The multimodal prospects for neuroprotection and disease modification in epilepsy: Relationship to its challenging neurobiology
Titel:
The multimodal prospects for neuroprotection and disease modification in epilepsy: Relationship to its challenging neurobiology
Auteur:
Hamed, Sherifa A.
Verschenen in:
Restorative neurology and neuroscience
Paginering:
Jaargang 28 (2010) nr. 3 pagina's 323-348
Jaar:
2010-05-17
Inhoud:
Cumulative evidences from experimental and clinical studies indicate that in some patients, not only prolonged but also repetitive brief seizures, may trigger series of damage promoting mechanisms which evolve over a period of time (up to years). They result in progressive degeneration and loss of function of several neuronal cell populations, thus rending the brain abnormal and resistant to antiepileptic medications (AEDs). This probably explains that in some patients, a) there is a delay from the onset of brain insult to the seizure onset, and b) suppression of seizures by AEDs is alone insufficient without clear prediction of disease progression. In this review, the analysis of information follows the assumption that epilepsy is a slowly progressive and a neurobiologically pleotropic disorder. Interaction between genes, neurotransmitters, ion channels, acid-base balance, mitochondria, calcium, glutamate and oxidative/antioxidants mechanisms, will determine the fate of the epilepsy process. The concept of neuroprotection aims not only to suppress seizures (anticonvulsant effect), but also to strengthen the auto-protective and repair mechanisms (antiepileptogenic and disease-modification effects) which prevent the development of spontaneous seizures, cognitive and behavioral problems later in life. This review is focusing on molecular evaluation of several models of epilepsy for the potential to follow disease modification and neuroprotection. Although AEDs of today possess multiple mechanisms of action, but mostly they are treating one part of the disease which is the seizures and do not offer high prospects of modification of the disease. This review is also discussing the prospects of novel drugs, molecular manipulations and cell therapy which address disease modification as approachs that will dominate the field of drug development and research on epilepsy in the future.
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