How a stinky chemical offers neuroprotection for a seizing brain

What did Socrates, Plato, Hercules, and Ajax have in common? Other than greatness, they were also epileptics according to the 17th century French physician, Jean Taxil.

An epileptic seizure consists of abnormal excessive or synchronous neuronal activity in the brain which can lead to convulsions, loss of awareness, full body slump, or even the experience of deja vu. Unprovoked seizures are typically related to epilepsy and other seizure related disorders while provoked seizures have multiple contributing factors including, but not limited to traumatic brain injury, kidney failure, sleep deprivation, brain lesions, metabolic disturbances, stroke, and tricyclic antidepressants. Sometimes seizures are just idiopathic (unknown cause).

Is epilepsy really the "sacred disease" Hippocrates had once thought it was? Not really. Serious complications may arise such as difficulty learning, aspiration pneumonia, injury from falls, and even permanent brain damage (I recommend the book The Spirit Catches You and You Fall Down).

A recent study by Bell and colleagues published in the latest Nature Neuroscience investigated whether polyamines, organic compounds having two or more primary amino groups, acted as a neuroprotective factor against subsequent seizures. Past studies have shown that polyamines increase after a seizure, but their regulatory role in epileptic seizures remain a mystery. 

The authors exposed Xenopus laevis tadpoles (aka African clawed tadpoles) to pentylenetetrazol (PTZ), a well known convulsant, to see if polyamines would regulate neural excitability following a seizure. After a priming exposure, they again exposed the poor tadpoles to PTZ 4 hours later. What they found was quite remarkable. Compared to a control group (tadpoles that did not receive a priming exposure to PTZ), the seizure onset in the primed group during the second exposure was delayed a whopping 25%. Something was protecting them from having a subsequent seizure, but what was it?

The authors found that a stinky type of polyamine known as prutescine (more like "putrid-scine" ::rimshot::) was involved in decreasing seizure susceptibility. They suggest that when prutescine is released after the first seizure, it converts into GABA, an inhibitory neurotransmitter. The extracellular GABA then activates presynaptic GABA receptors on inhibitory interneurons, temporarily decreasing inhibitory drive and increasing seizure susceptibility (a kindling effect). The inhibitory neurons respond to this activation with a compensatory release of more GABA. When the prutescine and GABA levels return back to normal, the inhibitory frequency stays elevated. When another seizure occurs, the animal is well protected.

The findings of this study shed further light on the development of the seizing brain and bring the field closer to developing preventative measures for both short-term and long-term seizure susceptibility. Prutescine may indeed be the golden ticket to improving resiliency to seizures. Now all we need to figure out is what to do with that horrific stench. 

Bell MR, Belarde JA, Johnson HF, & Aizenman CD (2011). A neuroprotective role for polyamines in a Xenopus tadpole model of epilepsy. Nature neuroscience, 14 (4), 505-12 PMID: 21378970