Mesial temporal lobe epilepsy (MTLE) is a neurological disorder associated with spontaneous recurrent complex partial seizures and hippocampal sclerosis. Although increased hippocampal neurogenesis has been reported in animal models of MTLE, increased neurogenesis has not been reported in the hippocampus of adult human MTLE cases. Here we showed that cells expressing doublecortin (Dcx), a microtubule-associated protein expressed in migrating neuroblasts, were present in the hippocampus and temporal cortex of the normal and MTLE adult human brain. In particular, increased numbers of Dcx-positive cells were observed in the epileptic compared with the normal temporal cortex. Importantly, 56% of Dcx-expressing cells in the epileptic temporal cortex coexpressed both the proliferative cell marker, proliferating cell nuclear antigen and early neuronal marker, TuJ1, suggesting that they may be newly generated neurons. A subpopulation of Dcx-positive cells in the epileptic temporal cortex also coexpressed the mature neuronal marker, NeuN, suggesting that epilepsy may promote the generation of new neurons in the temporal cortex. This study has identified, for the first time, a novel population of Dcx-positive cells in the adult human temporal cortex that can be upregulated by epilepsy and thus, raises the possibility that these cells may have functional significance in the pathophysiology of epilepsy.

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The ability to culture neural progenitor cells from the adult human brain has provided an exciting opportunity to develop and test potential therapies on adult human brain cells. To achieve a reliable and reproducible adult human neural progenitor cell (AhNPC) culture system for this purpose, this study fully characterized the cellular composition of the AhNPC cultures, as well as the possible changes to this in vitro system over prolonged culture periods. We isolated cells from the neurogenic subventricular zone/hippocampus (SVZ/HP) of the adult human brain and found a heterogeneous culture population comprised of several types of post-mitotic brain cells (neurons, astrocytes, and microglia), and more importantly, two distinct mitotic cell populations; the AhNPCs, and the fibroblast-like cells (FbCs). These two populations can easily be mistaken for a single population of AhNPCs, as they both proliferate under AhNPC culture conditions, form spheres and express neural progenitor cell and early neuronal markers, all of which are characteristics of AhNPCs in vitro. However, despite these similarities under proliferating conditions, under neuronal differentiation conditions, only the AhNPCs differentiated into functional neurons and glia. Furthermore, AhNPCs showed limited proliferative capacity that resulted in their depletion from culture by 5–6 passages, while the FbCs, which appear to be from a neurovascular origin, displayed a greater proliferative capacity and dominated the long-term cultures. This gradual change in cellular composition resulted in a progressive decline in neurogenic potential without the apparent loss of self-renewal in our cultures. These results demonstrate that while AhNPCs and FbCs behave similarly under proliferative conditions, they are two different cell populations. This information is vital for the interpretation and reproducibility of AhNPC experiments and suggests an ideal time frame for conducting AhNPC-based experiments.

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The purpose of the present study was to investigate potential prognostic factors in low-grade oligodendrogliomas (LGOs), particularly 1p19q deletion, due to its proven prognostic significance in anaplastic oligodendrogliomas. We carried out a retrospective review of patients with a histological diagnosis of LGO between 1990 and 2000 in Auckland and Wellington, New Zealand. All cases underwent central histopathological review and FISH testing for 1p19q status. Univariate analysis of potential prognostic factors including 1p19q status, age, tumour size, tumour crossing midline, tumour enhancement, extent of surgery and seizures at diagnosis was carried out. Thirty-one patients were eligible and FISH testing was successful in 28 specimens (90%). Twenty-three specimens (82%) had 1p19q deletion; four (14%) had no 1p19q deletion; and one (4%) had 1p deletion alone. At a median follow-up of 87 months (0-147 months), median survival had not been reached and no significant difference in overall survival (OS) based on 1p19q status was detected (1p19q deletion OS 56%; 1p19q intact OS 0%; 1p deletion alone 100% (P = 0.38)). None of the other prognostic factors investigated reached statistical significance. We confirmed the high incidence (82%) of combined 1p19q deletion in LGOs and the feasibility of successful FISH testing in paraffin embedded specimens up to 10-years-old. Analysis of potential prognostic factors was limited by the lack of events during the follow-up period.

Mesial temporal lobe epilepsy (mTLE) is a neurological condition characterized by the occurrence of spontaneous recurrent seizures originating from mesial structures involving the hippocampus within the temporal lobe. This condition is often associated with pathological features in the hippocampus such as neuronal cell loss, widening of the granule cell layer, astrogliosis and mossy fibre spouting. At present, the mechanisms underlying these pathological features are unclear. However, recent advances in adult neurogenesis studies in mTLE animals and patients suggest that newly generated neurons may contribute to the pathogenesis of ongoing epileptogenesis. This article will review the recent animal and human studies on adult neurogenesis in mTLE and discuss how these results suggests that adult endogenous neurogenesis may not always be reparative in the mTLE and may be targeted in new therapeutic strategies for mTLE.