Brain recruitment of dendritic cells following Li-pilocarpine induced status epilepticus in adult rats.

Activation of inflammatory and immune pathways may contribute to the development of epilepsy. Dendritic cells (DCs), a heterogeneous group of professional antigen presenting cells, can be detected in the brain under several inflammatory conditions. However, the spatiotemporal distribution and origin of seizure-induced DCs accumulation in the brain have not been explored yet. In the present study, we demonstrate the presence of CD11c-positive DCs in the hippocampus, thalamus and temporal cortex following Li-pilocarpine induced status epilepticus (SE) in rats. Recruitment of DCs occurs as early as 1 day following the induction of SE, reaching peak time at day 3, and still evident until day 5. The recruitment of DCs in the brain following lithium chloride administration was not detected. The observed DCs cannot be double-labeled with Iba-1 (an activated microglia marker) and whole-body radiation prevents seizure-induced DCs accumulation in brain parenchyma. Our data suggest that the recruitment of DCs in the epileptic brain may be derived from peripheral circulation and this population of immune cells may be involved in the immune processes after SE.

Idiopathic hypereosinophilic syndrome revealed by encephalopathy.

Idiopathic hypereosinophilic syndrome (HES) is characterized by persistent hypereosinophilia ( ≥ 1500/mm(3)) with evidence of end-organ damage without a definite underlying cause. Hypereosinophilia-induced encephalopathy is a rare clinical syndrome. We present a male patient with idiopathic HES with distinctive encephalopathy who had hypereosinophilia for more than 6 months. Eosinophils in repeated blood tests were more than 1500/mm(3). He had hematological, brain, bone-marrow, and possible cardiac involvement. Although numerous efforts were made to identify the underlying cause of hypereosinophilia, specific causes could not be found in this patient. Bone-marrow analysis confirmed the diagnosis. The unique features were the prominent involvement of the cerebral cortex and the dramatic response to steroids with marked improvement of eosinophilia and brain function. The mechanisms of hypereosinophilia-induced encephalopathy are discussed.

Effects of lamotrigine and topiramate on hippocampal neurogenesis in experimental temporal-lobe epilepsy.

Lamotrigine (LTG) and topiramate (TPM), two of the most commonly used new-generation antiepileptic drugs (AEDs), have been shown to produce no adverse and impaired cognitive effects in patients with epilepsy, respectively. As seizure-induced neurogenesis might contribute to cognitive deficits that are associated with status epilepticus (SE), we examined whether these two drugs produce differential effects on seizure-induced neurogenesis in the hippocampus of adult rats. Lithium pilocarpine model was used to mimic human temporal-lobe epilepsy. Five hours after SE, LTG and TPM were administered intragastrically twice daily throughout the entire length of the experiment with total daily dose of 20 and 80 mg/kg, respectively. The hippocampal neurogenesis was examined using 5-bromodeoxyuridine and doublecortin immunohistochemistry. Both LTG and TPM treatments significantly inhibited seizure-induced proliferation of neural progenitors in the hippocampus, but did not affect the neuronal differentiation of newborn cells. Long-term treatment with both AEDs decreased the number of spontaneous recurrent seizures after SE and alleviated chronic seizure-induced neuronal injury in the dentate hilus. Eventually, TPM significantly increased the number of newborn neurons in the dentate granular cell layer after seizures likely by promoting the survival of newborn neurons. In contrast, LTG treatment significantly reduced the number of ectopic hilar newborn neurons after seizures. Neither of them prevented the formation of hilar basal dendrites of newborn neurons in the epileptic hippocampus. These results indicate that TPM but not LTG promotes aberrant neuron regeneration in the hippocampus after SE, which might be partially related to their differential effects on cognitive function.

Different effects of mild and severe seizures on hippocampal neurogenesis in adult rats.

Recent evidence shows that functional neurogenesis exists in the adult hippocampus and that epileptic seizures can increase neurogenesis in the dentate gyrus (DG). However, it is unknown whether different seizure severity has different effects on neurogenesis in the DG of adult rats. In this study, we examined hippocampal neurogenesis in the rat mild and severe seizure preparations characterized with frequent wet dog shakes and severe status epilepticus, respectively. Both mild and severe seizures promoted the mitotic activity in the DG, but severe seizures caused a stronger cell proliferative response than mild seizures. Less than 20% of newborn cells in the DG differentiated into neurons in rats suffering severe seizures, whereas more than 60% of newborn dentate cells differentiated into neurons in control and mild seizure groups. Most newborn neurons migrated into the granular cell layer in control and mild seizure groups, but severe seizures were associated with an aberrant migration of newborn neurons into the dentate hilus. Severe seizures induced astrocyte activation and the expression of nestin and the migration directional molecules netrin 1 and Sema-3A in the hilus, which were not present in the hilus of control and mild seizure-attacked rats, suggesting that these molecules are involved in the aberrant migration of newborn neurons.

Effects of nitric oxide on dentate gyrus cell proliferation after seizures induced by pentylenetrazol in the adult rat brain.

Epileptic seizures have been shown to increase the proliferation of granule cell precursors in the adult brain, but the underlying mechanisms remain largely unknown. This study examined the effect of nitric oxide (NO) on the proliferation of granule cell precursors in adult rats after pentylenetrazol (PTZ)-induced generalized clonic seizures. Using systemic bromodeoxyuridine (BrdU) to label dividing cells, we found that injection of the neuronal nitric oxide synthase (nNOS) inhibitor 7-nitroindazole (50 mg/kg i.p.) 10 min before PTZ significantly reduced the number of BrdU labeled cells in the dentate gyrus 3, 7, and 14 days after seizures (P < 0.05). Administration of the inducible NOS (iNOS) inhibitor aminoguanidine (100 mg/kg i.p.) also significantly inhibited the proliferation rate of neural precursor cells in the dentate gyrus at various time points after PTZ-induced seizures. Our findings suggest that epileptic seizures lead to increased cell proliferation in the adult rat dentate gyrus through NO-dependent mechanisms. Both the NO originating from nNOS and iNOS may be involved in brain repair after seizures.

Response of seizure-induced newborn neurons in the dentate gyrus of adult rats to second episode of seizures.

In this study we examined the unknown issue of whether seizure-induced newborn hippocampal neurons in freely moving adult rats are able to respond to pathophysiological stimuli in the same way as their neighboring neurons do. Three days after pentylenetrazol (PTZ)-induced generalized seizures, rats received 5-bromodeoxyuridine (BrdU) injections to label dividing cells, followed 4 weeks later by the second PTZ injection to induce second episode of generalized seizures. We observed that the first episode of PTZ-induced seizures resulted in a significant increase in the number of newborn neurons in the adult hippocampal dentate gyrus. In comparison with vehicle-injected control rats that exhibited no Fos immunoreactivity and mild glutamic acid decarboxylase 67 (GAD67) expression in the dentate granule cells, rats killed 2-6 h following the second PTZ injection showed intensive Fos and GAD67 expression in virtually all granule cells with or without BrdU double-labeling. These findings provide important evidence indicating that seizure-induced newborn neurons in freely moving adult rats are able to respond to pathophysiological stimuli in the same way as neighboring neurons do.