Intrastriatal carotid body (CB) grafts produce trophic protection of the dopaminergic nigrostriatal pathway in rodent and primate models of Parkinson’s disease (PD), which is mediated by glial cell line-derived neurotrophic factor (GDNF) produced by CB implants. Phase I/II open trials showed that CB autotrasplantation improve motor symptoms in PD patients. To explore limiting factors that affect the efficacy of human CB transplants, we have studied how aging and chronic hypoxia present in intracerebral grafts can modify CB GDNF expression. Human CB xenografts from young donors induced an important protection of the nigrostriatal dopaminergic neurons of parkinsonian mice, while CB implants from aged donors failed to produce a significant effect. Finally, we performed a study of the methylation status of human and murine GDNF promoter from young and aged CBs, identifying hypermethylated hypoxia-related regions.

As a consequence of the coronavirus pandemic, experiments with human samples had to be stopped. The fact that the CB expressed the ACE2 receptor led us to study the brain SARS-CoV-2 infection in the K18-hACE2 mouse model of severe COVID-19 disease. Remarkably, SARS-CoV-2 brain replication occurs primarily in neurons, producing important pathological alterations such as neuronal loss, incipient signs of glial activation, and vascular damage in SARS-CoV-2. Notably, a modified vaccinia virus Ankara (MVA) vector expressing the SARS-CoV-2 spike (S) protein (MVA-CoV2-S) conferred full protection against SARS-CoV-2 cerebral infection, preventing virus replication in all areas of the brain and its associated damage.