Brain; Epilepsy; Nervous System; Neurobiology; Neurosurgery; Seizures; Trauma, Nervous System
In many types of epilepsy, notably in Temporal Lobe Epilepsy (TLE), seizures originate from regions of the brain that are anatomically and physiologically disorganized (seizure foci). The goal of our research is the analysis of the neuropathology of seizure foci to determine how they generate and maintain seizures. State-of-the-art molecular neuroanatomical techniques are employed to define the neuroanatomical substrates for specific types of epilepsy, while high-throughput gene expression analyses and proteomics are further employed to define the molecular complexity that underlies seizure foci.
Astrocytes in human seizure foci are targeted in studies to define their role in seizure maintenance and epileptogenesis. Our hypothesis is that astrocytes are the source of high extracellular glutamate at seizure foci through their responsiveness to inflammatory factors and modification of the blood-brain barrier at seizure foci. The laboratory is also developing new animal models of epilepsy, based on results of human studies, for translational research.
Our studies on traumatic brain research are focused primarily on brain injury caused by explosive blast pressure waves as encountered by soldiers in warfare.
Specialized Terms: Molecular and cellular neuropathology of human seizure foci; Development of animal models of human temporal lobe epilepsy; Neuropathology of Traumatic brain injury
Extensive Research Description
My laboratory is engaged in a study of the pathophysiology of seizure foci in the brains of patients with epilepsy. Our work has concentrated on the molecular and cellular organization of hippocampal seizure foci in patients with medically intractable temporal lobe epilepsy, who have this seizure focus removed in our epilepsy surgery program for the control of seizures. In the past our work has defined the anatomical, cellular and molecular organization of the hippocampal seizure focus in patients with mesial temporal lobe epilepsy.
Our current work focuses on the molecular characterization these seizure foci through the use of high throughput techniques such as DNA microarray analysis and proteomics. The work completed using these techniques has focused attention on the molecular changes in reactive astrocytes at seizure foci, which appear to play a critical role in causing an excitable environment in the brain. Our studies specially focus on the role of inflammatory processes in epileptogenesis and the maintenance of seizures.
In parallel with studies on human seizure foci, the laboratory is also developing and characterizing new animal models of temporal lobe epilepsy that better reflect the pathophysiological changes in human seizure foci. These translational studies are aimed at developing and testing new antiepileptic drugs and developing methods for seizure prediction.
In a second line of investigations the laboratory focusses on the neuropathology of the brain in soldiers and large animals exposed to explosive blast pressure waves in order to understand the neural mechanisms underlying neuropsychiatric disorders associated with exposure to blast. Completed studies have found for the first time unequivocal evidence of injury to the anterior hippocampaus correlated with memory impairments, and a unique pattern of periventricular axonal injury. Present work is further exploring the relationship of periventricular injury to suicide and depression.Efficacy of erythropoietin (EPO) and EPO analogues in the treatment of temporal lobe epilepsy.
Neuropathology of blast related traumatic brain injury.
The role of glia in the development of hippocampal seizure foci.
Neuropathology of traumatic brain injury: Comparison of penetrating, non-penetrating direct impact and explosive blast etiologies
de Lanerolle, N.C., J.H. Kim, and F.A. Bandak (2015) Neuropathology of traumatic brain injury: Comparison of penetrating, non-penetrating direct impact and explosive blast etiologies. Seminars in Neurol, 35: 12-19
Concussive brain injury from explosive blast
de Lanerolle, NC., Hamid, H., Kulas, J., Pan, J., Czlapinski, R., Rinaldi, A., Ling, G., Bandak, F. and Hetherington, H. (2014) Concussive brain injury from explosive blast. Annals Clin Transl. Neurol. 1: 692 - 702
- De Lanerolle, N.C. Lee. T-S. and Spencer, D.D. Histopathology of human epilepsy In: Jasper’s Basic Mechanisms of Epilepsies, 4th Edition (Eds) J.L. Noebels, M. Avoli, M.A. Rogawski, and R.W. Olsen. Chapter 30, p. 387 Oxford University Press, 2012
Astrocytes and epilepsy
de Lanerolle, N.C., Lee, T-S. and Spencer, D.D. (2010)Astrocytes and epilepsy. Neurotherapeutics 6: 135-144
Full List of PubMed Publications
- Goodrich JA, Kim JH, Situ R, Taylor W, Westmoreland T, Du F, Parks S, Ling G, Hwang JY, Rapuano A, Bandak FA, de Lanerolle NC: Neuronal and glial changes in the brain resulting from explosive blast in an experimental model. Acta Neuropathol Commun. 2016 Nov 24; 2016 Nov 24. PMID: 27884214
- Wu Y, Pearce PS, Rapuano A, Hitchens TK, de Lanerolle NC, Pan JW: Metabolic changes in early poststatus epilepticus measured by MR spectroscopy in rats. J Cereb Blood Flow Metab. 2015 Nov; 2015 Jun 24. PMID: 26104287
- de Lanerolle NC, Kim JH, Bandak FA: Neuropathology of traumatic brain injury: comparison of penetrating, nonpenetrating direct impact and explosive blast etiologies. Semin Neurol. 2015 Feb; 2015 Feb 25. PMID: 25714863
- Bandak FA, Ling G, Bandak A, De Lanerolle NC: Injury biomechanics, neuropathology, and simplified physics of explosive blast and impact mild traumatic brain injury. Handb Clin Neurol. 2015. PMID: 25702211
- de Lanerolle NC, Hamid H, Kulas J, Pan JW, Czlapinski R, Rinaldi A, Ling G, Bandak FA, Hetherington HP: Concussive brain injury from explosive blast. Ann Clin Transl Neurol. 2014 Sep; 2014 Sep 30. PMID: 25493283
- Hetherington HP, Hamid H, Kulas J, Ling G, Bandak F, de Lanerolle NC, Pan JW: MRSI of the medial temporal lobe at 7 T in explosive blast mild traumatic brain injury. Magn Reson Med. 2014 Apr; 2013 Aug 5. PMID: 23918077
- Eid T, Lee TS, Wang Y, Perez E, Drummond J, Lauritzen F, Bergersen LH, Meador-Woodruff JH, Spencer DD, de Lanerolle NC, McCullumsmith RE: Gene expression of glutamate metabolizing enzymes in the hippocampal formation in human temporal lobe epilepsy. Epilepsia. 2013 Feb; 2012 Nov 13. PMID: 23384343
- de Lanerolle NC, Lee TS, Spencer DD, Noebels JL, Avoli M, Rogawski MA, Olsen RW, Delgado-Escueta AV: Histopathology of Human Epilepsy 2012. PMID: 22787669
- de Lanerolle NC, Bandak F, Kang D, Li AY, Du F, Swauger P, Parks S, Ling G, Kim JH: Characteristics of an explosive blast-induced brain injury in an experimental model. J Neuropathol Exp Neurol. 2011 Nov. PMID: 22002430
- de Lanerolle NC, Lee TS, Spencer DD: Astrocytes and epilepsy. Neurotherapeutics. 2010 Oct. PMID: 20880506
- Eid T, Ghosh A, Wang Y, Beckström H, Zaveri HP, Lee TS, Lai JC, Malthankar-Phatak GH, de Lanerolle NC: Recurrent seizures and brain pathology after inhibition of glutamine synthetase in the hippocampus in rats. Brain. 2008 Aug; 2008 Jul 6. PMID: 18669513
- Eid T, Williamson A, Lee TS, Petroff OA, de Lanerolle NC: Glutamate and astrocytes--key players in human mesial temporal lobe epilepsy? Epilepsia. 2008. PMID: 18226171
- Eid T, Hammer J, Rundén-Pran E, Roberg B, Thomas MJ, Osen K, Davanger S, Laake P, Torgner IA, Lee TS, Kim JH, Spencer DD, Ottersen OP, de Lanerolle NC: Increased expression of phosphate-activated glutaminase in hippocampal neurons in human mesial temporal lobe epilepsy. Acta Neuropathol. 2007 Feb; 2006 Nov 18. PMID: 17115168
- Lee TS, Mane S, Eid T, Zhao H, Lin A, Guan Z, Kim JH, Schweitzer J, King-Stevens D, Weber P, Spencer SS, Spencer DD, de Lanerolle NC: Gene expression in temporal lobe epilepsy is consistent with increased release of glutamate by astrocytes. Mol Med. 2007 Jan-Feb. PMID: 17515952
- Lee TS, Bjørnsen LP, Paz C, Kim JH, Spencer SS, Spencer DD, Eid T, de Lanerolle NC: GAT1 and GAT3 expression are differently localized in the human epileptogenic hippocampus. Acta Neuropathol. 2006 Apr; 2006 Feb 3. PMID: 16456667
- de Lanerolle NC, Lee TS: New facets of the neuropathology and molecular profile of human temporal lobe epilepsy. Epilepsy Behav. 2005 Sep. PMID: 16098816
- Eid T, Lee TS, Thomas MJ, Amiry-Moghaddam M, Bjørnsen LP, Spencer DD, Agre P, Ottersen OP, de Lanerolle NC: Loss of perivascular aquaporin 4 may underlie deficient water and K+ homeostasis in the human epileptogenic hippocampus. Proc Natl Acad Sci U S A. 2005 Jan 25; 2005 Jan 18. PMID: 15657133
- Lee TS, Eid T, Mane S, Kim JH, Spencer DD, Ottersen OP, de Lanerolle NC: Aquaporin-4 is increased in the sclerotic hippocampus in human temporal lobe epilepsy. Acta Neuropathol. 2004 Dec; 2004 Oct 26. PMID: 15517312
- Eid T, Thomas MJ, Spencer DD, Rundén-Pran E, Lai JC, Malthankar GV, Kim JH, Danbolt NC, Ottersen OP, de Lanerolle NC: Loss of glutamine synthetase in the human epileptogenic hippocampus: possible mechanism for raised extracellular glutamate in mesial temporal lobe epilepsy. Lancet. 2004 Jan 3. PMID: 14723991
- Eid T, Brines ML, Cerami A, Spencer DD, Kim JH, Schweitzer JS, Ottersen OP, de Lanerolle NC: Increased expression of erythropoietin receptor on blood vessels in the human epileptogenic hippocampus with sclerosis. J Neuropathol Exp Neurol. 2004 Jan. PMID: 14748563
- de Lanerolle NC, Kim JH, Williamson A, Spencer SS, Zaveri HP, Eid T, Spencer DD: A retrospective analysis of hippocampal pathology in human temporal lobe epilepsy: evidence for distinctive patient subcategories. Epilepsia. 2003 May. PMID: 12752467
- Eid T, Kovacs I, Spencer DD, de Lanerolle NC: Novel expression of AMPA-receptor subunit GluR1 on mossy cells and CA3 pyramidal neurons in the human epileptogenic hippocampus. Eur J Neurosci. 2002 Feb. PMID: 11876779
- Zaveri HP, Duckrow RB, de Lanerolle NC, Spencer SS: Distinguishing subtypes of temporal lobe epilepsy with background hippocampal activity. Epilepsia. 2001 Jun. PMID: 11422326
- Jiang W, Duong TM, de Lanerolle NC: The neuropathology of hyperthermic seizures in the rat. Epilepsia. 1999 Jan. PMID: 9924896
- Xie H, Brines ML, de Lanerolle NC: Transcripts of the transposon mariner are present in epileptic brain. Epilepsy Res. 1998 Sep. PMID: 9761316
- de Lanerolle NC, Eid T, von Campe G, Kovacs I, Spencer DD, Brines M: Glutamate receptor subunits GluR1 and GluR2/3 distribution shows reorganization in the human epileptogenic hippocampus. Eur J Neurosci. 1998 May. PMID: 9751141
- O'Connor ER, Sontheimer H, Spencer DD, de Lanerolle NC: Astrocytes from human hippocampal epileptogenic foci exhibit action potential-like responses. Epilepsia. 1998 Apr. PMID: 9578024
- de Lanerolle NC, Williamson A, Meredith C, Kim JH, Tabuteau H, Spencer DD, Brines ML: Dynorphin and the kappa 1 ligand [3H]U69,593 binding in the human epileptogenic hippocampus. Epilepsy Res. 1997 Oct. PMID: 9332884
- Brines ML, Sundaresan S, Spencer DD, de Lanerolle NC: Quantitative autoradiographic analysis of ionotropic glutamate receptor subtypes in human temporal lobe epilepsy: up-regulation in reorganized epileptogenic hippocampus. Eur J Neurosci. 1997 Oct. PMID: 9421164
- von Campe G, Spencer DD, de Lanerolle NC: Morphology of dentate granule cells in the human epileptogenic hippocampus. Hippocampus. 1997. PMID: 9347345
- de Lanerolle NC, Gunel M, Sundaresan S, Shen MY, Brines ML, Spencer DD: Vasoactive intestinal polypeptide and its receptor changes in human temporal lobe epilepsy. Brain Res. 1995 Jul 24. PMID: 7583284
- Brines ML, Dare AO, de Lanerolle NC: The cardiac glycoside ouabain potentiates excitotoxic injury of adult neurons in rat hippocampus. Neurosci Lett. 1995 May 26. PMID: 7644134
- Johnson EW, de Lanerolle NC, Kim JH, Sundaresan S, Spencer DD, Mattson RH, Zoghbi SS, Baldwin RM, Hoffer PB, Seibyl JP: "Central" and "peripheral" benzodiazepine receptors: opposite changes in human epileptogenic tissue. Neurology. 1992 Apr. PMID: 1314342
- de Lanerolle NC, Brines ML, Kim JH, Williamson A, Philips MF, Spencer DD: Neurochemical remodelling of the hippocampus in human temporal lobe epilepsy. Epilepsy Res Suppl. 1992. PMID: 1363041
- de Lanerolle NC, Brines M, Williamson A, Kim JH, Spencer DD: Neurotransmitters and their receptors in human temporal lobe epilepsy. Epilepsy Res Suppl. 1992. PMID: 1361331
- de Lanerolle NC: A pontine call site in the domestic cat: behavior and neural pathways. Neuroscience. 1990. PMID: 2243592
- de Lanerolle NC, Kim JH, Robbins RJ, Spencer DD: Hippocampal interneuron loss and plasticity in human temporal lobe epilepsy. Brain Res. 1989 Aug 28. PMID: 2569920