Spontaneous Mononuclear Cell Infiltrates and Inflammation in the Brain and Spinal Cord of Rodent and Nonrodent Laboratory Species

Mononuclear cell infiltrates (MCIs) and inflammation in the central nervous system (CNS) can be challenging in nonclinical studies, particularly in nonrodent species. A retrospective study was performed to determine the incidences of spontaneous MCI and inflammation in the brain and spinal cord of rodent and nonrodent species considering age (rodents), administration routes and geographical origin (primates). Historical control data (HCD) were collected from rats, mice, beagle dogs, Göttingen minipigs, cynomolgus macaques, and New Zealand White (NZW) rabbits. Perivascular MCI in the brain (choroid plexus and meninges most frequently affected) had the highest incidence in cynomolgus macaques (8.25% males/7.38% females), followed by Göttingen minipigs (3.23% males/3.27% females), beagle dogs (3.18% males/3.14% females). CD-1 mice, Sprague-Dawley rats, Han Wistar rats and NZW rabbits were the species with the least commonly identified perivascular MCI in the brain. Brain inflammation was a rare event. Perivascular MCI in the spinal cord (meninges most frequently affected) had the highest incidence in cynomolgus macaques, Göttingen minipigs, and beagle dogs. This HCD review will help in the interpretation of inflammatory CNS findings in toxicological safety studies and should allow discrimination of spontaneous and induced lesions in nonclinical studies.