Evolution of Spinal Cord Transection of Rhesus Monkey Implanted with Polymer Synthesized by Plasma Evaluated by Diffusion Tensor Imaging.

In spinal cord injury (SCI) there is damage to the nervous tissue, due to the initial damage and pathophysiological processes that are triggered subsequently. There is no effective therapeutic strategy for motor functional recovery derived from the injury. Several studies have demonstrated neurons growth in cell cultures on polymers synthesized by plasma derived from pyrrole, and the increased recovery of motor function in rats by implanting the polymer in acute states of the SCI in contusion and transection models. In the process of transferring these advances towards humans it is recommended to test in mayor species, such as nonhuman primates, prioritizing the use of non-invasive techniques to evaluate the injury progression with the applied treatments. This work shows the ability of diffusion tensor imaging (DTI) to evaluate the evolution of the SCI in nonhuman primates through the fraction of anisotropy (FA) analysis and the diffusion tensor tractography (DTT) calculus. The injury progression was analysed up to 3 months after the injury day by FA and DTT. The FA recovery and the DTT re-stabilization were observed in the experimental implanted subject with the polymer, in contrast with the non-implanted subject. The parameters derived from DTI are concordant with the histology and the motor functional behaviour.

Sensory and memory processing in old female and male Wistar rat brain, and its relationship with the cortical and hippocampal redox state.

The brain is one of the most sensitive organs damaged during aging due to its susceptibility to the aging-related oxidative stress. Hence, in this study, the sensory nerve pathway integrity and the memory were evaluated and related to the redox state, the antioxidant enzymes function, and the protein oxidative damage in the brain cortex (Cx) and the hippocampus (Hc) of young (4-month-old) and old (24-month-old) male and female Wistar rats. Evoked potentials (EP) were performed for the auditory, visual, and somatosensory pathways. In both males and females, the old rat groups' latencies were larger in almost all waves when compared to the young same-sex animals. The novel object test was performed to evaluate memory. The superoxide dismutase and catalase antioxidant activity, as well as the protein oxidative damage, and the redox state were evaluated. Magnetic resonance (MR) imaging was used to obtain the diffusion tensor imaging, and the brain volume, while MR spectroscopy was used to obtain the brain metabolite concentrations (glutamine, glutamate, Myo-inositol, N-acetyl-aspartate, creatine) in the Cx and the Hc of young and old females. Our data suggest that, although there are limited variations regarding memory and nerve conduction velocity by sex, the differences concerning the redox status might be important to explain the dissimilar reactions during brain aging between males and females. Moreover, the increment in Myo-inositol levels in the Hc of old rats and the brain volume decrease suggest that redox state alterations might be correlated to neuroinflammation during brain aging.

Effect of different anesthetic mixtures-ketamine-xylazine, ketamine-acepromazine and tiletamine-zolazepam-on the physiological and blood biochemistry parameters of male rhesus monkeys (Macaca mulatta) at different ages.

BACKGROUND: Anesthetic agents are commonly utilized in the handling of non-human primates for prevent the stress caused in physical exploration or physical restrain. For this reason, the objective of this work was to describe the effect of age and dissociative anesthetics (ketamine and tiletamine), and their combinations with acepromazine, xylazine and zolazepam, on the physiological and blood biochemical parameters in Macaca mulatta. METHODS: Eighty male Macaca mulatta were divided into four experimental groups depending on the anesthetic mixture applied. Each group of 20 males was divided into five sub-groups according to age. Physiological parameters were recorded every 5 minutes during a 30-minute period. A blood sample was drawn to analyze blood biochemistry. RESULTS: Statistical analyses revealed significant differences in the physiological parameters between the ketamine-acepromazine and ketamine-xylazine groups compared to the control group. The analysis of blood biochemistry found significant differences by age and by anesthetic mixture among all groups. CONCLUSION: These findings contribute to standardizing this animal model in biological research.

Computed tomography is a feasible method for quantifying bone density in Macaca mulatta.

Osteopathologies are a result of advanced age and decreased bone density and represent a global health problem. It is therefore important to generate models for longitudinal studies of the pathophysiology in order to improve early diagnosis and develop preventive therapies. For this kind of research, the use of computed tomography (CT) to evaluate bone health offers advantages over other techniques since it provides more complete information. The aim of this prospective, pilot study was to obtain measurements of the left femur from a population in captivity of 32 rhesus monkeys (Macaca mulatta) in order to standardize the model for future research. Healthy subjects from 5 to 28 years old were chosen. Three groups with different ages were formed as follows: (1) 5-9 years, (2) 10-19 years, and (3) 20-28 years. Semi-automatic segmentation by threshold defined the regions of interest, which were subdivided in the range of 300-700 Hounsfield units (HU) for trabecular bone and >700 HU for cortical bone. Then, the proportional ratios of the volumes of trabecular bone and cortical bone were obtained. Significant differences (analysis of variance test) in the averages of Hounsfield units, cortical, and trabecular bone proportions from each age group proved that a decrease in bone density begins at approximately 20 years of age. The values presented here, as well as the method to obtain them from CT scans, can be used as a baseline in a primate model for long-term research in bone pathology diagnosis and treatment.

Effect of age on electrical nerve conduction in the somatosensory pathway and its correlation with somatometry and plasma concentrations of musculoskeletal enzymes in male rhesus monkeys (Macaca mulatta) held in captivity.

BACKGROUND: Somatosensory evoked potentials (SEPs) make it possible to obtain functional data on the activity of somatosensory pathway. OBJECTIVE: To evaluate the ontogeny of electrical nerve conduction in male rhesus monkeys using SEPs in correlation with the development of the musculoskeletal system based on somatometry and musculoskeletal enzymes. METHODS: Somatosensory evoked potentials of the medial and tibial nerves were performed, and somatometric measurements were obtained: total length, arm and forearm length, and thigh and calf length. Analysis of the musculoskeletal enzymes, lactic dehydrogenase, and creatininase was conducted using blood samples in 20 rhesus monkeys divided into 5 groups. RESULTS: Statistical analysis manifested a delay in the appearance of latencies as age increased. Also evident was a strong, direct relation between the lengths and the value of the latencies of the SEP, together with an inverse relation between the musculoskeletal enzymes. CONCLUSIONS: These findings contribute to standardizing this animal model in the neurophysiological sciences.

Multiple extrauterine pregnancy with early and near full-term mummified fetuses in a New Zealand white rabbit (Oryctolagus cuniculus).

Extrauterine pregnancy (EP) is infrequent in mammalian species and occurs when fertilized ova implant and develop outside the uterus. A common outcome is abdominal pregnancy resulting in mummified fetuses (lithopedia). Here we describe an unusual case of abdominal pregnancy with early and near full-term lithopedia. Macroscopic findings supported the diagnosis of lithopedia with distinct age differences and facilitated further characterization of primary ectopia and risk factors leading to this occurrence.

Absence of the right wing of the ilium generated a compensatory scoliosis in rhesus monkey in captivity: diagnostic imaging and its alteration on the SEPNT.

BACKGROUND: Congenital scoliosis (CS) is defined as lateral curvatures of the spine provoked by the anomalous development of the vertebral bodies. It is associated with neuromuscular anomalies, which can be genetic, caused by the compensation of discrepancies in the length of the extremities or intrarachidian anomalies. METHODS: This study was carried out in 2-year-old female, showed alterations in the gait, mainly in the hind limbs, a clumsy gait and a slight claudication in the right hindlimb. To perform the imaging study were: X-Ray projections and Computerized Axial Tomography, neurophysiological evaluation was performed by means somatosensory-evoked potentials of the tibial nerve (SEPTN). RESULTS: The results showed an enlargement of the latencies from the L5 to the cortex, mainly in the left afference, correlated with the imaging studies. CONCLUSIONS: There is no doubt that the concurrent use of different diagnostic tools complements knowledge regarding the physiopathogenesis of these osteopathologies.

Changes in blood parameters in rhesus monkeys (Macaca mulatta) during the first trimester of gestation.

BACKGROUND: Regarding the good practice in the laboratory work, it is essential to have a broad spectrum of biochemical and hematological references in pregnant females to determine the health status of the colony. OBJECTIVE: To establish reference values to reveal changes in hematology and blood chemistry in pregnant rhesus monkeys (Macaca mulatta) in their first trimester of pregnancy. METHODS: Twenty-eight females in reproductive stage were used, divided into two groups: 14 pregnant macaques in their first trimester and 14 non-pregnant used as the control group. Blood samples were collected for the hematological test and blood chemistry. RESULTS: The results showed significant difference in the blood chemistry for the following parameters: glucose, total bilirubin, and total protein. The hematological evaluation revealed significant difference in leukocytes and neutrophils. CONCLUSIONS: These findings offer a reference range and provide a basis for improvement in techniques and refinement of clinical processes in these specimens.

Preliminary studies of neurosensory and cardiopulmonary health compromise in captive- bred Rhesus macaques (Macaca mulatta) suffering scoliosis.

BACKGROUND: It has been widely documented that quadrupedal animals rarely display natural spontaneous scoliotic rachis deviations of the spinal column. The objective was to determine spinal deformities developed by geriatric monkeys of the Macaca mulatta species, by radiographical and tomographical studies of the vertebral column correlating morphological changes with altered physiological parameters and electrical neurosensorial conductivity of somatosensory-evoked potentials (SEPs). MATERIALS AND METHODS: A cohort of six geriatric monkeys was used: three non-scoliotic subjects and three monkeys with naturally acquired true scoliosis. RESULTS: Radiographic and tomographic studies depicted a thoracic curvature displaying a left-sided thoracic vertebral rotation. The evaluation of physiological parameters demonstrated significant differences in the respiratory rate, as it was observed for the diastolic blood pressures, which showed a decrease in the monkeys with scoliosis compared with healthy monkeys. Regarding the SEPs studies, the non-parametric test for independent samples Mann-Whitney U test displayed a significant difference observed at the left and right thoracic derivative in P1; while regarding the study of upper limbs, a significant difference was seen at the Erb's point derivative, left afferency in P1, showing in all the derivatives an increase in latency in monkeys with scoliosis versus monkeys in the control group. CONCLUSIONS: This study has demonstrated that quadrupedal animals can develop true scoliosis showing an analogous way to that occurring in humans.

New approach for graded compression spinal cord injuries in Rhesus macaque: method feasibility and preliminary observations.

BACKGROUND: Current models of spinal cord injury (SCI) have been ineffective for translational research. Primate blunt SCI, which more closely resembles human injury, could be a promising model to fill this gap. METHODS: Graded compression SCI was produced by inflating at T9 an epidural balloon as a function of spinal canal dimensions in a non-uniform group of monkeys. RESULTS: Sham injury and cord compression by canal invasion of 50-75% produced minimal morpho-functional alterations, if at all. Canal invasion of 90-100% resulted in proportional functional deficits. Unexpectedly, these animals showed spontaneous gradual recovery over a 12-week period achieving quadruped walking, although with persistent absence of foot grasping reflex. Histopathology revealed predominance of central cord damage that correlated with functional status. CONCLUSIONS: Our preliminary results suggest that this model could potentially be a useful addition to translational work, but requires further validation by including animals with permanent injuries and expansion of replicates.

Characterization of spontaneous subclavian steal phenomenon in a female rhesus macaque (Macaca mulatta).

In subclavian steal phenomenon (SSP), the subclavian artery develops a stenoocclusive disease proximal to the origin of the vertebral artery, leading to pronounced hemodynamic changes such as arterial flow reversal. Although SSP is a common echographic finding in humans, the phenomenon occurs only rarely in animals; consequently its physiologic features have not been reported previously. Here we describe the clinical and morphologic features of a spontaneous left SSP that was an incidental finding in an 18-y-old female rhesus macaque (Macaca mulatta). Our findings were documented through high-quality imaging studies obtained by using a computerized 3D tomography apparatus and clinical assessment of systolic and diastolic blood pressures.

Latencies obtained of the somatosensory evoked potentials of the median and tibial nerve in rhesus monkey undergoing intrauterine laminectomy to simulate myelomeningocele.

BACKGROUND: Somatosensory evoked potentials (SSEP) have been described as excellent indicators of the degree of medullar injury in degenerative and metabolic diseases of the central nervous system (CNS). The prevalence of neural tube defects (NTD) is 6 cases/10,000 live newborns worldwide. It is thought that genetic as well as environmental factors contribute to the etiology of NTD. The objective of this study was to analyze and compare the latencies obtained by means of SSEP in a clinically healthy monkey vs. rhesus monkeys with intrauterine surgery in order to simulate surgically the neural tube defect (myelomengocele) by performing an intrauterine laminectomy and in which later the defect was corrected. METHODS: This study was performed using three non-human primates of the Macaca mulatta species. There were practice intrauterine surgeries in two monkeys to simulate the neurological defect produced by myelomeningocele, using the third monkey as control. For statistical methodology four monkeys were used. They were born by natural birth without any surgical manipulation. With the cesarean-obtained products, stimulation was performed of the tibial and median nerve. RESULTS: We observed that the hind limbs were the most affected, in particular, the left afferent of the monkey. The spinal cord was exposed to amniotic fluid, and there were no significant differences in the forelimbs. CONCLUSIONS: The use of SSEP provides valuable information regarding preservation of sensorial functions in a variety of experimental neurological abnormalities.

Somatosensory evoked potentials of median and tibial nerves in rhesus monkeys (Macaca mulatta) under captivity: influence of ontogenic status in neonatal, infant, young, adult, and senile stages.

BACKGROUND: Somatosensory evoked potentials (SEPs) constitute a useful neurophysiologic tool commonly used to assess the functionality and developmental degree of the nervous system. OBJECTIVE: To analyze somatosensory pathways of the Macaca mulatta species throughout different ontogenetic statuses. METHODS: Twenty non-human primates were divided into five age-dependant groups. Recording of SEPs was executed by stimulation of lower limb at the tibial nerve and upper limb and recorded at the median nerve. RESULTS: Two wave series were observed for all groups for both limbs studied. Significant differences were found at the upper right limb at C4, C7 and also for the antecubital fossa site. The lower limbs showed a single significant right-wing deflection. CONCLUSIONS: Differences found in signals generated by the nervous system in response to somatosensory stimuli among the studied groups are thought to be developmental in origin, as the most remarkable deviations were seen in younger monkeys.

Anesthetic management in intrauterine surgery to evaluate an experimental model of myelomeningocele in non human primates (Macaca mulatta) / Anestesia em cirurgia intra-uterina para avaliar um modelo experimental de mielomeningocele em primatas não humanos (Macaca mulatta)

PURPOSE: Evaluate the anesthetic management in intrauterine surgery to induce myelomeningocele in non human primates Macaca mulatta. METHODS: A total of nine fetuses had intrauterine surgery; laminectomy was performed on them in L5 and L6. The studied variables were: maternal death, fetus death, cardiac frequency, respiratory frequency, arterial pressure, temperature, and oxygen saturation. RESULTS: No maternal or fetal deaths occurred; the only variable that was reported below the normal ranges was temperature. CONCLUSION: No maternal or fetal deaths occurred; the only variable that was reported below the normal ranges was temperature.

OBJETIVO: Avaliar o manejo anestésico em cirurgia intra-uterina para induzir mielomeningocelo em primatas não humanos, Macaca mulatta. MÉTODOS: Operaram-se um total de nove fetos in útero que foram submetidos à laminectomia em L5 e L6. As variáveis a estudar foram mortes maternas ou fetais, freqüência cardíaca e respiratória, pressão arterial, temperatura e saturação de oxigênio. RESULTADOS: Não se apresentaram mortes maternas ou fetais, a temperatura se manteve abaixo dos 36°C, não tendo repercussões no bem-estar dos macacos. CONCLUSÃO: Não ocorreu nenhum óbito materno ou fetal, sendo que a única variável abaixo do normal foi a temperatura.

Anesthetic management in intrauterine surgery to evaluate an experimental model of myelomeningocele in non human primates (Macaca mulatta).

PURPOSE: Evaluate the anesthetic management in intrauterine surgery to induce myelomeningocele in non human primates Macaca mulatta. METHODS: A total of nine fetuses had intrauterine surgery; laminectomy was performed on them in L5 and L6. The studied variables were: maternal death, fetus death, cardiac frequency, respiratory frequency, arterial pressure, temperature, and oxygen saturation. RESULTS: No maternal or fetal deaths occurred; the only variable that was reported below the normal ranges was temperature. CONCLUSION: No maternal or fetal deaths occurred; the only variable that was reported below the normal ranges was temperature.

Radiographic incidence of spinal osteopathologies in captive rhesus monkeys (Macaca mulatta).

Degenerative spinal disease is a leading cause of chronic disability both in humans and animals. Although widely seen as a normal occurrence of aging, degenerative spinal disease can be caused by various genetic, iatrogenic, inflammatory, and congenital factors. The objective of this study was to characterize the degenerative spine-related diseases and the age at onset in a random subpopulation of 20 captive rhesus monkeys (Macaca mulatta; male, 13; female, 7; age: range, 4 to 27 y; median, 18.5 y). Spinal radiographic evaluation (left lateral, right lateral, and ventrodorsal views) of the spinal column (C1 to S1) was performed, and spinal degenerative disease was scored. The incidence of osteopathology was higher in the 14- to 18-y-old group, but incidence did not differ according to sex. In the studied population, degenerative changes were present in monkeys as young as 9 y of age.

[Development of an animal model of myelomeningocele and options for prenatal treatment in Macaca mulatta]. / Desarrollo de un modelo animal de mielomeningocele y opciones de tratamiento prenatal en Macaca mulatta.

BACKGROUND: Myelomeningocele is the most common congenital malformation of the central nervous system, with a reported incidence of 4.4-4.6 cases/10,000 live births in the U.S. Experimental studies demonstrated that the neurological deficit is not a cause for a primary defect in neurulation but is probably due to the progressive mechanical and chemical damage of amniotic liquid into the nerve tissue, which remained without protection during gestation. We undertook this study to develop an animal model in myelomeningocele in Macaca mulatta and compare the results of prenatal management between the colocations of an impermeable silicone mesh and closed with skin. METHODS: A total of nine macaques were surgically intervened, randomly assigned between 12 and 14 weeks of gestation. A laminectomy was carried out in a fetus with bone marrow exposure. The defect was closed with skin or mesh. Three fetuses were left completely exposed. Descriptive statistics were done by ANOVA. RESULTS: Of the four surviving fetuses (44%), none presented complications in mobility in the somatosensory evoked potential, hydrocephalus, or in sphincter control. Only one fetus developed bony deformities. The majority of time of the surgical procedure was due to the use of mesh and the least amount of time was involved in skin closing (p<0.005). CONCLUSIONS: Macaca mulatta is an appropriate model for reproducing myelomeningocele and to evaluate the different options for prenatal management. Colocation of an impermeable silicone mesh is feasible, protecting the spine from amniotic liquid, with results similar to skin closure.

Serum testosterone and electroencephalography spectra in developmental male rhesus Macaca mulatta monkeys.

BACKGROUND: The main objectives in this work were to determine whether the relationship between serum testosterone concentration and electroencephalography (EEG) develop mental change observed in human males is also present in Macaca mulatta and, if so, to determine which frequency bands are involved and which regions change in pre-pubertal monkeys as a function of serum testosterone concentration. METHODS: Nine healthy monkeys were divided into three groups according to age. Serum testosterone was measured using immunoenzymatic chemiluminescent assay. EEG results were processed using Fast Fourier transform; average relative spectral power analysis was calculated and separated into delta and theta bands. RESULTS: The main findings were higher delta relative power in temporal area of the youngest group. Significant positive correlations were observed between serum testosterone levels and theta relative power across the entire scalp, and between theta relative power at frontal and temporal locations and in negative direction between delta relative power in temporal areas. Partial correlations controlling for cephalic perimeter remained significant between testosterone and total theta relative power and theta relative power in temporal areas. Partial correlations remained significant for theta relative power controlling for age at temporal locations. CONCLUSIONS: Our data show that testosterone may be a significant covariate in EEG development in Macaca mulatta males.