A reliable and cost-effective protocol for creating bilirubin cerebral palsy model in rhesus macaque

J Med Primatol. 2024 Feb;53(1):e12691. doi: 10.1111/jmp.12691.

Abstract

Background: Cerebral palsy is a severe motor disability in childhood that poses challenges for children, families, and society. Rhesus macaques are the preferred animals for cerebral palsy model, but surgical excision of motor cortex has low success rate and high cost. In this work, we created cerebral palsy rhesus macaque models by intrathecal injection of bilirubin.

Methods: The puncture point for injection was identified as the intervertebral disc space two, located below the intersection of the iliac crest line and the posterior median line.

Results: The models showed abnormal posture and increased muscle tension. Diffuse deposits of bilirubin were found in the basal ganglia from the magnetic resonance imaging. Pathological slides also revealed the presence of brain lesions, such as vacuole formation, contraction of neuronal nuclei, and deep staining of nuclei in the histopathological sections of the hippocampus and basal ganglia.

Conclusion: The model's symptoms closely resemble those observed in humans with spastic cerebral palsy.

Keywords: animal model; bilirubin; cerebral palsy; intrathecal injection; rhesus macaque.

MeSH terms

  • Animals
  • Cerebral Palsy* / pathology
  • Cerebral Palsy* / veterinary
  • Cost-Benefit Analysis
  • Disabled Persons*
  • Humans
  • Macaca mulatta
  • Motor Disorders*