Raimondo D’Ambrosio, PhD, is Associate Professor of Neurological Surgery and a member of the UW Regional Epilepsy Center. His research focuses on mechanisms and treatments of epilepsy. He has National Institutes of Health (NIH), Department of Defence (DOD), and private foundation research grant support.
Dr. D'Ambrosio's research group focuses on the development of novel treatments for acquired epilepsy. They have developed the first clinically relevant rat model of posttraumatic epilepsy, and are using it to understand the cellular mechanisms of genesis and progression of human posttraumatic epileptogenesis, as well as possible treatments for it.
Follow the link below to read Dr. D'Ambrosio's article: Functional Definition of Seizure Provides New Insight into Post-Traumatic Epileptogenesis.
- Why have the last 30 years of research not yielded superior treatments for epilepsy?
After the great successes of the mid-20th century in the development of treatments for epilepsy, subsequent attempts to identify more efficacious therapies have led to incremental improvements but have not had an impact on the problem of medically intractable epilepsy. Indeed, one-third of epilepsy patients still continue to have uncontrolled seizures, and no method has been found to prevent the development of epilepsy in those at risk. Why?
New and better epilepsy treatments might be developed using models with chronic recurrent spontaneous seizures (epilepsy), as opposed to acute evoked seizures as currently done. Seizure semiologies and etiologies that approximate those of human epilepsy syndromes better than models currently used for drug discovery, are more likely to involve mechanisms of ictogenesis and epileptogenesis that are relevant to the corresponding human syndrome. Therefore, substantial efforts have recently been made to introduce into basic and translational research epilepsy models with realistic etiologies that more closely mimic human syndromes. Our group developed the model of epilepsy induced by a realistic head injury in the rat and is using it to test novel treatments.
- What mechanisms are responsible for the genesis and progression of posttraumatic epilepsy?
The mechanistic etiology of human posttraumatic epilepsy remains elusive. While seizures can result from neuronal or network abnormalities, they can also be precipitated by impaired homeostasis of the extracellular space. Normal neuronal activity results in extrusion of neurotransmitters and potassium, whose decreased extracellular clearance depolarizes neuronal membranes and collapses inhibitory electrochemical gradients, producing a potent endogenous proepileptic stimulus.
Astrocytes play a major role in the homeostasis of the extracellular space, and it has been hypothesized that injury-induced astroglial reaction involves changes in membrane properties that impair potassium homeostasis and cause posttraumatic epilepsy. We are investigating the role of astrocytes in posttraumatic epilepsy.
The mechanisms responsible for the onset of epilepsy after insult to the central nervous system are still unknown. My research aims to identify these mechanisms, and develop better treatments for epilepsy.
- In vivo electrophysiology (ECoG, EEG, depth electrode recordings)
- Rat models of traumatic brain injury
- high pressure liquid chromatography
- acute brain slices
- patch clamp (single channel and whole cell recordings
- ion-selective microelectrodes
- live cell imaging
Bibliography of Selected Publications
- Eastman CL, Verley DR, Fender JS, Stewart TH, Nov E, Curia G, and
D'Ambrosio R. Antiepileptic and Antiepileptogenic Performance of
Carisbamate after Head Injury in The Rat: Blind and Randomized Studies.
Journal of Pharmacology and Experimental Therapeutics, in press
- Curia G, Levitt M, Fender JS, Miller JW, Ojemann J, D'Ambrosio R.
Impact of injury location and severity on posttraumatic epilepsy in the
rat: role of frontal neocortex. Cerebral Cortex, in press. PMID: 21112931
- Stewart TH, Eastman CL, Groblewski PA, Fender JS, Verley DR, Cook
DG, D'Ambrosio R. Chronic dysfunction of astrocytic inwardly rectifying K+
channels specific to the neocortical epileptic focus after fluid
percussion injury in the rat. J Neurophysiol. 2010 Dec; 104(6):3345-60. Epub 2010 Sep 22
- Eastman CL, Verley DR, Fender JS, Temkin NR and D'Ambrosio R. ECoG
studies of valproate, carbamazepine and halothane in frontal lobe epilepsy
induced by head injury in the rat . Experimental Neurology Exp Neurol.
2010, 224(2):369-88 (PubMed # 20420832 NIHMSID # 201020)
- D'Ambrosio R, and Miller JW. What is an Epileptic Seizure?
Unifying Definitions in Clinical Practice and Animal Research to Develop
Novel Treatments. Epilepsy Currents, 2010, 10(3):61-66. review.
- D'Ambrosio R, Hakimian, S, Stewart T, Verley DR, Fender JS,
Eastman CL, Sheerin AH, Gupta P, Diaz-Arrastia R, Ojemann J, Miller JW.
Functional Definition of Seizures Provides New Insights into Posttraumatic
Epileptogenesis. Brain, 2009, 132(10):2805-2821. Cover article.
- Janigro D., Gasparini S., D’Ambrosio R., McKhann G. and DiFrancesco D. (1997) Reduction of K+ uptake in glia prevents Long-Term Depression maintenance and causes epileptiform activity. Journal of Neuroscience, 17(8): 2813-24.
- Gasparini S, Maccaferri G, D’Ambrosio R, and DiFrancesco D. (1996) The hyperpolarization-activated current (Ih/Iq) in rat hippocampal neurons. In: Neurobiology: Ionic Channels, Neurons and the brain, V. Torre and F. Conti eds., pp 63-74, Plenum Publishing Corporation.
- McKhann G. II, D’Ambrosio R. and Janigro D. (1997) Heterogeneity of astrocyte resting membrane potentials and intracellular coupling revealed by whole cell and gramicidin-perforated patch recordings from cultured neocortical and hippocampal slice astrocytes. Journal of Neuroscience, 17(18): 6850-63.
- D’Ambrosio R., Maris D.O., Grady M.S., Winn H.R. and Janigro D. (1998) Selective loss of Long-Term Potentiation, but not Depression, following fluid percussion injury. Brain Research, Vol. 786 (1-2) pp. 64-79.
- D’Ambrosio R., Wenzel J., Schwartzkroin P.A., McKhann G. II and Janigro D. (1998) Functional specialization and topographic segregation of three types of hippocampal astrocytes. Journal of Neuroscience, 18(12):4425-38.
- Hochman D.W., D’Ambrosio R., Janigro D., and Schwartzkroin P.A. (1999) Extracellular chloride and the maintenance of spontaneous epileptiform activity in rat hippocampal slices. Journal of Neurophysiology, 81:49-59.
- Ngai A.C., Jolley M.A., D’Ambrosio R., Meno J.R. and Winn H.R. (1999) Frequency-dependent changes in cerebral blood flow and evoked potentials during somatosensory stimulation in the rat. Brain Research, 837:221-228.
- D’Ambrosio R., Maris D.O., Grady S.M., Winn H.R., and Janigro D. (1999) Impaired K+ homeostasis and altered electrophysiological properties of post-traumatic hippocampal glia. Journal of Neuroscience, 19(18): 8152-62.
- D’Ambrosio R., Gordon D.S., and Winn H.R. (2002) Differential roles of KIR channel and Na+/K+-pump in the regulation of extracellular K+ accumulation in rat hippocampus. Journal of Neurophysiology, Vol 87: 87-102.
- D’Ambrosio R. (2002) The perforated patch technique. In: Neuromethods: Patch Clamp Applications and Protocols. Boulton AA, Baker GB, and Walz W eds. The Humana Press.
- Iliff JJ, Ngai AC, D’Ambrosio R, and Winn HR (2003) Adenosine receptors mediate glutamate-evoked arteriolar dilation in the rat cerebral cortex. American Journal of Physiology, 284(5):H1631-1637
- D’Ambrosio R (2003) Basic science of posttraumatic epilepsy. In: Youman’s Neurological Surgery. 5th edition, pp2449-2460. Elsevier.
- Meno JR, Higashi H, , Cambray AJ, Zhou J, D’Ambrosio R and Winn HR. Hippocampal injury and neurobehavioral deficits are improved by PD 81,723 following hyperglycemic cerebral ischemia. Experimental Neurology, (2003):183(1):188-96.
- D’Ambrosio R, Fairbanks JP, Fender JS, Born DE, Doyle D and Miller JW. Posttraumatic epilepsy following fluid percussion injury in the rat. Brain 2004, 127(Pt 2):304-14. Epub 2003 Nov 7.
- D’Ambrosio R. The role of glial ion channels in seizures and epileptogenesis. Pharmacology & Therapeutics, 2004, 03(2):95-108.
- D’Ambrosio R. Progression of posttraumatic epilepsy following fluid percussion injury. In: Loscher W, Schmidt D (2004) New horizons in the development of antiepileptic drugs. Epilepsy Research, 60(2-3):77-159.
- D’Ambrosio R and Perucca E. Epilepsy after head injury. Current Opinion in Neurology, 2004, 17(6):731-735.
- D’Ambrosio R, Fender JS, Fairbanks JP, Simon E, Born DE, Doyle D, Miller JW. Progression from frontal-parietal to mesial-temporal epilepsy after fluid percussion injury in the rat. Brain 2005, 128(Pt 1):174-88. Epub 2004 Nov 24.
- D'Ambrosio R. A possible causative role for blood brain barrier failure and reactive astrocytosys in acquired epilepsy. Epilepsy Currents, 2005, 5(6):244-6.
- D'Ambrosio R (2006) Does glutamate released by astrocytes cause focal epilepsy? Epilepsy Currents, 6(5):12-15.
- Miller JW and D'Ambrosio R (2007) When Basic Research Doesn’t Translate to the Bedside—Lessons from the Magnesium Brain Trauma Study. Epilepsy Currents, Epilepsy Curr. 2007 Sep-Oct;7(5):133-5.
- Jung S, Jones TD, Lugo JN Jr, Sheerin AH, Miller JW, D'Ambrosio R, Anderson AE, Poolos NP.Progressive dendritic HCN channelopathy during epileptogenesis in the rat pilocarpine model of epilepsy.J Neurosci. 2007 Nov 21;27(47):13012-21.
- D’Ambrosio R (2008) Posttraumatic epilepsy induced by fluid percussion injury. Encyclopedia of Basic Epilepsy Research VII-B, in press.
Published Research Articles
View complete lists of current research publications by faculty from the Department of Neurological Surgery.
Samuel Browd, MD, PhD
Dr. Browd specializes in pediatric neurosurgery, specifically with children who have hydrocephalus, brain & spinal cord tumors, pediatric cervical spine, spina bifida, chiari malformations, and spacticity.
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