Nest-building in breeding mice: Impact of macro- and micro-environment.

The housing conditions of laboratory mice must be strictly controlled in order to reduce the impact of pathophysiological changes that affect animal health and welfare, possibly resulting in increased variability within experimental results. One way to improve the activity and survival of laboratory mice is to provide nesting material. The objective of this study was to determine if nest-building quality could be used to detect changes in murine mating behaviour in a rodent facility under controlled conditions. Nesting scores of 847 cages with monogamous pairs from three different genetic backgrounds (129, B6 and BALB/c) of both sexes were correlated with 18 predefined variables. The effects on nest quality were evaluated using descriptive data analysis, correspondence analysis and ordinal logistic model fitting. The results showed a strong relationship between nest quality and nest position. Humidity, genetic background, cage change and the number and age of pups in the cage affected the nest-building scores. The most important indicators were cage change and relative humidity, both of which exerted significant negative effects on nest-building quality. Even though the criteria were well defined, the observer could still influence nest score appraisal. However, in a long-term observational study, observers could improve their assessment by training and acquiring greater experience in score assignment. Nest-building scores are easy to assess in the cage, with little discomfort to the animal. Moreover, the nest score is a valid indicator of the health and well-being of laboratory mice and can provide valuable support in the management of animal facilities.

Alteration of hippocampal Egr3, GABA A receptors, Il-1ß, Il6 and Ccl3 expression in audiogenic tremor mice after seizure.

Neuroinflammation plays a protective role in the brain; however, in neurological diseases such as epilepsy, overactivated neuroinflammation, along with overexpression of inflammatory mediators, can cause neuronal tissue damage, which can trigger seizures due to loss of ionic or neurotransmitter homeostasis. Therefore, we aimed to evaluate mRNA expression levels of proinflammatory cytokines, early growth response factor 3 (Egr3), and GABA A receptors in the hippocampus of naive audiogenic mutant tremor mice, and stimulated tremor mice after a seizure. Gene expression of Il-1ß, Il-6, Tnf-α, Ccl2, Ccl3, Egr3, Gabra1, and Gabra4 from hippocampal samples of naive and stimulated tremor mice were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Relative to resistant mice, Ccl3 gene expression was increased and Il6 was decreased in the hippocampus of naïve tremor mice. Thirty minutes after a seizure, Ccl3 and Il-1ß mRNA expression were decreased (p < 0.0001; p = 0.0034, respectively) while Il6 was increased (p = 0.0052) in stimulated tremor mice, relative to naïve animals. In addition, Egr3, Gabra1, and Gabra4 mRNA expression was decreased in the hippocampus of naive tremor mice, relative to resistant mice, which increased 30 minutes after a seizure (p = 0.0496; p = 0.0447, and p = 0.0011, respectively), relative to naïve animals. In conclusion, overexpression of Ccl3 in the hippocampus of naive tremor mice, followed by downregulation soon after seizure in stimulated tremor mice, could be involved in changes in the blood-brain barrier (BBB) permeability in epilepsy. Il-1ß may be involved in hippocampal downregulation of GABA A receptors of naive tremor mice, characterizing an important mechanism in audiogenic seizures triggering. Hippocampal alterations of proinflammatory cytokines, Egr3, and GABA A receptors in tremor mice reinforce them as an alternative tool to modeling temporal lobe epilepsy.

Oxygen supply as a refining technique for injectable anesthesia in laboratory rats

Well-controlled anesthesia is critical to reducing potential surgical complications and ensuring safe and successful procedures. Respiratory depression, inducing hypoxia, and hypercapnia are adverse effects of injectable anesthesia in laboratory rats. This study aimed to determine the effect of oxygen supply in laboratory rats anesthetized with the combination of ketamine (K) and xylazine (X) plus acepromazine (A) or methadone (Me). The results showed that oxygenation allowed adequate levels of SO2 and paO2, avoiding hypoxemia. However, all anesthetized rats showed respiratory acidosis with low pH and high paCO2 levels, which was not reversed after oxygen administration. The acidosis could be related to hypoventilation due to respiratory depression induced by the XKMe association, as well as absorption atelectasis with the CO2 accumulation during anesthesia. Despite respiratory acidosis, oxygen administration was beneficial for anesthetized rats preventing hypoxemia. This makes it possible to prevent all the metabolic alterations that cause cell death by hypoxia, improving the well-being of anesthetized rats, as well as the quality of the results obtained.

Assessment of general activity and anxiety-like behavior in mice following tramadol and meloxicam administration for managing immediate post-operative pain

After analgesic administration, we evaluated general activity in the Open-Field and anxiety-like behavior in the Elevated Plus Maze of vasectomized mice. We divided C57BL/6J male mice into eight groups: saline, three non-operated control groups treated with 10 mg/kg meloxicam, 20 mg/kg tramadol, or both intraperitoneally, and four vasectomized mice groups treated with the same analgesic protocol as the control groups. One group of vasectomized mice received both treatments and an additional 10 mg/kg lidocaine at the incision site. We conducted the vasectomy via scrotal approach under isoflurane inhalation anesthesia and performed behavioral tests after full anesthesia recovery. Mice treated with meloxicam demonstrated low ambulation, spontaneous activity, and rearing frequency. Mice treated with tramadol showed spontaneous behavior compared with the saline control. Due to behavior changes demonstrated by meloxicam controls, we were unable to identify whether meloxicam provided adequate analgesia. Vasectomized mice treated with tramadol showed general activity behavior similar to their control but displayed significantly less rearing, suggesting that they were under potential signs of pain or discomfort. In conclusion, the Open Field test and the Elevated Plus Maze can usefully pre-evaluate analgesic protocols to identify possible interference caused by adverse drug effects. For future directions, an appropriate regimen of meloxicam and tramadol for enhancing mice welfare post vasectomy should be better investigated.

Behavioral and neurochemical characterization of the spontaneous mutation tremor, a new mouse model of audiogenic seizures

The tremor mutant phenotype results from an autosomal recessive spontaneous mutation arisen in a Swiss–Webster mouse colony. The mutant mice displayed normal development until three weeks of age when they began to present motor impairment comprised by whole body tremor, ataxia, and decreased exploratory behavior. These features increased in severity with aging suggesting a neurodegenerative profile. In parallel, they showed audiogenic generalized clonic seizures. Results from genetic mapping identified the mutation tremor on chromosome 14, in an interval of 5 cM between D14Mit37 (33.21cM) and D14Mit115 (38.21cM), making Early Growth Response 3 (Egr3) the main candidate gene. Comparing with wild type (WT) mice, the tremor mice showed higher hippocampal gene expression of Egr3 and Gabra1 and increased concentrations of noradrenalin (NOR; p=.0012), serotonin (5HT; p=.0083), 5-hydroxyindoleacetic acid (5-HIAA; p=.0032), gama-amino butyric acid (GABA; p=.0123), glutamate (p=.0217) and aspartate (p=.0124). In opposition, the content of glycine (p=.0168) and the vanillylmandelic acid (VMA)/NOR ratio (p=.032) were decreased. Regarding to dopaminergic system, neither dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) contents nor the turnover rate of DA showed statistically significant differences between WT and mutant mice. Data demonstrated that audiogenic seizures of tremor mice are associated with progressive motor impairment as well as to hippocampal alterations of the Egr3 and Gabra1 gene expression and amino acid and monoamine content. In addition, the tremor mice could be useful for study of neurotransmission pathways as modulators of epilepsy and the pathogenesis of epilepsies occurring with generalized clonic seizures.

Síndrome de Horner em cães e gatos: revisão / Horner's syndrome in dogs and cats: a review / Síndrome de Horner en perros y gatos: revisión

Em cães e gatos, a síndrome de Horner (SH) é caracterizada por um conjunto de sinais clínicos oculares oriundos de disfunção ipsilateral da inervação simpática do globo ocular e de seus anexos. Esses sinais incluem ptose palpebral, miose, anisocoria e protrusão da terceira pálpebra e enoftalmia. Lesões que afetem direta ou indiretamente a inervação simpática do globo ocular, tais como traumas, neoplasias, lesões iatrogênicas, otites e encefalites, entre outras, podem causar a SH. O presente estudo teve por objetivo revisar as características anatômicas e fisiológicas da inervação simpática para o globo ocular, com ênfase na descrição das particularidades da SH, incluindo sua etiologia, os sinais clínicos e as ferramentas diagnósticas, além do seus possíveis tratamentos e prognóstico.

In dogs and cats, Horner's syndrome (HS) is characterized by a group of clinical signs arising from an ipsilateral dysfunction of sympathetic innervation of the eye andits appendages. These signs include ptosis, miosis, anisocoria, prolapse of the third eyelid, and enophtalmos. Lesions that may affect directly or indirectly the sympathetic innervation of the eye, such as trauma, neoplasms, iatrogenic lesions, otitis, encephalitis, among others, can induce HS. The aim of the present study was to review the anatomical and physiological characteristics of sympathetic innervation for the ocular globe, with emphasis on the description of the peculiarities of HS, including its etiology, clinical signs, diagnostic tools, as well as its possible treatments and prognosis.

En perros y gatos, el síndrome de Horner (SH) esta caracterizado por una serie de signos clínicos oculares que se originan en una disfunción ipsilateral de la inervación simpática del globo ocular y sus anexos. Los signos clínicos más comunes son la ptosis palpebral, miosis, anisocoria, protrusión del tercer párpado y enoftalmia. Las lesiones que pueden provocar el SH son todas aquelias que afectan directa o indirectamente la inervación simpática del globo ocular, como traumas, neoplasias, lesiones iatrogénicas, otitis y encefalitis. La presente revisión tuvo como objetivo analizar las características anatómicas y fisiológicas de la inervación simpática del globo ocular, con énfasis en las particularidades del SH como su etiología, signos clínicos y herramientas diagnósticas, además de sus posibles tratamientos y pronóstico.

Síndrome de Horner em cães e gatos: revisão / Horner's syndrome in dogs and cats: a review / Síndrome de Horner en perros y gatos: revisión

Em cães e gatos, a síndrome de Horner (SH) é caracterizada por um conjunto de sinais clínicos oculares oriundos de disfunção ipsilateral da inervação simpática do globo ocular e de seus anexos. Esses sinais incluem ptose palpebral, miose, anisocoria e protrusão da terceira pálpebra e enoftalmia. Lesões que afetem direta ou indiretamente a inervação simpática do globo ocular, tais como traumas, neoplasias, lesões iatrogênicas, otites e encefalites, entre outras, podem causar a SH. O presente estudo teve por objetivo revisar as características anatômicas e fisiológicas da inervação simpática para o globo ocular, com ênfase na descrição das particularidades da SH, incluindo sua etiologia, os sinais clínicos e as ferramentas diagnósticas, além do seus possíveis tratamentos e prognóstico.(AU)

In dogs and cats, Horner's syndrome (HS) is characterized by a group of clinical signs arising from an ipsilateral dysfunction of sympathetic innervation of the eye andits appendages. These signs include ptosis, miosis, anisocoria, prolapse of the third eyelid, and enophtalmos. Lesions that may affect directly or indirectly the sympathetic innervation of the eye, such as trauma, neoplasms, iatrogenic lesions, otitis, encephalitis, among others, can induce HS. The aim of the present study was to review the anatomical and physiological characteristics of sympathetic innervation for the ocular globe, with emphasis on the description of the peculiarities of HS, including its etiology, clinical signs, diagnostic tools, as well as its possible treatments and prognosis.(AU)

En perros y gatos, el síndrome de Horner (SH) esta caracterizado por una serie de signos clínicos oculares que se originan en una disfunción ipsilateral de la inervación simpática del globo ocular y sus anexos. Los signos clínicos más comunes son la ptosis palpebral, miosis, anisocoria, protrusión del tercer párpado y enoftalmia. Las lesiones que pueden provocar el SH son todas aquelias que afectan directa o indirectamente la inervación simpática del globo ocular, como traumas, neoplasias, lesiones iatrogénicas, otitis y encefalitis. La presente revisión tuvo como objetivo analizar las características anatómicas y fisiológicas de la inervación simpática del globo ocular, con énfasis en las particularidades del SH como su etiología, signos clínicos y herramientas diagnósticas, además de sus posibles tratamientos y pronóstico.(AU)

Capacitação em Ciência de Animais de Laboratório / Training Course on Laboratory Animal Science

A Ciência de Animais de Laboratório envolve uma abordagem multi-disciplinar com conhecimento do modelo animal e suas necessidades etológicas espécie-específicas, refinamento de experimentos que melhoram o bem-estar animal com reconhecimento e tratamento da dor, anestesia e eutanásia, bem como delineamento experimental e análise estatística dos resultados experimentais. Para atender à essas necessidades, pessoas que realizam, participam, supervisionam procedimentos experimentais em animais, ou cuidam de animais de laboratório, devem receber treinamento, com programas voltados à implementação dos 3Rs e promoção do bem-estar dos animais de laboratório, garantindo assim a qualidade e reprodutibilidade de experimentos com benefícios éticos, científicos e econômicos. Nos países da Europa e nos Estados Unidos, e requerido mais recen-temente pelo Conselho Nacional de Controle de Experimentação Animal (CONCEA) no Brasil, um veterinário com experiência em medicina de animais de laboratório precisa fazer parte da equipe do Biotério. Este veterinário tem um papel fundamental na orientação de profissionais e pesquisadores em questões relacionadas ao bem--estar e cuidado com animais. Diante desta recomendação, fica clara a importância da formação de graduação e de médicos-veterinários para atuar na área de Animais de Laboratório, e poder desempenhar seu papel nos biotérios visando melhorar o cuidado e apoiar estudos experimentais que envolvem esses animais.

Laboratory Animal Science requires a multidisciplinary approach. Professionals working with laboratory animals should have the knowledge on how to choose the right animal model and its species-specific ethological needs, how to choose the best anesthesia, analgesia and euthanasia protocol, how to refine the care procedures including recognition and treatment of pain in order to improve the animals welfare , as well as how to design an experimental and to conduct statistical analysis of the experimental data. To meet these needs, professionals who perform, take part, supervise experimental procedures on animals, or take care of laboratory animals, should receive training, with programs aimed to implement the 3Rs and to promote the welfare of laboratory animals, and therefore guarantee the quality and reproducibility of experiments with ethical, scientific and economic benefits. Veterinarians with experience in laboratory animal medicine are required to be part of the Animal Facility staff in Europe and in the United States, and most recently, in Brazil, established by the National Council for the Control of Animal Experimentation (Concea). Veterinarians working with laboratory animals have a key role in guiding other professionals and researchers regarding issues related to animal welfare and care. Since it is necessary to follow the Concea recommendation, it is visible the importance to have the veterinary undergraduate students and veterinarians properly trained in order to provide the best quality of life for the animals used in research and consequently having relevant, translatable scientific data and the most beneficial use of these animals.

Capacitação em Ciência de Animais de Laboratório / Training Course on Laboratory Animal Science

A Ciência de Animais de Laboratório envolve uma abordagem multi-disciplinar com conhecimento do modelo animal e suas necessidades etológicas espécie-específicas, refinamento de experimentos que melhoram o bem-estar animal com reconhecimento e tratamento da dor, anestesia e eutanásia, bem como delineamento experimental e análise estatística dos resultados experimentais. Para atender à essas necessidades, pessoas que realizam, participam, supervisionam procedimentos experimentais em animais, ou cuidam de animais de laboratório, devem receber treinamento, com programas voltados à implementação dos 3Rs e promoção do bem-estar dos animais de laboratório, garantindo assim a qualidade e reprodutibilidade de experimentos com benefícios éticos, científicos e econômicos. Nos países da Europa e nos Estados Unidos, e requerido mais recen-temente pelo Conselho Nacional de Controle de Experimentação Animal (CONCEA) no Brasil, um veterinário com experiência em medicina de animais de laboratório precisa fazer parte da equipe do Biotério. Este veterinário tem um papel fundamental na orientação de profissionais e pesquisadores em questões relacionadas ao bem--estar e cuidado com animais. Diante desta recomendação, fica clara a importância da formação de graduação e de médicos-veterinários para atuar na área de Animais de Laboratório, e poder desempenhar seu papel nos biotérios visando melhorar o cuidado e apoiar estudos experimentais que envolvem esses animais.(AU)

Laboratory Animal Science requires a multidisciplinary approach. Professionals working with laboratory animals should have the knowledge on how to choose the right animal model and its species-specific ethological needs, how to choose the best anesthesia, analgesia and euthanasia protocol, how to refine the care procedures including recognition and treatment of pain in order to improve the animals welfare , as well as how to design an experimental and to conduct statistical analysis of the experimental data. To meet these needs, professionals who perform, take part, supervise experimental procedures on animals, or take care of laboratory animals, should receive training, with programs aimed to implement the 3Rs and to promote the welfare of laboratory animals, and therefore guarantee the quality and reproducibility of experiments with ethical, scientific and economic benefits. Veterinarians with experience in laboratory animal medicine are required to be part of the Animal Facility staff in Europe and in the United States, and most recently, in Brazil, established by the National Council for the Control of Animal Experimentation (Concea). Veterinarians working with laboratory animals have a key role in guiding other professionals and researchers regarding issues related to animal welfare and care. Since it is necessary to follow the Concea recommendation, it is visible the importance to have the veterinary undergraduate students and veterinarians properly trained in order to provide the best quality of life for the animals used in research and consequently having relevant, translatable scientific data and the most beneficial use of these animals.(AU)

A rabies virus vampire bat variant shows increased neuroinvasiveness in mice when compared to a carnivore variant

Rabies is one of the most important zoonotic diseases and is caused by several rabies virus (RABV) variants. These variants can exhibit differences in neurovirulence, and few studies have attempted to evaluate the neuroinvasiveness of variants derived from vampire bats and wild carnivores. The aim of this study was to evaluate the neuropathogenesis of infection with two Brazilian RABV street variants (variant 3 and crab-eating fox) in mice. BALB/c mice were inoculated with RABV through the footpad, with the 50% mouse lethal dose (LD50) determined by intracranial inoculation. The morbidity of rabies in mice infected with variant 3 and the crab-eating fox strain was 100% and 50%, respectively, with an incubation period of 7 and 6 days post-inoculation (dpi), respectively. The clinical disease in mice was similar with both strains, and it was characterized initially by weight loss, ruffled fur, hunched posture, and hind limb paralysis progressing to quadriplegia and recumbency at 9 to 12 dpi. Histological lesions within the central nervous system (CNS) characterized by nonsuppurative encephalomyelitis with neuronal degeneration and necrosis were observed in mice infected with variant 3 and those infected with the crab-eating fox variant. However, lesions and the presence of RABV antigen, were more widespread within the CNS of variant-3-infected mice, whereas in crab-eating fox-variant-infected mice, RABV antigens were more restricted to caudal areas of the CNS, such as the spinal cord and brainstem. In conclusion, the results shown here demonstrate that the RABV vampire bat strain (variant 3) has a higher potential for neuroinvasiveness than the carnivore variant. (AU) i

A rabies virus vampire bat variant shows increased neuroinvasiveness in mice when compared to a carnivore variant.

Rabies is one of the most important zoonotic diseases and is caused by several rabies virus (RABV) variants. These variants can exhibit differences in neurovirulence, and few studies have attempted to evaluate the neuroinvasiveness of variants derived from vampire bats and wild carnivores. The aim of this study was to evaluate the neuropathogenesis of infection with two Brazilian RABV street variants (variant 3 and crab-eating fox) in mice. BALB/c mice were inoculated with RABV through the footpad, with the 50% mouse lethal dose (LD50) determined by intracranial inoculation. The morbidity of rabies in mice infected with variant 3 and the crab-eating fox strain was 100% and 50%, respectively, with an incubation period of 7 and 6 days post-inoculation (dpi), respectively. The clinical disease in mice was similar with both strains, and it was characterized initially by weight loss, ruffled fur, hunched posture, and hind limb paralysis progressing to quadriplegia and recumbency at 9 to 12 dpi. Histological lesions within the central nervous system (CNS) characterized by nonsuppurative encephalomyelitis with neuronal degeneration and necrosis were observed in mice infected with variant 3 and those infected with the crab-eating fox variant. However, lesions and the presence of RABV antigen, were more widespread within the CNS of variant-3-infected mice, whereas in crab-eating fox-variant-infected mice, RABV antigens were more restricted to caudal areas of the CNS, such as the spinal cord and brainstem. In conclusion, the results shown here demonstrate that the RABV vampire bat strain (variant 3) has a higher potential for neuroinvasiveness than the carnivore variant.