{{short description|Israeli neuroscientist}} {{Infobox scientist | name = Alon Friedman | native_name = אלון פרידמן | native_name_lang = he | image = File:AlonFriedmanPicturewiki.png | caption = Prof. Alon Friedman | birth_date = {{birth date and age|1964|10|9}} | birth_place = Jaffa, Israel | field = Translational neuroscience | work_institution = Ben-Gurion University of the Negev, Dalhousie University | alma_mater = Ben-Gurion University of the Negev | doctoral_advisor = Michael Gutnick | known_for = The link between Blood–brain barrier disruption and epilepsy }}

'''Alon Friedman''' ({{Langx|he|אלון פרידמן}}) 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.

==Biography== Friedman was born in Jaffa, Israel. Graduated from Handasaim Herzliya High School at 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-lasting 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.<ref>{{cite journal |last1=Kaufer |first1=D. |last2=Friedman |first2=A. |last3=Seidman |first3=S. |last4=Soreq |first4=H. |title=Acute stress facilitates long-lasting changes in cholinergic gene expression |journal=Nature |date=1998 |volume=393 |issue=6683 |pages=373–377 |doi=10.1038/30741 |pmid=9620801 |bibcode=1998Natur.393..373K }} {{Erratum|doi=10.1038/nature16180|pmid=26605528|checked=yes}}</ref><ref>{{cite journal | last1=Korn | first1=A. | last2=Golan | first2=H. | last3=Melamed | first3=I. | last4=Pascual-Marqui | first4=R. | last5=Friedman | first5=A. | title=Focal cortical dysfunction and blood-brain barrier disruption in patients with Postconcussion syndrome | journal=Journal of Clinical Neurophysiology | date=2005 | volume=22 | issue=1 | pages=1–9 | doi=10.1097/01.wnp.0000150973.24324.a7 | pmid=15689708 }}</ref> 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.<ref>{{cite journal | last1=Seiffert | first1=E. | last2=Dreier | first2=J. P. | last3=Ivens | first3=S. | last4=Bechmann | first4=I. | last5=Tomkins | first5=O. | last6=Heinemann | first6=U. | last7=Friedman | first7=A. | title=Lasting blood-brain barrier disruption induces epileptic focus in the rat somatosensory cortex | journal=The Journal of Neuroscience | date=2004 | volume=24 | issue=36 | pages=7829–7836 | doi=10.1523/JNEUROSCI.1751-04.2004 | pmid=15356194 | pmc=6729929 }}</ref> 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.<ref>{{cite journal | last1=Ivens | first1=S. | last2=Kaufer | first2=D. | last3=Flores | first3=L. P. | last4=Bechmann | first4=I. | last5=Zumsteg | first5=D. | last6=Tomkins | first6=O. | last7=Seiffert | first7=E. | last8=Heinemann | first8=U. | last9=Friedman | first9=A. | title=TGF-beta receptor-mediated albumin uptake into astrocytes is involved in neocortical epileptogenesis | journal=Brain: A Journal of Neurology | date=2007 | volume=130 | issue=Pt 2 | pages=535–547 | doi=10.1093/brain/awl317 | pmid=17121744 | doi-access=free }}</ref><ref>{{cite journal | last1=Cacheaux | first1=L. P. | last2=Ivens | first2=S. | last3=David | first3=Y. | last4=Lakhter | first4=A. J. | last5=Bar-Klein | first5=G. | last6=Shapira | first6=M. | last7=Heinemann | first7=U. | last8=Friedman | first8=A. | last9=Kaufer | first9=D. | title=Transcriptome profiling reveals TGF-beta signaling involvement in epileptogenesis | journal=The Journal of Neuroscience | date=2009 | volume=29 | issue=28 | pages=8927–8935 | doi=10.1523/JNEUROSCI.0430-09.2009 | pmid=19605630 | pmc=2875073 }}</ref><ref>{{cite journal | last1=David | first1=Y. | last2=Cacheaux | first2=L. P. | last3=Ivens | first3=S. | last4=Lapilover | first4=E. | last5=Heinemann | first5=U. | last6=Kaufer | first6=D. | last7=Friedman | first7=A. | title=Astrocytic dysfunction in epileptogenesis: Consequence of altered potassium and glutamate homeostasis? | journal=The Journal of Neuroscience | date=2009 | volume=29 | issue=34 | pages=10588–10599 | doi=10.1523/JNEUROSCI.2323-09.2009 | pmid=19710312 | pmc=2875068 }}</ref> Furthermore, they showed that this process is mediated by a unique inflammatory pattern <ref>{{cite journal | last1=Cacheaux | first1=L. P. | last2=Ivens | first2=S. | last3=David | first3=Y. | last4=Lakhter | first4=A. J. | last5=Bar-Klein | first5=G. | last6=Shapira | first6=M. | last7=Heinemann | first7=U. | last8=Friedman | first8=A. | last9=Kaufer | first9=D. | title=Transcriptome profiling reveals TGF-beta signaling involvement in epileptogenesis | journal=The Journal of Neuroscience | date=2009 | volume=29 | issue=28 | pages=8927–8935 | doi=10.1523/JNEUROSCI.0430-09.2009 | pmid=19605630 | pmc=2875073 }}</ref><ref>{{cite journal | last1=Levy | first1=N. | last2=Milikovsky | first2=D. Z. | last3=Baranauskas | first3=G. | last4=Vinogradov | first4=E. | last5=David | first5=Y. | last6=Ketzef | first6=M. | last7=Abutbul | first7=S. | last8=Weissberg | first8=I. | last9=Kamintsky | first9=L. | last10=Fleidervish | first10=I. | last11=Friedman | first11=A. | last12=Monsonego | first12=A. | title=Differential TGF-β Signaling in Glial Subsets Underlies IL-6-Mediated Epileptogenesis in Mice | journal=Journal of Immunology | date=2015 | volume=195 | issue=4 | pages=1713–1722 | doi=10.4049/jimmunol.1401446 | pmid=26136430 }}</ref> and the formation of excitatory synapses.<ref>{{cite journal | last1=Weissberg | first1=I. | last2=Wood | first2=L. | last3=Kamintsky | first3=L. | last4=Vazquez | first4=O. | last5=Milikovsky | first5=D. Z. | last6=Alexander | first6=A. | last7=Oppenheim | first7=H. | last8=Ardizzone | first8=C. | last9=Becker | first9=A. | last10=Frigerio | first10=F. | last11=Vezzani | first11=A. | last12=Buckwalter | first12=M. S. | last13=Huguenard | first13=J. R. | last14=Friedman | first14=A. | last15=Kaufer | first15=D. | title=Albumin induces excitatory synaptogenesis through astrocytic TGF-β/ALK5 signaling in a model of acquired epilepsy following blood-brain barrier dysfunction | journal=Neurobiology of Disease | date=2015 | volume=78 | pages=115–125 | doi=10.1016/j.nbd.2015.02.029 | pmid=25836421 | pmc=4426044 }}</ref> 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 <ref>{{cite journal | last1=Prager | first1=O. | last2=Chassidim | first2=Y. | last3=Klein | first3=C. | last4=Levi | first4=H. | last5=Shelef | first5=I. | last6=Friedman | first6=A. | title=Dynamic in vivo imaging of cerebral blood flow and blood-brain barrier permeability | journal=NeuroImage | date=2010 | volume=49 | issue=1 | pages=337–344 | doi=10.1016/j.neuroimage.2009.08.009 | pmid=19682584 | pmc=3646266 }}</ref> and promoted the investigation of the mechanism of seizure induced BBB disruption <ref>{{cite journal | last1=Vazana | first1=U. | last2=Veksler | first2=R. | last3=Pell | first3=G. S. | last4=Prager | first4=O. | last5=Fassler | first5=M. | last6=Chassidim | first6=Y. | last7=Roth | first7=Y. | last8=Shahar | first8=H. | last9=Zangen | first9=A. | last10=Raccah | first10=R. | last11=Onesti | first11=E. | last12=Ceccanti | first12=M. | last13=Colonnese | first13=C. | last14=Santoro | first14=A. | last15=Salvati | first15=M. | last16=d'Elia | first16=A. | last17=Nucciarelli | first17=V. | last18=Inghilleri | first18=M. | last19=Friedman | first19=A. | title=Glutamate-Mediated Blood-Brain Barrier Opening: Implications for Neuroprotection and Drug Delivery | journal=The Journal of Neuroscience | date=2016 | volume=36 | issue=29 | pages=7727–7739 | doi=10.1523/JNEUROSCI.0587-16.2016 | pmid=27445149 | pmc=4951577 }}</ref> and the impairment of neurovascular coupling during seizure.<ref>{{cite journal | last1=Prager | first1=O. | last2=Kamintsky | first2=L. | last3=Hasam-Henderson | first3=L. A. | last4=Schoknecht | first4=K. | last5=Wuntke | first5=V. | last6=Papageorgiou | first6=I. | last7=Swolinsky | first7=J. | last8=Muoio | first8=V. | last9=Bar-Klein | first9=G. | last10=Vazana | first10=U. | last11=Heinemann | first11=U. | last12=Friedman | first12=A. | last13=Kovács | first13=R. | title=Seizure-induced microvascular injury is associated with impaired neurovascular coupling and blood-brain barrier dysfunction | journal=Epilepsia | date=2019 | volume=60 | issue=2 | pages=322–336 | doi=10.1111/epi.14631 | pmid=30609012 }}</ref> 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<ref>{{cite journal | last1=Weissberg | first1=I. | last2=Veksler | first2=R. | last3=Kamintsky | first3=L. | last4=Saar-Ashkenazy | first4=R. | last5=Milikovsky | first5=D. Z. | last6=Shelef | first6=I. | last7=Friedman | first7=A. | title=Imaging blood-brain barrier dysfunction in football players | journal=JAMA Neurology | date=2014 | volume=71 | issue=11 | pages=1453–1455 | doi=10.1001/jamaneurol.2014.2682 | pmid=25383774 }}</ref> 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 <ref>{{cite journal | last1=Friedman | first1=A. | last2=Bar-Klein | first2=G. | last3=Serlin | first3=Y. | last4=Parmet | first4=Y. | last5=Heinemann | first5=U. | last6=Kaufer | first6=D. | title=Should losartan be administered following brain injury? | journal=Expert Review of Neurotherapeutics | date=2014 | volume=14 | issue=12 | pages=1365–1375 | doi=10.1586/14737175.2014.972945 | pmid=25346269 }}</ref> inspired investigations that found BBB disruption as a potential biomarker of stroke <ref>{{cite journal | last1=Bar-Klein | first1=G. | last2=Lublinsky | first2=S. | last3=Kamintsky | first3=L. | last4=Noyman | first4=I. | last5=Veksler | first5=R. | last6=Dalipaj | first6=H. | last7=Senatorov Jr | first7=V. V. | last8=Swissa | first8=E. | last9=Rosenbach | first9=D. | last10=Elazary | first10=N. | last11=Milikovsky | first11=D. Z. | last12=Milk | first12=N. | last13=Kassirer | first13=M. | last14=Rosman | first14=Y. | last15=Serlin | first15=Y. | last16=Eisenkraft | first16=A. | last17=Chassidim | first17=Y. | last18=Parmet | first18=Y. | last19=Kaufer | first19=D. | last20=Friedman | first20=A. | title=Imaging blood-brain barrier dysfunction as a biomarker for epileptogenesis | journal=Brain: A Journal of Neurology | date=2017 | volume=140 | issue=6 | pages=1692–1705 | doi=10.1093/brain/awx073 | pmid=28444141 }}</ref> and specific EEG patterns as predictors of epilepsy <ref>{{cite journal | last1=Milikovsky | first1=D. Z. | last2=Weissberg | first2=I. | last3=Kamintsky | first3=L. | last4=Lippmann | first4=K. | last5=Schefenbauer | first5=O. | last6=Frigerio | first6=F. | last7=Rizzi | first7=M. | last8=Sheintuch | first8=L. | last9=Zelig | first9=D. | last10=Ofer | first10=J. | last11=Vezzani | first11=A. | last12=Friedman | first12=A. | title=Electrocorticographic Dynamics as a Novel Biomarker in Five Models of Epileptogenesis | journal=The Journal of Neuroscience | date=2017 | volume=37 | issue=17 | pages=4450–4461 | doi=10.1523/JNEUROSCI.2446-16.2017 | pmid=28330876 | pmc=6596657 }}</ref>

==Awards== He was awarded the international league against epilepsy [https://www.ilae.org/about-ilae/awards/michael-prize Michael Prize] for Epilepsy Research in 2007.

== References == {{reflist}}

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{{DEFAULTSORT:Friedman, Alon}} Category:Academic staff of Ben-Gurion University of the Negev Category:Academic staff of Dalhousie University Category:Epileptologists Category:Israeli neuroscientists Category:People from Jaffa Category:Ben-Gurion University of the Negev alumni Category:1964 births Category:Living people