Washington University School of Medicine

Lawrence Eisenman, MD, PhD

Dr. Eisenman is an Assistant Professor of Neurology specializing in the evaluation and treatment of adults with epilepsy including diagnosis, pharmacological treatment and intensive evaluation for surgical treatment including video/EEG monitoring. In addition, he is the director of the Clinical Neurophysiology Training Program and the recipient of a K08 career development award from the NIH.

My primary research interest in the role of GABA receptors both in the normal physiology of the brain and in pathological states, particularly epilepsy. GABA is the major inhibitory neurotransmitter in the central nervous system and dysfunction in the GABA system is a major component of the pathology of epilepsy. I am currently working in the laboratories of Drs. Steven Mennerick and Charles Zorumski on two main projects.

The first project is to explore the properties of the endogenous neurosteroid pregnenolone sulfate. Neurosteroids are steroid compounds produced de-novo within the brain. Many neurosteroids act directly on GABA receptors to augment inhibition while others such as pregnenolone sulfate have the opposite effect. Current data would suggest that pregnenolone sulfate is not present in high enough concentrations to have any relevant physiological effect. However, our recent work has demonstrated that pregenolone sulfate is activation dependent, which may allow lower concentrations than previously appreciated to have significant effects on GABA receptors. Current work is aimed at further characterizing the properties of pregnenolone sulfate to better understand its potential physiological significance.

In a related project, we have recently demonstrated that fluorescently labeled neurosteroid analogues can potentiate both GABA and NMDA receptors when illuminated with blue light. This allows for precise spatial and temporal control of potentiation, making this a valuable new research tool with potential clinical applications.

The second project involves the study of neuronal network activity dissociated hippocampal cultures using multi-electrode arrays in addition to single cell recording. The goal of this work is to elucidate the role of GABA receptors in the development of normal patterns of neuronal activity and in seizures.
In addition, I am interested in clinical research aimed at improving outcomes and quality of life in patients with epilepsy. I also participate in pharmaceutical trials designed to better delineate the optimal use of our current treatment options and to test promising new agents.

Medical Training

Dr. Eisenman completed undergraduate studies in Biomedical Engineering at the Johns Hopkins University in 1988. His undergraduate research project involved computational modeling of cardiac fibrillation induced by extra stimulation in the laboratory of Dr. N. V. Thakor.

He received both MD and PhD degrees from Northwestern University in 1997 as part of the Medical Scientist Training Program. His PhD thesis work on compuational modelling of repetitive activation of glutamate receptors was performed in the laboratory of Dr. James C. Houk in the Department of Physiology.
He completed an internship in Internal Medicine in 1998 at Rush Presbyterian-St. Lukes Medical Center in Chicago, Il. He went on to complete a Neurology residency in 2001 and an Epilepsy fellowship in 2003, both at Barnes-Jewish Hospital. He then joined the faculty in the Epilepsy division of the Department of Neurology at Washington University.

He is also certified in Clinical Neurophysiology by the ABPN and certified by the American Board of Clinical Neurophysiology in Clinical Neurophysiology and Epilepsy Monitoring.

Selected Publications

Eisenman LN, Shu H-J, Akk G, Wang C, Manion BD, Kress GJ, Evers AS, Steinbach JH, Covey DF, Zorumski CF, Mennerick S, Anticonvulsant and anesthetic effects of a fluorescent neurosteroid analog activated by visible light. Nat Neurosci 2007: 10:523-530

Eisenman LN, Kress G, Zorumski CF, Mennerick S, A spontaneous, tonic chloride conductance in solitary glutamatergic hippocampal neurons. Brain Res 2006: 1118:66-74.

Eisenman LN, Attarian H, Fessler AJ, Vahle VJ, Gilliam F, Self-reported seizure frequency and time to first event in the seizure monitoring unit. Epilepsia 2005: 46:664-668.

Eisenman, LN Attarian HP, Sleep epilepsy. Neurolog. 2003: 9:200-206.

Eisenman LN, He Y, Fields C, Zorumski CF, Mennerick S, Activation dependent properties of pregnenolone sulfate inhibition of GABAA receptor-mediated current. J. Physiol. (Lond) 2003: 550:679-691.Gallagher MJ, Eisenman LN, Brown KM, Erbayat-Altay E, Hecimovic H, Fessler AJ, Attarian HP, Gilliam FG, Levetiracetam reduces spike-wave densisty and duration during continuous EEG monitoring in patients with idiopathic generalized epilepsy. Epilepsia 2004: 45:90-91.

Shu HJ, Eisenman LN, Jinadasa D, Covey DF, Zorumski CF, Mennerick S, Slow actions of neuroactive steroids at GABA-A receptors. J Neurosci. 2004: 24:6667-6675.
7. Eisenman LN, Attarian H, Fessler AJ, Vahle VJ, Gilliam F, Self-reported seizure frequency and time to first event in the seizure monitoring unit. Epilepsia 2005: 46:664-668.

Eisenman LN, Kress G, Zorumski CF, Mennerick S, A spontaneous, tonic chloride conductance in solitary glutamatergic hippocampal neurons. Brain Res 2006: 1118:66-74. PMCID: 1821090.

Eisenman LN, Shu H-J, Akk G, Wang C, Manion BD, Kress GJ, Evers AS, Steinbach JH, Covey DF, Zorumski CF, Mennerick S, Anticonvulsant and anesthetic effects of a fluorescent neurosteroid analog activated by visible light. Nat Neurosci 2007: 10:523-530

Mennerick S, Lamberta M, Shu HJ, Hogins J, Wang C, Covey DF, Eisenman LN, Zorumski CF. Effects on membrane capacitance of steroids with antagonist properties at GABAA receptors. Biophys J. 2008;95(1):176-85. PMCID: 2426621.

Anderson NR, Wisneski K, Eisenman L, Moran DW, Leuthardt EC, Krusienski DJ. An offline evaluation of the autoregressive spectrum for electrocorticography. IEEE Trans Biomed Eng. 2009;56(3):913-6.

Eisenman LN, Shu HJ, Wang C, Aizenman E, Covey DF, Zorumski CF, Mennerick S. NMDA potentiation by visible light in the presence of a fluorescent neurosteroid analogue. J Physiol. 2009;587(Pt 12):2937-47.

Shu HJ, Eisenman LN, Wang C, Bandyopadhyaya AK, Krishnan K, Taylor A, Benz AM, Manion B, Evers AS, Covey DF, Zorumski CF, Mennerick S. Photodynamic effects of steroid conjugated fluorophores on GABAA receptors. Mol. Pharm. 2009;76:754-65.

Chisari M, Eisenman LN, Krishnan K, Bandyopadhyaya AK, Wang C, Taylor A, Benz A, Covey DF, Zorumski CF, Mennerick S. The influence of neuroactive steroid lipophilicity on GABAA receptor modulation: evidence for a low affinity interaction. J Neurophysiol. 2009;102:1254-64.

Kress GJ, Dowling M, Eisenman LN, Mennerick S. The role of sodium channel clustering in the depolarized action potential threshold of dentate granule neurons. Hippocampus. In Press.

Mennerick SM, Chisari M, Shu HJ, Taylor A, Vasek M, Eisenman LN, Zorumski CF. Diverse voltage-sensitive dyes modulate GABAA receptor function. J Neurosci. In Press.