A new cerebral hemorrhage model in cynomolgus macaques created by injection of autologous anticoagulated blood into the brain

Abstract

The aim of this study was to establish and validate a clinically relevant model of intracerebral hemorrhage (ICH) via injection of autologous blood into the brains of cynomolgus macaques (Macaca fascicularis). Eight male cynomolgus macaques received 1.5 mL of fresh anticoagulated autologous femoral artery blood into the inner side of the claustrum near the right basal ganglia under stereotactic guidance. Animals were evaluated with MRI and positron emission tomography (PET) scanning before and 24 hours after surgery and once per week thereafter. A neurological deficit scale was used to assess the animals on days 1, 2, 3, 7, 14, 21, and 28 after surgery. Animals showed focal neurological signs corresponding to the MRI-located hematoma. The behavioral impairment progressively ameliorated over time, but never fully resolved. The hematoma was absorbed over time but was still present 4 weeks after surgery, with persistent metabolic deficit detected using PET scanning. Histological examinations confirmed the in vivo findings. This ICH model in a non-human primate mimics human ICH in the basal ganglia and may be useful for assessing the safety and efficacy of neuroprotective agents.