Severe traumatic brain injury — such as that associated with military head wounds — is basically untreatable. In addition to cognitive and motor impairments, it leads to epilepsy about 20 to 50 percent of the time; anticonvulsants given after trauma have been tried as a preventative but have not worked. “After head trauma, physicians often watch symptoms evolve, and there’s nothing we can do to prevent them,” says Alexander Rotenberg, a neurologist and neurobiology investigator at Children’s Hospital Boston.
The brain damage begins within seconds of the actual trauma, but a punishing series of biochemical events in the brain unfold over the subsequent days and weeks, making matters worse by causing neurons to become over-excited.
“Our question is, can we prophylaxe against these changes?” says Rotenberg. “At what point is the horse out of the barn, and when is the best time to intervene?”
Enter huperzine A, a botanical used in traditional Chinese medicine to treat swelling, fever, inflammation, blood disorders and schizophrenia. Evidence from cell culture and animal models suggests that this moss extract might dampen down the excitatory response to brain trauma, since its actions include blocking the NMDA glutamate receptors, the gateway to excitatory brain activity. Many other drugs also target the NMDA receptor, says Rotenberg, but have toxic effects, whereas huperzine A is documented to be safe.
“Here’s something already sold in health food stores,” says Rotenberg. “It’s a low-lying fruit since there’s not much of a physiologic cost to giving it; it’s fairly harmless.”
In collaboration with epileptologist Steve Schachter of Beth Israel Deaconess Medical Center, Rotenberg began feeding huperzine A to rats with induced head trauma. Wanting to increase concentrations actually available to the brain, they came up with the idea of giving it intranasally. “One can get drugs to the brain very effectively through the nose,” says Rotenberg. “This might be a way to circumvent the blood-brain barrier and also reduce the risk of side effects.”
Rotenberg, Schachter and a third investigator, Dana Ekstein of Hadassah Medical Center in Israel, are now testing intranasal delivery in a pilot project funded by the Center for Integration of Medicine and Innovative Technology. CIMIT, a non-profit consortium of Boston teaching hospitals and engineering schools, seeks to develop new technologies to solve medical problems, particularly in military settings.
And that’s where intranasal delivery could have a real advantage. In cases of trauma, intravenous routes may not be available if the patients’ blood circulation is compromised by shock, and if first responders cannot find a vein. Nasal delivery would use a direct conduit provided by olfactory neurons deep in the nose.
The pilot study will first compare brain levels of huperzine in rats after intranasal versus oral administration, then will test whether animals treated with intranasal huperzine A lose fewer neurons and glial cells after injury. Finally, the investigators will monitor the rats for seizures, to see intranasal huperzine A prevents them.
Huperzine is also being talked about in Alzheimer’s circles, since it also increases concentrations of acetylcholine, a neurotransmitter in the brain, though its actual efficacy is uncertain based on clinical trials involving oral delivery.
Whether huperzine A delivered by any method can minimize the severity of brain injury and neurologic symptoms after head trauma may become clearer with the experiments planned over the next year. These investigators are cautiously optimistic that it may work.