Evaluación de células progenitoras de tipo OPCs (Oligodendroglial precursor cells) en especímenes cerebrales quirúrgicos obtenidos de pacientes con epilepsia focal farmacorresistente : análisis inmunohistoquímico y molecular
Introduction. Epilepsy is a frequent neurological disease which affects about 50 million people worldwide. Surgical intervention is considered when the seizures are refractory to pharmacological treatment during more than two years. The three most common clinic-pathological diseases observed in surg...
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| Formato: | Tesis de maestría acceptedVersion |
| Lenguaje: | Español |
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Facultad de Farmacia y Bioquímica
2016
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| Acceso en línea: | http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=afamaster&cl=CL1&d=HWA_2809 http://repositoriouba.sisbi.uba.ar/gsdl/collect/afamaster/index/assoc/HWA_2809.dir/2809.PDF |
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| Sumario: | Introduction. Epilepsy is a frequent neurological disease which affects about 50 million people worldwide. Surgical intervention is considered when the seizures are refractory to pharmacological treatment during more than two years. The three most common clinic-pathological diseases observed in surgical cerebral specimens from patients with therapy-refractory epilepsies are hippocampal sclerosis (HS), long-term epilepsy-associated tumors and malformations of cortical development. Focal cortical dysplasia (FCD) belongs to the last group. There is a histopathological classification of both HS and FCD published by the International League against Epilepsy. When HS is associated to FCD type II is defined as Dual Pathology (DP). Both in some of these pathologies and in not well defined histopathological entities associated with therapy-refractory epilepsies have been described an increase of oligo-like cells in white matter and in deep cortical gray matter. Few of those publications have identified that some of the cells were oligodendroglial precursor cells (OPCs). Objectives. Evaluating the OPCs in FCD, HS and DP with the aim of determining their implication in these entities. Material and Methods. OPCs have been evaluated using both dual immunohistochemical with PDGF?R and Olig2 antibodies and Real time PCR to study relative expression of PDGF?R and NG2 mRNA transcripts (putative markers of OPCs). The study was performed in the neocortex grey matter of 8 cases with FCD, 5 cases of HS and 3 cases with DP. Average age of patients was 33 years old; ten were females and six were males. Results. There were not significant differences in the relative expression of both transcripts between the three analyzed pathologies. Neither has it been observed significant differences in the median of double positive cells. We detected a statistical significant increase of total number of OPCs in the group of patients older than16 years old compared to those patients younger than 5 years old at seizure onset (p=0.022, Kruskal Wallis test). We also observed a positive significant correlation between age of seizure onset and total number of OPCs (r=0.706, p=0.0020; Spearman correlation) and perineuronal OPCs (r=0.695, p=0.003). There were no significant differences in the number of OPCs or in the expression levels of transcripts based on epilepsy duration. We found an increase in the number of perineuronal OPCs in the group of patients older than thirty-six years old at the surgical time in relation to patients younger than twenty years old (p=0.049). We also detected positive significant correlation between the number of perineuronal OPCs and age of patients at surgical time (r=0.694, p=0.003). Then we noticed that patients older than thirty-six years old at the surgical time were in part those with the later onset. Conclusions. Focal cortical dysplasia, hippocampal sclerosis and dual pathology did not show significant differences in oligodendroglial precursor cell population, deducing that these cells would not be affected in a different way between these entities. In association with previous publications we speculate that OPCs are not a significant component of the oligo-like cell increase described in these kinds of pathologies. Moreover, we have also identified that suffering seizures since early life ages would produce a reduction of the number of OPCs in comparison with an onset at higher ages than sixteen years old. We consider that this find might be a consequence of a greater susceptibility of these cells in front of damages generated by seizures in pediatric patients younger than five years old. |
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