Subchronic Intranasal Administration of NeuroEPO Prevents Brain Atrophy and Long-Term Electrophysiological Changes after Severe Traumatic Brain Injury in Male Rats
Abstract number :
2.441
Submission category :
1. Basic Mechanisms / 1C. Electrophysiology/High frequency oscillations
Year :
2025
Submission ID :
1353
Source :
www.aesnet.org
Presentation date :
12/7/2025 12:00:00 AM
Published date :
Authors :
Presenting Author: Félix Iván López-Preza, MSc – Center for Research and Advanced Studies of the National Polytechnic Institute (CINVESTAV)
Maria de los angeles nuñez-lumberas, PhD – Center for Research and Advanced Studies of the National Polytechnic Institute (CINVESTAV)
Luis Concha, PhD – Institute of Neurobiology, National Autonomous University of Mexico (UNAM)
Cesar Santana-Gómez, PhD – Department of Neurology, David Geffen School of Medicine, University of California
Luisa Rocha, PhD – Center for Research and Advanced Studies of the National Polytechnic Institute (CINVESTAV)
Rationale: Traumatic brain injury (TBI) is a brain disorder that can lead to chronic sequelae such as Alzheimer’s disease, Parkinson’s disease, and post-traumatic epilepsy. Current therapies do not prevent these damages. NeuroEPO, a derivative of erythropoietin with low sialic acid content, has shown neuroprotective effects in Alzheimer’s and Parkinson’s disease, conditions associated with electrophysiological alterations and brain atrophy.
Methods: This study evaluated the effect of intranasal NeuroEPO administration (0.136 mg/kg), delivered 3 hours after TBI and repeated every 8 hours for four consecutive days, in male rats subjected to severe TBI using the lateral fluid percussion model. Telemetry recordings were performed starting on day 20 post-TBI for six consecutive days to assess electrophysiological changes. On day 31, animals were perfused, and magnetic resonance imaging was carried out to evaluate brain volume.
Results: TBI rats treated with vehicle showed decreased brain volume in structures such as the cortex (ipsi-; contra-, p=0.001), hippocampus (p=0.0009), amygdala (ipsi-, p=0.041; contra-, p=0.023), thalamus (p=0.025), and hypothalamus (p=0.007), compared with Sham-vehicle rats. They also exhibited an increased incidence of high-frequency oscillations (HFOs) (p=0.005). In contrast, TBI rats treated with NeuroEPO showed brain volume (cortex: ipsi-, p=0.999; contra-, p=0.408; hippocampus: ipsi-, p=0.446; contra-, p=0.290; amygdala: ipsi-, p=0.997; contra-, p=0.882; thalamus: p=0.319; hypothalamus: p=0.966) and HFO incidence rates similar to Sham-vehicle rats (p=0.820). No differences were observed between Sham rats treated with NeuroEPO or vehicle.
Conclusions: These findings support NeuroEPO as a promising therapeutic strategy to prevent brain atrophy in key structures and hyperexcitability after a severe TBI.
Funding: This study was supported by the Secretaría de Ciencia, Humanidades, Tecnología e Innovación (SECIHTI Fellowship No. 839363, FILP). NeuroEPO was kindly provided by the joint venture IncuBIO S.A. (Cimab S.A. and Neuronic S.A. de C.V.).
Basic Mechanisms