Protein expression of P-glycoprotein in neocortex from patients with frontal lobe epilepsy.

Frontal lobe epilepsy (FLE) is the second most frequent type of epilepsy and the surgical outcome depends on the etiology. For instance, patients with posttraumatic FLE (PTE) have a worse surgical outcome compared to patients with FLE related to a tumoral lesion (TL). The present study focuses to determine if the FLE etiology is associated with the P-glycoprotein (P-gp) expression, a condition associated with drug resistance. P-gp expression and cellular localization were determined by Western Blot and immunohistochemical experiments in cortical brain samples obtained from patients with PTE (n = 5), TL (n = 5), and autopsies (n = 5). The neuronal count was estimated by Nissl and stereology procedure. Results showed that the autopsies tissue showed a neuronal count of 3514 ± 304.2 neurons per mm3. The P-gp expression ratio was 0.33 ± 0.02. Its expression was found in endothelial cells. Negligible P-gp expression was detected in neurons and astrocytes. Compared to the autopsies group, the TL group showed no changes in the neuronal count but, there was a decreased P-gp expression ratio (46%, p < 0.05). P-gp was located mainly in neurons, slight in astroglial, and endothelial cells. The PTE group showed a similar P-gp expression ratio compared to the autopsies group. P-gp was expressed in neurons, astrocytes, and endothelial cells in these samples. However, experiments revealed a high P-gp expression in a lower neuronal count (38%, p < 0.05 vs autopsy group). The present study reveals that patients with PTE present neuronal P-gp overexpression. This finding could underlie their worst surgical outcome.

Dose-Dependent Behavioral and Antioxidant Effects of Quercetin and Methanolic and Acetonic Extracts from Heterotheca inuloides on Several Rat Tissues following Kainic Acid-Induced Status Epilepticus.

Kainic acid (KA) has been used to study the neurotoxicity induced after status epilepticus (SE) due to activation of excitatory amino acids with neuronal damage. Medicinal plants can protect against damage caused by KA-induced SE; in particular, organic extracts of Heterotheca inuloides and its metabolite quercetin display antioxidant activity and act as hepatoprotective agents. However, it is unknown whether these properties can protect against the hyperexcitability underlying the damage caused by KA-induced SE. Our aim was to study the protective effects (with regard to behavior and antioxidant activity) of administration of natural products methanolic (ME) and acetonic (AE) extracts and quercetin (Q) from H. inuloides at doses of 30 mg/kg (ME30, AE30, and Q30 groups), 100 mg/kg (ME100, AE100, and Q100 groups), and 300 mg/kg (ME300, AE300, and Q300 groups) against damage in brain regions of male Wistar rats treated with KA. We found dose-dependent effects on behavioral and biochemical studies in the all-natural product groups vs. the control group, with decreases in seizure severity (Racine's scale) and increases in seizure latency (p < 0.05 in the ME100, AE100, Q100, and Q300 groups and p < 0.01 in the AE300 and ME300 groups); on lipid peroxidation and carbonylated proteins in all brain tissues (p < 0.0001); and on GPx, GR, CAT, and SOD activities with all the treatments vs. KA (p ≤ 0.001). In addition, there were strong negative correlations between carbonyl levels and latency in the group treated with KA and in the group treated with methanolic extract in the presence of KA (r = -0.9919, p = 0.0084). This evidence suggests that organic extracts and quercetin from H. inuloides exert anticonvulsant effects via direct scavenging of reactive oxygen species (ROS) and modulation of antioxidant enzyme activity.