The maturation of GABA_A receptor-mediated signaling from depolarizing to inhibitory is an age-related process controlled by cation chloride cotransporters, such as KCC2. As a result, GABA exerts dual functions, being an important neurotrophic factor during early development and the principal inhibitory neurotransmitter of the mature central nervous system. In our laboratory we have been investigating the age and gender specific mechanisms through which early life stressors and seizures may disrupt the normal patterns of brain development, by disrupting the neurotrophic effects of GABA. We are also studying methods to reverse these adverse processes. Furthermore, we are very interested in understanding how epileptogenesis proceeds in the developing brain and what is the specific role of GABA_A receptors in this process.

To better understand the pathophysiology and design better methods to treat catastrophic early life epilepsies, we are developing and studying new models of early life epilepsy. These include models of symptomatic infantile spasms that recapitulate most of the features of the human condition. Several projects are under way to (a) elucidate the pathophysiology of infantile spasms, and (b) conduct preclinical trials to find better treatments for spasms and the associated comorbidities. Our studies have provided preclinical evidence for new potential treatments with disease modifying properties for these early life epileptic encephalopathies, such as mTOR inhibitor, carisbamate and a new vigabatrin analog.

Post-traumatic epilepsy is a common consequence of traumatic brain injury leading to high morbidity and morbidity. Our lab is participating in an international multicenter preclinical consortium, EpiBioS4Rx, leading efforts to develop better therapies for post-traumatic epilepsy. We use a rodent model of traumatic brain injury to identify targets and test for better therapies, through a combination of expression studies, in vivo behavioral and electrophysiologic monitoring and therapy screening to identify antiepileptogenic compounds. Furthermore, through a separate project, we are looking into factors predicting epilepsy and behavioral outcomes after traumatic brain injury.

Genetic etiologies are often identified in patients with epilepsies. Our lab has been investigating genes involved in lissencephaly associated epilepsies and developmental disorders as well as Rett syndrome which is due to MeCP2 gene mutations. Through the use of mouse models we have been investigating genotype-phenotype correlations and mechanisms involved with the ultimate goal of testing therapies.

Students interested in these projects will gain exposure to a variety of in vivo and in vitro techniques that combine molecular biology, in vivo and in vitro electrophysiology, histological, and behavioral studies and will be involved in projects with direct translational relevance to the clinical practice, i.e. identification of novel therapies. 

1.     Galanopoulou AS: “Dissociated gender-specific effects of recurrent seizures on GABA signaling in CA1 pyramidal neurons: role of GABA_A receptors”: J Neurosci 28 (7): 1557-67 (2008). PMID 18272677. https://www.jneurosci.org/content/28/7/1557.long

2.     Briggs SW, Mowrey W, Hall CB, Galanopoulou AS. CPP-115, a vigabatrin analogue, decreases spasms in the multiple-hit rat model of infantile spasms. Epilepsia (2014) 55(1):94-102. PMID 24321005. https://onlinelibrary.wiley.com/doi/full/10.1111/epi.12424 

3.     Galanopoulou AS and Moshé SL. Pathogenesis and new candidate treatments for infantile spasms and early life epileptic encephalopathies: a view from preclinical studies. Neurobiology of Disease (2015): Neurobiol Dis. 2015 Jul;79:135-49. PMID 25968935.  https://www.sciencedirect.com/science/article/pii/S096999611500162X?via%3Dihub

4.     Galanopoulou AS, Mowrey WB, Liu W, Li Q, Shandra O, Moshe SL. Preclinical Screening for Treatments for Infantile Spasms in the Multiple Hit Rat Model of Infantile Spasms: An Update. Neurochem Res. 2017;42:1949-61. PMID 28462453.  https://link.springer.com/article/10.1007%2Fs11064-017-2282-0

5.     Galanopoulou AS, French JA, O’Brien T, Simonato M. “Harmonization in preclinical epilepsy research: a joint AES/ILAE translational initiative”. Epilepsia (2017) 58 (Suppl 4):7-9. PMID 29105072. https://onlinelibrary.wiley.com/doi/full/10.1111/epi.13921

6.     Ono T, Wagenaar J, Giorgi FS et al, Galanopoulou AS. A companion to the preclinical common data elements and case report forms for rodent EEG studies. A report of the TASK3 EEG Working Group of the ILAE/AES Joint Translational Task Force. Epilepsia Open. 2018;3:90-103. PMID 30450486. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6210053/pdf/EPI4-3-90.pdf

7.     Akman O, Raol YH, Auvin S et al, Galanopoulou AS. Methodologic recommendations and possible interpretations of video-EEG recordings in immature rodents used as experimental controls: A TASK1-WG2 report of the ILAE/AES Joint Translational Task Force. Epilepsia Open. (2018) vol 3: 437-459. PMID 30525114. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6276777/pdf/EPI4-3-437.pdf

8.     Katsarou AM, Li, Q, Liu W, Moshé SL, Galanopoulou AS. “Acquired parvalbumin-selective interneuronopathy in the multiple-hit model of infantile spasms: a putative basis for the partial responsiveness to vigabatrin analogs?” Epilepsia Open (2018) vol 3 (S2): 155-164. PMID 30564774. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6293059/pdf/EPI4-3-155.pdf

9.     Salar S, Moshe SL, Galanopoulou AS. Metabolic etiologies in West syndrome. Epilepsia Open. 2018;3:134-66.https://www.ncbi.nlm.nih.gov/pubmed/29881795

10.  Saletti PG, Ali I, Casillas-Espinosa PM et al, Galanopoulou AS. In search of antiepileptogenic treatments for post-traumatic epilepsy. Neurobiol Dis. (2019) 123: 86-99 (2019).  PMID: 29936231. https://www.sciencedirect.com/science/article/pii/S0969996118301980?via%3Dihub

11.  Galanopoulou AS, Ferastraoaru V, Correa DJ, Cherian K, Duberstein S, Gursky J, Hanumanthu R, Hung C, Molinero I, Khodakivska O, Legatt AD, Patel P, Rosengard J, Rubens E, Sugrue W, Yozawitz E, Mehler MF, Ballaban-Gil K, Haut SR, Moshe SL, Boro A. EEG findings in acutely ill patients investigated for SARS-CoV-2/COVID-19: A small case series preliminary report. Epilepsia Open. 2020;5:314-24.https://www.ncbi.nlm.nih.gov/pubmed/32537529

12.  Parihar R, Ferastraoaru V, Galanopoulou AS, Geyer HL, Kaufman DM. Outcome of Hospitalized Parkinson's Disease Patients with and without COVID-19. Mov Disord Clin Pract. 2021;8:859-67.https://www.ncbi.nlm.nih.gov/pubmed/34226870

13.  Akman O, Briggs SW, Mowrey WB, Moshe SL, Galanopoulou AS. Antiepileptogenic effects of rapamycin in a model of infantile spasms due to structural lesions. Epilepsia. 2021;62:1985-99.https://www.ncbi.nlm.nih.gov/pubmed/34212374

14.  Galanopoulou AS, Loscher W, Lubbers L, O'Brien TJ, Staley K, Vezzani A, D'Ambrosio R, White HS, Sontheimer H, Wolf JA, Twyman R, Whittemore V, Wilcox KS, Klein B. Antiepileptogenesis and disease modification: Progress, challenges, and the path forward-Report of the Preclinical Working Group of the 2018 NINDS-sponsored antiepileptogenesis and disease modification workshop. Epilepsia Open. 2021;6:276-96.https://www.ncbi.nlm.nih.gov/pubmed/34033232

15.  Katsarou AM, Kubova H, Auvin S, Mantegazza M, Barker-Haliski M, Galanopoulou AS, Reid CA, Semple BD. A companion to the preclinical common data elements for rodent models of pediatric acquired epilepsy: A report of the TASK3-WG1B, Pediatric and Genetic Models Working Group of the ILAE/AES Joint Translational Task Force. Epilepsia Open. 2022.https://www.ncbi.nlm.nih.gov/pubmed/35950641

16.  Medel-Matus JS, Lagishetty V, Santana-Gomez C, Shin D, Mowrey W, Staba RJ, Galanopoulou AS, Sankar R, Jacobs JP, Mazarati AM. Susceptibility to epilepsy after traumatic brain injury is associated with preexistent gut microbiome profile. Epilepsia. 2022;63:1835-48.https://www.ncbi.nlm.nih.gov/pubmed/35366338

17.  Saletti PG, Mowrey WB, Liu W, Li Q, McCullough J, Aniceto R, Lin IH, Eklund M, Casillas-Espinosa PM, Ali I, Santana-Gomez C, Coles L, Shultz SR, Jones N, Staba R, O'Brien TJ, Moshe SL, Agoston DV, Galanopoulou AS, EpiBio SRSG. Early preclinical plasma protein biomarkers of brain trauma are influenced by early seizures and levetiracetam. Epilepsia Open. 2023;8:586-608.https://www.ncbi.nlm.nih.gov/pubmed/37026764

18.  Coles L, Forcelli PA, Leclercq K, Katsarou AM, Klein BD, Potschka H, Koehling R, Harte-Hargrove L, Galanopoulou AS, Metcalf CS. Preclinical common data elements for general pharmacological studies (pharmacokinetic sample collection, tolerability, and drug administration). A report of the TASK3-WG1A General Pharmacology Working Group of the ILAE/AES Joint Translational Task Force. Epilepsia Open. 2023.https://www.ncbi.nlm.nih.gov/pubmed/36896626

19.  Guerrini R, Conti V, Mantegazza M, Balestrini S, Galanopoulou AS, Benfenati F. Developmental and epileptic encephalopathies: from genetic heterogeneity to phenotypic continuum. Physiol Rev. 2023;103:433-513.https://www.ncbi.nlm.nih.gov/pubmed/35951482

20.  Auvin S, Galanopoulou AS, Moshe SL, Potschka H, Rocha L, Walker MC. Revisiting the concept of drug-resistant epilepsy: A TASK1 report of the ILAE/AES Joint Translational Task Force. Epilepsia. 2023;64:2891-908. https://www.ncbi.nlm.nih.gov/pubmed/37676719

21.  Grandizoli Saletti P, Casillas-Espinosa PM, Panagiotis Lisgaras C, Bi Mowrey W, Li Q, Liu W, Brady RD, Ali I, Silva J, Yamakawa G, Hudson M, Li C, Braine EL, Coles L, Cloyd JC, Jones NC, Shultz SR, Moshe SL, O'Brien TJ, Galanopoulou AS. Tau Phosphorylation Patterns in the Rat Cerebral Cortex After Traumatic Brain Injury and Sodium Selenate Effects: An Epibios4rx Project 2 Study. J Neurotrauma. 2024;41:222-43.https://www.ncbi.nlm.nih.gov/pubmed/36950806

22.  Lucasius C, Grigorovsky V, Nariai H, Galanopoulou AS, Gursky J, Moshe SL, Bardakjian BL. Biomimetic Deep Learning Networks With Applications to Epileptic Spasms and Seizure Prediction. IEEE Trans Biomed Eng. 2024;71:1056-67.https://www.ncbi.nlm.nih.gov/pubmed/37851549

23.  Samfira IMA, Galanopoulou AS, Nariai H, Gursky JM, Moshe SL, Bardakjian BL. EEG-based spatiotemporal dynamics of fast ripple networks and hubs in infantile epileptic spasms. Epilepsia Open. 2024;9:122-37.https://www.ncbi.nlm.nih.gov/pubmed/37743321

24.  Perucca E, French JA, Aljandeel G, Balestrini S, Braga P, Burneo JG, Felli AC, Cross JH, Galanopoulou AS, Jain S, Jiang Y, Kalviainen R, Lim SH, Meador KJ, Mogal Z, Nabbout R, Sofia F, Somerville E, Sperling MR, Triki C, Trinka E, Walker MC, Wiebe S, Wilmshurst JM, Wirrell E, Yacubian EM, Kapur J. Which terms should be used to describe medications used in the treatment of seizure disorders? An ILAE position paper. Epilepsia. 2024;65:533-41.https://www.ncbi.nlm.nih.gov/pubmed/38279786

25.  Pease M, Gupta K, Moshe SL, Correa DJ, Galanopoulou AS, Okonkwo DO, Gonzalez-Martinez J, Shutter L, Diaz-Arrastia R, Castellano JF. Insights into epileptogenesis from post-traumatic epilepsy. Nat Rev Neurol. 2024;20:298-312. https://www.ncbi.nlm.nih.gov/pubmed/38570704