PURPOSE: The hypothesis addressed by this study is that a glutamine synthetase (GS) deficiency in neoplastic astrocytes is a possible molecular basis associated with seizure generation in glioblastoma multiforme (GBM). METHODS: Quantitative Western blot analysis of GS was performed in 20 individuals operated for malignant glioma. RESULTS: The levels of GS in patients with GBM and epilepsy were significantly lower (range 0.04-1.15; mean 0.35 +/- 0.36; median 0.25) than in non-epileptic GBM individuals (range 0.78-3.97; mean 1.64 +/- 0.99; median 1.25; P = 0.002). No relationship has been found between histological features (i.e. necrosis, gliosis, stroma, inflammatory cells, giant cells, and haemosiderine) and GS expression or epilepsy. DISCUSSION: Even though the epileptogenesis in glioma is multifactorial, it is conceivable that a down-regulation of GS may have an important pro-epileptogenic role in GBM, through the slowing of glutamate-glutamine cycle. This study suggests that seizures in GBM are coupled with a highly localized enzyme deficiency. The manipulation of GS activity might constitute a novel principle for inhibiting seizures in patients with glioma epilepsy.
PURPOSE: The hypothesis addressed by this study is that a glutaminesynthetase (GS) deficiency in neoplastic astrocytes is a possible molecular basis associated with seizure generation in glioblastoma multiforme (GBM). METHODS: Quantitative Western blot analysis of GS was performed in 20 individuals operated for malignant glioma. RESULTS: The levels of GS in patients with GBM and epilepsy were significantly lower (range 0.04-1.15; mean 0.35 +/- 0.36; median 0.25) than in non-epileptic GBM individuals (range 0.78-3.97; mean 1.64 +/- 0.99; median 1.25; P = 0.002). No relationship has been found between histological features (i.e. necrosis, gliosis, stroma, inflammatory cells, giant cells, and haemosiderine) and GS expression or epilepsy. DISCUSSION: Even though the epileptogenesis in glioma is multifactorial, it is conceivable that a down-regulation of GS may have an important pro-epileptogenic role in GBM, through the slowing of glutamate-glutamine cycle. This study suggests that seizures in GBM are coupled with a highly localized enzyme deficiency. The manipulation of GS activity might constitute a novel principle for inhibiting seizures in patients with glioma epilepsy.
Authors: T Eid; M J Thomas; D D Spencer; E Rundén-Pran; J C K Lai; G V Malthankar; J H Kim; N C Danbolt; O P Ottersen; N C de Lanerolle Journal: Lancet Date: 2004-01-03 Impact factor: 79.321
Authors: Sharon Berendsen; Meri Varkila; Jérôme Kroonen; Tatjana Seute; Tom J Snijders; Frans Kauw; Wim G M Spliet; Marie Willems; Christophe Poulet; Marike L Broekman; Vincent Bours; Pierre A Robe Journal: Neuro Oncol Date: 2015-09-29 Impact factor: 12.300