Kinetics and MR-Based Monitoring of AAV9 Vector Delivery into Cerebrospinal Fluid of Nonhuman Primates.

Here we evaluated the utility of MRI to monitor intrathecal infusions in nonhuman primates. Adeno-associated virus (AAV) spiked with gadoteridol, a gadolinium-based MRI contrast agent, enabled real-time visualization of infusions delivered either via cerebromedullary cistern, lumbar, cerebromedullary and lumbar, or intracerebroventricular infusion. The kinetics of vector clearance from the cerebrospinal fluid (CSF) were analyzed.

Targeted Delivery and Tolerability of MRI-Guided CED Infusion into the Cerebellum of Nonhuman Primates.

This study explored the feasibility of intraparenchymal delivery (gadoteridol and/or Serotype 5 Adeno-Associated Viral Vector-enhanced Green Fluorescent Protein [AAV5-eGFP]) into the cerebellum of nonhuman primates using real-time magnetic resonance imaging-guided convection enhanced delivery (MRI-CED) technology. All animals tolerated the neurosurgical procedure without any clinical sequela. Gene expression was detected within the cerebellar parenchyma at the site of infusion and resulted in transduction of neuronal cell bodies and fibers.

Intermittent convection-enhanced delivery of GDNF into rhesus monkey putamen: absence of local or cerebellar toxicity.

Glial cell line-derived neurotrophic factor (GDNF) has demonstrated neurorestorative and neuroprotective effects in rodent and nonhuman primate models of Parkinson's disease. However, continuous intraputamenal infusion of GDNF (100 µg/day) resulted in multifocal cerebellar Purkinje cell loss in a 6-month toxicity study in rhesus monkeys. It was hypothesized that continuous leakage of GDNF into the cerebrospinal fluid compartment during the infusions led to down-regulation of GDNF receptors on Purkinje cells, and that subsequent acute withdrawal of GDNF then mediated the observed cerebellar lesions.

Plasma and CSF oxytocin levels after intranasal and intravenous oxytocin in awake macaques.

Oxytocin (OT) is a neuropeptide that mediates a variety of complex social behaviors in animals and humans. Intranasal OT has been used as an experimental therapeutic for human conditions characterized by deficits in social functioning, especially autism spectrum disorder and schizophrenia. However, it is currently under intense debate whether intranasal delivery of OT reaches the central nervous system.

Microsatellite markers for standardized genetic management of captive colonies of rhesus macaques (Macaca mulatta).

To preserve genetic variability and minimize genetic subdivision among captive Macaca mulatta at each of the U.S. National Institutes of Health (NIH)-sponsored regional research colonies, the genetic structure of each colony must be characterized.

Comparative efficacy of a canine distemper-measles and a standard measles vaccine for immunization of rhesus macaques (Macaca mulatta).

Measles virus (MV), a highly infective paramyxovirus, has caused sporadic epizootics characterized by high morbidity and increased mortality in nonhuman primates. Measles vaccines for human use, although effective, are cost prohibitive for use in primate colonies. We compared the efficacy of one or two doses of Vanguard D-M, a canine distemper-measles (CD-M) vaccine, with a single dose of Attenuvax, a human measles vaccine.