Monocarboxylate transporter 1 is deficient on microvessels in the human epileptogenic hippocampus.
Level 4 - case-series / case-control
Case-control study evaluating post-resection and autopsy human brain tissue
PubMed 21081165 · doi:10.1016/j.nbd.2010.11.005
What was done
Immunohistochemistry and immunogold electron microscopy were performed on hippocampal tissue specimens to examine the expression and subcellular distribution of monocarboxylate transporter 1 (MCT1). The study compared three groups: patients with temporal lobe epilepsy (TLE) and hippocampal sclerosis (mesial TLE or MTLE, n=15), patients with TLE without hippocampal sclerosis (non-MTLE, n=13), and neurologically normal autopsy controls (n=8).
What was found
MCT1 was extensively present on microvessels throughout the hippocampus in autopsy controls and to a lesser extent in non-MTLE specimens. In patients with MTLE, microvascular MCT1 was markedly reduced across hippocampal subregions; CA1 endothelial plasma membranes showed a 37% to 48% loss of MCT1 relative to non-MTLE specimens.
Why it matters
This study provides human histological evidence that microvascular MCT1 is depleted in sclerotic epileptogenic hippocampi, highlighting a possible anatomical basis for impaired brain energy metabolism and reduced transport of acidic antiepileptic drugs like valproate.
Limits
The total sample size was small (n=36 across surgical and autopsy groups). As a static cross-sectional tissue study, it cannot establish whether MCT1 downregulation is a primary driver of epileptogenesis and drug resistance or a secondary consequence of chronic seizures, neuronal loss, or sclerosis. Direct transport kinetics and functional uptake of fuels or drugs were not assessed.
Cited by
- supports Lactate crosses the blood-brain barrier via MCT transporters to enter the brain.