[Intermittent convulsions for 1.5 years and psychomotor retardation in a girl].

The study reports a girl with pyridoxine-dependent epilepsy. The girl was admitted at the age of 2 years because of intermittent convulsions for 1.5 years and psychomotor retardation. She had a history of "hypoxia" in the neonatal period. At the age of 5 months recurrent epileptic seizures occurred. The child was resistant to antiepileptic drugs, and had many more seizures when she got cold or fever. She also had a lot of convulsive status epilepticus. No discharges were found during several video-EEG monitorings. Cerebral MRI examinations showed normal results. So Dravet syndrome was clinically suspected. ALDH7N1 gene mutation analysis revealed two heterozygote mutations, and pyridoxine-dependent epilepsy was thus confirmed. Seizures were generally controlled after pyridoxine supplementation.

Neuroprotective effects of caffeic acid phenethyl ester against sevoflurane­induced neuronal degeneration in the hippocampus of neonatal rats involve MAPK and PI3K/Akt signaling pathways.

Millions of infants and children are exposed to anesthesia every year during medical care. Sevoflurane is a volatile anesthetic that is frequently used for pediatric anesthesia. However, previous reports have suggested that the administration of sevoflurane promotes neurodegeneration, raising concerns regarding the safety of its usage. The present study aimed to investigate caffeic acid phenethyl ester (CAPE) and its protective effect against sevoflurane­induced neurotoxicity in neonatal rats. Rat pups were administered with CAPE at 10, 20 or 40 mg/kg body weight from postnatal day 1 (P1) to P15. The P7 rats were exposed to sevoflurane (2.9%) for 6 h. Control group rats received no sevoflurane or CAPE. Neuronal apoptosis was determined by terminal deoxynucleotidyl transferase dUTP nick­end labeling assay. The expression levels of caspases (caspase­3, ­8 and ­9), apoptotic pathway proteins [Bcl­2­associated X protein (Bax), B cell CCL/lymphoma 2 (Bcl­2), Bcl­2­like 1 (Bcl­xL), Bcl­2­associated agonist of cell death (Bad) and phosphorylated (p)­Bad], mitogen­activated protein kinases (MAPK) signaling pathway proteins [c­Jun N­terminal kinase (JNK), p­JNK, extracellular signal­regulated kinase (ERK)1/2, p­ERK1/2, p38, p­p38 and p­c­Jun] and the phosphoinositide 3­kinase (PI3K)/Akt cascade were evaluated by western blotting following sevoflurane and CAPE treatment. In addition, the expression of cleaved caspase­3 was analyzed by immunohistochemistry. CAPE significantly reduced sevoflurane­induced apoptosis, downregulated the expression levels of caspases and pro­apoptotic proteins (Bax and Bad) and elevated the expression levels of Bcl­2 and Bcl­xL when compared with sevoflurane treatment. Furthermore, CAPE appeared to modify the expression levels of MAPKs and activate the PI3K/Akt signaling pathway. Thus, the present study demonstrated that CAPE effectively inhibited sevoflurane­induced neuroapoptosis by modulating the expression and phosphorylation of apoptotic pathway proteins and MAPKs, and by regulating the PI3K/Akt pathway.

Neuroprotection by epigallo catechin gallate against bupivacaine anesthesia induced toxicity involves modulation of PI3/Akt/PTEN signalling in N2a and SH-SY5Y cells.

Bupivacaine, an amide type long-acting local anaesthetic is commonly employed for epidural anesthesia and as well for nerve blockades. However, studies have shown neurotoxicity following local administration of bupivacaine raising concerns over the use of the drug. Compounds that could minimize or inhibit toxic effects of bupivacaine are of high value in operative settings and in pain management. The present study aims to investigate if epigallo catechin gallate (EGCG) could inhibit or prevent bupivacaine toxicity in neuroblastoma cells (N2a and SH-SY5Y). The viability of N2a and SH-SY5Y cells following exposure to EGCG (10-50 µM) were assessed by MTT assay and Annexin V/PI staining. The influence of EGCG on ROS generation was determined. The expression of apoptotic cascade proteins (Caspases-3, -8 and -9, Bcl-xL, Bad, Bax, Bcl-2) and PI3/Akt pathway proteins (Akt, p-Akt, GSK-3ß, p-GSK-3ß, PTEN) were analyzed by western blotting. EGCG improved the viability of the cells and inhibited apoptosis by potentially decreasing the expression of caspases and pro-apoptotic proteins. Bupivacaine induced ROS generations were reduced on EGCG exposure. EGCG significantly promoted the phosphorylation of Akt and GSK-3ß and down-regulated PTEN, thus activating PI3/Akt signalling. EGCG effectively improved the cell viability and inhibited apoptosis of N2a and SH-SY5Y cells via suppression of ROS generation and modulation of PI3K/Akt signalling cascade.