Research interest
We have studied tyhe effects of
blood-brain barrier disruption in animal models as well as in patients. We have discovered that even slight changes in blood-brain barrier permeability cause altered brain homeostasis which can lead to acute seizures or delayed autoimmune disorders. We used anti-inflammatory corticosteroids to successfully restore BBB integrity, as judged by MRI scans. This resulted in a huge therapeutic benefit in a pediatric population of multiple drug resistant epileptics.
Another study is based on the intraoperative detection of blood in brain. We have measured drug levels in epileptics but plan to do so also in patients undergoing brain resections for any other reason. The main outcome of this study is the unexpected discovery of a toxic metabolite of carbamazepine, and old antiepileptic drug. This metabolite was produced by the blood-brain barrier and not as predicted by other studies by hepatocytes.
In another study we are measuring serum markers of blood-brain barrier function. These are useful diagnostic tools to detect even slight alterations in BBB as seen in mTBI, metastatic brain tumors or stroke. The use of one of these markers, S100B, is used as means to rule out TBI in the emergency room.
In other words ...
We study how the blood vessels that feed the brain also protect the neurons from outside molecules. This phenomenon is due to the presence of a brain-brain barrier which acts as a bouncer, by allowing entry for the good guys and keeping out the riff-raff.
We discovered that even small and transient breaches in this barrier may cause acute (seizures) and delayed (trauma) consequences. We also found that inflammation occurring elsewhere in the body is the cause of this barrier leakage. We also found that using inexpensive drugs that have been used for arthritis pr other peripheral diseases can effectively prevent seizures in animals or treat epileptic seizures in human subjects.
Most of our work is done in humans and only a few experiments use rats or other animals. In one of the most recent studies we tested blood samples taken from young athletes and discovered that even the mildest forms of concussion (so-called "ding injuries") cause an opening of the protective shield that isolates the brain from the periphery.
Highlighted Publications
1: Ghosh C, Marchi N, Hossain M, Rasmussen P, Alexopoulos AV, Gonzalez-Martinez
J, Yang H, Janigro D. A pro-convulsive carbamazepine metabolite: Quinolinic acid
in drug resistant epileptic human brain. Neurobiol Dis. 2012 Mar 9.
2: Marchi N, Granata T, Alexopoulos A, Janigro D. The blood-brain barrier
hypothesis in drug resistant epilepsy. Brain. 2012
3: Marchi N, Johnson AJ, Puvenna V, Johnson HL, Tierney W, Ghosh C, Cucullo L,
Fabene PF, Janigro D. Modulation of peripheral cytotoxic cells and ictogenesis in
a model of seizures. Epilepsia. 2011 Sep;52(9):1627-34.
4: Marchi N, Tierney W, Alexopoulos AV, Puvenna V, Granata T, Janigro D. The
etiological role of blood-brain barrier dysfunction in seizure disorders.
Cardiovasc Psychiatry Neurol. 2011;2011:482415.
5: Neuwelt EA, Bauer B, Fahlke C, Fricker G, Iadecola C, Janigro D, Leybaert L,
Molnár Z, O'Donnell ME, Povlishock JT, Saunders NR, Sharp F, Stanimirovic D,
Watts RJ, Drewes LR. Engaging neuroscience to advance translational research in
brain barrier biology. Nat Rev Neurosci. 2011 Mar;12(3):169-82. Review.
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