ABSTRACT
Inhibitory extracellular matrices form around mature neurons as perineuronal nets containing chondroitin sulfate proteoglycans that limit axonal sprouting after CNS injury. The enzyme chondroitinase (Chase) degrades inhibitory chondroitin sulfate proteoglycans and improves axonal sprouting and functional recovery after spinal cord injury in rodents. We evaluated the effects of Chase in rhesus monkeys that had undergone C7 spinal cord hemisection. Four weeks after hemisection, we administered multiple intraparenchymal Chase injections below the lesion, targeting spinal cord circuits that control hand function. Hand function improved significantly in Chase-treated monkeys relative to vehicle-injected controls. Moreover, Chase significantly increased corticospinal axon growth and the number of synapses formed by corticospinal terminals in gray matter caudal to the lesion. No detrimental effects were detected. This approach appears to merit clinical translation in spinal cord injury.
Subject(s)
Chondroitinases and Chondroitin Lyases/therapeutic use , Spinal Cord Injuries/drug therapy , Animals , Axons/pathology , Chondroitinases and Chondroitin Lyases/administration & dosage , Chondroitinases and Chondroitin Lyases/adverse effects , Gray Matter/pathology , Hand/innervation , Hand/physiopathology , Injections, Intralesional , Macaca mulatta , Male , Microglia/pathology , Motor Neurons/pathology , Psychomotor Performance , Pyramidal Tracts/pathology , Recovery of Function , Spinal Cord Injuries/physiopathology , Swine , Synapses/pathology , Treatment OutcomeABSTRACT
The goal of this study was to generate reference intervals for echocardiographic variables in a population of clinically normal geriatric rhesus macaques (Macaca mulatta). To do this, we studied 51 animals (age, 18-29 y; weight, 5.24-17.04 kg). The normal values for cardiac indices, including geometry and systolic and diastolic function, were determined by 2D, M-mode, spectral Doppler, and tissue Doppler echocardiography under ketamine hydrochloride sedation. Statistical correlations between the echocardiographic parameters and age, body weight, sex, and heart rate were investigated. All echocardiographic indices were acquired, and their reference intervals were established. Multiple weak to strong correlations emerged between variables and echocardiographic parameters, but no moderate or strong correlations between body weight or sex and these parameters were noted. Of the 51 geriatric rhesus macaques evaluated, 36 (71%) fulfilled the criteria for diastolic dysfunction. Valve regurgitation, especially tricuspid regurgitation (43%), and aortic regurgitation (51%) also were common in geriatric rhesus macaques. Although these findings merit follow-up, they are unlikely to have clinical significance given their prevalence in these apparently healthy animals.
Subject(s)
Macaca mulatta/physiology , Animals , Diastole , Echocardiography, Doppler/veterinary , Female , Humans , Hypnotics and Sedatives/administration & dosage , Ketamine/administration & dosage , Male , Reference Values , SystoleABSTRACT
Endometriosis affects a large percentage of the rhesus macaques (Macaca mulatta) at our institution. When the disease is diagnosed in macaques on long-term research protocols, the treatment of choice in our facility is monthly administration of medroxyprogesterone acetate (MPA) to decrease estrogen release and subsequently diminish clinical signs associated with the disease. Because hormonal fluctuations associated with the normal menstrual cycle are known to affect parameters of glucoregulatory function in rhesus macaques, we evaluated the effect of MPA treatment on glucoregulatory function cross-sectionally in 6 animals and longitudinally in 4 animals with endometriosis. Our hypothesis was that monthly administration of MPA for the treatment of endometriosis would negatively affect glucoregulatory function in rhesus macaques. We found that adult female rhesus macaques on MPA therapy for 1.4 to 36.1 mo had lower insulin sensitivity than did age- and weight-matched healthy control animals. In addition, glucoregulatory function was reduced after MPA treatment as compared with pretreatment levels in a group of 4 macaques. These data suggest that glucoregulatory function should be considered when endometriosis treatment is planned for rhesus macaques.
