Search

• FGF13 was significantly higher in cortical lesions from patients with FCDs. • FGF13 was localized in misshapen neurons in FCDs. • FGF13 protein levels in FCDs were positively correlated with the frequency of seizures. • FGF13 might provide a new direction for the treatment of epilepsy caused by FCDs. Focal cortical dysplasias (FCDs) are well recognized as important causes of medically intractable epilepsy in both children and adults. To explore the potential role of fibroblast growth factor 13 (FGF13) in intractable epilepsy caused by FCDs, we examined the expression of FGF13 in cortical lesions from 23 patients with FCD type Ia (FCDIa), 24 patients with FCD type IIa (FCDIIa), and 12 patients with FCD type IIb (FCDIIb), and we compared the results with the FGF13 expression levels in control cortex (CTX) brain tissues from 12 nonepileptic normal subjects. Both the mRNA levels and protein levels of FGF13 were significantly higher in the cortical lesions from patients with FCD than in the control cortices. The immunohistochemical results showed that strong FGF13 immunoreactivity was observed in misshapen cells, including neuronal microcolumns, hypertrophic neurons, dysmorphic neurons, and most balloon cells. Moreover, double-label immunofluorescence analyses confirmed that FGF13 was mainly localized in neurons and nearly absent in glia-like cells. Taken together, our results suggest that the overexpression of FGF13 in FCDs and the cell-specific distribution patterns of FGF13 in misshapen neurons in FCDs could potentially contribute to intractable epilepsy caused by FCDs. [ABSTRACT FROM AUTHOR]

Focal cortical dysplasia type IIb (FCD IIb) and tuberous sclerosis complex (TSC) are very frequently associated with epilepsy in pediatric patients. Human leukocyte immunoglobulin-like receptor B2 (LILRB2) participates in the process of neurite growth, synaptic plasticity, and inflammatory reaction, suggesting a potential role of LILRB2 in epilepsy. However, little is known about the distribution and expression of LILRB2 in cortical lesions of FCD IIb and cortical tubers of TSC. In this study, we have described the distribution and expression of LILRB2 signaling pathway in cortical lesions of pediatric patients with FCD IIb (n = 15) and TSC (n = 12) relative to age-matched autopsy control samples (CTX, n = 10), respectively. The protein levels of LILRB2 pathway molecules were assessed by western blotting and immunohistochemistry. The expression pattern was investigated by immunohistochemistry and double labeling experiment. Spearman correlation analysis to explore the correlation between LILRB2 protein level and seizure frequency. The protein levels of LILRB2 and its downstream molecules POSH, SHROOM3, ROCK1, ROCK2 were increased in cortices of patients compared to CTX. Protein levels of LILRB2 negatively correlated with the frequency of seizures in FCD IIb and TSC patients, respectively. Moreover, all LILRB2 pathway molecules were strongly expressed in dysmorphic neurons, balloon cells, and giant cells, LILRB2 co-localized with neuron marker and astrocyte marker. Taken together, the special expression patterns of LILRB2 signaling pathway in cortical lesions of FCD IIb and TSC implies that it may be involved in the process of epilepsy. [ABSTRACT FROM AUTHOR]

The infiltration of immune cells is observed in the epileptogenic zone; however, the relationship between epilepsy and regulatory T cells (Tregs) remains only partially understood. We aimed to investigate brain-infiltrating Tregs to reveal their underlying role in epilepsy. We analyzed the infiltration of Tregs in the epileptogenic zones from patients with epilepsy and a pilocarpine-induced temporal lobe epilepsy (TLE) model. Next, we evaluated the effects of brain Treg depletion on neuroinflammation, neuronal loss, oxidative stress, seizure activity and behavioral changes in the pilocarpine model. We also explored the impact of Treg expansion in the brain on seizure activity. There were a large number of Tregs in the epileptogenic zones of human and experimental epilepsy. The number of brain Tregs was negatively correlated with the frequency of seizures in patients with epilepsy. Our further findings demonstrated that brain Treg depletion promoted astrocytosis, microgliosis, inflammatory cytokine production, oxidative stress, and neuronal loss in the hippocampus after status epilepticus (SE). Moreover, brain Treg depletion increased seizure activity and contributed to behavioral impairments in experimental chronic TLE. Interestingly, intracerebroventricular injection of CCL20 amplified Tregs in brain tissue, thereby inhibiting seizure activity. Taken together, our study highlights the therapeutic potential of regulating Tregs in epileptic brain tissue. • Brain Treg depletion exacerbates hippocampal neuroinflammation and oxidative stress after status epilepticus. • Brain Treg depletion reduces neuronal survival in the hippocampus caused by status epilepticus. • Brain Treg depletion aggravates seizure activity in temporal lobe epilepsy. • Brain Treg depletion contributes to behavioral impairments in temporal lobe epilepsy. • Brain Treg amplification exerts an antiepileptic effect in epileptic mice. [ABSTRACT FROM AUTHOR]