Abstract
ObjectiveTemporal lobe epilepsy patients (TLE) often present with hippocampal atrophy, increased T2 relaxation, and reduced magnetization transfer ratio (MTR) in magnetic resonance images (MRI). The histological correlates of the reduced hippocampal MTR are so far unknown. Since MTR is dependent on the tissue’s macromolecules, our aim was to evaluate the correlations between cellular populations, extracellular matrix molecules and the MTR in TLE patients. MethodsPatients with TLE (n = 26) and voluntaries (=20) were scanned in a 3 Tesla MRI scanner, and MTR images were calculated from 3DT1 sequences with magnetization pulse on resonance. Immunohistochemistry for neurons, reactive astrocytes, activated microglia, and extracellular matrix chondroitin sulfate were performed in formalin fixed, paraffin embedded tissues of TLE and autopsy controls (n = 10). Results were considered significant with adjusted p < 0.05. ResultsCompared to the respective controls, TLE patients had reduced hippocampal MTR, increased reactive astrocytes and activated microglia, increased extracellular chondroitin sulfate, and reduced neuron density, compares to controls. MTR correlated positively with neuron density in CA3 and with chondroitin sulfate in CA3 and CA1. Multiple linear regressions reinforced the correlations between chondroitin sulfate and MTR. SignificanceOur data indicate that extracellular matrix molecules are the most significant histological correlates of magnetization transfer ratio in the hippocampus of TLE patients.
Highlights
We previously found that extracellular matrix (ECM) chondroitin sulfate proteoglycan (CSPG) could impact both hippocampal volume (Peixoto-Santos et al, 2015) and T2 signal relax ation time (Peixoto-Santos et al, 2017)
Since magnetization transfer ratio (MTR) is influenced by the macromolecules present in the tissue, our objective was to evaluate the correlations between the MTR and chondroitin sulfate, as well as with cellular populations, in the hippocampus of drug-resistant temporal lobe epilepsy patients
Thirty age-matched control cases consisted on: twenty healthy vol unteers that underwent the same presurgical magnetic resonance imaging (MRI) protocol used for temporal lobe epilepsy patients (TLE) cases, used for defining MRI differences in TLE; ten autopsy cases whose hippocampi were collected to serve as a standard for immunohistochemistry analysis
Summary
Hippocampal sclerosis (HS) is the most common pathological finding in adults with drug-resistant epilepsy (Blumcke et al, 2017). Gliosis can even be seen in the hippocampi of temporal lobe epilepsy patients (TLE) without neuron loss (Thom, 2014). The normal MRI patients often have only milder or no neuron loss, some can have neuron loss and other patho logical changes as severe as those cases with hippocampal sclerosis detected on MRI (Peixoto-Santos et al, 2015; Jackson et al, 1994). Since the presence of HS is often an indicator of good surgical outcome in TLE (Blumcke et al, 2013; Thom, 2014), it is crucial to improve the presurgical detection of those MRI-negative cases with pathologically proven HS, as well as more subtle pathological changes in the hippocampus. Since MTR is influenced by the macromolecules present in the tissue, our objective was to evaluate the correlations between the MTR and chondroitin sulfate, as well as with cellular populations, in the hippocampus of drug-resistant temporal lobe epilepsy patients
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
