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

Area of Science:

• Neuroscience
• Toxicology
• Comparative Pathology

Background:

• Mononuclear cell infiltrates (MCIs) and central nervous system (CNS) inflammation present diagnostic challenges in nonclinical safety studies, especially in non-rodent species.
• Establishing baseline incidences of spontaneous CNS lesions is crucial for accurate interpretation of drug-induced effects.

Purpose of the Study:

• To determine the incidence of spontaneous mononuclear cell infiltrates (MCIs) and inflammation in the brain and spinal cord of various rodent and nonrodent species.
• To provide historical control data (HCD) for interpreting CNS findings in toxicological studies.
• To differentiate spontaneous lesions from treatment-induced changes.

Main Methods:

• Retrospective analysis of historical control data from multiple species including rats, mice, dogs, minipigs, macaques, and rabbits.
• Evaluation of brain and spinal cord tissues for perivascular MCIs and inflammation.
• Consideration of factors like age, administration routes, and geographical origin where applicable.

Main Results:

• Perivascular MCIs in the brain were most frequent in cynomolgus macaques, followed by Göttingen minipigs and beagle dogs.
• Rodent species (mice, rats) and New Zealand White rabbits exhibited the lowest incidence of brain perivascular MCIs.
• Brain inflammation was rare across all species studied.
• Spinal cord perivascular MCIs were most common in cynomolgus macaques, Göttingen minipigs, and beagle dogs.

Conclusions:

• This study provides valuable incidence data for spontaneous CNS mononuclear cell infiltrates and inflammation in key nonclinical species.
• The findings facilitate the accurate interpretation of CNS lesions in toxicological safety studies.
• Distinguishing spontaneous background lesions from treatment-related effects is enhanced by this comparative pathological data.