Mouse Behavior in the Open-field Test after Meloxicam Administration.

Several analgesics are suggested for pain management in mice. Nonsteroidal antiinflammatories (NSAIDs), such as meloxicam can be administered for the treatment of inflammation and acute pain; however, several side effects can occur which include gastrointestinal ulceration and renal and hepatic toxicity. We previously performed a pilot study to test the antinociceptive activity of meloxicam in mice, but we observed behavioral changes in unoperated control mice. These observations spurred further investigation. One hypothesis for the result was potential differences in formulation between commercial brands of meloxicam. Thus, this current study aimed to evaluate the effects of 3 different commercial brands of meloxicam (20 mg/kg) in the general activity of mice using the open field test. Our results showed that meloxicam had several effects on mouse behavior and caused the formation of skin lesions at the injection site, depending on the brand of the drug. The most significant adverse effect observed was decreased exploratory activity. Grooming frequency was reduced in all groups. These adverse effects might be related to the quality of the drugs because meloxicam formulations can contain crystal polymorphisms that affect drug quality and efficacy. This study points out the importance of drug quality variation that can affect the outcome of behavioral studies in mice.

Equine herpesvirus 1 elicits a strong pro-inflammatory response in the brain of mice.

Equine herpesvirus type 1 (EHV-1) is an emerging pathogen that causes encephalomyelitis in horses and non-equid species. Several aspects of the immune response in the central nervous system (CNS), mainly regarding the role of inflammatory mediators during EHV-1 encephalitis, remain unknown. Moreover, understanding the mechanisms underlying extensive neuropathology induced by viruses would be helpful to establish therapeutic strategies. Therefore, we aimed to evaluate some aspects of the innate immune response during highly neurovirulent EHV-1 infection. C57BL/6 mice infected intranasally with A4/72 and A9/92 EHV-1 strains developed a fulminant neurological disease at 3 days post-inoculation with high viral titres in the brain. These mice developed severe encephalitis with infiltration of monocytes and CD8+ T cells to the brain. The inflammatory infiltrate followed the detection of the chemokines CCL2, CCL3, CCL4, CCL5, CXCL2, CXCL9 and CXCL-10 in the brain. Notably, the levels of CCL3, CCL4, CCL5 and CXCL9 were higher in A4/72-infected mice, which presented higher numbers of inflammatory cells within the CNS. Pro-inflammatory cytokines, such as interleukins (ILs) IL-1α, IL-1ß, IL-6, IL-12ß, and tumour necrosis factor (TNF), were also detected in the CNS, and Toll-like receptor (TLR) TLR2, TLR3 and TLR9 genes were also upregulated within the brain of EHV-1-infected mice. However, no expression of interferon-γ (IFN-γ) and IL-12α, which are important for controlling the replication of other herpesviruses, was detected in EHV-1-infected mice. The results show that the activated innate immune mechanisms could not prevent EHV-1 replication within the CNS, but most likely contributed to the extensive neuropathology. The mouse model of viral encephalitis proposed here will also be useful to study the mechanisms underlying extensive neuropathology.

A Simple and Fast Battery Test for Phenotypic Characterization of Mice.

Despite the great number of test batteries already known to assess the behavior of genetically modified and inbred strains of mice, only a few of them focus on basic neurological parameters. The purpose of the battery test proposed is to settle a specific methodology to characterize the phenotype of neurological disease models in mutant or genetically modified mice. This methodology is simple and efficient in order to analyze several parameters, including general activity, sensory nervous system, sensorimotor system, central nervous system and autonomous nervous system. This can aid the choice of specific additional tests as well as the determination of an interrelationship among phenotypic alterations observed. Although being efficient for a first analysis of a mouse model, interpretation of the results must be carefully made because phenotype manifestation may vary due to many parameters, including mouse strain, environmental and housing condition, animal-experimenter interaction, sample size and tests order. It is important to consider as a critical point if handling procedures are aversive. The results acquired with the analysis of 18 parameters together provide preliminary data to characterize mouse phenotype and helps selecting more specific tests.

Combination of ketamine and xylazine with opioids and acepromazine in rats: Physiological changes and their analgesic effect analysed by ultrasonic vocalization.

In this study, the effect of four anaesthetic protocols that included the combination of xylazine (X) and ketamine (K) with acepromazine (A) and opioids (methadone (Me), morphine (Mo) or tramadol (T)) was evaluated in laboratory rats of both sexes. Ultrasonic vocalization (USV) was used as an indicator of pain during the recovery period. The objective was to evaluate the physiological parameters and the analgesic effect of each protocol to determine which protocol was the safest and fulfil the requirements of a balanced anaesthesia. The better protocols were the XKA protocol for both sexes and the XKMe protocol for females because the combinations achieve surgical plane of anaesthesia in rats. However, pain assessment during the formalin test revealed that rats anaesthetized with XKA produced more numbers of USV, suggesting that it is not a good protocol for the control of immediate postoperative pain. All protocols produced depression in body temperature and respiratory and heart rates, and had important effects, such as micturition and maintenance of open eyes. Only rats anaesthetized with XKA protocol did not present piloerection. These results demonstrated that good monitoring and care during anaesthesia must be included to prevent complications that compromise the life of the animal and to ensure a good recovery. The inclusion of analgesia in anaesthesia protocols must be used routinely, ensuring minimal presence of pain and thus more reliable results in the experimental procedures.

Genetic and behavioral characterization of a Kmt2d mouse mutant, a new model for Kabuki Syndrome.

The recessive mutant mice bate palmas (bapa) - claps in Portuguese arose from N-ethyl-N-nitrosourea mutagenesis. A single nucleotide, T > C, change in exon 13, leading to a Thr1289 Ala substitution, was identified in the lysine (K)-specific methyltransferase 2D gene (Kmt2d) located on chromosome 15. Mutations with a loss-of-function in the KMT2D gene on chromosome 12 in humans are responsible for Kabuki syndrome (KS). Phenotypic characterization of the bapa mutant was performed using a behavioral test battery to evaluate the parameters related to general activity, the sensory nervous system, the psychomotor system, and the autonomous nervous system, as well as to measure motor function and spatial memory. Relative to BALB/cJ mice, the bapa mutant showed sensory and psychomotor impairments, such as hypotonia denoted by a surface righting reflex impairment and hindquarter fall, and a reduction in the auricular reflex, suggesting hearing impairment. Additionally, the enhanced general activity showed by the increased rearing and grooming frequency, distance traveled and average speed possibly presupposes the presence of hyperactivity of bapa mice compared with the control group. A slight motor coordination dysfunction was showed in bapa mice, which had a longer crossing time on the balance beam compared with BALB/cJ controls. Male bapa mice also showed spatial gait pattern changes, such as a shorter stride length and shorter step length. In conclusion, the bapa mouse may be a valuable animal model to study the mechanisms involved in psychomotor and behavior impairments, such as hypotonia, fine motor coordination and hyperactivity linked to the Kmt2d mutation.

Equine herpesvirus type 1 induces both neurological and respiratory disease in Syrian hamsters.

The equine herpesvirus type 1 (EHV-1) is an important cause of myeloencephalopathy and respiratory disease in horses. Animal models for EHV-1 infection have been specially developed using mice and Syrian hamsters (Mesocricetus auratus). However, few studies have attempted to evaluate the pathogenesis of EHV-1 infection in the central nervous system (CNS) and respiratory system of hamsters. Therefore, the aim of this study was to evaluate the pathogenesis of four Brazilian EHV-1 strains within the CNS and lungs of Syrian hamsters. Hamsters intranasally infected with A4/72, A9/92, A3/97, and Iso/72 EHV-1 strains developed severe neurological and respiratory signs and died during acute EHV-1 infection within 3 to 5days post-inoculation. However, neurological signs were more severe in A4/72 and A9/92-infected hamsters, whereas respiratory signs were more prominent in A3/97 and Iso/72-infected hamsters. In the latter, lesions in the CNS were predominantly inflammatory, whereas in A4/72 and A9/92-infected hamsters, neuronal and liquefactive necrosis were the predominant lesions. EHV-1 infected hamsters also developed an interstitial pneumonia with infiltration of alveolar septa by macrophages, neutrophils, and lymphocytes, with the exception of A9/92-infected hamsters, which developed severe hemorrhages within the airways. EHV-1 antigens were detected along with CNS and pulmonary lesions. EHV-1 was also recovered from CNS of all infected hamsters, whereas the virus was recovered from the lungs of A4/72, A9/92, and Iso/72-infected hamsters. Brazilian EHV-1 strains caused both severe CNS and respiratory disease in hamsters, thus making this species an interesting model for EHV-1 infection in the CNS and respiratory system.

Equine herpesvirus type 1 induces both neurological and respiratory disease in Syrian hamsters

The equine herpesvirus type 1 (EHV-1) is an important cause of myeloencephalopathy and respiratory disease in horses. Animal models for EHV-1 infection have been specially developed using mice and Syrian hamsters (Mesocricetus auratus). However, few studies have attempted to evaluate the pathogenesis of EHV-1 infection in the central nervous system (CNS) and respiratory system of hamsters. Therefore, the aim of this study was to evaluate the pathogenesis of four Brazilian EHV-1 strains within the CNS and lungs of Syrian hamsters. Hamsters intranasally infected with A4/72, A9/92, A3/97, and Iso/72 EHV-1 strains developed severe neurological and respiratory signs and died during acute EHV-1 infection within 3 to 5 days post-inoculation. However, neurological signs were more severe in A4/72 and A9/92-infected hamsters, whereas respiratory signs were more prominent in A3/97 and Iso/72-infected hamsters. In the latter, lesions in the CNS were predominantly inflammatory, whereas in A4/72 and A9/92-infected hamsters, neuronal and liquefactive necrosis were the predominant lesions. EHV-1 infected hamsters also developed an interstitial pneumonia with infiltration of alveolar septa by macrophages, neutrophils, and lymphocytes, with the exception of A9/92-infected hamsters, which developed severe hemorrhages within the airways. EHV-1 antigens were detected along with CNS and pulmonary lesions. EHV-1 was also recovered from CNS of all infected hamsters, whereas the virus was recovered from the lungs of A4/72, A9/92, and Iso/72-infected hamsters. Brazilian EHV-1 strains caused both severe CNS and respiratory disease in hamsters, thus making this species an interesting model for EHV-1 infection in the CNS and respiratory system.(AU) i