Taiwanese Journal of Obstetrics and Gynecology
Volume 46, Issue 1 , Pages 15-25, March 2007

Human Umbilical Cord Blood Cells or Estrogen may be Beneficial in Treating Heatstroke

  • Sheng-Hsien Chen

      Affiliations

    • Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan
    • Department of Obstetrics and Gynecology, Chi Mei Medical Center, Tainan, Taiwan
    • Department of Medicine, Taipei Medical University, Taipei, Taiwan
    • ,
  • Kuo-Feng Huang

      Affiliations

    • Department of Obstetrics and Gynecology, Chi Mei Medical Center, Tainan, Taiwan
    • ,
  • Mao-Tsun Lin

      Affiliations

    • Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan
    • ,
  • Fong-Ming Chang

      Affiliations

    • Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan
    • Corresponding Author InformationCorrespondence to: Dr Fong-Ming Chang, Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 710, Taiwan

Accepted 16 August 2006.

Article Outline

Summary 

This current review summarized animal models of heatstroke experimentation that promote our current knowledge of therapeutic effects on cerebrovascular dysfunction, coagulopathy, and/or systemic inflammation with human umbilical cord blood cells (HUCBCs) or estrogen in the setting of heatstroke. Accumulating evidences have demonstrated that HUCBCs provide a promising new therapeutic method against neurodegenerative diseases, such as stroke, traumatic brain injury, and spinal cord injury as well as blood disease. More recently, we have also demonstrated that postor pretreatment by HUCBCs may resuscitate heatstroke rats with by reducing circulatory shock, and cerebral nitric oxide overload and ischemic injury. Moreover, CD34+ cells sorted from HUCBCs may improve survival by attenuating inflammatory, coagulopathy, and multiorgan dysfunction during experimental heatstroke. Many researchers indicated pro(e.g. tumor necrosis factor-α [TNF-α]) and anti-inflammatory (e.g. interleukin-10 [IL-10]) cytokines in the peripheral blood stream correlate with severity of circulatory shock, cerebral ischemia and hypoxia, and neuronal damage occurring in heatstroke. It has been shown that intravenous administration of CD34+ cells can secrete therapeutic molecules, such as neurotrophic factors, and attenuate systemic inflammatory reactions by decreasing serum TNF-α but increasing IL-10 during heatstroke. Another line of evidence has suggested that estrogen influences the severity of injury associated with cerebrovascular shock. Recently, we also successfully demonstrated estrogen resuscitated heatstroke rats by ameliorating systemic inflammation. Conclusively, HUCBCs or estrogen may be employed as a beneficial therapeutic strategy in prevention and repair of cerebrovascular dysfunction, coagulopathy, and/or systemic inflammation during heatstroke.

Key Words:  CD34+ cell , cytokine , estrogen , heatstroke , human umbilical cord blood cell , inflammation

No full text is available. To read the body of this article, please view the PDF online.

 

Back to Article Outline

References 

  1. Bouchama A , Knochel JP . Heat stroke . N Engl J Med . 2002;346:1978–1988
  2. Shih CJ , Lin MT , Tsai SH . Experimental study on the pathogenesis of heat stroke . J Neurosurg . 1984;60:1246–1252
  3. Chen SH , Niu KC , Lin MT . Cerebrovascular dysfunction is an attractive target for therapy in heat stroke . Clin Exp Pharmacol Physiol . 2006;33:663–672
  4. Lee-Chiong TL , Stitt JT . Heatstroke and other heat-related illnesses. The maladies of summer . Postgrad Med . 1995;98:26–28 31–3, 36
  5. Hassanein T , Razack A , Gavaler JS , Van Thiel DH . Heatstroke: its clinical and pathological presentation, with particular attention to the liver . Am J Gastroenterol . 1992;87:1382–1389
  6. Parsons LR . Surviving the hot zone . Emerg Med Serv . 1993;22:42–46
  7. Hsu SF , Niu KC , Lin CL , Lin MT . Brain cooling causes attenuation of cerebral oxidative stress, systemic inflammation, activated coagulation, and tissue ischemia/injury during heatstroke . Shock . 2006;26:210–220
  8. Hillered L , Persson L . Neurochemical monitoring of the acutely injured human brain . Scand J Clin Lab Invest Suppl . 1999;229:9–18
  9. Hillered L , Persson L , Ponten U , Ungerstedt U . Neurometabolic monitoring of he ischemic human brain using microdialysis . Acta Neurochir . 1990;102:991–997
  10. Hillered L , Valtysson J , Enblad P , Person L . Interstitial glycerol as a marker for membrane phospholipid degradation in the acutely injured human brain . J Neurol Neurosurg Psychiatry . 1998;64:486–494
  11. Nilsson OG , Saveland H , Boris-Moller F , Brandt L , Wieloch T . Increased levels of glutamate in patients with subarachnoid haemorrhage as measured by intracerebral microdialysis . Acta Neurochir Suppl . 1996;667:45–47
  12. Persson L , Hillered L . Chemical monitoring of neurosurgical intensive care patients using intracerebral microdialysis . J Neurosurg . 1992;76:72–80
  13. Ungerstedt U . Microdialysis–a new technique for monitoring local tissue events in the clinic . Acta Anaesthesiol Scand Suppl . 1997;110:123; [Abstract]
  14. Chang CP , Lee CC , Chen SH , Lin MT . Aminoguanidine protects against intracranial hypertension and cerebral ischemic injury in experimental heatstroke . J Pharmacol Sci . 2004;95:56–64
  15. Chen SH , Chang FM , Tsai YC , Huang KF , Lin MT . Resuscitation from experimental heatstroke by transplantation of human umbilical cord blood cells . Crit Care Med . 2005;33:1377–1383
  16. Kuo JR , Lin CL , Chio CC , Wang JJ , Lin MT . Effects of hypertonic (3%) saline in rats with circulatory shock and cerebral ischemia after heatstroke . Intensive Care Med . 2003;29:1567–1573
  17. Lee JJ , Lin MT , Wang NL , Lin CL , Chang CK . Platonin, a cyanine photosensitizing dye, causes attenuation of circulatory shock, hypercoagulable state, and tissue ischemia during heat stroke . Shock . 2005;24:577–582
  18. Chou YT , Lai ST , Lee CC , Lin MT . Hypothermia attenuates circulatory shock and cerebral ischemia in experimental heatstroke . Shock . 2003;19:388–393
  19. Sharma HS , Alm P . Nitric oxide synthase inhibitors influence dynorphin A (1-17) immunoreactivity in the rat brain following hyperthermia . Amino Acids . 2002;23:242–259
  20. Sharma HS , Westman J , Cervos-Navarro J , Dey PK , Nyberg F . Opioid receptor antagonists attenuate heat stress-induced reduction in cerebral blood flow, increased blood–brain barrier permeability, vasogenic edema and cell changes in the rat . Ann N Y Acad Sci . 1997;813:559–571
  21. Sharma HS , Westman J , Alm P , et al.   Involvement of nitric oxide in the pathophysiology of acute heat stress in the rat. Influence of a new antioxidant compound H-290/51 . Ann N Y Acad Sci . 1997;813:581–590
  22. Chatterjee S , Premachandran S , Sharma D , Bagewadikar RS , Poduval TB . Therapeutic treatment with L-arginine rescues mice from heat stroke-induced death: physiological and molecular mechanisms . Shock . 2005;24:341–347
  23. Leon LR , DuBose DA , Mason CW . Heat stress induces a biphasic thermoregulatory response in mice . Am J Physiol Regul Integr Com Physiol . 2005;288:197–204
  24. Leon LR , Blaha MD , DuBose DA . Time course of cytokine, corticosterone, and tissue injury responses in mice during heat strain recovery . J Appl Physiol . 2006;100:1400–1409
  25. Lee WC , Wen HC , Chang CP , Chen MY , Lin MT . Heat shock protein 72 overexpression protects against hyperthermia, circulatory shock, and cerebral ischemia during heatstroke . J Appl Physiol . 2006;100:2073–2082
  26. Bouchama A , Roberts G , Al Mohanna F , et al.   Inflammatory, hemostatic, and clinical changes in a baboon experimental model for heatstroke . J Appl Physiol . 2005;98:697–705
  27. Kordower JH , Freeman TB , Snow BJ , et al.   Neuropathological evidence of graft survival and striatal reinnervation afer the transplantation of fetal mesencephalic tissue in a patient with Parkinson's disease . N Engl J Med . 1995;332:1118–1124
  28. Jansen EM , Solberg L , Underhill S , et al.   Transplantation of fetal neocortex ameliorates sensorimotor and locomotor deficits following neonatal ischemic-hypoxic brain injury in rats . Exp Neurol . 1997;147:487–497
  29. Prockop DJ . Marrow stromal cells as stemal cells as stem cells for nonhematopoietic tissues . Science . 1997;147:487–497
  30. Pittenger MF , Mackay AM , Beck SC , et al.   Multilineage potential of adult human mesenchymal stem cells . Science . 1999;284:143–147
  31. Bianco P , Gehron Robey P . Marrow stromal stem cells . J Clin Invest . 2000;105:1663–1668
  32. Lu L , Shen RN , Broxmeyer HE . Stem cells from bone marrow, umbilical cord blood and peripheral blood for clinical application: current status and future application . Crit Rev Oncol Hematol . 1996;22:61–78
  33. Kelly P , Kurtxberg J , Vichinsky E , Lubin B . Umbilical cord blood stem cells: application for the treatment of patients with hemoglobinnopathies . J Pediatr . 1997;130:695–703
  34. Erices A , Conget P , Minguell JJ . Mesenchymal progenitor cells in human umbilical cord blood . Br J Haematol . 2000;109:235–242
  35. Gage FH . Mammalian neural stem cells . Science . 2000;287:1433–1438
  36. Nieda M , Nicol A , Denning-Kendall P , et al.   Endothelial cell precursors are normal components of human umbilical cord blood . Br J Haematol . 1997;98:775–777
  37. Sirchia G , Rebulla P . Placental/umbilical cord blood transplantation . Hematologia . 1999;84:738–747
  38. Sanchez-Ramos JR , Song S , Kamath SG , et al.   Expression of neural markers in human umbilical cord blood . Exp Neurol . 2001;171:109–115
  39. Bicknese AR , Goodwin HS , Quinn CO , et al.   Human umbilical cord blood cells can be induced to express markers for neurons and glia . Cell Transplant . 2002;11:261–264
  40. Buzanska L , Machaj EK , Zablocka B , et al.   Human cord blood–derived cells attain neuronal and glial features in vitro . J Cell Sci . 2002;115:2131–2138
  41. Zigova T , Song S , Willing AE , et al.   Human umbilical cord blood cells express neural antigens after transplantation into the developing rat brain . Cell Transplant . 2002;11:265–274
  42. Chen J , Sanberg PR , Li Y , et al.   Intravenous administration human umbilical cord blood reduces behavioral deficits after stroke in rats . Stroke . 2001;32:2682–2688
  43. Willing AE , Vendrame M , Mallery J , et al.   Mobilized peripheral blood cells administered intravenously produce functional recovery in stroke . Cell Transplant . 2003;12:449–454
  44. Vendrame M , Cassady J , Newcomb J , et al.   Infusion of human umbilical cord blood cells in a rat model of stroke dose-dependently rescues behavioral deficits and reduces infarct volume . Stroke . 2004;35:2390–2395
  45. Lu D , Sanberg PR , Mahmood A . Intravenous administration of human umbilical cord blood reduces neurological deficit in the rat after traumatic brain injury . Cell Transplant . 2002;11:275–281
  46. Saporta S , Kim JJ , Willing AE , et al.   Human umbilical cord blood stem cells infusion in spinal cord injury: engraftment and beneficial influence on behavior . J Hematother Stem Cell Res . 2003;12:271–278
  47. Li Y , Chopp M , Chen J , et al.   Intrastriatal transplantation of bone marrow nonhematopoietic cells improves functional recovery after stroke in adult mice . J Cereb Blood Flow Metab . 2000;20:1311–1319
  48. Sharma HS , Westman J , Nyberg F . Pathophysiology of brain edema and cell changes following hyperthermic brain injury . Prog Brain Res . 1998;115:351–412
  49. Ha Y , Choi DH , Yeon DS , et al.   Neural phenotype expression cultured human cord blood cells in vitro . Neuroreport . 2001;12:3523–3527
  50. Zigova T , Song S , Willing AE , et al.   Human umbilical cord blood cells express neural antigens after transplantation into the developing rat brain . Cell Transplant . 2002;11:265–274
  51. Lobel DA , Hadman M , Sanberg PR , et al.   Early intracerebral and intra-arterial transplantation of human umbilical cord blood cells into an ischemic rat brain model . Exp Neurol . 2003;181:97
  52. Wagner JE , Broxmeyer HE , Byrd RL , et al.   Transplantation of umbilical cord blood after myeloablative therapy: analysis of engraftment . Blood . 1992;79:1874–1881
  53. Chen SH , Chang FM , Tsai YC , et al.   Infusion of human umbilical cord blood cells protect against cerebral ischemia and damage during heat stroke in the rat . Exp Neurol . 2006;199:67–76
  54. Newman M , Willing A , Cassady CJ , et al.   In vitro migration and phenotype identification of human umbilical cord blood (HUCB) cells to stroke brain . Exp Neurol . 2003;181:84–112 (Abstract)
  55. Borlongan CV , Hadman M , Sanberg CD , Sanberg PR . Central nervous system entry of peripherally injected umbilical cord blood cells is not required for neuroprotection in stroke . Stroke . 2004;35:2385–2389
  56. Wen YS , Huang MS , Lin MT , Lee CH . Hypothermic retrograde jugular perfusion reduces brain damage in rats with heatstroke . Crit Care Med . 2003;31:2641–2645
  57. Wang JL , Ke DS , Lin MT . Heat shock pretreatment may protect against heatstroke-induced circulatory shock and cerebral ischemia by reducing oxidative stress and energy depletion . Shock . 2004;23:161–167
  58. Ourednik J , Ourednik V , Lynch WP , Schachner M , Snyder EY . Neural stem cells display an inherent mechanism for rescuing dysfunctional neurons . Nat Biotech . 2002;20:1103–1110
  59. Teng YD , Lavik EB , Qu X , et al.   Functional recovery following traumatic spinal cord injury mediated by a unique polymer scaffold seeded with neural stem cells . Proc Natl Acad Sci USA . 2002;99:3024–3029
  60. Wu X , Kochanek PM . Should we add stem cells to the code cart in resuscitation of heatstroke? . Crit Care Med . 2005;33:1458–1459
  61. Kao TY , Chio CC , Lin MT . Hypothalamic dopamine release and local cerebral blood flow during onset of heatstroke in rats . Stroke . 1994;25:2483–2487
  62. Kao TY , Lin MT . Brain serotonin depletion attenuates heatstroke-induced cerebral ischemia and cell death in rats . J Appl Physiol . 1996;80:680–684
  63. Ye Z , Gee AP , Bowers WE , et al.   In vitro expansion and characterization of dendritic cells derived from human bone marrow CD34+ cells . Bone Marrow Transplant . 1996;18:997–1008
  64. Chen J , Li Y , Wang L , et al.   Therapeutic benefit of intravenous administration of bone marrow stromal cells after cerebral ischemia in rats . Stroke . 2001;32:1005–1011
  65. Taguchi A , Soma T , Tanaka H , et al.   Administration of CD34+ cells after stroke enhances neurogenesis via angiogenesis in a mouse model . J Clin Invest . 2004;114:330–338
  66. Hung CH , Chang NC , Cheng BC , Lin MT . Progressive exercise preconditioning protects against circulatory shock during experimental heatstroke . Shock . 2005;23:426–433
  67. Lin MT , Liu HH , Yang YL . Involvement of interleukin-1 receptor mechanism in development of arterial hypotension in rat heat stroke . Am J Physiol . 1997;273:H2072–H2077
  68. Liu CC , Chien CH , Lin MT . Glucocorticoids reduce interleukin-1 concentration and result in neuroprotective effects in rat heatstroke . J Physiol . 2000;527:333–343
  69. Nakamura T , Suzuki S , Ushiyama C , Shimada N , Koide H . Effect of phosphodiesterase III inhibitor on plasma concentrations of endothelin-1 and tumour necrosis factor in patients with acute heart failure . Acta Cardiol . 2002;57:19–21
  70. Schirmer WJ , Schirmer JM , Fry DE . Recombinant human tumor necrosis factor produces hemodynamic changes characteristic of sepsis and endotoxemia . Arch Surg . 1989;124:445–448
  71. Oberholzer A , Oberholzer C , Moldawer LL . Cytokine signaling–regulation of the immune response in normal and critically ill states . Crit Care Med . 2000;28:N3–12
  72. Moore KW , de Waal Malefyt R , Coffman RL , O'Garra A . Interleukin-10 and the interleukin-10 receptor . Annu Rev Immunol . 2001;19:683–765
  73. Abe K , Hayashi T . Expression of the glial cell line-derived neurotrophic factor gene in rat brain after transient MCA occlusion . Brain Res . 1997;776:230–234
  74. Kokaia Z , Zhao Q , Kokaia M , et al.   Regulation of brainderived neurotrophic factor gene expression after transient middle cerebral artery occlusion with and without brain damage . Exp Neurol . 1995;136:73–88
  75. Lin TN , Wang PY , Chi SI , Kuo JS . Differential regulation of ciliary neurotrophic factor (CNTF) and CNTF receptor alpha (CNTFR alpha) expression following focal cerebral ischemia . Brain Res Mol Brain Res . 1998;55:71–80
  76. Kurozumi K , Nakamura K , Tamiya T , et al.   Mesenchymal stem cells that produce neurotrophic factors reduce ischemic damage in the rat middle cerebral artery occlusion model . Mol Ther . 2005;11:96–104
  77. Sherwin BB . Hormones, mood, and cognitive functioning in postmenopausal women . Obstet Gynecol . 1996;87:20S–206
  78. Sherwin BB . Estrogen effects on cognition in menopausal women . Neurology . 1997;48:S21–S26
  79. Wise PM, Dubal DB, Wilson ME, Rau SW, Liu Y. Estradiol: a trophic and protective factor in the adult brain. Front Neuroendocrinol 2000. [In press]
  80. Dubal DB , Kashon ML , Pettigrew LC , et al.   Estradiol protects against ischemic injury . J Cereb Blood Flow Metab . 1998;18:1253–1258
  81. Zhang Y-Q , Shi J , Rajakumar G , Day AL , Simpkins JW . Effects of gender and estradiol treatment on focal brain ischemia . Brain Res . 1998;784:321–324
  82. Alkayed NJ , Harukuni I , Kimes AS , et al.   Gender-linked brain injury in experimental stroke . Stroke . 1998;29:159–166
  83. Angele MK , Knoferl MW , Schwacha MG , et al.   Sex steroids regulate proand anti-inflammatory cytokine release by macrophages after trauma-hemorrhage . Am J Physiol . 1999;277:C35–C42
  84. Ito A , Bebo BF , Matejuk A , et al.   Estrogen treatment down-regulates TNF-alpha production and reduces the severity of experimental autoimmune encephalomyelitis in cytokine knockout mice . J Immunol . 2001;167:542–552
  85. Lang TJ . Estrogen as an immunomodulator . Clin Immunol . 2004;113:224–230
  86. Kim S , Liva SM , Dalal MA , Verity MA , Voskuhl RR . Estriol ameliorates autoimmune demyelinating disease: implications for multiple sclerosis . Neurology . 1999;12:1230–1238
  87. Howard M , O'Garra A . Biological properties of interleukin 10 . Immunol Today . 1992;13:198–200
  88. Moore KW , O'Garra A , de Waal Malefyt R , Vieira P , Mosmann TR . Interleukin 10 . Annu Rev Immunol . 1993;11:165–190
  89. Bouchama A , Parhar RS , el-Yazigi A , Sheth K , al-Sedairy S . Endotoxemia and release of tumor necrosis factor and interleukin 1 alpha in acute heatstroke . J Appl Physiol . 1991;70:2640–2644
  90. Bouchama A , al-Sedairy S , Siddiqui S , Shail E , Rezeig M . Elevated pyrogenic cytokines in heatstroke . Chest . 1993;104:1498–1502
  91. Lin MT , Kao TY , Jin YT , Chen CF . Interleukin-1 receptor antagonist attenuates the heat stroke-induced neuronal damage by reducing the cerebral ischemia in rats . Brain Res Bull . 1995;37:595–598
  92. Lin MT . Heatstroke-induced cerebral ischemia and neuronal damage. Involvement of cytokines and monoamines . Ann N Y Acad Sci . 1997;813:572–580
  93. Chen SH , Chang FM , Niu KC , Lin MYS , Lin MT . Resuscitation from experimental heatstroke by estrogen therapy . Crit Care Med . 2006;34:1113–1118
  94. Toung TJ , Traystman RJ , Hurn PD . Estrogen-mediated neuroprotection after experimental stroke in male rats . Stroke . 1998;39:1666–1670
  95. Jett EA , Lerner MR , Lightfoot SA , et al.   Prevention of rat mammary carcinoma utilizing leuprolide as an equivalent to oophorectomy . Breast Cancer Res Treat . 1999;58:131–136
  96. Liu CC , Ke D , Chen ZC , Lin MT . Hydroxyethyl starch produces attenuation of circulatory shock and cerebral ischemia during heatstroke . Shock . 2004;22:288–294
  97. Bouchama A , Hammami MM , Al Shail E , De Vol E . Differential effects of in vitro and in vivo hyperthermia on the production of interleukin-10 . Intensive Care Med . 2000;26:1646–1651
  98. Lu KC , Wang JY , Lin SH , Chu P , Lin YF . Role of circulating cytokines and chemokines in exertional heatstroke . Crit Care Med . 2004;32:399–403
  99. McCullough LD , Alkayed NJ , Traystman RJ , et al.   Postischemic estrogen reduces hypoperfusion and secondary ischemia after experimental stroke. . Stroke . 2001;32:796–802
  100. Jarrar D , Wang P , Cioffi WG , et al.   The female reproductive cycle is an important variable in the response to trauma-hemorrhage. . Am J Physiol Heart Cric Physiol . 2000;279:H1015–H1021
  101. Rosenfeld CR , Killam AP , Battaglia FC , et al.   Effect of estradiol-17, on the magnitude and distribution of uterine blood flow in nonpregnant, oophorectomized ewes. . Pediatr Res . 1973;7:139–148
  102. Magness RR , Phernetton TM , Zheng J . Systemic and uterine blood flow distribution during prolonged infusion of 17beta-estradiol . Am J Physiol . 1998;275:H731–H743

PII: S1028-4559(08)60101-1

doi:10.1016/S1028-4559(08)60101-1

Taiwanese Journal of Obstetrics and Gynecology
Volume 46, Issue 1 , Pages 15-25, March 2007

Article Tools