Darrell V Lewis Jr., Professor of Pediatrics
- Contact Info:
|M.D.||University of Minnesota, Twin Cities||1969|
- Research Interests:
Current Research Efforts:
A) Basic Science:
1) Mechanism of NMDA receptor antagomist neuroneurotoxicity: Although NMDA receptor antagonists are useful in protecting against excitotoxicity and ischemic injury, they also can cause neuronal apoptosis in the cingulate gyrus and clinically abused NMDA receptor antagomists such as angels dust can produce a schizoprenic like syndrome. We are studying the disinhibitory effects of NMDA receptor antagonists on the cortical puramidal cells of the posterior cingulate region to determine how these agents produce neuronal injury (Li, Q, Clark, S, Lewis, DV, and Wilson, WA. NMDA receptor antagonists disinhibit rat posterior cingulate and retrosplenial cortices: A potential mechanism of neurotoxicity. J Neurosci, In Press, 2001).
2) Mechanism of development of tolerance and dependence to GHB (gammahydroxybutyric acid), a commonly abused sedative agent. We are studying the effect of GHB on the inhibitory circuitry of the neocortex in rats to determine the changes in GABA receptor expression and sensitivity that may underlie the development of tolerance, dependence and withdrawal phenomena associated with GHB abuse.
B) Clinical Research
1) Relationship between complex febrile convulsions and hippocampal sclerosis; The hypothesis that complex febrile convulsions (CFCs) cause hippocampal injury that evolves to sclerosis and then to temporal love epilepsy has been promulgated for decades since the advent of surgical treatment of temporal love epilepsy. However, this concept has never been addressed with a prospective clinical study. With the availability of magnetic resonance imaging techniques capable of discerning hippocampal edema and measuring hippocampal volume, patients suffering CFCs can now be studied acutely and chronically to determine if hippocampal injury does occur using CFCs and under what clinical circumstances. We are planning a multicenter study of this phenomenon based on the publication describing our initial findings ina small group of infants with CFCs (VanLandingham et al., Annals of Neurology, 43:413-426, 1998; Lewis DV. Febrile convulsions and mesial temporal sclerosis. Current Opinion in Neurology, 12:197-201, 1999; Lewis, DV et al. Do Prolonged Febrile Seizures Produce Mesial Temporal Sclerosis? Hypotheses, MRI Evidence and Unanswered Questions, Prog. Brain Res. In Press, 2001; Mitchell, TV and Lewis, DV. Do prolonged febrile seizures injure the hippocampus: Human MRI studies. In, Febrile Seizures, Eds. TZ Baram and S Shinnar, In Press, 2001.
- Magnetic Resonance Imaging • Psychosurgery • Blood Circulation • Monitoring, Physiologic • Oxygen Consumption • Television • Hemodynamics • Hippocampus • Infant, Premature • Intensive Care Units, Neonatal • Synaptic Transmission • Cell Membrane Permeability • Membrane Potentials • Adaptation, Physiological • Theta Rhythm • Cholinesterase Inhibitors • Electrophysiology • Electroencephalography • Blood Volume • Cerebrovascular Circulation • Tomography, Emission-Computed • Penicillin G • Potassium • Aluminum • Aluminum Oxide • Evoked Potentials • Pertussis Toxin
- Representative Publications
- JM Provenzale, DP Barboriak, K VanLandingham, J MacFall, D Delong, DV Lewis, Hippocampal MRI signal hyperintensity after febrile status epilepticus is predictive of subsequent mesial temporal sclerosis.,
AJR. American journal of roentgenology, vol. 190 no. 4
pp. 976-83, ISSN 1546-3141 [doi] [abs]
- Q Li, CM Kuhn, WA Wilson, DV Lewis, Effects of gamma hydroxybutyric acid on inhibition and excitation in rat neocortex.,
Neuroscience, vol. 150 no. 1
pp. 82-92, ISSN 0306-4522 [doi] [abs]
- DV Lewis, Losing neurons: selective vulnerability and mesial temporal sclerosis.,
Epilepsia, vol. 46 Suppl 7
pp. 39-44, ISSN 0013-9580 [doi] [abs]
- Li, Q, Guo-Ross, S, Lewis, DV, Turner, D, White, AM, Wilson, WA, and Swartzwelder, HS. Dietary prenatal choline supplementation enhances excitatory function and morphology of hippocampal CA1 pyramidal cells. Journal of Neurophysiology. 91(4):1545-55, 2004 Apr.
- Q Li, S Clark, DV Lewis, WA Wilson, NMDA receptor antagonists disinhibit rat posterior cingulate and retrosplenial cortices: a potential mechanism of neurotoxicity.,
The Journal of neuroscience : the official journal of the Society for Neuroscience, vol. 22 no. 8
pp. 3070-80, ISSN 1529-2401 [doi] [abs]
- DV Lewis, DP Barboriak, JR MacFall, JM Provenzale, TV Mitchell, KE VanLandingham, Do prolonged febrile seizures produce medial temporal sclerosis? Hypotheses, MRI evidence and unanswered questions.,
Progress in brain research, vol. 135
pp. 263-78, ISSN 0079-6123 [abs]
- MS Wainwright, PL Martin, RP Morse, M Lacaze, JM Provenzale, RE Coleman, MA Morgan, C Hulette, J Kurtzberg, C Bushnell, L Epstein, DV Lewis, Human herpesvirus 6 limbic encephalitis after stem cell transplantation.,
Annals of neurology, vol. 50 no. 5
pp. 612-9, ISSN 0364-5134 [abs]
- Verma, A, Lewis, D, Vanlandingham, KE, Husain, AM, Friedman, AH, Thompson, E, and Radtke, RA. Lateralized seizure termination: relationship to outcome following anterior temporal lobectomy. Epil Res 47:9-15, 2001.
- H Kassem-Moussa, JM Provenzale, JR Petrella, DV Lewis, Early diffusion-weighted MR imaging abnormalities in sustained seizure activity.,
AJR. American journal of roentgenology, vol. 174 no. 5
pp. 1304-6, ISSN 0361-803X [doi]
- N Foldvary, B Nashold, E Mascha, EA Thompson, N Lee, JO McNamara, DV Lewis, JS Luther, AH Friedman, RA Radtke, Seizure outcome after temporal lobectomy for temporal lobe epilepsy: a Kaplan-Meier survival analysis.,
Neurology, vol. 54 no. 3
pp. 630-4, ISSN 0028-3878 [abs]
- DD Mott, Q Li, MM Okazaki, DA Turner, DV Lewis, GABAB-Receptor-mediated currents in interneurons of the dentate-hilus border.,
Journal of neurophysiology, vol. 82 no. 3
pp. 1438-50, ISSN 0022-3077 [abs]
- Xie, C.W. and Lewis, D.V. Blocking opioid receptors unmasks LTP of synaptic inhibition in the dentate gyrus. Regulatory Peptides 54:73-74,1994.