Impaired transmission in GABAergic circuits is thought to contribute to the pathogenesis of epilepsy. Although it is well established that major reorganization of GABA(A) receptor subtypes occurs in the hippocampus of patients with medically refractory temporal lobe epilepsy (TLE), it is unclear whether this disorder is also associated with alterations in GABA(A) receptor subtypes in the neocortex. Here we have investigated immunohistochemically the subunit composition and neocortical distribution of three major GABA(A) receptor subtypes using antibodies specifically recognizing the subunits alpha1, alpha2, alpha3, beta2/3 and gamma2. Cortical tissue was obtained at surgery from patients with TLE and hippocampal sclerosis (HS; n = 9), TLE associated with neocortical lesions (non-HS; n = 12) and frontal lobe epilepsy (FLE; n = 5), with post-mortem samples serving as controls (n = 4). A distinct laminar and neuronal expression pattern of the alpha-subunit variants was found across the neocortical regions examined in the temporal and frontal lobes in both control and patient tissue samples. In the five patients with FLE, GABA(A) receptor subunit staining was unchanged as compared to controls. In patients with TLE we observed a marked decrease in alpha3-subunit staining in the superficial neocortical layers (I-III), but no change in the deep layers (V and VI) or in the expression pattern of the alpha1 and alpha2-subunits. Reduced expression in alpha3-containing GABA(A) receptors was detected in six out of nine patients of the HS group and four out of twelve patients of the non-HS group. Histopathological changes were present in eight out of the ten patients with decreased alpha3-subunit staining. The selective reduction in alpha3-containing GABA(A) receptors was confirmed using semiquantitative measurements of optical density (OD). The specific changes unique to alpha3-subunit expression in the superficial neocortical layers of patients with TLE suggest that this subtype is of particular significance in the reorganization of cortical GABAergic systems in focal epilepsy.

In spite of having been the object of considerable attention, the histopathological grading of oligodendrogliomas is still controversial. The determination of reliable biomarkers capable of improving the malignancy grading remains an essential step in working toward better therapeutic management of patients.

Summary:Purpose: The present study aims at characterizing remote memory in patients with temporal lobe epilepsy (TLE); it also considers the impact of its most important variables (lateralization of the lesion, duration of epilepsy, age at onset, and seizure frequency) on remote memory.Methods: We examined the performance of 38 patients with unilateral TLE (19 right TLE and 19 left TLE) and 35 healthy subjects on six remote memory tasks. Memory for personal events was assessed by using the Autobiographical Memory Interview and the Modified Crovitz Test. Memory for public events was evaluated by means of photographs of famous faces and famous scenes, questions about famous events, and the Dead/Alive Test.Results: Both right-TLE and left-TLE groups had impaired memory for autobiographic episodes and public events relative to normal subjects. In contrast, personal semantic memory was preserved. In addition, an effect of laterality was recorded, with right-TLE patients obtaining significantly better scores than left-TLE patients on every test. Duration of epilepsy, age at onset, and seizure frequency did not influence performance on remote memory measures.Conclusions: The comprehensive neuropsychological study of 38 TLE patients showed that this neurologic condition affects remote memory systems differently. We discuss the different factors that could account for this pattern of performance on the bases of both functional brain organization and memory theories.

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