title: Involvement of bone marrow cells and neuroinflammation in hypertension.
abstract: BACKGROUND
  Microglial activation in autonomic brain regions is a hallmark of neuroinflammation in neurogenic hypertension. Despite evidence that an impaired sympathetic nerve activity supplying the bone marrow (BM) increases inflammatory cells and decreases angiogenic cells, little is known about the reciprocal impact of BM-derived inflammatory cells on neuroinflammation in hypertension.
  
  
  OBJECTIVE
  To test the hypothesis that proinflammatory BM cells from hypertensive animals contribute to neuroinflammation and hypertension via a brain-BM interaction.
  
  
  RESULTS
  After BM ablation in spontaneously hypertensive rats, and reconstitution with normotensive Wistar Kyoto rat BM, the resultant chimeric spontaneously hypertensive rats displayed significant reduction in mean arterial pressure associated with attenuation of both central and peripheral inflammation. In contrast, an elevated mean arterial pressure along with increased central and peripheral inflammation was observed in chimeric Wistar-Kyoto rats reconstituted with spontaneously hypertensive rat BM. Oral treatment with minocycline, an inhibitor of microglial activation, attenuated hypertension in both the spontaneously hypertensive rats and the chronic angiotensin II-infused rats. This was accompanied by decreased sympathetic drive and inflammation. Furthermore, in chronic angiotensin II-infused rats, minocycline prevented extravasation of BM-derived cells to the hypothalamic paraventricular nucleus, presumably via a mechanism of decreased C-C chemokine ligand 2 levels in the cerebrospinal fluid.
  
  
  CONCLUSIONS
  The BM contributes to hypertension by increasing peripheral inflammatory cells and their extravasation into the brain. Minocycline is an effective therapy to modify neurogenic components of hypertension. These observations support the hypothesis that BM-derived cells are involved in neuroinflammation, and targeting them may be an innovative strategy for neurogenic resistant hypertension therapy.
authors.affiliation: From the Physiology and Functional Genomics, College of Medicine (M.M.S., J.M.C., M.B.Z., S.K., J.J., M.K.R.), Physiological Sciences, College of Veterinary Medicine (N.A., F.G.-P., R.D.J., J.Z.), Cardiology, College of Medicine (Y.Q.), and Pharmacodynamics, College of Pharmacy (V.S.), University of Florida, Gainesville.
authors.forename: Monica M
authors.initials: MM
authors.lastname: Santisteban
authors.affiliation: From the Physiology and Functional Genomics, College of Medicine (M.M.S., J.M.C., M.B.Z., S.K., J.J., M.K.R.), Physiological Sciences, College of Veterinary Medicine (N.A., F.G.-P., R.D.J., J.Z.), Cardiology, College of Medicine (Y.Q.), and Pharmacodynamics, College of Pharmacy (V.S.), University of Florida, Gainesville.
authors.forename: Niousha
authors.initials: N
authors.lastname: Ahmari
authors.affiliation: From the Physiology and Functional Genomics, College of Medicine (M.M.S., J.M.C., M.B.Z., S.K., J.J., M.K.R.), Physiological Sciences, College of Veterinary Medicine (N.A., F.G.-P., R.D.J., J.Z.), Cardiology, College of Medicine (Y.Q.), and Pharmacodynamics, College of Pharmacy (V.S.), University of Florida, Gainesville.
authors.forename: Jessica Marulanda
authors.initials: JM
authors.lastname: Carvajal
authors.affiliation: From the Physiology and Functional Genomics, College of Medicine (M.M.S., J.M.C., M.B.Z., S.K., J.J., M.K.R.), Physiological Sciences, College of Veterinary Medicine (N.A., F.G.-P., R.D.J., J.Z.), Cardiology, College of Medicine (Y.Q.), and Pharmacodynamics, College of Pharmacy (V.S.), University of Florida, Gainesville.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Zingler
authors.affiliation: From the Physiology and Functional Genomics, College of Medicine (M.M.S., J.M.C., M.B.Z., S.K., J.J., M.K.R.), Physiological Sciences, College of Veterinary Medicine (N.A., F.G.-P., R.D.J., J.Z.), Cardiology, College of Medicine (Y.Q.), and Pharmacodynamics, College of Pharmacy (V.S.), University of Florida, Gainesville.
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Qi
authors.affiliation: From the Physiology and Functional Genomics, College of Medicine (M.M.S., J.M.C., M.B.Z., S.K., J.J., M.K.R.), Physiological Sciences, College of Veterinary Medicine (N.A., F.G.-P., R.D.J., J.Z.), Cardiology, College of Medicine (Y.Q.), and Pharmacodynamics, College of Pharmacy (V.S.), University of Florida, Gainesville.
authors.forename: Seungbum
authors.initials: S
authors.lastname: Kim
authors.affiliation: From the Physiology and Functional Genomics, College of Medicine (M.M.S., J.M.C., M.B.Z., S.K., J.J., M.K.R.), Physiological Sciences, College of Veterinary Medicine (N.A., F.G.-P., R.D.J., J.Z.), Cardiology, College of Medicine (Y.Q.), and Pharmacodynamics, College of Pharmacy (V.S.), University of Florida, Gainesville.
authors.forename: Jessica
authors.initials: J
authors.lastname: Joseph
authors.affiliation: From the Physiology and Functional Genomics, College of Medicine (M.M.S., J.M.C., M.B.Z., S.K., J.J., M.K.R.), Physiological Sciences, College of Veterinary Medicine (N.A., F.G.-P., R.D.J., J.Z.), Cardiology, College of Medicine (Y.Q.), and Pharmacodynamics, College of Pharmacy (V.S.), University of Florida, Gainesville.
authors.forename: Fernando
authors.initials: F
authors.lastname: Garcia-Pereira
authors.affiliation: From the Physiology and Functional Genomics, College of Medicine (M.M.S., J.M.C., M.B.Z., S.K., J.J., M.K.R.), Physiological Sciences, College of Veterinary Medicine (N.A., F.G.-P., R.D.J., J.Z.), Cardiology, College of Medicine (Y.Q.), and Pharmacodynamics, College of Pharmacy (V.S.), University of Florida, Gainesville.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Johnson
authors.affiliation: From the Physiology and Functional Genomics, College of Medicine (M.M.S., J.M.C., M.B.Z., S.K., J.J., M.K.R.), Physiological Sciences, College of Veterinary Medicine (N.A., F.G.-P., R.D.J., J.Z.), Cardiology, College of Medicine (Y.Q.), and Pharmacodynamics, College of Pharmacy (V.S.), University of Florida, Gainesville.
authors.forename: Vinayak
authors.initials: V
authors.lastname: Shenoy
authors.affiliation: From the Physiology and Functional Genomics, College of Medicine (M.M.S., J.M.C., M.B.Z., S.K., J.J., M.K.R.), Physiological Sciences, College of Veterinary Medicine (N.A., F.G.-P., R.D.J., J.Z.), Cardiology, College of Medicine (Y.Q.), and Pharmacodynamics, College of Pharmacy (V.S.), University of Florida, Gainesville. mraizada@ufl.edu jasenkaz@ufl.edu.
authors.forename: Mohan K
authors.initials: MK
authors.lastname: Raizada
authors.affiliation: From the Physiology and Functional Genomics, College of Medicine (M.M.S., J.M.C., M.B.Z., S.K., J.J., M.K.R.), Physiological Sciences, College of Veterinary Medicine (N.A., F.G.-P., R.D.J., J.Z.), Cardiology, College of Medicine (Y.Q.), and Pharmacodynamics, College of Pharmacy (V.S.), University of Florida, Gainesville. mraizada@ufl.edu jasenkaz@ufl.edu.
authors.forename: Jasenka
authors.initials: J
authors.lastname: Zubcevic
mesh_terms: D000804:Angiotensin II; D000818:Animals; D017704:Baroreflex / Q000502:physiology; D001854:Bone Marrow Cells / Q000502:physiology*; D016026:Bone Marrow Transplantation; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D006973:Hypertension / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000502:physiology*; D008911:Minocycline / Q000627:therapeutic use; D020078:Neurogenic Inflammation / Q000150:complications*; D009638:Norepinephrine / Q000097:blood; D010286:Paraventricular Hypothalamic Nucleus / Q000276:immunology / Q000503:physiopathology*; D011828:Radiation Chimera; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D053583:Interleukin-1beta; D000804:Angiotensin II; D008911:Minocycline; D009638:Norepinephrine
keywords: autonomic nervous system; bone marrow cells; hypertension; immune system; microglia