Cortical dysplasia is a major cause of intractable epilepsy in children. However, the precise mechanisms linking cortical malformations to epileptogenesis remain elusive. The neuronal-specific activator of cyclin-dependent kinase 5, p35, has been recognized as a key factor in proper neuronal migration in the neocortex. Deletion of p35 leads to severe neocortical lamination defects associated wi...

Epilepsy is a common, chronic neurologic disorder characterized by recurrent unprovoked seizures. Experimental modeling and clinical neuroimaging of patients has shown that certain seizures are capable of causing neuronal death. Such brain injury may contribute to epileptogenesis, impairments in cognitive function or the epilepsy phenotype. Research into cell death after seizures has identified...

Neuron-restrictive silencer factor (NRSF), also known as repressor element-1 silencing transcription factor, is a transcriptional repressor that plays important roles in embryonic development and neurogenesis. Recent findings show that NRSF is upregulated after seizures activity however, the link between NRSF and epileptogenesis remains poorly understood. To investigate the role of NRSF in epil...

Seizures are a prominent clinical feature of encephalitis. Recent data suggest the adaptive as well as innate immune system to be involved directly in the pathomechanism of epileptogenesis. Cytotoxic T-cells and antibody-mediated complement activation are major components of the adaptive immune system, which can induce neurodegeneration, thereby probably contributing to epileptic encephalitis. ...

Brain cholesterol homeostasis has been shown to be disrupted in neurodegenerative conditions such as Alzheimer's and Huntington's diseases. Investigations in animal models of seizure-induced brain injury suggest that brain cholesterol levels are altered by prolonged seizures (status epilepticus) and are a feature of the pathophysiology of temporal lobe epilepsy. The present study measured hippo...

Chronically isolated neocortex develops chronic hyperexcitability and focal epileptogenesis in a period of days to weeks. The mechanisms operating in this model of post-traumatic epileptogenesis are not well understood. We hypothesized that the spontaneous burst discharges recorded in chronically isolated neocortex result from homeostatic plasticity (a mechanism generally assumed to stabilize n...

Epileptogenesis following neocortical trauma from two sources of disinhibition. J. Neurophysiol. 78: 2804-2810, 1997. Intracellular and field potential recordings were obtained from superficial and deep neurons from both intact coronal rat somatosensory slices, and from slices which had been acutely divided into a superficial strip of cortex ( approximately 450 micron from the pia) and a deep s...

Accumulation of abnormally integrated, adult-born, hippocampal dentate granule cells (DGCs) is hypothesized to contribute to the development of temporal lobe epilepsy (TLE). DGCs have long been implicated in TLE, because they regulate excitatory signaling through the hippocampus and exhibit neuroplastic changes during epileptogenesis. Furthermore, DGCs are unusual in that they are continually g...

Fleeting activation of NMDA receptors (NMDARs) induces long-term modification of synaptic connections and refinement of neuronal circuits, which may underlie learning and memory and contribute to pathogenesis of a diversity of neurological diseases, including epilepsy. Here, we found that NR2A and NR2B subunit-containing NMDARs were coupled to distinct intracellular signaling, resulting in diff...

The administration of lithium-pilocarpine (LiPilo) in adult rats is a validated model reproducing the main clinical and neuropathological features of temporal lobe epilepsy (TLE). Previous studies have shown that carisbamate (CRS) has the property of modifying epileptogenesis in this model. When treated with CRS, about 50% of rats undergoing LiPilo status epilepticus (SE) develop non-convulsive...