Valproic acid and epilepsy: From molecular mechanisms to clinical evidences
| Autor: | Cinzia Costa, Paolo Calabresi, Michele Romoli, Alberto Verrotti, Petra Mazzocchetti, Renato D'Alonzo, Victoria Elisa Rinaldi, Sabrina Siliquini |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Traumatic Dendritic spine Traumatic brain injury medicine.medical_treatment Neuroprotection Epileptogenesis Article Histone Deacetylases 03 medical and health sciences Epilepsy Glutamatergic 0302 clinical medicine Status Epilepticus Seizures Brain Injuries Traumatic Medicine Animals Humans Pharmacology (medical) Pharmacology Neurons Valproic Acid business.industry Epigenetics Valproic acid General Medicine medicine.disease Psychiatry and Mental health Settore MED/26 - NEUROLOGIA 030104 developmental biology Anticonvulsant Neurology Brain Injuries lipids (amino acids peptides and proteins) Anticonvulsants Neurology (clinical) business Neuroscience 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Current Neuropharmacology |
| Popis: | After more than a century from its discovery, valproic acid (VPA) still represents one of the most efficient antiepileptic drugs (AEDs). Pre and post-synaptic effects of VPA depend on a very broad spectrum of actions, including the regulation of ionic currents and the facilitation of GABAergic over glutamatergic transmission. As a result, VPA indirectly modulates neurotransmitter release and strengthens the threshold for seizure activity. However, even though participating to the anticonvulsant action, such mechanisms seem to have minor impact on epileptogenesis. Nonetheless, VPA has been reported to exert anti-epileptogenic effects. Epigenetic mechanisms, including histone deacetylases (HDACs), BDNF and GDNF modulation are pivotal to orientate neurons toward a neuroprotective status and promote dendritic spines organization. From such broad spectrum of actions comes constantly enlarging indications for VPA. It represents a drug of choice in child and adult with epilepsy, with either general or focal seizures, and is a consistent and safe IV option in generalized convulsive status epilepticus. Moreover, since VPA modulates DNA transcription through HDACs, recent evidences point to its use as an anti-nociceptive in migraine prophylaxis, and, even more interestingly, as a positive modulator of chemotherapy in cancer treatment. Furthermore, VPA-induced neuroprotection is under investigation for benefit in stroke and traumatic brain injury. Hence, VPA has still got its place in epilepsy, and yet deserves attention for its use far beyond neurological diseases. In this review, we aim to highlight, with a translational intent, the molecular basis and the clinical indications of VPA. |
| Databáze: | OpenAIRE |
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