed and acyclic synaptic connectivity in the human layer 2-3 cortical microcircuit.

The computational capabilities of neuronal networks are fundamentally constrained by their specific connectivity. Previous studies of cortical connectivity have mostly been carried out in rodents; whether the principles established therein also apply to the evolutionarily expanded human cortex is unclear. We studied network properties within the human temporal cortex using samples obtained from brain surgery. We analyzed multineuron patch-clamp recordings in layer 2-3 pyramidal neurons and identified substantial differences compared with rodents. Reciprocity showed random distribution, synaptic strength was independent from connection probability, and connectivity of the supragranular temporal cortex followed a directed and mostly acyclic graph topology. Application of these principles in neuronal models increased dimensionality of network dynamics, suggesting a critical role for cortical computation.

Optimizing semen cryopreservation in Calomys laucha: a step forward in rodent reproductive research.

BACKGROUND: Examining semen cryopreservation in Calomys laucha offers valuable insights for reproductive research and species conservation. OBJECTIVE: To determine the most effective sugar for the cryopreservation of C. laucha semen. MATERIALS AND METHODS: Using 36 epididymides from C. laucha, semen samples were diluted in a 3% skimmed milk medium supplemented with one of four sugars (glucose, fructose, lactose, or sucrose) at a concentration of 0.3 M. These mixtures underwent a conditioning phase at 37 degree C for 10 min, cooled to -80 degree C for another 10 min, and were subsequently stored in liquid nitrogen. RESULTS: Upon thawing, samples treated with lactose and glucose solutions show superior sperm motility, achieving 8.2% and 10.0% respectively, in contrast to the fructose (2.0%) and sucrose (4.1%) mixtures. Furthermore, samples preserved in glucose registered the highest sperm penetration rates, reaching 44.9%. CONCLUSION: Our findings suggest that a cryopreservation medium containing 0.3 M glucose can contribute to the safeguarding C. laucha rodent semen. https://doi.org/10.54680/fr24210110612.

Homeobox gene-encoded transcription factors in development and mature circadian function of the rodent pineal gland.

Homeobox genes encode transcription factors that are widely known to control developmental processes. This is also the case in the pineal gland, a neuroendocrine brain structure devoted to nighttime synthesis of the hormone melatonin. Thus, in accordance with high prenatal gene expression, knockout studies have identified a specific set of homeobox genes that are essential for development of the pineal gland. However, as a special feature of the pineal gland, homeobox gene expression persists into adulthood, and gene product abundance exhibits 24 h circadian rhythms. Recent lines of evidence show that some homeobox genes even control expression of enzymes catalyzing melatonin synthesis. We here review current knowledge of homeobox genes in the rodent pineal gland and suggest a model for dual functions of homeobox gene-encoded transcription factors in developmental and circadian mature neuroendocrine function.

No evidence tube entrapment distresses rodents in typical empathy tests.

In the first two experiments an empty tube open at one end was placed in different locations. Male hamsters, tested one at a time, tended to stay close to the tube or in it. During the first minute of the first 4 sessions of Experiment 3, the hamster was unrestrained. If it entered the tube, it was locked within the tube. If it did not enter the tube during the first min, it was placed in it, and the tube was locked. Fifteen min later, the tube was opened, and the hamster was unrestrained for a further 20 min. The tube remained open during Session 5. Hamsters spent more time near the tube than predicted by chance and continued to enter the tube although tube-occupancy duration did not differ from chance levels. In Experiment 4, male rats were tested in two groups: rats in one group had been previously trapped in a tube and rats in the other group allowed to freely explore the test space. For the first two min of each of four 20-min sessions, trapped-group subjects were permitted to move about the chamber unless they entered the tube. In that case, they were locked in for the remainder of the session. If, after two min, they did not enter the tube, they were locked in it for the remaining 18 min. Free rats were unrestricted in all sessions. In Session 5, when both groups were permitted to move freely in the chamber, trapped and free rats spent more time in and near the tube than predicted by chance. These data show tube restraint does not seem to distress either hamsters or rats.

Health of Holochilus chacarius (Rodentia: Cricetidae) in rice agroecosystem in a neotropical wetland assessed by histopathology.

Small mammals have a short lifetime and are strictly associated with their environment. This work aimed to use histopathology to assess the health of Holochilus chacarius in a rice agroecosystem in the Pantanal of Mato Grosso do Sul. During necropsy, fragments of the lung, kidney, skin, liver, and reproductive system of 33 animals were collected and submitted to histological processing. Tissue damages were evaluated as mild, moderate, and severe and arranged in a matrix for further statistical analysis. Furthermore, we used generalized linear models to verify the influence of tissue changes on the body condition, obtained by a regression between body mass and length. In the lungs, we found an intense inflammatory infiltrate associated with anthracosis that had a negative influence on the body's condition. Also, we observed degenerative and inflammatory changes in the liver, kidneys, skin, and reproductive system that ranged from mild to moderate. The histopathological lesions observed in this study may be associated with environmental alterations of anthropic origin such as the exposure to soot from wildfires and heavy metals, evidenced by lesions in the lung, kidney, and liver. The present study provided a histopathological matrix as a new approach that allows to classify and quantify the tissue alterations. Tissue changes when associated with body condition demonstrated to be an effective tool to assess the health of small free-living mammals, showing that these animals can be used as bioindicators of environmental condition.

Space wandering in the rodent default mode network.

The default mode network (DMN) is a large-scale brain network known to be suppressed during a wide range of cognitive tasks. However, our comprehension of its role in naturalistic and unconstrained behaviors has remained elusive because most research on the DMN has been conducted within the restrictive confines of MRI scanners. Here, we use multisite GCaMP (a genetically encoded calcium indicator) fiber photometry with simultaneous videography to probe DMN function in awake, freely exploring rats. We examined neural dynamics in three core DMN nodes-the retrosplenial cortex, cingulate cortex, and prelimbic cortex-as well as the anterior insula node of the salience network, and their association with the rats' spatial exploration behaviors. We found that DMN nodes displayed a hierarchical functional organization during spatial exploration, characterized by stronger coupling with each other than with the anterior insula. Crucially, these DMN nodes encoded the kinematics of spatial exploration, including linear and angular velocity. Additionally, we identified latent brain states that encoded distinct patterns of time-varying exploration behaviors and found that higher linear velocity was associated with enhanced DMN activity, heightened synchronization among DMN nodes, and increased anticorrelation between the DMN and anterior insula. Our findings highlight the involvement of the DMN in collectively and dynamically encoding spatial exploration in a real-world setting. Our findings challenge the notion that the DMN is primarily a "task-negative" network disengaged from the external world. By illuminating the DMN's role in naturalistic behaviors, our study underscores the importance of investigating brain network function in ecologically valid contexts.

Systematic review of rodent studies of deep brain stimulation for the treatment of neurological, developmental and neuropsychiatric disorders.

Deep brain stimulation (DBS) modulates local and widespread connectivity in dysfunctional networks. Positive results are observed in several patient populations; however, the precise mechanisms underlying treatment remain unknown. Translational DBS studies aim to answer these questions and provide knowledge for advancing the field. Here, we systematically review the literature on DBS studies involving models of neurological, developmental and neuropsychiatric disorders to provide a synthesis of the current scientific landscape surrounding this topic. A systematic analysis of the literature was performed following PRISMA guidelines. 407 original articles were included. Data extraction focused on study characteristics, including stimulation protocol, behavioural outcomes, and mechanisms of action. The number of articles published increased over the years, including 16 rat models and 13 mouse models of transgenic or healthy animals exposed to external factors to induce symptoms. Most studies targeted telencephalic structures with varying stimulation settings. Positive behavioural outcomes were reported in 85.8% of the included studies. In models of psychiatric and neurodevelopmental disorders, DBS-induced effects were associated with changes in monoamines and neuronal activity along the mesocorticolimbic circuit. For movement disorders, DBS improves symptoms via modulation of the striatal dopaminergic system. In dementia and epilepsy models, changes to cellular and molecular aspects of the hippocampus were shown to underlie symptom improvement. Despite limitations in translating findings from preclinical to clinical settings, rodent studies have contributed substantially to our current knowledge of the pathophysiology of disease and DBS mechanisms. Direct inhibition/excitation of neural activity, whereby DBS modulates pathological oscillatory activity within brain networks, is among the major theories of its mechanism. However, there remain fundamental questions on mechanisms, optimal targets and parameters that need to be better understood to improve this therapy and provide more individualized treatment according to the patient's predominant symptoms.

Glycerol Trinitrate Acts Downstream of Calcitonin Gene-Related Peptide in Trigeminal Nociception-Evidence from Rodent Experiments with Anti-CGRP Antibody Fremanezumab.

Calcitonin gene-related peptide (CGRP) and nitric oxide (NO) have been recognized as important mediators in migraine but their mechanisms of action and interaction have not been fully elucidated. Monoclonal anti-CGRP antibodies like fremanezumab are successful preventives of frequent migraine and can be used to study CGRP actions in preclinical experiments. Fremanezumab (30 mg/kg) or an isotype control monoclonal antibody was subcutaneously injected to Wistar rats of both sexes. One to several days later, glyceroltrinitrate (GTN, 5 mg/kg) mimicking nitric oxide (NO) was intraperitoneally injected, either once or for three consecutive days. The trigeminal ganglia were removed to determine the concentration of CGRP using an enzyme-linked immunosorbent assay (ELISA). In one series of experiments, the animals were trained to reach an attractive sugar solution, the access to which could be limited by mechanical or thermal barriers. Using a semi-automated registration system, the frequency of approaches to the source, the residence time at the source, and the consumed solution were registered. The results were compared with previous data of rats not treated with GTN. The CGRP concentration in the trigeminal ganglia was generally higher in male rats and tended to be increased in animals treated once with GTN, whereas the CGRP concentration decreased after repetitive GTN treatment. No significant difference in CGRP concentration was observed between animals having received fremanezumab or the control antibody. Animals treated with GTN generally spent less time at the source and consumed less sugar solution. Without barriers, there was no significant difference between animals having received fremanezumab or the control antibody. Under mechanical barrier conditions, all behavioral parameters tended to be reduced but animals that had received fremanezumab tended to be more active, partly compensating for the depressive effect of GTN. In conclusion, GTN treatment seems to increase the production of CGRP in the trigeminal ganglion independently of the antibodies applied, but repetitive GTN administration may deplete CGRP stores. GTN treatment generally tends to suppress the animals' activity and increase facial sensitivity, which is partly compensated by fremanezumab through reduced CGRP signaling. If CGRP and NO signaling share the same pathway in sensitizing trigeminal afferents, GTN and NO may act downstream of CGRP to increase facial sensitivity.

Microbiome and mitogenomics of the chigger mite Pentidionis agamae: potential role as an Orientia vector and associations with divergent clades of Wolbachia and Borrelia.

BACKGROUND: Trombiculid mites are globally distributed, highly diverse arachnids that largely lack molecular resources such as whole mitogenomes for the elucidation of taxonomic relationships. Trombiculid larvae (chiggers) parasitise vertebrates and can transmit bacteria (Orientia spp.) responsible for scrub typhus, a zoonotic febrile illness. Orientia tsutsugamushi causes most cases of scrub typhus and is endemic to the Asia-Pacific Region, where it is transmitted by Leptotrombidium spp. chiggers. However, in Dubai, Candidatus Orientia chuto was isolated from a case of scrub typhus and is also known to circulate among rodents in Saudi Arabia and Kenya, although its vectors remain poorly defined. In addition to Orientia, chiggers are often infected with other potential pathogens or arthropod-specific endosymbionts, but their significance for trombiculid biology and public health is unclear. RESULTS: Ten chigger species were collected from rodents in southwestern Saudi Arabia. Chiggers were pooled according to species and screened for Orientia DNA by PCR. Two species (Microtrombicula muhaylensis and Pentidionis agamae) produced positive results for the htrA gene, although Ca. Orientia chuto DNA was confirmed by Sanger sequencing only in P. agamae. Metagenomic sequencing of three pools of P. agamae provided evidence for two other bacterial associates: a spirochaete and a Wolbachia symbiont. Phylogenetic analysis of 16S rRNA and multi-locus sequence typing genes placed the spirochaete in a clade of micromammal-associated Borrelia spp. that are widely-distributed globally with no known vector. For the Wolbachia symbiont, a genome assembly was obtained that allowed phylogenetic localisation in a novel, divergent clade. Cytochrome c oxidase I (COI) barcodes for Saudi Arabian chiggers enabled comparisons with global chigger diversity, revealing several cases of discordance with classical taxonomy. Complete mitogenome assemblies were obtained for the three P. agamae pools and almost 50 SNPs were identified, despite a common geographic origin. CONCLUSIONS: P. agamae was identified as a potential vector of Ca. Orientia chuto on the Arabian Peninsula. The detection of an unusual Borrelia sp. and a divergent Wolbachia symbiont in P. agamae indicated links with chigger microbiomes in other parts of the world, while COI barcoding and mitogenomic analyses greatly extended our understanding of inter- and intraspecific relationships in trombiculid mites.

Large-scale coupling of prefrontal activity patterns as a mechanism for cognitive control in health and disease: evidence from rodent models.

Cognitive control of behavior is crucial for well-being, as allows subject to adapt to changing environments in a goal-directed way. Changes in cognitive control of behavior is observed during cognitive decline in elderly and in pathological mental conditions. Therefore, the recovery of cognitive control may provide a reliable preventive and therapeutic strategy. However, its neural basis is not completely understood. Cognitive control is supported by the prefrontal cortex, structure that integrates relevant information for the appropriate organization of behavior. At neurophysiological level, it is suggested that cognitive control is supported by local and large-scale synchronization of oscillatory activity patterns and neural spiking activity between the prefrontal cortex and distributed neural networks. In this review, we focus mainly on rodent models approaching the neuronal origin of these prefrontal patterns, and the cognitive and behavioral relevance of its coordination with distributed brain systems. We also examine the relationship between cognitive control and neural activity patterns in the prefrontal cortex, and its role in normal cognitive decline and pathological mental conditions. Finally, based on these body of evidence, we propose a common mechanism that may underlie the impaired cognitive control of behavior.

Prevalence, genetic diversity and eco-epidemiology of pathogenic Leptospira species in small mammal communities in urban parks Lyon city, France.

Rodents are recognized as the main reservoirs of Leptospira spp. Rats, in particular, serve as hosts for the widely predominant Leptospira interrogans serovar Icterohaemorrhagiae, found worldwide. Several studies have shown the importance of other reservoirs, such as mice or hedgehogs, which harbor other leptospires' serovars. Nevertheless, our knowledge of circulating Leptospira spp. in reservoirs other than rats remains limited. In this context, we proposed an eco-health approach to assess the health hazard associated with leptospires in urban green spaces, where contacts between human/small mammals and domestic animals are likely. We studied the prevalence, the diversity of circulating strains, and epidemiology of pathogenic Leptospira species in small terrestrial mammal communities (rodents and shrews), between 2020-2022, in two parks in Lyon metropolis, France. Our study showed a significant carriage of Leptospira spp. in small terrestrial mammals in these parks and unveiled a global prevalence rate of 11.4%. Significant variations of prevalence were observed among the small mammal species (from 0 to 26.1%), with Rattus norvegicus exhibiting the highest infection levels (26.1%). We also observed strong spatio-temporal variations in Leptospira spp. circulation in its reservoirs. Prevalence seems to be higher in the peri-urban park and in autumn in 2021 and 2022. This is potentially due to differences in landscape, abiotic conditions and small mammal communities' composition. Our study suggests an important public health relevance of rats and in a lesser extent of other rodents (Apodemus spp., Clethrionomys glareolus and Mus musculus) as reservoirs of L. interrogans, with rodent species carrying specific serogroups/serovars. We also emphasize the potential hazard associated between the shrew Crocidura russula and L. kirschneri. Altogether, these results improve our knowledge about the prevalence of leptospirosis in an urban environment, which is an essential prerequisite for the implementation of prevention of associated risks.

Ultrasoft platelet-like particles stop bleeding in rodent and porcine models of trauma.

Uncontrolled bleeding after trauma represents a substantial clinical problem. The current standard of care to treat bleeding after trauma is transfusion of blood products including platelets; however, donated platelets have a short shelf life, are in limited supply, and carry immunogenicity and contamination risks. Consequently, there is a critical need to develop hemostatic platelet alternatives. To this end, we developed synthetic platelet-like particles (PLPs), formulated by functionalizing highly deformable microgel particles composed of ultralow cross-linked poly (N-isopropylacrylamide) with fibrin-binding ligands. The fibrin-binding ligand was designed to target to wound sites, and the cross-linking of fibrin polymers was designed to enhance clot formation. The ultralow cross-linking of the microgels allows the particles to undergo large shape changes that mimic platelet shape change after activation; when coupled to fibrin-binding ligands, this shape change facilitates clot retraction, which in turn can enhance clot stability and contribute to healing. Given these features, we hypothesized that synthetic PLPs could enhance clotting in trauma models and promote healing after clotting. We first assessed PLP activity in vitro and found that PLPs selectively bound fibrin and enhanced clot formation. In murine and porcine models of traumatic injury, PLPs reduced bleeding and facilitated healing of injured tissue in both prophylactic and immediate treatment settings. We determined through biodistribution experiments that PLPs were renally cleared, possibly enabled by ultrasoft particle properties. The performance of synthetic PLPs in the preclinical studies shown here supports future translational investigation of these hemostatic therapeutics in a trauma setting.

Impact of light-emitting diodes on visual cortex layer 5 pyramidal neurons (V1-L5PNs)-A rodent study.

Purpose: Light-induced neural retinal insult leads to alterations in the visual cortex neurons. We examined light-induced neuronal alterations in the visual cortex layer 5 pyramidal neurons (V1-L5PNs) of adult male Wistar rats. Methods: A total of 24 rats were divided into the following groups (n=6 each): control (NC), blue (BL), white (WL), and yellow (YL). The exposure groups were subjected to light-emitting diodes (LED) exposure (450-500 lx) of differing wavelengths for 90 days (12:12 16 light-dark cycle). After LED exposure, the animals were sacrificed, and the brain tissues were removed and impregnated in freshly prepared Golgi-Cox stain for 21 days. Sholl's grading analysis was used to quantify the apical and basal dendritic branching points and intersections of the V1-L5PNs. Results: There was a significant difference in the number of apical branching points among all groups (p<0.001), with a particularly notable difference between the BL and WL groups (p<0.001). A post hoc test revealed that all exposure groups (BL, WL, and YL) had fewer apical branching points (p<0.001) on an average of 3.6 µm and a significant reduction in the dendritic intersections (p<0.001) compared to the number of branching points extending from layer Va (V1) neurons. Conclusions: Chronic and cumulative exposure to blue and white LEDs led to the pruning of V1-L5PNs, which might impair visual processing.

Anatomy of the brain of capybara (Hydrochoerus hydrochaeris) using magnetic resonance imaging.

Capybara is considered the largest living rodent and is widespread distributed in the South America and in the Brazilian territory. The purpose of this study was to provide the anatomical description of the brain in the capybara (Hydrochoerus hydrochaeris) using magnetic resonance imaging (MRI). Brains of ten normal capybaras were imaged and sectioned in the anatomical studies. MRI was acquired on 0.25 Tesla equipment, promoting good-quality images capable to identify and classify the main anatomical structures of clinical interest. MRI reference images were validated by comparing them with gross anatomical sections. The capybara sulci and gyri were named for its similar location and orientation to those described in the previous descriptions in the capybara and in the domestic dog. Capybaras presented prominent cerebral sulcus and gyrus in relation to other caviomorph rodents, but in reduced number when compared to domestic animals and other wild mammals such as elephants and giraffes. The findings of this study indicate that the shape of the capybara brain is remarkably similar to that of the caviomorph rodents with a higher neocortilization. The capybara rhinencephalon was well-developed implying a good sense of smell. Due to this development of the rhinencephalon, we can suggest that capybara brain is a macrosmatic brain. The MRI and gross anatomical sections of capybara brain may help veterinary researchers and clinicians increase the accuracy of brain MRI scans interpretation in these animals.

Ibrutinib disrupts blood-tumor barrier integrity and prolongs survival in rodent glioma model.

In malignant glioma, cytotoxic drugs are often inhibited from accessing the tumor site due to the blood-tumor barrier (BTB). Ibrutinib, FDA-approved lymphoma agent, inhibits Bruton tyrosine kinase (BTK) and has previously been shown to independently impair aortic endothelial adhesion and increase rodent glioma model survival in combination with cytotoxic therapy. Yet additional research is required to understand ibrutinib's effect on BTB function. In this study, we detail baseline BTK expression in glioma cells and its surrounding vasculature, then measure endothelial junctional expression/function changes with varied ibrutinib doses in vitro. Rat glioma cells and rodent glioma models were treated with ibrutinib alone (1-10 µM and 25 mg/kg) and in combination with doxil (10-100 µM and 3 mg/kg) to assess additive effects on viability, drug concentrations, tumor volume, endothelial junctional expression and survival. We found that ibrutinib, in a dose-dependent manner, decreased brain endothelial cell-cell adhesion over 24 h, without affecting endothelial cell viability (p < 0.005). Expression of tight junction gene and protein expression was decreased maximally 4 h after administration, along with inhibition of efflux transporter, ABCB1, activity. We demonstrated an additive effect of ibrutinib with doxil on rat glioma cells, as seen by a significant reduction in cell viability (p < 0.001) and increased CNS doxil concentration in the brain (56 ng/mL doxil alone vs. 74.6 ng/mL combination, p < 0.05). Finally, Ibrutinib, combined with doxil, prolonged median survival in rodent glioma models (27 vs. 16 days, p < 0.0001) with brain imaging showing a - 53% versus - 75% volume change with doxil alone versus combination therapy (p < 0.05). These findings indicate ibrutinib's ability to increase brain endothelial permeability via junctional disruption and efflux inhibition, to increase BTB drug entry and prolong rodent glioma model survival. Our results motivate the need to identify other BTB modifiers, all with the intent of improving survival and reducing systemic toxicities.