Alon Friedman

Alon Friedman is a professor of Neuroscience at both Ben-Gurion University of the Negev (BGU) in Beersheba, Israel, and in Dalhousie University, Halifax, Nova Scotia, Canada. He is best known for his discoveries of the link between blood–brain barrier (BBB) disruption and Epileptogenesis (development of epilepsy) and the mechanisms underlying it, and for the utilization of BBB imaging as a potential Biomarker of epilepsy and other brain diseases.

Alon Friedman
Prof. Alon Friedman
Born (1964-10-09) October 9, 1964
Jaffa, Israel
Alma materBen-Gurion University of the Negev
Known forThe link between Blood–brain barrier disruption and epilepsy
Scientific career
FieldsTranslational neuroscience
InstitutionsBen-Gurion University of the Negev, Dalhousie University
Doctoral advisorMichael Gutnick

Biography

Friedman was born in Jaffa, Israel. Graduated from Handasaim Herzliya High School in his former campus in Tel Aviv. He earned both MD and PhD (Under the supervision of Prof. Michael Gutnick) degrees at BGU (1991), Faculty of health sciences as an Atuda cadet. While serving as an army doctor he began his ongoing collaboration with Prof. Hermona Soreq and Prof. Daniela Kaufer. After this term he joined the residency program at the neurosurgical department in Soroka Medical Center (1997). After a while (2002), he went to Berlin, Germany for a period as a guest scientist at Charité Medical University and established a long-last collaboration with Uwe Heinemann. Then he came back to his alma mater at BGU where he became a full professor in 2012, and from 2014 he is an acting principal investigator and a full professor in both Dalhousie University, Faculty of Medicine and BGU.

Scientific career

In his early career, while being an army doctor and collaborating with Prof. Soreq and Prof. Kaufer, Friedman made his first discoveries regarding the functioning of the cholinergic system under stress conditions.[1][2] Later on, based on clinical observations,[3] he began to challenge the hypothesis that BBB disruption, as a common implication of multiple epilepsy inducing conditions such as stroke and traumatic brain injury, serves as a mechanistic factor in epileptogenesis. He went to Berlin to establish a novel model of epilepsy which enabled him to show causality for the first time between BBB disruption and epileptogenesis.[4] Then, in collaboration with Prof. Kaufer he exposed that albumin, the most frequent protein in the serum is the agent that leaks from the blood into the brain parenchyma under BBB disruption conditions and induces epileptogenesis by activation of the transforming growth factor beta receptor on astrocytes.[5][6][7] Furthermore, they showed that this process is mediated by a unique inflammatory pattern [8][9] and the formation of excitatory synapses.[10] In sought of a cure or a preventive means for this devastating process, they found that losartan, a commonly used drug for hypertension treatment may prevent epilepsy and facilitate BBB healing. This line of discoveries was facilitated by the development of a novel method for direct imaging of the BBB in-vivo [11] and promoted the investigation of the mechanism of seizure induced BBB disruption [12] and the impairment of neurovascular coupling during seizure.[13] Nowadays, much of his research group attention is devoted to translation of the animal findings into the clinical practice. The development of a BBB imaging method in human enabled the group's pioneering discovery of BBB disruption among players of American football[14] and raised the hypothesis that BBB disruption is the link between repeated traumatic brain injury and Chronic traumatic encephalopathy. Understanding that clinical trials in possible antiepileptogenic agents (e.g. losartan) or BBB healing drugs necessitate biomarkers for patients selection and treatment-followup [15] inspired investigations that found BBB disruption as a potential biomarker of stroke [16] or epilepsy [17] and specific EEG patterns as predictors of epilepsy [18]

Awards

He was awarded the international league against epilepsy Michael Prize for Epilepsy Research in 2007.

References
  1. Kaufer, Daniela; Friedman, Alon; Seidman, Shlomo; Soreq, Hermona (1998). "Acute stress facilitates long-lasting changes in cholinergic gene expression". Nature. 393 (6683): 373–7. doi:10.1038/30741. PMID 9620801
  2. Friedman, Alon; Kaufer, Daniela; Shemer, Joshua; Hendler, Israel; Soreq, Hermona; Tur-Kaspa, Ilan (1996). "Pyridostigmine brain penetration under stress enhances neuronal excitability and induces early immediate transcriptional response". Nature Medicine. 2 (12): 1382–5. doi:10.1038/nm1296-1382. PMID 8946841.
  3. Korn A., Golan, H., Pascual-Marqui, R and Friedman, A. 2005, Focal Cortical Dysfunction and Blood-Brain Barrier Disruption in Patients with Post-Concussion Syndrome, J. Clinical Neurophysiology, 22:1-9. PMID 15689708
  4. Seiffert, E., Dreier, J.P., Ivens, S., Bechmann, I., Heinemann, U. and Friedman, A. 2004, Lasting blood-brain barrier disruption induces epileptic focus in the rat somatosensory cortex. J. Neuroscience, 24:7829-36. PMID 15356194
  5. Ivens, S., Kaufer, D., Seiffert, E., Bechmann, I., Tomkins, O., Heinemann, U. and Friedman, A. 2007, TGF-beta receptor mediated albumin uptake into astrocytes is involved in neocortical epileptogenesis. Brain, 130:535-47. PMID 17121744
  6. Luisa P Cacheaux, Sebastian Ivens, Yaron David, Alexander J Lakhter, Guy Bar-Klein, Michael Shapira, Uwe Heinemann, Alon Friedman and Daniela Kaufer, 2009. Transcriptome profiling reveals TGF-beta signaling involvement in epileptogenesis. Journal of Neuroscience, 29(28): 8927-8935. PMID 19605630
  7. Yaron David, Luisa P Flores, Sebastian Ivens, Uwe Heinemann, Daniela Kaufer and Alon Friedman. 2009. Astrocytic dysfunction in epileptogenesis: consequences of altered potassium and glutamate buffering? Journal of Neuroscience,29(34):10588-99 PMID 19710312
  8. Luisa P Cacheaux, Sebastian Ivens, Yaron David, Alexander J Lakhter, Guy Bar-Klein, Michael Shapira, Uwe Heinemann, Alon Friedman and Daniela Kaufer, 2009. Transcriptome profiling reveals TGF-beta signaling involvement in epileptogenesis. Journal of Neuroscience, 29(28): 8927-8935. PMID 19605630
  9. Differential TGF-β Signaling in Glial Subsets Underlies IL-6-Mediated Epileptogenesis in Mice. Levy N, Milikovsky DZ, Baranauskas G, Vinogradov E, David Y, Ketzef M, Abutbul S, Weissberg I, Kamintsky L, Fleidervish I, Friedman A, Monsonego A PMID 26136430
  10. Albumin induces excitatory synaptogenesis through astrocytic TGF-β/ALK5 signaling in a model of acquired epilepsy following blood-brain barrier dysfunction. Weissberg I, Wood L, Kamintsky L, Vazquez O, Milikovsky DZ, Alexander A, Oppenheim H, Ardizzone C, Becker A, Frigerio F, Vezzani A, Buckwalter MS, Huguenard JR, Friedman A, Kaufer D. Neurobiol Dis. 2015 Jun;78:115-25. doi: 10.1016/j.nbd.2015.02.029. Epub 2015 Mar 30. PMID 25836421
  11. Ofer Prager, Yoash Chassidim, Chen Klein, Haviv Levi, Ilan Shelef and Alon Friedman, 2010. Dynamic in-vivo imaging of cerebral blood flow and blood-brain barrier permeability. NeuroImage, 49: 337-344. PMID 19682584
  12. Glutamate-Mediated Blood-Brain Barrier Opening: Implications for Neuroprotection and Drug Delivery. Vazana U, Veksler R, Pell GS, Prager O, Fassler M, Chassidim Y, Roth Y, Shahar H, Zangen A, Raccah R, Onesti E, Ceccanti M, Colonnese C, Santoro A, Salvati M, D'Elia A, Nucciarelli V, Inghilleri M, Friedman A. PMID 27445149
  13. Seizure-induced microvascular injury is associated with impaired neurovascular coupling and blood-brain barrier dysfunction. Prager O, Kamintsky L, Hasam-Henderson LA, Schoknecht K, Wuntke V, Papageorgiou I, Swolinsky J, Muoio V, Bar-Klein G, Vazana U, Heinemann U, Friedman A, Kovács R. Epilepsia. 2019 Feb;60(2):322-336. doi: 10.1111/epi.14631. PMID 30609012
  14. Imaging blood-brain barrier dysfunction in football players. Weissberg I1, Veksler R1, Kamintsky L1, Saar-Ashkenazy R2, Milikovsky DZ1, Shelef I3, Friedman A4. JAMA Neurol. 2014 Nov;71(11):1453-5. doi: 10.1001/jamaneurol PMID 25383774
  15. Should losartan be administered following brain injury? Friedman A, Bar-Klein G, Serlin Y, Parmet Y, Heinemann U, Kaufer D. Expert Rev Neurother. 2014 Dec;14(12):1365-75. PMID 25346269
  16. Blood-Brain Barrier Leakage - A New Biomarker in Transient Ischemic Attacks. Yonatan Serlin , Jonathan Ofer , Gal Ben-Arie , Ronel Veksler , Gal Ifergane , Ilan Shelef Jeffrey Minuk , Anat Horev , Alon Friedman
  17. Imaging blood-brain barrier dysfunction as a biomarker for epileptogenesis. Bar-Klein G, Lublinsky S, Kamintsky L, Noyman I, Veksler R, Dalipaj H, Senatorov VV Jr, Swissa E, Rosenbach D, Elazary N, Milikovsky DZ, Milk N, Kassirer M, Rosman Y, Serlin Y, Eisenkraft A, Chassidim Y, Parmet Y, Kaufer D, Friedman A. Brain. 2017 Jun 1;140(6):1692-1705. PMID 28444141
  18. Electrocorticographic Dynamics as a Novel Biomarker in Five Models of Epileptogenesis. Milikovsky DZ, Weissberg I, Kamintsky L, Lippmann K, Schefenbauer O, Frigerio F, Rizzi M, Sheintuch L, Zelig D, Ofer J, Vezzani A, Friedman A5. J. Neurosci. 2017 Apr 26;37(17):4450-4461 PMID 28330876
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