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Cerebrovascular Laboratory          |          Neuroanatomy / Skull Base Laboratory


Research Interests



  • Angiogenesis and neurogenesis in focal cerebral ischemia
  • Intinsic anatomy of the brain
  • Neuroanatomy and skull base anatomy
  • Predictors of poor outcome after subarachnoid hemorrhage and vasospasm
  • Predictors of outcome after resection of atypical menengiomas
  • Neuropsychological outcomes after treatment of intracranial aneurysms.


Personnel



Current Members:

  • Ulaş Cıkla, MD (International Research Fellow, June 2012-)
  • Tevfik Yilmaz, MD (International Research Fellow, 2013-)
  • Abdulbaki Kozan, MD (International Research Fellow, 2014-)
  • Nural Celik, MD (International Research Fellow, 2014-)
  • Abdullah Karakoc, MD (International Research Fellow, 2014-)
  • Gabriel Neves (Premed student)
  • Tomer Hananya (Premed student)

Past Members:

  • Erkin Ozgiray, MD (International Research Fellow, November 2010 - October 2011, currently Assistant Professor of Neurosurgery at Ege University, Turkey)
  • Shadi  S. Mustafa (Premed student, 2010 - 2011)
  • Kutluay Uluç , MD (International Research Fellow, 2008-2011, currently junior resident at Univeristy of Wisconsin)
  • Almaz Kurbanov, MD (Visiting Medical Student from Uludağ University, Bursa, Turkey,  April 2011 - June 2011)
  • Emel Avci, MD (International Research fellow, May 2008-August 2008 and May 2010, currently Professor of Neurosurgery at Mersin University, Mersin, Turkey)
  • Casmir Turnquist (PhD student in National Institutes of Health-University and Oxford Scholars Program)
  • Ozkan Ateş, MD (International Research fellow,  April 2007-October 2007, currently Associate Professor of Neurosurgery, Tekirdag University, Turkey)
  • Yusuf İzci, MD (International Research fellow, September 2006- August 2007, currently Associate Professor of Neurosurgery, Gulhane Military Academy Hospital, Ankara, Turkey)
  • Yi-ping Liu, PhD (Research Scientist, molecular biologist, 2006-2008)
  • Amrendra S.  Miranpuri, MD (Chief Resident, elective)
  • Roham Moftakhar, MD (Senior Resident, elective and graduated)
  • Hakan Seçkin, MD (International Research Fellow,  February 2008-September 2008, currently Associate Professor of Neurosurgery, Diskapi Hospital, Ankara, Turkey)
  • Hayri Kertmen, MD (International Research Fellow, July 2009-January 2010)
  • Erhan Turkoğlu, MD (International Research Fellow, July 2009-January 2010)
  • Hakan Korkmaz, MD (International Research Fellow, November 2009-March 2010)
  • İlkan Tatar, MD, PHD (International Research Fellow, currently Associate Professor of Anatomy, Hacettepe University, Ankara, Turkey)
  • Karthikeyan Perumal, MD (International Research Fellow, September 2010- December 2010)
  • Mert Öztaş (Visiting Medical Student, July 2010)
  • Ahmed Mossad, MD (International Observer, January 2010- March 2010)
  • Vuslat Ecem Güneş (Visiting Medical Student, June 2010-August 2010)
  • Erinç Aktüre, MD (2009- June 2012, International Research Fellow, Currently Neurosurgery Resident at University of Vermont)
  • Melih Bozkurt MD (International Research Fellow, August 2011- March 2012, Currently Instructor at the Ankara University, Department of Neurosurgery)
  • Suat Canbay MD (International Research Fellow, October 2011- February 2012, Currently Stuff Neurosurgeon at Ankara Oncology Hospital)
  • Veysel Antar, MD (International Research Fellow, August 2012-February 2013)
  • Mehmet Ali Ekici, MD (International Research Fellow, October 2012-February 2013)
  • Bora Gürer, MD (International Research Fellow, October 2012-February 2013)
  • Alice Kirst, MD (International Research Fellow, March 2014-October 2014)
  • Tae Kyu Chung (Premed Student)
  • Sanser Gul, MD (July 2013-Sept 2013) Currently Associated Professor at Zoyouldak University, Turkey
  • Colin Liu, Medical Student at George Washington university
  • Kamak Masodkar (Research Fellow, India, currently Psychiatry Resident at University of Texas)
  • Abdullah Keles, Medical Student at University of Istanbul, Turkey
  • Alireza Sadighi, MD (International Research Fellow, May 2012-December 2014)
  • Guner Menekse MD, International Research Fellow,  January 2014 - April 2014, Currently Specialist at the Ankara Training and Research Hospital, Department of Neurosurgery, Ankara, TURKEY )

  • Mehmet Onen, MD (International Research Fellow, October 2014-March 2015)

  • Mehmet Gunaydin, MD (International Research Fellow, 2014-2015)
  • Gregory Kujoth, PhD (Assistant Scientist, 2009-2015)
  • Joshgun Mammadov, MD (International Research Fellow, December 2014-2015)



Grants



  • University of Wisconsin Medical School start up funds
    (1/2006-09)


Recent Research Publications



  • Nickele C, Akture E, Gubbels S, Baskaya MK. A stepwise illustration of the translabyrinthine approach to a large cystic vestibular schwannoma.  Neurosurgical Focus Sep; 33(3):E11, 2012
  • Akture E, Salamat MS, Baskaya MK. Intracranial blastomycosis presenting as an enhancing cerebellopontine angle mass. Turkish Neurosurgery 23(2)252-255, 2013.
  •  Miranpuri A, Akture E, Baggot C, Miranpuri A, Uluc K, Gunes E, Lin Y, Niemann D, Baskaya MK. Demographic, circadian and climatic factors in aneurysmal versus non-aneurysmal subarachnoid hemorrhage: 384 cases from Midwestern US. Clinical Neurology & Neurosurgery 11(3):298-303, 2013
  • Nickele C, Amgad H, Baskaya MK. Osteotomy for laminoplasty without soft tissue penetration, performed using Harmonic bone scalpel. Journal of Neurological Surgery. Part A : Central European Neurosurgery 74(3):183-186, 2013
  • Ozgiray E, Akture E, Patel N, Baggot C, Bozkurt M, Niemann D, Baskaya MK. How reliable and accurate is Indocyanine green video angiography in the evaluation of aneurysm obliteration? Clinical Neurology and Neurosurgery 115:870-878, 2013.
  • Figueiredo N, Brooks N, Hanna A, Baskaya MK, Trost GR, Resnick D. Intraspinal ependymomas: case series study of myxopapillary and intramedullary ependymomas. Chirurgia 26:101-110, 2013
  • Lake W, Chang J, Kennedy T, Salamat MS, Baskaya MK. A case series of primary central nervous system post-transplant lymphoproliferative disorder: Imaging and clinical characteristics. Neurosurgery 72(6):960-970, 2013.
  • Gürer B, Bozkurt M, Neves G, Cıkla U, Hananya T, Antar V, Salamat S, Başkaya MK. Subparietal and parietooccipital sulci: An anatomical study. Clinical Anatomy 26(6):667-674, 2013
  • Canbay S, Gurer B, Bozkurt M, Baskaya MK. Anatomical relationship and positions of the lumbar and sacral segments of the spinal cord according to the vertebral bodies and spinal roots. Clinical Anatomy 27(2):227-233, 2014.
  •  Gurer B, Canbay S, Bozkurt M, Cikla U, Hananya T, Okut H, Baskaya MK. Microsurgical anatomy of the denticulate ligaments and their relationship with the axilla of the spinal nerve roots. Clinical Anatomy 27:733-737, 2014.
  • Gurer B, Antar V, Cikla U, Bauer A, Baskaya MK. Intraoperative assessment of the posterior communicating artery and its branches by indocyanine-green videoangiography. Surgical Neurology International Sept 25;4:122, 2013.
  • Anderson BM, Khuntia D, Bentzen SM, Geye HM, Hayes LL, Kuo JS, Baskaya MK, Badie B, Basavatia A, Pyle GM, Tome WA, Mehta MP. Single institution experience treating 100 vestibular schwannomas with fractionated stereotactic radiation therapy or stereotactic radiosurgery. Journal of Neurooncology 16(1):187-193, 2014.
  • Dağtekin A, Avcı E, Uzmansel D, Kurtoglu Z, Kara E, Uluç K, Aktüre E, Başkaya MK. Revisiting the regional microsurgical anatomy and variations of the anterior clinoid process in relation to supra- and parasellar lesions.Turkish Neurosurgery 24(4):484-493, 2014  
  • Cikla U, Kujoth GC, Baskaya MK. A stepwise illustration of the retrosigmoid approach for resection of a cerebellopontine angle meningioma. Neurosurgical Focus Jan:36 (1 Suppl):1, 2014
  • Motzkin JC, Philippi CL, Baskaya MK, Koenigs M. Ventromedial prefrontal cortex is critical for the regulation of amygdala activity in humans. Biological Psychiatry Feb 26. pii:S0006-3223 (14)00109-7, 2014.
  • Cikla U, Giampietro PF, Sadighi A, Baskaya MK. Ruptured posterior communicating artery aneurysm associated with Aarskog syndrome. Neurologia Medico-chirurgica (in press).
  •  Kertmen H, Gurer B, Turkoglu E, Uluc K, Cikla U, Salamat S, Baskaya MK. The determination and comparison of the vascular configurations of the posterior cerebral and posterior communicating arteries by two different techniques. Journal of Neurosurgical Science (in press).
  • Cikla U, Sadighi A, Bauer A, Baskaya MK. Fatal ruptured blood blister-like aneurysms of middle cerebral artery associated with Ehlers-Danlos syndrome type VIII (periodontitis type). Journal of Neurological Surgery-Reports 75:e210-e213, 2014.
  • Turkoglu E, Seckin H, Ahmed A, Uluc K, Pulfer K, Arat A, Niemann D, Baskaya MK. Cadaveric perfusion and angiography as a teaching tool: imaging the intracranial vasculature in cadavers. Journal of Neurological Surgery - Skull Base 75:435-444, 2014  
  • Motzkin JC, Philippi C, Wolf RC, Baskaya MK, and Koenigs M. Ventromedial prefrontal cortex lesions alter neural and physiological correlates of anticipation. Journal of Neuroscience Jul. 30;34(31):10430-10437, 2014
  • Cikla U, Baggott C, Baskaya MK. How I do it: Treatment of blood blister-like aneurysms of the supraclinoid internal carotid artery by extracranial to intracranial bypass and trapping. Acta Neurochirurgica 156(11);2071-2077, 2014
  • Cıkla U, Aagaard Kienitz B, Niemann DB, Turski PA,  MD1Başkaya MK.Familial Perimesencephalic Subarachnoid Hemorrhage: Association or coincidence? Case report.  Journal of Medical Case Reports. Nov. 22;8:380, 2014Cikla U, Baggot C, Baskaya MK. Gross total resection of large cervical intramedullary ependymoma: Demonstration of microsurgical techniques. Turkish Neurosurgery 24(5):763-764, 2014.
  • Yoon H, Mehta MP, Perumal K, Helenowski IB, Chappell RJ, Akture E, Lin Y, Marymont MH, Sejpal S, Parsa A, Chandler J, Bendok BR,  Rosenow J, Salamat S,  Kumthekar P, Raizer J, Baskaya MK. Atypical meningioma: randomized trials are required to resolve contradictory retrospective results regarding the role of adjuvant radiotherapy. Journal of Cancer Research and Therapeutics 11(1):59-66, 2015
  • Cikla U, Uluc K, Baskaya MK. Clip reconstruction of an 8 cm giant internal carotid artery bifurcation aneurysm: Microsurgical technique. Neurosurgical Focus Jan; 38(VideoSuppl 1);Video 20, 2015.
  •  Andreoli MJ, Nadkarni TN, Nair VA, Yin P, Young B, Kundu B, Pankratz J, Radtke A, Holdsworth R, Kuo JS, Field AS, Baskaya MK, Moritz CH, Meyerand MA, Prabhakaran V. Usage of fMRI for pre-surgical planning in tumor and vascular lesion patients: task and statistical threshold effects on language literalization.  Neuroimage: Clinical 24;7:415-423, 2014         
  • Turkoglu E, Kertmen H, Uluc K, Akture E, Gurer B, Cikla U, Salamat S, Baskaya MK. Microsurgical anatomy of the posterior median septum of the human spinal cord. Clinical Anatomy Jan. 28(1):45-51, 2015.
  • Li Y, Ulas C, Baggot C, Baskaya MK. Surgical treatment of  adult moyamoya disease with combined STA-MCA bypass and EDAS: Demonstration of technique in video presentation. Turkish Neurosurgery 25(1):126-131, 2015
  •  Cikla U, Li Y, Duran SH , Kozan A, Baskaya MK. Treatment of Supraclinoid Internal Carotid Artery Iatrogenic Pseudoaneurym with Extracranial-to-Intracranial Bypass and Trapping: Demonstration of Technique with Video Presentation. Turkish Neurosurgery (in press)
  • Motzkin JC, Philippi C, Oler JA, Kalin NH, Baskaya MK, and Koenigs M. Ventromedial prefrontal cortex damage alters resting blood flow to the bed nucleus of stria terminalis. Cortex 64:281-288, 2015.
  • Liu CY, Baskaya MK. The Congress of Neurological Surgeons InternationalDivision 2014. Clinical Neurosurgery. Aug Suppl 1:79-80, 2015.
  • Sandoval-Garcia C, Royalty K, Yang P, Niemann DB, Ahmed A, Aagaard-Kienitz B, Baskaya MK, Schafer S, Strother C. 4D DSA a New Technique for AVM Evaluation and Treatment Planning. Journal of Neurointerventional Surgery (in press)
  •  Garg RK, Lee KS, Kohn SC, Baskaya MK, Afifi AM. Can ultrasound distinguish a supraorbital notch from a foramen? Journal of Ultrasound in Medicine (in press)
  • Yilmaz T, Cikla U, KirstA, Baskaya MK. Gliablastoma multiforme in Klippel-Trenaunay-Weber syndrome. Case report. Journal of Medical Case Reports Apr 17;9:83, 2015
  • Cikla U, Uluc K, Baskaya MK.  Microsurgical clipping of a giant vertebrobasilar  junction aneurysm under hypothermic circulatory arrest. Neurosurgical Focus July 39 (Videosuppl1):V13, 2015.
  •  Cıkla U, Yılmaz T, Li Y, Baskaya MK. Clip Reconstruction of Giant Distal Anterior Cerebral Artery Aneurysm: 3-Dimensional Operative Video. Operative Neurosurgery Sept;11 Supll 3:463, 2015
  • Ekici MA, Cıkla U, Bauer A, Başkaya MK. Osteopetrosis and Chiari type I malformation: a rare association. Journal of Surgical Case Reports (in press).
  •  Yilmaz T, Cikla U, Baskaya MK. Microsurgical treatment of thalamic cavernous malformation: 3 Dimensional Operative Video. Operative Neurosurgery (in press).
  • Garg RK, Poore SO, Wieland AM, Sanchez R, Baskaya MK, Hartig GK. Recipient vessel selection in the difficult neck: outcomes of external carotid artery transposition and end-to-end microvascular anastomosis.  Microsurgery (in press).
  • Mammadov J, Li Y, Cikla U, Hanna R, Baskaya MK. Cerebral vasospasm: Part I – Pathogenesis. Contemporary Neurosurgery 37 (9): 1-4, 2015.
  • Li Y, Cikla U, Mammadov J, Hanna R, Baskaya MK. Cerebral vasospasm: Part II – Diagnosis and treatment. Contemporary Neurosurgery 37(10):1-8, 2015.
  • Kujoth GC, Neves GF, Cıkla U, Aktüre E, Uluç K, Song C, Hananya T, Sadighi A, Ferrazzano P, Başkaya MK. Monitoring ischemic cerebral injury in hypertensive rats by diffusion tensor imaging. Turkish Neurosurgery (in press)       
  • Swanson K, Cikla U, Uluc K, Baskaya MK. Supracerebellar transtentorial approach to the tentorial incisura and beyond. Neurosurgical Focus (in press).                                              
  • Pujara MS, Wolf RC, Baskaya MK, Koenigs M. Ventromedial prefontal cortex damage alters relative risk tolerance for prospective gains and losses. Neuropsychologia 79:70-75, 2015

 

     


    Submitted Papers



     

    • Ekici MA, Cıkla U, Bauer A, Başkaya MK. Osteopetrosis and Chiari type I malformation: a rare association. (submitted to Journal of Surgical Case Reports).                               
    • Kujoth GC, Neves GF, Cıkla U, Aktüre E, Uluç K, Song C, Hananya T, Sadighi A, Ferrazzano P, Başkaya MK. Monitoring ischemic cerebral injury in hypertensive rats by diffusion tensor imaging. (submitted to Brain Research)      
    • Yilmaz T, Cikla U, Maternowski A, Baskaya MK. Gliablastoma multiforme in Klippel-Trenaunay-Weber syndrome. Case report. (submitted to Journal of Medical Case Reports).
    • Andreoli MJ, Nadkarni TN, Nair VA, Yin P, Young B, Kundu B, Pankratz J, Radtke A, Holdsworth R, Kuo JS, Field AS, Baskaya MK, Moritz CH, Meyerand MA, Prabhakaran V. Usage of fMRI for pre-surgical planning in tumor and vascular lesion patients: task and statistical threshold effects on language literalization. (Submitted to AJNR)            
    • Sandoval-Garcia C, Royalty K, Yang P, Niemann DB, Ahmed A, Aagaard-Kienitz B, Baskaya MK, Schafer S, Strother C. 4D DSA a New Technique for AVM Evaluation and Treatment Planning. (submitted to Journal of Neurointerventional Surgery)
    • Motzkin JC, Philippi C, Oler JA, Kalin NH, Baskaya MK, and Koenigs M. Ventromedial prefrontal cortex damage alters resting blood flow to the bed nucleus of stria terminalis. (submitted to Cortex).
    • Cikla U, Li Y, Duran SH , Kozan A, Baskaya MK. Treatment of Supraclinoid Internal Carotid Artery Iatrogenic Pseudoaneurym with Extracranial-to-Intracranial Bypass and Trapping: Demonstration of Technique with Video Presentation (submitted to Turkish Neurosurgery). 
    • Cikla U, Uluc K, Baskaya MK.  Microsurgical clipping of a giant vertebrobasilar  junction aneurysm under hypothermic circulatory arrest (submitted to Neurosurgical Focus).
    • Uluc K, Cikla U, Baskaya MK. Double Barrel bypass (STA-MCA) and trapping of a pseudoaneurysm of the internal carotid artery. (submitted to Neurosurgical Focus)


    Cerebrovascular Laboratory



    Stroke is a major cause of morbidity and mortality in the U.S. population, particularly among aged individuals. Current demographic projections suggest that as the elderly population continues to expand, the need for developing improved treatment options for stroke patients will become even more pressing. Our lab is interested in the molecular events that occur during focal ischemia and in the use of stem cell approaches to improving neurological outcomes following stroke. Our main experimental model involves middle cerebral artery occlusion (MCAO) to generate focal ischemia in spontaneously hypertensive rats (SHR).
    Over the past several years, we have differentiated green fluorescent protein-expressing human embryonic stem cells (GFP-hESC) into mesenchymal stem cell-like cells (eMSCs). These eMSCs expressed markers (CD-29, CD-44, CD-73, CD-105, CD-166 and Nestin, but not CD-34, C45, CD-106, SSEA-4 or Oct-4) which are consistent with a mesenchymal stem cell state. We have transplanted eMSCs into the femoral veins of SHRs following MCAO. The expression of GFP allows us to follow the migration and further differentiation of the eMSCs in the ischemic brain. We observed migration of the injected eMSCs to the infarction region (Fig. 1) and their subsequent differentiation into neurons (which expressed β-tubulin III, MAP2, HuC and neurofilament) (see Fig. 2) and vascular endothelial cells (which expressed vWF; see Fig. 3). The grafted cells do not appear to differentiate into astrocytes.


    Figure 1: Human ES cell-derived mesenchymal stem cells (eMSCs) expressing green fluorescent protein were injected into the femoral vein of rats two days after induction of stroke via middle cerebral artery occlusion. Injected eMSCs migrated to the brain and were found not only in the infarction core (A), but also in the ischemic penumbra as well as remote regions such as cortex and striatum (B, C, D).  eMSCs did not migrate to the contralateral hemisphere (E, F). No GFP-positive cells were observed in the infarction (G) or penumbra (H) regions of PBS-injected control rats.

     

     


     

    Figure 2: A subset of transplanted eMSCs (staining positive for GFP and human nuclear antigen) showed evidence of neuronal differentiation (indicated by b tubulin III staining in "Neural Marker" panel) in triple-stained brain sections from the ischemic infarction region two days after injection. Arrows indicate triple-stained cells. (Bar=100µm).

     

     

     

     

     

     


     

    Figure 3: A subset of transplanted eMSCs (GFP+) showed expression of the endothelial cell marker, von Wildebrand factor (vWF) by 1 week after injection. At 2 weeks, vWF and GFP double-positive cells were observed to form vascular channels. White arrows indicate co-localization of GFP and vWF at 1 week and 2 weeks after transplantation. (Bar=100µm). (vWF positivity was not detected at day 2 after cell transplantation.)

     

     

    The injected cells survived in the infarction region for at least four weeks after infusion. The infarction volume at 4 weeks post-MCAO was significantly reduced in eMSC transplant recipients relative to that in brains from rats that received only PBS injection. Importantly, post-ischemic behavioral functioning significantly improved in transplant recipients.
    In these experiments, we found that the engrafted cells did not survive beyond ~4 weeks. The loss of transplanted cells from the infarction region after 4 weeks occurred despite the use of cyclosporin A to suppress the immunological response. We are therefore seeking ways to improve engrafted cell survival in order to enhance the neurogenesis and angiogenesis of the transplanted cells and sustain or improve the neurological recovery of the whole animal. Some approaches include pre-conditioning the eMSCs in culture before transplant, engineering the stem cells to produce specific trophic factors, and treating the SH rats with dietary or pharmaceutical supplements before or after MCAO.
    We are also interested in determining whether other stem cell types, including induced pleuripotent (iPS) cells may offer greater neurologic protection or longer post-transplant survival.


    Ongoing Projects:

    • Neuroprotection in transplanting mesenchymal stem cells after focal cerebral ischemia in rats
    • Role of angiogenesis in ischemic pre-conditioning
    • Role of conditioned media of mesenchymal stem cells in Neuroprotection


    Neuroanatomy / Skull Base Laboratory



    Weekly resident training course on microsurgical neuroanatomy and skull base approaches led by Dr. Baskaya takes place in this laboratory.

      

    Ongoing Projects:
    • Microsurgical anatomy of craniofacial approaches
    • Gyral and sulcal variations in the posterior mediobasal temporal region
    • Safe entry zones to the brain stem
    • Gyral and Sulcal anatomy of the orbito frontal cortex with its arterial supply and white matter fiber connections
    • Neurosurgical and neuroradiological anatomy of facial colliculus
    • Neurosurgical anatomy of vestibular area


     



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