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Cortical expression of IL1-β, Bcl-2, Caspase-3 and 9, SEMA-3a, NT-3 and P-glycoprotein as biological markers of intrinsic severity in drug-resistant temporal lobe epilepsy

Vega-García, A. ; Orozco-Suárez, S. ; Villa, A. ; Rocha, L. ; Feria-Romero, I. ; Alonso Vanegas, M.A. ; Guevara-Guzmán, R.

Brain research, 2021-05, Vol.1758, p.147303-147303, Article 147303 [Periódico revisado por pares]

Netherlands: Elsevier B.V

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  • Título:
    Cortical expression of IL1-β, Bcl-2, Caspase-3 and 9, SEMA-3a, NT-3 and P-glycoprotein as biological markers of intrinsic severity in drug-resistant temporal lobe epilepsy
  • Autor: Vega-García, A. ; Orozco-Suárez, S. ; Villa, A. ; Rocha, L. ; Feria-Romero, I. ; Alonso Vanegas, M.A. ; Guevara-Guzmán, R.
  • Assuntos: Aberrant Connection ; Adult ; Aged ; Antiepileptic Drug Resistance ; ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism ; Biomarkers - analysis ; Biomarkers - metabolism ; Caspase 3 - metabolism ; Caspase 9 - metabolism ; Drug Resistant Epilepsy - metabolism ; Epilepsy, Temporal Lobe - metabolism ; Female ; Humans ; Interleukin-1beta - metabolism ; Male ; Mesial Temporal Lobe Epilepsy ; Middle Aged ; Neurotrophin 3 - metabolism ; Proto-Oncogene Proteins c-bcl-2 - metabolism ; Semaphorin-3A - metabolism ; Spontaneous Recurrent Seizures ; Temporal Cortex ; Young Adult
  • É parte de: Brain research, 2021-05, Vol.1758, p.147303-147303, Article 147303
  • Notas: ObjectType-Article-1
    SourceType-Scholarly Journals-1
    ObjectType-Feature-2
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  • Descrição: Pathological mechanism of mTLE-DR. Seizure activity propagation in the temporal cortex is related to the protein expression of Bcl-2, Caspase-3 and Caspase-9, which are involved in neuronal death, IL1-β, which is involved in the neuroinflammation response and decreased seizure threshold, increased release of P-glycoprotein, a drug transport protein, aberrant connection formation by NT-3 and SEMA-3a, and the relationship of their expression patterns with clinical data. These are key factors in recurrent epileptic seizures, and the increased expression of these intrinsic severity like factors allows the generation of hyperexcitable circuits in the temporal cortex that, in turn promote recurrent epileptic seizures and drug resistance progression. [Display omitted] •The protein expression of neuronal death, neuroinflammation and aberrant connections in cerebral tempora cortex and their relation with intrinsic severity hypothesis in the mTLE-DR.•The protein expresion of Bcl-2, Caspase-3 and Caspase-9, P-glycoprotein and SEMA-3a with mTLE-DR clinical data.•Increased of Bcl-2, Caspase-9 and P-glycoprotein are associated with severity and recurrent seizures. Mesial temporal lobe epilepsy (mTLE) is the most common epilepsy induced by previous cerebral injury, and one out of three mTLE patients develops drug resistance (DR). To assess the expression of Bcl-2, Caspase-3, Caspase-9, IL1-β, SEMA-3a, NT-3 and P-glycoprotein in the temporal cortex and their relationship with the progression of mTLE-DR clinical features in patients with mTLE-DR. Tissue samples from 17 patients were evaluated for protein expression by Western blot and the relationships of the evaluated proteins with the clinical features of the mTLE were assessed through hierarchical cluster analysis. The mTLE-DR group showed significantly higher P-glycoprotein, Bcl-2 and Caspase-9 levels ***p < 0.0001, ***p < 0.0001 and ***p < 0.0002, respectively, than the autopsy control group. Four patient clusters were identified: Clusters 1 and 3 showed relationships among the age of mTLE onset, duration of mTLE-DR, average number of epileptic seizures per week, number of previous antiepileptic drugs (AEDs) and increased expression of Caspase-3, Caspase-9, Neurotrophin-3 and Semaphorin-3a. Clusters 2 and 4 showed relationships among the mTLE onset age, current age, average number of epileptic seizures per week, number of previous AEDs and increased expression of IL1-β, Bcl-2, P-glycoprotein, Caspase-3 and NT-3. The relationships among the clinical data the age of mTLE onset, DR duration, number of previous AEDs, and average number of seizures per week and the expression of proteins involved in neuronal death, neuroinflammation and aberrant connection formation, as which are biological markers in the cerebral temporal cortex, are important factors in the progression and severity of mTLE-DR and support the intrinsic severity hypothesis.
  • Editor: Netherlands: Elsevier B.V
  • Idioma: Inglês
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