Epilepsy after the Decade of the Brain: Misunderstandings, challenges, and opportunities

Department of Neurology and Center for Neuroscience, University of Wisconsin, Madison, WI, USA.
Epilepsy & Behavior (Impact Factor: 2.06). 06/2005; 6(3):296-302. DOI: 10.1016/j.yebeh.2005.02.009
Source: PubMed
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    ABSTRACT: While substantial progress over the past 60 years has enabled a greater proportion of persons with epilepsy (PWE) to live without seizures and treatment-related side effects, numerous challenges in the diagnosis, treatment and social management of epilepsy remain to be solved over the next 60 years so that no person with epilepsy is limited by any aspect of the condition. This achievement is within our reach, but will require professional and lay epilepsy organisations to work closely together to ensure that clinical, scientific and sociological advances are made and applied to the medical and social management of epilepsy.
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    ABSTRACT: Inhibition of mTOR by rapamycin has been shown to suppress seizures in TSC/PTEN genetic models. Rapamycin, when applied immediately before or after a neurological insult, also prevents the development of spontaneous recurrent seizures (epileptogenesis) in an acquired model. In the present study, we examined the mTOR pathway in rats that had already developed chronic spontaneous seizures in a pilocarpine model. We found that mTOR is aberrantly activated in brain tissues from rats with chronic seizures. Furthermore, inhibition of mTOR by rapamycin treatment significantly reduces seizure activity. Finally, mTOR inhibition also significantly suppresses mossy fiber sprouting. Our findings suggest the possibility for a much broader window for intervention for some acquired epilepsies by targeting the mTOR pathway.
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    ABSTRACT: Although traumatic brain injury is a major cause of symptomatic epilepsy, the mechanism by which it leads to recurrent seizures is unknown. An animal model of posttraumatic epilepsy that reliably reproduces the clinical sequelae of human traumatic brain injury is essential to identify the molecular and cellular substrates of posttraumatic epileptogenesis, and perform preclinical screening of new antiepileptogenic compounds. We studied the electrophysiologic, behavioral, and structural features of posttraumatic epilepsy induced by severe, non-penetrating lateral fluid-percussion brain injury in rats. Data from two independent experiments indicated that 43% to 50% of injured animals developed epilepsy, with a latency period between 7 weeks to 1 year. Mean seizure frequency was 0.3+/-0.2 seizures per day and mean seizure duration was 113+/-46 s. Behavioral seizure severity increased over time in the majority of animals. Secondarily-generalized seizures comprised an average of 66+/-37% of all seizures. Mossy fiber sprouting was increased in the ipsilateral hippocampus of animals with posttraumatic epilepsy compared with those subjected to traumatic brain injury without epilepsy. Stereologic cell counts indicated a loss of dentate hilar neurons ipsilaterally following traumatic brain injury. Our data suggest that posttraumatic epilepsy occurs with a frequency of 40% to 50% after severe non-penetrating fluid-percussion brain injury in rats, and that the lateral fluid percussion model can serve as a clinically-relevant tool for pathophysiologic and preclinical studies.
    Neuroscience 07/2006; 140(2):685-97. DOI:10.1016/j.neuroscience.2006.03.012 · 3.33 Impact Factor