Researching the effects of anti-seizure drugs on neonatal development
I am currently a full-time researcher at the Forcelli laboratory at Georgetown University, investigating the effects of hypoxia-induced seizures on neurodevelopment as well as the effects of anti-seizure drugs on normal physiological processes.
Epilepsy is the fourth most common clinical neurological disorder, defined as recurrent seizures in a short time frame. Seizures are events of abnormal and excessive neuronal activities, resulting in a variety of outcomes including loss of function, loss of consciousness, and in prolonged events, significant brain damage. Seizures are most common in early development; hypoxic insults suffered in utero and in early life can result in brain damage and seizure events.
Pharmacotherapies are a common clinical option to terminate seizures and treat the symptoms of epilepsy. The most common anti-seizure drug used is Phenobarbital, a GABAa agonist. In adults, phenobarbital has been found to significantly reduce the number of seizures observed. GABAa in adults is associate with inhibitory action and phenobarbital can increase inhibition to terminate hyperactive neuronal circuits.
Although effective in adults, Phenobarbital can have significant detrimental effects when administered to patients early in life.
GABAa in early development is associated with excitation in neuronal circuits, modifying during critical developmental periods into its mature function as an inhibitory neuron affecter.
Phenobarbital administered in early development results in further exciting hyperactive neuronal circuits, increasing the severity and damage from seizures.
The effects of phenobarbital and other anti-seizure drugs are not well understood, which limits the ability to responsibly administer treatments in a clinical setting. The purpose of our investigation is to understand how these drugs work and their effects on short and long-term neurological functions.
We are currently administering anti-seizure drugs to Sprague-Dawley experimental models and observing the acute effects of the drugs using histological techniques and observing long term effects via behavioral testing when they grow to maturity.