ABCC2 rs2273697 is associated with valproic acid concentrations in patients with epilepsy on valproic acid monotherapy.

Valproic acid (VPA), a widely used antiepileptic drug, is characterized by intensive inter-individual variability in concentration. Both efflux and influx transporters are reported to play important roles in the disposition of VPA, however, no comprehensive investigation into the association of the single nucleotide polymorphism (SNP) in ABC/SLC families with VPA concentration are reported. In the present study, we investigated the association of 12 SNPs in ABCC2, ABCC4, ABCG2, MCT1, MCT2, and OATP2B1 in 187 Chinese patients with epilepsy on VPA monotherapy with the trough concentrations of VPA. The data showed that VPA concentration in patients with ABCC2 rs2273697 AA genotype was significantly higher than that in those with GA+GG genotypes (p=0.000). The findings of the present study suggest that ABCC2 polymorphisms influence VPA concentrations in patients with epilepsy on VPA monotherapy, which may affect the treatment outcomes.

Cultured human embryonic neocortical cells survive and grow in infarcted cavities of adult rat brains and interconnect with host brain.

BACKGROUND: There are no reports on exnografting cultured human fetal neocortical cells in this infracted cavities of adult rat brains. This study was undertaken to observe whether cultured human cortical neurons and astrocytes can survive and grow in the infarcted cavities of adult rat brains and whether they interconnect with host brains. METHODS: The right middle cerebral artery was ligated distal to the striatal branches in 16 adult stroke-prone renovascular hypertensive rats. One week later, cultured cells from human embryonic cerebral cortexes were stereotaxically transferred to the infarcted cavity of 11 rats. The other 5 rats receiving sham transplants served as controls. For immunosuppression, all transplanted rats received intraperitoneal injection of cyclosporine A daily starting on the day of grafting. Immunohistochemistry for glial fibrillary acidic protein (GFAP), synaptophysin, neurofilament, and microtubule associated protein-2 (MAP-2) was performed on brain sections perfused in situ 8 weeks after transplantation. RESULTS: Grafts in the infarcted cavities of 6 of 10 surviving rats consisted of bands of neurons with an immature appearance, bundles of fibers, and GFAP-immunopositive astrocytes, which were unevenly distributed. The grafts were rich in synaptophysin, neurofilament, and MAP2-positive neurons with long processes. The graft/host border was diffuse with dendrites apparently bridging over to the host brain, into which neurofilament immunopositive fibers protruded. CONCLUSION: Cultured human fetal brain cells can survive and grow in the infarcted cavities of immunodepressed rats and integrate with the host brain.

[Study on effect of electrical stimulus on repairing of astrocytes and neurons in rehabilitation after middle cerebral artery occlusion in rats].

OBJECTIVE: To explore the mechanism of rehabilitation after middle cerebral artery occlusion (MCAO). METHODS: MCAO model was reproduced with two-kidney, two clip renovascular hypertensive rats stroke-prone (RHRSP), which were divided into two groups, the treated group (treated with electric stimulus) and the control group (untreated model) randomly. The rehabilitation of rats was evaluated by balance beam walking test. The ultrastructural changes of neurons and astrocytes, expressions of glial fibrillary acidic protein (GFAP)-positive cells, neurofilament (NF) protein, and cerebral capillary dilatation M-associated protein-2 (MAP2), as well as the neurons apoptosis and the number of dilatation of cerebral capillary in the margin of infarcted area were observed by the end of 1st, 3rd, 6th and 9th week after modeling. RESULTS: The motor function of paralysed limbs recovered better in the treated group than that in the control group by the end of 3-9th week after MCAO, the expression of GFAP-positive cells in astrocytes and NF, MAP2 in neurons as well as the number of cerebral capillary dilatation at the margin of infarcted area were higher than those in the control group (P < 0.05). CONCLUSION: Electric stimulation treatment could improve the recovery of motor function of paralyzed limbs. It might be due to the effect of electric stimulus in increasing astrocytes proliferation, reinforcing activity of neurons and evoking the dilatation of cerebral capillary.