Abstracts

Intracerebral Hemorrhage and Iron Deposits in the Lateral Fluid Percussion Injury in Adult Rats: An EpiBioS4Rx Project 2 Study

Abstract number : 1.041
Submission category : 1. Basic Mechanisms / 1D. Mechanisms of Therapeutic Interventions
Year : 2021
Submission ID : 1826512
Source : www.aesnet.org
Presentation date : 12/4/2021 12:00:00 PM
Published date : Nov 22, 2021, 06:54 AM

Authors :
Patricia Saletti, PhD - Albert Einstein College of Medicine, Bronx, New York, U.S.A.; Min-Hui Cui - Department of Radiology, Albert Einstein College of Medicine, Bronx, New York, U.S.A., Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, U.S.A.; Kamalakar Ambadipudi - Department of Radiology, Albert Einstein College of Medicine, Bronx, New York, U.S.A.; Florencia Chena-Becerra - Saul R. Korey Department of Neurology, Laboratory of Developmental Epilepsy, Albert Einstein College of Medicine, Bronx, New York, U.S.A.; Christos Panagiotis Lisgaras - Saul R. Korey Department of Neurology, Laboratory of Developmental Epilepsy, Albert Einstein College of Medicine, Bronx, New York, U.S.A.; Lisa Coles - Department of Experimental & Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, U.S.A.; Wenzhu Mowrey - Division of Biostatistics, Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, U.S.A.; Qianyun Li - Saul R. Korey Department of Neurology, Laboratory of Developmental Epilepsy, Albert Einstein College of Medicine, Bronx, New York, U.S.A.; Wei Liu - Saul R. Korey Department of Neurology, Laboratory of Developmental Epilepsy, Albert Einstein College of Medicine, Bronx, New York, U.S.A.; Pablo Casillas-Espinosa - The Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia; Idrish Ali - The Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia; Rhys Brady - The Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia; Glenn Yamakawa - The Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia; Juliana Silva - The Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia; Ezgi Ozturk - The Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia; Nigel Jones - The Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia; Sandy Shultz - The Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia; Terence O’Brien - The Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia; Solomon Moshé - Saul R. Korey Department of Neurology, Laboratory of Developmental Epilepsy, Albert Einstein College of Medicine, Bronx, New York, U.S.A., Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York, U.S.A., Isabelle Rapin Division of Child Neurology, Montefiore/Einstein Epilepsy Center, Albert Einstein College of Medicine, Bronx, New York, U.S.A., Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York, U.S.A.; Craig Branch - Department of Radiology, Albert Einstein College of Medicine, Bronx, New York, U.S.A., Department of Physiology & Biophysics, Albert Einstein College of Medicine, Bronx, New York, U.S.A.; Aristea Galanopoulou - Saul R. Korey Department of Neurology, Laboratory of Developmental Epilepsy, Albert Einstein College of Medicine, Bronx, New York, U.S.A., Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York, U.S.A., Isabelle Rapin Division of Child Neurology, Montefiore/Einstein Epilepsy Center, Albert Einstein College of Medicine, Bronx, New York, U.S.A.

Rationale: Traumatic brain injury (TBI) often leads to intracranial hemorrhage, resulting in iron deposits in the brain, due to blood-brain barrier disruption. Iron accumulation can increase the risk of post-traumatic epilepsy (PTE) after TBI. In this EpiBioS4Rx Project 2 study, we investigated the spatial and temporal patterns of intracerebral hemorrhages and iron accumulation after lateral fluid percussion injury (LFPI) induced brain trauma in adult male rats.

Methods: Adult male Sprague-Dawley rats (11 weeks old) were used: lateral fluid percussion injury (LFPI) (n=12), LFPI and deferiprone (DEF) (LFPI+DEF; n=9), sham (n=12) and naïve (n=4). Sham rats underwent a left parietal 5mm craniotomy only, whereas LFPI were also subjected to ~3.2atm pressure pulse. The LFPI+DEF group received DEF, a chelating agent with an affinity for ferric ion, 100mg/kg ip followed by 7.6mg/kg/day via a minipump infusion sc right after TBI and for 7 days. Rats were perfused at 2 days, and 1, 2, 4, or 8 weeks after LFPI. Coronal brain sections were stained with Pearl Prussian blue stain for iron using qualitative (distribution in the brain) and quantitative analyses, to determine the iron-stained areas (pixels/mm2) of corpus callosum/external capsule (CC/EC). Additional rats underwent LFPI or sham surgeries (n=10/group) and subsequently had a MRI at 9d and 5 months (mo) post-surgery. Multi-echo gradient echo (MGE) 3D sequences, with outer volume suppression and fat suppression, were used. MGE data was used to calculate T2* maps, anatomical mixed contrast images and field maps.

Results: Iron deposits were seen at the CC/EC, parasagittal and lateral cortices, hippocampus, striatum and thalamus of LFPI rats, rarely in sham, but never in control rats. Quantitative results in EC/CC show significant effects for group (p=0.012), side (p=0.03). LFPI and LFPI+DEF rats had significantly larger iron-stained deposits in CC/EC than the other groups (p < 0.001), particularly ipsilateral to the lesion and across all time points. LFPI+DEF group had significantly less iron pixels/mm
Basic Mechanisms