Altered Cerebrospinal Fluid Concentrations of TGFβ1 in Patients with Drug-Resistant Epilepsy

Abstract

Transforming growth factor beta (TGFβ) signaling participates in pathogenesis of epilepsy. TGFβ1, as a transmitter of TGFβ signaling, might be a useful marker for predicting the prognosis of patients with epilepsy. The present study aimed to measure TGFβ1 level in the cerebrospinal fluid (CSF) of patients with drug-resistant epilepsy and non-resistant epilepsy. A total of 43 patients with epilepsy were recruited, 28 were non-resistant epilepsy subgroup, 15 drug-resistant epilepsy subgroup. 11 patients with intracranial infection and 11 individuals with primary headache were used as controls. The concentration of CSF and serum TGFβ1 was measured by enzyme-linked immunosorbent assay. The concentration of CSF-TGFβ1 was 209.26 ± 81.07 pg/ml in the drug-resistant epilepsy subgroup, 121.80 ± 40.32 pg/ml in the non-resistant epilepsy subgroup, 552.17 ± 456.20 pg/ml in intracranial infection control, 133.80 ± 68.55 pg/ml in headache control, respectively. TGFβ1 level was significantly increased in the drug-resistant epilepsy subgroup compared to the non-resistant epilepsy subgroup. TGFβ1 level in intracranial infection control was higher than that in the non-resistant epilepsy subgroup. There was no statistically difference of CSF-TGFβ1 between the non-resistant epilepsy subgroup and headache controls, between the resistant epilepsy subgroup and intracranial infection controls. TGFβ levels are increased in the CSF of patients with drug-resistant epilepsy. High CSF-TGFβ1 levels may be a potential screening biomarker of antiepileptic drug resistance in patients with epilepsy.

TGF-β as a Key Modulator of Astrocyte Reactivity: Disease Relevance and Therapeutic Implications

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Activation of TRPV1 Contributes to Recurrent Febrile Seizures via Inhibiting the Microglial M2 Phenotype in the Immature Brain

“…In addition, TRPV1 inhibits the microglial M2 phenotype, which is also a complementary pathway in epileptogenesis. Some studies have already confirmed that M2 markers are upregulated or downregulated during epileptogenesis (Xanthos and Sandkuhler, 2014; Yu et al, 2014; Benson et al, 2015; Ali et al, 2017), and insufficient Arg1 or Ym1 is a susceptibility element for epileptogenesis (Boche et al, 2013; Benson et al, 2015; Cantero et al, 2016). One recent study reported that microglial-specific expression levels of M2 markers (Arg1, Ym1) were significantly downregulated at the early chronic phase in a pilocarpine-induced epilepsy model (Benson et al, 2015).…”

Neuroinflammation in epileptogenesis: from pathophysiology to therapeutic strategies

“…Recent mounting evidences show that TGF-β signaling pathways are intricated in epileptogenesis ( 92 ). In resected brain regions from epileptic patients and animal models, the increased expression of TβR1 is observed in cortex, amygdala, and hippocampus, particularly in the piriform cortex ( 61 , 93 ). Activation of TGF-β signaling pathways in astrocytes can mediate albumin uptake, potassium (K + ) buffering, glutamate metabolism, pro-inflammatory mediators releasing, and synaptogenesis, which collectively lead to neuronal hyperexcitability and epileptogenesis ( 94 , 95 ).…”