Abstract
Diphenylhydantoin (phenytoin) is an antiepileptic drug that generates hyperplasia in some tissue by stimulating Epidermal Growth Factor (EGFR) and Platelet-Derived Growth Factor beta (PDGFR-β) receptors and by increasing serum levels of basic fibroblast growth factor (bFGF, FGF2 or FGF-β). Neural stem cells in the adult brain have been isolated from three regions: the Subventricular Zone (SVZ) lining the lateral wall of the lateral ventricles, the Subgranular Zone (SGZ) in the dentate gyrus at the hippocampus and the Subgranular Zone (SZC) lining between the hippocampus and the corpus callosum. Neural stem cells actively respond to bFGF, PDGFR-β or EGF by increasing their proliferation, survival and differentiation. The aim of this study was to evaluate the effect of phenytoin on proliferation and apoptosis in the three neurogenic niches in the adult brain. We orally administrated phenytoin with an oropharyngeal cannula for 30 days: 0 mg kg-1 (controls), 1, 5, 10, 50 and 100 mg kg-1. To label proliferative cells, three injections of 100 mg kg-1 of BrdU was administrated every 12 h. Immunohistochemistry against BrdU or Caspase-3 active were performed to determine the number of proliferative or apoptotic cells. Our results showed that phenytoin induces proliferation in the SVZ and the SGZ in a dose-dependent manner. No statistically significant effects on cell proliferation in the SCZ neither in the apoptosis rate at the SVZ, SGZ and SCZ were found. These data indicate that phenytoin promotes a dose-dependent proliferation in the SVZ and SGZ of the adult brain. The clinical relevance of these findings remain to be elucidated.
Highlights
Of sodium action potentials by stimulating the sodium pump, inhibition of calcium influx in neurons, blockage
The aim of this study was to analyze whether phenytoin promoted proliferation or apoptosis in the Subventricular Zone (SVZ), the Subgranular Zone (SGZ) and the Subcallosal Zone (SCZ)
We found an increase in the number of BrdU+ cells in the SGZ with the dose of 10 mg kg−1 of phenytoin (5.87±0.34 cells per field) as compared to controls (4.01±0.26 cells per field; p
Summary
Of sodium action potentials by stimulating the sodium pump, inhibition of calcium influx in neurons, blockage. Phenylhydantoin) known as phenytoin is an effective anticonvulsant in tonic-clonic epilepsy of ionotropic receptors for glutamate and enhancement of GABA neurotransmission (Escueta and Appel, 1971; Kaindl et al, 2006; Yang et al, 2007). The primary target of phenytoin in depolarizing neurons is voltage-dependent sodium channels, where phenytoin blocks sodium influx, for the seizure prophylaxis and the control of status epilepticus. Some of side effects of phenytoin include gingival hyperplasia (Eyer et al, 2008), hypertrichosis (hirsutism) (Vivard et al, 1989), acne (Jenkins and reducing neuronal excitability and limiting the spread Ratner , 1972), cerebellar atrophy (Ohmori et al, 1999), of electrical activity of seizures (Shaw et al, 2007). Type-2 (FGF-2) (Saito et al, 1996; Sasaki and Maita, 1998; Turan et al, 2004) and Epidermal Growth Factor Bromodeoxiuridine (BrdU) administration: BrdU is Receptors (EGFR)
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