Richard Kraig

Research Summary
Dr. Richard Kraig is an expert in migraine patient care, migraine research and cerebrovascular disease research. His clinical interests focus on the diagnosis and treatment of migraine headaches. He oversees the Cerebrovascular Disease and Aging Laboratories, which focus on migraine, stroke, epilepsy and cognitive decline from aging. An active researcher, Dr. Kraig leads investigations to determine how physical, mental and social activities can lessen the impact of neurological disease. Examination of such mechanisms by which the brain naturally protects itself may lead to more selective cellular and molecular targets, as well as new therapeutic strategies against brain disease. Dr. Kraig's research helps him to develop individualized treatment plans for patients in the Migraine Headache Clinic. He is also involved in teaching medical students, graduate students and residents.
migraine, enrichment, green exercise, exosomes, IGF-1, multiple sclerosis, trauma
  • Cornell Medical College, NY, Residency
  • The University of Chicago Medicine, IL, Internship
  • New York University, NY, M.D.
  • University of Iowa, IA, Ph.D.
Biosciences Graduate Program Association
  1. Pusic KM, Kraig RP, Pusic AD. IFN?-stimulated dendritic cell extracellular vesicles can be nasally administered to the brain and enter oligodendrocytes. PLoS One. 2021; 16(8):e0255778. View in: PubMed

  2. Pusic KM, Won L, Kraig RP, Pusic AD. Environmental Enrichment and Its Benefits for Migraine: Dendritic Cell Extracellular Vesicles as an Effective Mimetic. J Cell Immunol. 2021; 3(4):215-225. View in: PubMed

  3. Won L, Kraig RP. Insulin-like growth factor-1 inhibits nitroglycerin-induced trigeminal activation of oxidative stress, calcitonin gene-related peptide and c-Fos expression. Neurosci Lett. 2021 04 23; 751:135809. View in: PubMed

  4. Won L, Kraig RP. Insulin-like growth factor-1 inhibits spreading depression-induced trigeminal calcitonin gene related peptide, oxidative stress & neuronal activation in rat. Brain Res. 2020 04 01; 1732:146673. View in: PubMed

  5. Pusic KM, Won L, Kraig RP, Pusic AD. IFN?-Stimulated Dendritic Cell Exosomes for Treatment of Migraine Modeled Using Spreading Depression. Front Neurosci. 2019; 13:942. View in: PubMed

  6. Grinberg YY, Zitzow LA, Kraig RP. Intranasally administered IGF-1 inhibits spreading depression in vivo. Brain Res. 2017 Dec 15; 1677:47-57. View in: PubMed

  7. Ochocinska MJ, Zlokovic BV, Searson PC, Crowder AT, Kraig RP, Ljubimova JY, Mainprize TG, Banks WA, Warren RQ, Kindzelski A, Timmer W, Liu CH. NIH workshop report on the trans-agency blood-brain interface workshop 2016: exploring key challenges and opportunities associated with the blood, brain and their interface. Fluids Barriers CNS. 2017 May 01; 14(1):12. View in: PubMed

  8. Pusic KM, Pusic AD, Kraig RP. Environmental Enrichment Stimulates Immune Cell Secretion of Exosomes that Promote CNS Myelination and May Regulate Inflammation. Cell Mol Neurobiol. 2016 Apr; 36(3):313-325. View in: PubMed

  9. Quesenberry PJ, Aliotta J, Camussi G, Abdel-Mageed AB, Wen S, Goldberg L, Zhang HG, Tetta C, Franklin J, Coffey RJ, Danielson K, Subramanya V, Ghiran I, Das S, Chen CC, Pusic KM, Pusic AD, Chatterjee D, Kraig RP, Balaj L, Dooner M. Potential functional applications of extracellular vesicles: a report by the NIH Common Fund Extracellular RNA Communication Consortium. J Extracell Vesicles. 2015; 4:27575. View in: PubMed

  10. Pusic AD, Kraig RP. Phasic Treatment with Interferon Gamma Stimulates Release of Exosomes that Protect Against Spreading Depression. J Interferon Cytokine Res. 2015 Oct; 35(10):795-807. View in: PubMed

  11. Pusic AD, Mitchell HM, Kunkler PE, Klauer N, Kraig RP. Spreading depression transiently disrupts myelin via interferon-gamma signaling. Exp Neurol. 2015 Feb; 264:43-54. View in: PubMed

  12. Pusic KM, Pusic AD, Kemme J, Kraig RP. Spreading depression requires microglia and is decreased by their M2a polarization from environmental enrichment. Glia. 2014 Jul; 62(7):1176-94. View in: PubMed

  13. Pusic AD, Pusic KM, Kraig RP. What are exosomes and how can they be used in multiple sclerosis therapy? Expert Rev Neurother. 2014 Apr; 14(4):353-5. View in: PubMed

  14. Pusic AD, Kraig RP. Youth and environmental enrichment generate serum exosomes containing miR-219 that promote CNS myelination. Glia. 2014 Feb; 62(2):284-99. View in: PubMed

  15. Pusic AD, Pusic KM, Clayton BL, Kraig RP. IFN?-stimulated dendritic cell exosomes as a potential therapeutic for remyelination. J Neuroimmunol. 2014 Jan 15; 266(1-2):12-23. View in: PubMed

  16. Grinberg YY, Dibbern ME, Levasseur VA, Kraig RP. Insulin-like growth factor-1 abrogates microglial oxidative stress and TNF-a responses to spreading depression. J Neurochem. 2013 Sep; 126(5):662-72. View in: PubMed

  17. Walters R, Kraig RP, Medintz I, Delehanty JB, Stewart MH, Susumu K, Huston AL, Dawson PE, Dawson G. Nanoparticle targeting to neurons in a rat hippocampal slice culture model. ASN Neuro. 2012 Oct 23; 4(6):383-92. View in: PubMed

  18. Grinberg YY, van Drongelen W, Kraig RP. Insulin-like growth factor-1 lowers spreading depression susceptibility and reduces oxidative stress. J Neurochem. 2012 Jul; 122(1):221-9. View in: PubMed

  19. Cipolla MJ, Pusic AD, Grinberg YY, Chapman AC, Poynter ME, Kraig RP. Pregnant serum induces neuroinflammation and seizure activity via TNFa. Exp Neurol. 2012 Apr; 234(2):398-404. View in: PubMed

  20. Cipolla MJ, Kraig RP. Seizures in Women with Preeclampsia: Mechanisms and Management. Fetal Matern Med Rev. 2011 May; 22(2):91-108. View in: PubMed

  21. Pusic AD, Grinberg YY, Mitchell HM, Kraig RP. Modeling neural immune signaling of episodic and chronic migraine using spreading depression in vitro. J Vis Exp. 2011 Jun 13; (52). View in: PubMed

  22. Cipolla MJ, Houston EM, Kraig RP, Bonney EA. Differential effects of low-dose endotoxin on the cerebral circulation during pregnancy. Reprod Sci. 2011 Dec; 18(12):1211-21. View in: PubMed

  23. Grinberg YY, Milton JG, Kraig RP. Spreading depression sends microglia on Lévy flights. PLoS One. 2011 Apr 26; 6(4):e19294. View in: PubMed

  24. Domowicz MS, Henry JG, Wadlington N, Navarro A, Kraig RP, Schwartz NB. Astrocyte precursor response to embryonic brain injury. Brain Res. 2011 May 10; 1389:35-49. View in: PubMed

  25. Kraig RP, Mitchell HM, Christie-Pope B, Kunkler PE, White DM, Tang YP, Langan G. TNF-a and Microglial Hormetic Involvement in Neurological Health & Migraine. Dose Response. 2010 Feb 18; 8(4):389-413. View in: PubMed

  26. Mitchell HM, White DM, Domowicz MS, Kraig RP. Cold pre-conditioning neuroprotection depends on TNF-a and is enhanced by blockade of interleukin-11. J Neurochem. 2011 Apr; 117(2):187-96. View in: PubMed

  27. Mitchell HM, White DM, Kraig RP. Strategies for study of neuroprotection from cold-preconditioning. J Vis Exp. 2010 Sep 02; (43). View in: PubMed

  28. Hulse RE, Swenson WG, Kunkler PE, White DM, Kraig RP. Monomeric IgG is neuroprotective via enhancing microglial recycling endocytosis and TNF-alpha. J Neurosci. 2008 Nov 19; 28(47):12199-211. View in: PubMed

  29. Lin W, Kunkler PE, Harding HP, Ron D, Kraig RP, Popko B. Enhanced integrated stress response promotes myelinating oligodendrocyte survival in response to interferon-gamma. Am J Pathol. 2008 Nov; 173(5):1508-17. View in: PubMed

  30. Kunkler PE, Hulse RE, Schmitt MW, Nicholson C, Kraig RP. Optical current source density analysis in hippocampal organotypic culture shows that spreading depression occurs with uniquely reversing currents. J Neurosci. 2005 Apr 13; 25(15):3952-61. View in: PubMed

  31. Kunkler PE, Hulse RE, Kraig RP. Multiplexed cytokine protein expression profiles from spreading depression in hippocampal organotypic cultures. J Cereb Blood Flow Metab. 2004 Aug; 24(8):829-39. View in: PubMed

  32. Kunkler PE, Kraig RP. P/Q Ca2+ channel blockade stops spreading depression and related pyramidal neuronal Ca2+ rise in hippocampal organ culture. Hippocampus. 2004; 14(3):356-67. View in: PubMed

  33. Hulse RE, Kunkler PE, Fedynyshyn JP, Kraig RP. Optimization of multiplexed bead-based cytokine immunoassays for rat serum and brain tissue. J Neurosci Methods. 2004 Jun 15; 136(1):87-98. View in: PubMed

  34. Aptowicz CO, Kunkler PE, Kraig RP. Homeostatic plasticity in hippocampal slice cultures involves changes in voltage-gated Na+ channel expression. Brain Res. 2004 Feb 20; 998(2):155-63. View in: PubMed

  35. Kunkler PE, Kraig RP. Hippocampal spreading depression bilaterally activates the caudal trigeminal nucleus in rodents. Hippocampus. 2003; 13(7):835-44. View in: PubMed

  36. Hulse RE, Winterfield J, Kunkler PE, Kraig RP. Astrocytic clasmatodendrosis in hippocampal organ culture. Glia. 2001 Feb; 33(2):169-79. View in: PubMed

  37. Caggiano AO, Kraig RP. Prostaglandin E receptor subtypes in cultured rat microglia and their role in reducing lipopolysaccharide-induced interleukin-1beta production. J Neurochem. 1999 Feb; 72(2):565-75. View in: PubMed

  38. Moskowitz MA, Kraig R. Comment on Ingvardsen et al., PAIN, 72 (1997) 407-415. Pain. 1998 May; 76(1-2):265-7. View in: PubMed

  39. Caggiano AO, Kraig RP. Prostaglandin E2 and 4-aminopyridine prevent the lipopolysaccharide-induced outwardly rectifying potassium current and interleukin-1beta production in cultured rat microglia. J Neurochem. 1998 Jun; 70(6):2357-68. View in: PubMed

  40. Kunkler PE, Kraig RP. Calcium waves precede electrophysiological changes of spreading depression in hippocampal organ cultures. J Neurosci. 1998 May 01; 18(9):3416-25. View in: PubMed

  41. Lascola CD, Nelson DJ, Kraig RP. Cytoskeletal actin gates a Cl- channel in neocortical astrocytes. J Neurosci. 1998 Mar 01; 18(5):1679-92. View in: PubMed

  42. Caggiano AO, Kraig RP. Neuronal nitric oxide synthase expression is induced in neocortical astrocytes after spreading depression. J Cereb Blood Flow Metab. 1998 Jan; 18(1):75-87. View in: PubMed

  43. Lascola C, Kraig RP. Astroglial acid-base dynamics in hyperglycemic and normoglycemic global ischemia. Neurosci Biobehav Rev. 1997 Mar; 21(2):143-50. View in: PubMed

  44. Kunkler PE, Kraig RP. Reactive astrocytosis from excitotoxic injury in hippocampal organ culture parallels that seen in vivo. J Cereb Blood Flow Metab. 1997 Jan; 17(1):26-43. View in: PubMed

  45. Caggiano AO, Breder CD, Kraig RP. Long-term elevation of cyclooxygenase-2, but not lipoxygenase, in regions synaptically distant from spreading depression. J Comp Neurol. 1996 Dec 16; 376(3):447-62. View in: PubMed

  46. Lascola CD, Kraig RP. Whole-cell chloride currents in rat astrocytes accompany changes in cell morphology. J Neurosci. 1996 Apr 15; 16(8):2532-45. View in: PubMed

  47. Caggiano AO, Kraig RP. Eicosanoids and nitric oxide influence induction of reactive gliosis from spreading depression in microglia but not astrocytes. J Comp Neurol. 1996 May 20; 369(1):93-108. View in: PubMed

  48. Moskowitz MA, Nozaki K, Kraig RP. Neocortical spreading depression provokes the expression of c-fos protein-like immunoreactivity within trigeminal nucleus caudalis via trigeminovascular mechanisms. J Neurosci. 1993 Mar; 13(3):1167-77. View in: PubMed

  49. Chesler M, Chen JC, Kraig RP. Determination of extracellular bicarbonate and carbon dioxide concentrations in brain slices using carbonate and pH-selective microelectrodes. J Neurosci Methods. 1994 Aug; 53(2):129-36. View in: PubMed

  50. Breder CD, Dewitt D, Kraig RP. Characterization of inducible cyclooxygenase in rat brain. J Comp Neurol. 1995 May 01; 355(2):296-315. View in: PubMed

  51. Kraig RP, Ferreira-Filho CR, Nicholson C. Alkaline and acid transients in cerebellar microenvironment. J Neurophysiol. 1983 Mar; 49(3):831-50. View in: PubMed

  52. Ault A, Kraig R. Isotopic dilution analysis. Cholesterol in gallstones and caffein in tea, cola, and NoDoz. J Chem Educ. 1969 Nov; 46(11):767-8. View in: PubMed

  53. Kraig RP, Pulsinelli WA, Plum F. Hydrogen ion buffering during complete brain ischemia. Brain Res. 1985 Sep 09; 342(2):281-90. View in: PubMed

  54. Kraig RP, Pulsinelli WA, Plum F. Heterogeneous distribution of hydrogen and bicarbonate ions during complete brain ischemia. Prog Brain Res. 1985; 63:155-66. View in: PubMed

  55. Arnold JB, Kraig RP, Rottenberg DA. In vivo measurement of regional brain and tumor pH using [14C]dimethyloxazolidinedione and quantitative autoradiography. II: Characterization of the extracellular fluid compartment using pH-sensitive microelectrodes and [14C]sucrose. J Cereb Blood Flow Metab. 1986 Aug; 6(4):435-40. View in: PubMed

  56. Kraig RP, Cooper AJ. Bicarbonate and ammonia changes in brain during spreading depression. Can J Physiol Pharmacol. 1987 May; 65(5):1099-104. View in: PubMed

  57. Kraig RP, Petito CK, Plum F, Pulsinelli WA. Hydrogen ions kill brain at concentrations reached in ischemia. J Cereb Blood Flow Metab. 1987 Aug; 7(4):379-86. View in: PubMed

  58. Kraig RP, Wagner RJ. Acid-induced changes of brain protein buffering. Brain Res. 1987 May 05; 410(2):390-4. View in: PubMed

  59. Kraig RP. Acid-induced injury in elasmobranch brain. Neurosci Lett. 1988 Jul 19; 90(1-2):119-24. View in: PubMed

  60. Plum F, Kraig RP, Pulsinelli WA. Compartmentation of acid-base balance in brain during complete ischemia. Neurochem Pathol. 1988 Jul-Dec; 9:139-44. View in: PubMed

  61. Chesler M, Kraig RP. Intracellular pH of astrocytes increases rapidly with cortical stimulation. Am J Physiol. 1987 Oct; 253(4 Pt 2):R666-70. View in: PubMed

  62. Kraig RP, Pulsinelli WA, Plum F. Carbonic acid buffer changes during complete brain ischemia. Am J Physiol. 1986 Mar; 250(3 Pt 2):R348-57. View in: PubMed

  63. Petito CK, Kraig RP, Pulsinelli WA. Light and electron microscopic evaluation of hydrogen ion-induced brain necrosis. J Cereb Blood Flow Metab. 1987 Oct; 7(5):625-32. View in: PubMed

  64. Kraig RP. Astroglial H+ and Ca2+ changes--signals for cell activation? Acta Physiol Scand Suppl. 1989; 582:32. View in: PubMed

  65. Goldman SA, Pulsinelli WA, Clarke WY, Kraig RP, Plum F. The effects of extracellular acidosis on neurons and glia in vitro. J Cereb Blood Flow Metab. 1989 Aug; 9(4):471-7. View in: PubMed

  66. Chesler M, Kraig RP. Intracellular pH transients of mammalian astrocytes. J Neurosci. 1989 Jun; 9(6):2011-9. View in: PubMed

  67. Kraig RP, Chesler M. Astrocytic acidosis in hyperglycemic and complete ischemia. J Cereb Blood Flow Metab. 1990 Jan; 10(1):104-14. View in: PubMed

  68. Kraig RP, Jaeger CB. Ionic concomitants of astroglial transformation to reactive species. Stroke. 1990 Nov; 21(11 Suppl):III184-7. View in: PubMed

  69. Nedergaard M, Kraig RP, Tanabe J, Pulsinelli WA. Dynamics of interstitial and intracellular pH in evolving brain infarct. Am J Physiol. 1991 Mar; 260(3 Pt 2):R581-8. View in: PubMed

  70. Kraig RP, Dong LM, Thisted R, Jaeger CB. Spreading depression increases immunohistochemical staining of glial fibrillary acidic protein. J Neurosci. 1991 Jul; 11(7):2187-98. View in: PubMed

  71. Iadecola C, Kraig RP. Focal elevations in neocortical interstitial K+ produced by stimulation of the fastigial nucleus in rat. Brain Res. 1991 Nov 01; 563(1-2):273-7. View in: PubMed

  72. Swain MS, Blei AT, Butterworth RF, Kraig RP. Intracellular pH rises and astrocytes swell after portacaval anastomosis in rats. Am J Physiol. 1991 Dec; 261(6 Pt 2):R1491-6. View in: PubMed

  73. Wietasch K, Kraig RP. Carbonic acid buffer species measured in real time with an intracellular microelectrode array. Am J Physiol. 1991 Sep; 261(3 Pt 2):R760-5. View in: PubMed

  74. Nicholson C, Kraig RP. Chloride and potassium changes measured during spreading depression in catfish cerebellum. Brain Res. 1975 Oct 17; 96(2):384-9. View in: PubMed

  75. Kraig RP, Nicholson C. Sodium liquid ion exchanger microelectrode used to measure large extracellular sodium transients. Science. 1976 Nov 12; 194(4266):725-6. View in: PubMed

  76. Kraig RP, Nicholson C. Extracellular ionic variations during spreading depression. Neuroscience. 1978; 3(11):1045-59. View in: PubMed

  77. Nicholson C, Kraig RP, ten Bruggencate G, Stöckle H, Steinberg R. Potassium, calcium, chloride and sodium changes in extracellular space during spreading depression in cerebellum [proceedings]. Arzneimittelforschung. 1978; 28(5):874-5. View in: PubMed