Histological correlates of hippocampal magnetization transfer images in drug-resistant temporal lobe epilepsy patients.

OBJECTIVE: Temporal 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. METHODS: Patients 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. RESULTS: Compared 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. SIGNIFICANCE: Our data indicate that extracellular matrix molecules are the most significant histological correlates of magnetization transfer ratio in the hippocampus of TLE patients.

Malnutrition during central nervous system growth and development impairs permanently the subcortical auditory pathway.

The brain that grows and develops under the continued influence of malnutrition presents permanent impairment on functioning and neurotransmitter release. The aim of this study was to investigate the chronic effects of neonatal food restriction on neurochemical and neurodynamical aspects within the primary auditory sensory pathway. Our working hypothesis is that neonatal malnutrition may affect the flow of primary sensory information both at a neurochemical and neurodynamical level. To test this hypothesis, three groups of rats were assigned, from birth to 370 days of life, to the following dietary scheme: a well-nourished (WN) group fed ad libitum lab chow diet; an undernourished (UN) group fed 60% of diet consumed by WN group; and a rehabilitated group, undergoing same dietary restriction as undernourished until 42 days of age and thereafter fed ad libitum until the end of the experiment. At 370 days of age, the animals were submitted to brainstem auditory-evoked potentials (BAEPs) recordings and sacrificed for neurochemical evaluation of glutamate release. Undernutrition decreased glutamate release in the cortex, hippocampus, midbrain and brainstem, and significantly increased the latency of BAEP wave V. In addition; the re-establishment of the dietary conditions was not sufficient to reverse the neurochemical and electrophysiological alterations observed in the UN group. Taken altogether, our results suggest that malnutrition imposed at a critical development period caused an irreversible effect within the auditory primary sensory pathway.