Post-injury ventricular enlargement associates with iron in choroid plexus but not with seizure susceptibility nor lesion atrophy—6-month MRI follow-up after experimental traumatic brain injury

Abstract

Ventricular enlargement is one long-term consequence of a traumatic brain injury, and a risk factor for memory disorders and epilepsy. One underlying mechanisms of the chronic ventricular enlargement is disturbed cerebrospinal-fluid secretion or absorption by choroid plexus. We set out to characterize the different aspects of ventricular enlargement in lateral fluid percussion injury (FPI) rat model by magnetic resonance imaging (MRI) and discovered choroid plexus injury in rats that later developed hydrocephalus. We followed the brain pathology progression for 6 months and studied how the ventricular growth was associated with the choroid plexus injury, cortical lesion expansion, hemorrhagic load or blood perfusion deficits. We correlated MRI findings with the seizure susceptibility in pentylenetetrazol challenge and memory function in Morris water-maze. Choroid plexus injury was validated by ferric iron (Prussian blue) and cytoarchitecture (Nissl) stainings. We discovered choroid plexus injury that accumulates iron in 90% of FPI rats by MRI. The amount of the choroid plexus iron remained unaltered 1-, 3- and 6-month post-injury. During this time, the ventricles kept on growing bilaterally. Ventricular growth did not depend on the cortical lesion severity or the cortical hemorrhagic load suggesting a separate pathology. Instead, the results indicate choroidal injury as one driver of the post-traumatic hydrocephalus, since the higher the choroid plexus iron load the larger were the ventricles at 6 months. The ventricle size or the choroid plexus iron load did not associate with seizure susceptibility. Cortical hypoperfusion and memory deficits were worse in rats with greater ventricular growth.

Blocking P2RX7 Attenuates Ferroptosis in Endothelium and Reduces HG-induced Hemorrhagic Transformation After MCAO by Inhibiting ERK1/2 and P53 Signaling Pathways

“…The left brain tissues of rats were xed by 4% paraformaldehyde, embedded in para n, and then stained by HE (C0105, Beyotime, CA) according to the instructions. Brain sections was stained with Perls' Prussian blue to determine ferric (Fe3+) iron content as described previously [19]. After the sections were sealed, the cerebral sections of each group were observed and photographed under a microscope.…”

Sleep Disturbance and Severe Hydrocephalus in a Normally Behaving Wistar Rat With Traumatic Brain Injury

“…Iron deposits in the choroid plexus, which were recently associated with post-TBI ventricle enlargement, were detected in all rats of the cohort with TBI. 7 Therefore, we consider post-injury choroidal hemorrhage as an unlikely etiological factor for the robust ventriculomegaly in rat #112.…”

CXCR4-BTK axis mediate pyroptosis and lipid peroxidation in early brain injury after subarachnoid hemorrhage via NLRP3 inflammasome and NF-κB pathway

“…Brain sections were stained with Nissl's staining to detect neuronal damage in CA1 as previously described [ 36 ].…”