Oxidative stress markers in the neocortex of drug-resistant epilepsy patients submitted to epilepsy surgery.
OBJECTIVE
While there is solid experimental evidence of brain oxidative stress in animal models of epilepsy, it has not been thoroughly verified in epileptic human brain. Our purpose was to determine and to compare oxidative stress markers in the neocortex of epileptic and non-epileptic humans, with the final objective of confirming oxidative stress phenomena in human epileptic brain.


METHODS
Neocortical samples from drug-resistant epilepsy patients submitted to epilepsy surgery (n=20) and from control, non-epileptic cortex samples (n=11) obtained from brain bank donors without neurological disease, were studied for oxidative stress markers: levels of reactive oxygen species (ROS), such as superoxide anion (O2(-)); activity of antioxidant enzymes: superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), and glutathione reductase (GR); and markers of damage to biomolecules (lipid peroxidation and DNA oxidation).


RESULTS
Compared with non-epileptic controls, the neocortex of epileptic patients displayed increased levels of superoxide anion (P≤0.001), catalase (P≤0.01), and DNA oxidation (P≤0.001); a decrease in GPx (P≤0.05), and no differences in SOD, GR and lipid peroxidation.


CONCLUSIONS
Our findings in humans are in agreement with those found in animal models, supporting oxidative stress as a relevant mechanism also in human epilepsy. The concurrent increase in catalase and decrease in GPx, together with unchanged SOD levels, suggests catalase as the main antioxidant enzyme in human epileptic neocortex. The substantial increase in the levels of O2(-) and 8-oxo-dG in epileptic patients supports a connection between chronic seizures and ROS-mediated neural damage.
Department of Neurosurgery, Hospital Clínic of the University of Barcelona, 08036 Barcelona, Spain. Electronic address: jrumia@clinic.ub.es.
Jordi
J
Rumià
Frederic
F
Marmol
Juan
J
Sanchez
José
J
Giménez-Crouseilles
Mar
M
Carreño
Núria
N
Bargalló
Teresa
T
Boget
Luis
L
Pintor
Xavier
X
Setoain
Antonio
A
Donaire
Guillermo T
GT
Saez
Teresa
T
Ribalta
Enric
E
Ferrer
Pere
P
Puig-Parellada
D000328:Adult; D000927:Anticonvulsants / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D004827:Epilepsy / Q000188:drug therapy / Q000378:metabolism* / Q000601:surgery; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D019579:Neocortex / Q000378:metabolism* / Q000601:surgery; D018384:Oxidative Stress / Q000502:physiology*; D011612:Psychosurgery; D019233:Retreatment; D013482:Superoxide Dismutase / Q000378:metabolism; D017211:Treatment Failure
D000927:Anticonvulsants; D015415:Biomarkers; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase
Drug-resistant epilepsy; Epilepsy surgery; Neocortex; Oxidative stress; Seizures