Post-traumatic Epilepsy model induced by lateral fluid percussion in non-human primates

• Grant number: 22/10520-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date until: September 01, 2022
• End date until: January 31, 2026
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Beatriz de Oliveira Monteiro
• Grantee: Viviam Sofia Sanabria Calvo
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 18/24561-5 - Epileptogenesis, biomarkers and post-traumatic epilepsy, AP.TEM

Abstract

Traumatic Brain Injury (TBI) has major impacts on the quality of life and can be considered the leading cause of death and disability in the world by 2030. One of the most important neurological consequences after TBI is the development of Post-Traumatic Epilepsy (PTE). Unfortunately, the relationship between traumatic brain injury and Epilepsy is not fully understood and PTE cannot be prevented. Only a limited number of TBI studies are focused on PTE. These studies typically use rodents. In addition, reports on the onset of late spontaneous seizures are scarce in these models, being restricted to the Lateral Fluid Percussion (LFP) model (D'Ambrosio et al., 2004; Kharatishvili et al., 2006; Pitkanen et al., 2009) and more recently for the controlled cortical impact model (Kelly et al., 2015; Guo et al., 2013). Still, when spontaneous seizures occur after brain injury, they tend to present milder characteristics in terms of epileptic events (when compared with seizures in other models, such as chemical or Ischemic): they are limited to a few subjects, require a long time to emerge and have a low frequency of occurrence. Non-human primates (common name marmoset: Callithrix sp.) require less severe lesions than rodents to generate spontaneous recurrent seizures in the classical pilocarpine Epilepsy model, and the restricted patterns of lesions after Status Epilepticus (SE) resemble better to the pathology observed in human patients (Perez-Mendes et al. 2011). In addition, seizures triggered in chronic epileptic marmosets have higher resistance to antiepileptogenic drugs than non-epileptic animals (Pontes et al., 2016). In addition, there is evidence of greater genetic diversity compared to rats brain function aspects (Sabino et al., 2014; Barros et al., 2015; Bittencourt et al., 2008). Our hypothesis is that LFP-induced injury, which simulates the mechanical trauma of TBI, can be used in non-human primates to develop a PTE model with a better translational value to study epileptogenesis markers and mechanisms than that used in rodents. To validate our hypothesis, we will investigate behavioral, electrographic, and anatomical alterations, as well as gene and protein expression profiles, then LFP-induced injury in marmosets and rodents. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SANABRIA, VIVIAM; ROMARIZ, SIMONE; BRAGA, MATHEUS; FORESTI, MAIRA LICIA; NAFFAH-MAZZACORATTI, MARIA DA GRACA; MELLO, LUIZ EUGENIO; LONGO, BEATRIZ M. M.. Anticholinergics: A potential option for preventing posttraumatic epilepsy. FRONTIERS IN NEUROSCIENCE, v. 16, p. 8-pg., 2023-02-24. (17/05242-3, 18/24561-5, 22/10520-0)