Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 Dec;103(2):237-44.
doi: 10.1016/j.pbb.2012.08.023. Epub 2012 Aug 31.

Chronic Central Administration of Valproic Acid: Increased Pro-Survival Phospho-Proteins and Growth Cone Associated Proteins With No Behavioral Pathology

Affiliations

Chronic Central Administration of Valproic Acid: Increased Pro-Survival Phospho-Proteins and Growth Cone Associated Proteins With No Behavioral Pathology

Ryan C Bates et al. Pharmacol Biochem Behav. .

Abstract

Valproic acid (VPA) is the most widely prescribed antiepileptic drug due to its ability to treat a broad spectrum of seizure types. However, potential complications of this drug include anticonvulsant polytherapy metabolism, organ toxicity and teratogenicity which limit its use in a variety of epilepsy patients. Direct delivery of VPA intracerebroventricularly (ICV) could circumvent the toxic effects normally seen with the oral route of administration. An additional potential benefit would be significantly reduced dosing while achieving high brain concentrations. Epileptogenic tissue from patients with intractable seizures has shown significant cell death which may be mitigated by maximizing cerebral VPA exposure. Here we show ICV administration of VPA localized to the periventricular zone increased pro-survival phospho-proteins (pAkt(Ser473), pAkt(Thr308), pGSK3β(Ser9), pErk1/2(Thr202/Tyr204)) and growth cone associated proteins (2G13p, GAP43) in a whole animal system. No significant changes in DCX, NeuN, synaptotagmin, and synaptophysin were detected. Assessment of possible behavioral alterations in rats receiving chronic central infusions of VPA was performed with the open field and elevated plus mazes. Neither paradigm revealed any detrimental effects of the drug infusion process.

Similar articles

See all similar articles

Cited by 1 article

Publication types

LinkOut - more resources

Feedback