Authors :
Presenting Author: Luiz Eugênio Mello, MD PhD – D'Or Institute of Research and Education
Viviam Sanabria, PhD – Universidade Federal de São Paulo
Christiane Gimenes, PhD – Universidade Federal de São Paulo
Simone Romariz, PhD – Universidade Federal de São Paulo
Matheus Braga, MSc – Universidade Federal de São Paulo
Amarildo Souza Gois, AS – Universidade Federal de São Paulo
Maira Licia Foresti, PhD – Instituto D'Or de Pesquisa e Ensino (IDOR) - SP, Brazil
Beatriz Longo, PhD – Universidade Federal de São Paulo
Rationale:
Traumatic brain injury (TBI) is a major global health challenge with limited treatment options and is a leading cause of acquired epilepsy1. The lateral fluid percussion injury (LFPI) model is commonly used in rodents to simulate non-penetrating traumatic brain injury (TBI)2; however, its translational relevance is limited due to structural and functional differences between rodent and human brains. The common marmoset (Callithrix jacchus), a New World primate with a gyrencephalic brain and complex cortical organization, presents a promising alternative3,4. We hypothesized that targeting different cortical regions with LFPI in marmosets would produce distinct inflammatory and degenerative responses, reflecting region-specific vulnerability and providing a foundation for future studies on post-traumatic epileptogenesis.
Methods:
Ten adult marmosets (3 males, 7 females) underwent LFPI in either the parietal (n = 3) or temporal lobe (n = 4). A naïve control group was included (n = 3).Two impact angles were tested to identify moderate TBI. Animals were euthanized 24 hours post-injury. Lesion volume was assessed with Nissl staining. Astrocytic and microglial responses were evaluated using GFAP and Iba-1 immunofluorescence, with quantification of integrated density and morphology. Neuronal degeneration was assessed by Fluoro-Jade B (FJB). Clinical indicators included righting reflex latency and presence of hemorrhages.
All experimental procedures followed ARRIVE, NIH, and IBAMA guidelines and were approved by the Animal Care and Use committee (protocol 5138271222).
Results:
The 17º angle was selected to model moderate TBI, as it resulted in longer righting reflex latency, indicating greater injury severity. Temporal lobe injuries produced significantly larger lesions (p < 0.01) than parietal lobe injuries. Frequent epidural and subdural hematomas and elevated neuronal degeneration (FJB signal: ~3.5-fold increase vs. Naïve, p = 0.0247) were observed in the TBI-Temporal group. Astrocytes in the injured cortex showed longer processes (34.70 ± 3.58 µm vs. 8.18 ± 2.16 µm in Naïve; p = 0.0219) and fewer branches in CA1 (25.78 ± 4.58 vs. 72.00 ± 2.02 in Naïve; p = 0.0211). Microglia also showed fewer branches in CA1 (21.85 ± 4.28 vs. 43.53 ± 6.16 in Naïve; p = 0.0171) and CA3 (20.09 ± 2.26 vs. 39.69 ± 4.21 in Naïve; p = 0.033), with longer processes in CA3 (42.26 ± 2.45 µm vs. 20.92 ± 4.49 µm in Naïve; p = 0.0253), consistent with a reactive, amoeboid phenotype.Conclusions:
Our findings reveal a clear regional vulnerability, with temporal lobe injury eliciting more severe inflammatory and neurodegenerative responses than parietal trauma. The standardized marmoset LFPI model successfully replicates key features of human TBI, including region-specific pathology and glial reactivity. Even though this is an acute study, it offers a valuable platform for studying injury mechanisms and a foundational framework for future exploration of the mechanisms of post-traumatic epileptogenesis in a translationally relevant primate model.
Funding:
This work was supported by FAPESP (grants 2018/24561-5, 2022/00249-8, and 2017/05242-3), CAPES (Finance Code 001), and CNPq (grants 311619/2019-3 and 312904/2021-5).