Breakdown of the Blood-Brain Barrier in Stress Alters Cognitive Dysfunction and Induces Brain Pathology: New Perspectives for Neuroprotective Strategies



Emotional, psychological or environmental stress (e.g., heat or nanoparticles) influences brain function. However, the detailed mechanisms of stress induced brain dysfunction are not well known. Research carried out in our laboratory since last 20 years show that various kinds of stressors depending on their magnitude and durations alter the blood-brain barrier (BBB) permeability to proteins leading to brain pathology. These stressed animals also show marked behavioral and cognitive deficits at the time of the BBB leakage. Entry of several restricted elements from the blood to the brain compartment after breakdown of the BBB results in immunological, biochemical and pathological reaction causing brain edema formation and cell injury. Blockade of several neurochemical receptors, e.g., serotonin, prostaglandin or opioids as well as neutralization of key neurodestructive elements, i.e., neuronal nitric oxide synthase (nNOS), Tumor necrosis factor-alpha (TNF-α), dynorphin A or hemeoxygenase-2 (HO-2) using specific drugs or antibodies against these factors reduces BBB disturbances, cognitive and behavioral dysfunction, and brain pathology. Based on these new evidences, it appears that the BBB is the gateway to neuropsychiatric diseases. Thus, efforts should be made to maintain a healthy BBB in various brain diseases to achieve neuroprotection. The possible mechanisns of BBB breakdown and brain pathology in stress in relation to altered cognitive and sensory-motor functions is discussed in this review.


Blood-brain barrier Stress Brain pathology Serotonin Prostaglandin Cytokines Cognitive dysfunction Sensory motor abnormalities Brain edema Neuropsychiatry diseases 



Blood-brain barrier




neuronal nitric oxide synthase


Tumor necrosis factor alpha




Information processing system


General adaptation syndrome


Corticotrophin releasing factor


Adrenocorticotrophic hormone


Hypothalamus pituitary adrenal axis


Thyrotrophin releasing hormone


Para ventricular nucleaus


dehydroepiandrosterone sulfate


West Nile virus


Semliki Forest virus


Evans blue albumin


Paradoxical sleep


Slow wave sleep


Reactive oxygen species


whole body hyperthermia


Blood-spinal cord barrier


Dynorphin A




Central nervous system




Histamine H1 receptor


Histamine H2 receptor







Author’s research described here is supported by Grants from Swedish Medical Research Council (2710), Stockholm Sweden, Göran Gustafsson Foundation, Stockholm, Sweden; Alexander von Humboldt Foundation, Bonn, Germany, European Office of Aerospace Research and Development (EOARD), London Office, UK. Technical assistant of Mari-Anne Carlsson, Kerstin Flink, Ingmarie Olsson and Kerstin Rystedt are highly appreciated.


  1. 1.
    Ehrlich P. Das Sauerstoff-Bedürfniss des Organismus: eine farbenanalytische Studie. Hirschwald, Berlin; 1885Google Scholar
  2. 2.
    Sharma HS, Dey PK. Impairment of blood-brain barrier (BBB) in rat by immobilization stress: role of serotonin (5-HT). Indian J Physiol Pharmacol 1981 Apr–Jun; 25(2):111–122PubMedGoogle Scholar
  3. 3.
    Sharma HS, Dey PK. Role of 5-HT on increased permeability of blood-brain barrier under heat stress. Indian J Physiol Pharmacol 1984 Oct–Dec; 28(4):259–267PubMedGoogle Scholar
  4. 4.
    Sharma HS. Blood-Brain Barrier in Stress, Ph D Thesis, Banaras Hindu University, Varanasi, India, 1982; pp. 1–85Google Scholar
  5. 5.
    Sharma HS, Dey PK. Influence of long-term immobilization stress on regional blood-brain barrier permeability, cerebral blood flow and 5-HT level in conscious normotensive young rats. J Neurol Sci 1986; 72:61–76PubMedCrossRefGoogle Scholar
  6. 6.
    Sharma HS, Dey PK. Influence of long-term acute heat exposure on regional blood-brain barrier permeability, cerebral blood flow and 5-HT level in conscious normotensive young rats. Brain Res 1987; 424:153–162PubMedCrossRefGoogle Scholar
  7. 7.
    Sharma HS, Dey PK. EEG changes following increased blood-brain barrier permeability under long-term immobilization stress in young rats. Neurosci Res 1988; 5:224–239PubMedCrossRefGoogle Scholar
  8. 8.
    Sharma HS, Cervós-Navarro J, Dey PK Acute heat exposure causes cellular alteration in cerebral cortex of young rats. NeuroReport 1991; 2:155–158PubMedCrossRefGoogle Scholar
  9. 9.
    Sharma HS, Nyberg F, Cervós-Navarro J, Dey PK Histamine modulates heat stress induced changes in blood-brain barrier permeability, cerebral blood flow, brain oedema and serotonin levels: an experimental study in conscious young rats. Neuroscience 1992; 50:445–454PubMedCrossRefGoogle Scholar
  10. 10.
    Sharma HS, Westman J, Cervós-Navarro J, Dey PK, Nyberg F Opioid receptor antagonists attenuate heat stress-induced reduction in cerebral blood flow, increased blood-brain barrier permeability, vasogenic brain edema and cell changes in the rat. Ann NY Acad Sci 1997; 813:559–571PubMedCrossRefGoogle Scholar
  11. 11.
    Sharma HS. Pathophysiology of blood-brain barrier, brain edema and cell injury following hyperthermia: New role of heat shock protein, nitric oxide and carbon monoxide. an experimental study in the rat using light and electron microscopy, Acta Universitatis Upsaliensis 1999; 830:1–94Google Scholar
  12. 12.
    Sharma HS. Blood-brain and spinal cord barriers in stress. In: Sharma HS, Westman J (eds) The Blood-Spinal Cord and Brain Barriers in Health and Disease, Elsevier Academic Press, San Diego, 2004; pp. 231–298CrossRefGoogle Scholar
  13. 13.
    Sharma HS. Blood-central nervous system barriers. A gateway to neurodegeneration, neuroprotection and neuroregeneration. Hand Book of Neurochem Mol Neurobiol, Vol. 24, Ch. 11, Springer, Berlin, New York, 2009; pp. 163–209Google Scholar
  14. 14.
    Rapoprt SI. Blood-Brain Barrier in Physiology and Medicine. Raven Press, New York; 1976Google Scholar
  15. 15.
    Bradbury MW. The Concept of a Blood Brain Barrier. Chicester, UK; 1979Google Scholar
  16. 16.
    Brightman MW, Reese TS. Junctions between intimately apposed cell membranes in the vertebrate brain. J Cell Biol 1969; 4:648–677CrossRefGoogle Scholar
  17. 17.
    Majno G, Palade GE. Studies on inflammation. 1. The effect of histamine and serotonin on vascular permeability: an electron microscopic study. J Biophys Biochem Cytol. 1961 Dec; 11:571–605PubMedCrossRefGoogle Scholar
  18. 18.
    Brightman MW. Morphology of blood-brain interfaces. Exp Eye Res. 1977; 25(Suppl):1–25. ReviewGoogle Scholar
  19. 19.
    Brightman MW. The brain’s interstitial clefts and their glial walls. J Neurocytol. 2002 Sep–Nov; 31(8–9):595–603. ReviewGoogle Scholar
  20. 20.
    Sharma HS. New perspectives for the treatment options in spinal cord injury. Expert Opin Pharmacother 2008 Nov; 9(16):2773–2800. ReviewGoogle Scholar
  21. 21.
    Sharma H S, Westman J. The Blood-Spinal Cord and Brain Barriers in Health and Disease, Academic Press, San Diego, USA, 2004; pp. 1–617 (Release date: Nov. 9, 2003)Google Scholar
  22. 22.
    Sharma H S, Alm P. Role of nitric oxide on the blood-brain and the spinal cord barriers. In: Sharma HS, Westman J (eds) The Blood-Spinal Cord and Brain Barriers in Health and Disease, Elsevier Academic Press, San Diego, 2004; pp. 191–230CrossRefGoogle Scholar
  23. 23.
    Sharma HS, Westman J, Nyberg F. Pathophysiology of brain edema and cell changes following hyperthermic brain injury. In: Sharma HS, Westman J (eds) Brain Functions in Hot Environment, Progress in Brain Research, 1998; 115:351–412Google Scholar
  24. 24.
    Sharma HS, Westman J, Cervós-Navarro J, Dey PK, Nyberg F. Blood-brain barrier in stress: a gateway to various brain diseases. In: Levy A, Grauer E, Ben-Nathan D, de Kloet ER (eds) New Frontiers of Stress Research: Modulation of Brain Function, Harwood Academic Publishers Inc., Amsterdam, 1998; pp. 259–276Google Scholar
  25. 25.
    Sharma HS. Influence of serotonin on the blood-brain and blood-spinal cord barriers. In: Sharma HS, Westman J (eds) The Blood-Spinal Cord and Brain Barriers in Health and Disease, Elsevier Academic Press, San Diego, 2004; pp. 117–158CrossRefGoogle Scholar
  26. 26.
    Sharma HS. Histamine influences the blood-spinal cord and brain barriers following injuries to the central nervous system. In: Sharma HS, Westman J (eds) The Blood-Spinal Cord and Brain Barriers in Health and Disease, Elsevier Academic Press, San Diego, 2004; pp. 159–190CrossRefGoogle Scholar
  27. 27.
    Sharma HS. Selective neuronal vulnerability, blood-brain barrier disruption and heat shock protein expression in stress induced neurodegeneration. Invited Review: In: Sarbadhikari SN (ed) Depression and Dementia: Progress in Brain Research, Clinical Applications and Future Trends , Nova Science Publishers Inc., New York, 2005; pp. 97–152Google Scholar
  28. 28.
    Sharma HS. Neurotrophic factors in combination: a possible new therapeutic strategy to influence pathophysiology of spinal cord injury and repair mechanisms. Curr Pharm Des 2007; 13(18):1841–1874. ReviewGoogle Scholar
  29. 29.
    Bradbury MWB. Physiology and pharmacology of the blood-brain barrier. Handbook Exp Pharmacol 1990; 103: 1–450, Springer, HeidelbergGoogle Scholar
  30. 30.
    Johansson BB, Auer LM. Neurogenic modification of the vulnerability of the blood-brain barrier during acute hypertension in conscious rats. Acta Physiol Scand 1983 Apr; 117(4):507–511PubMedCrossRefGoogle Scholar
  31. 31.
    Johansson BB. The blood-brain barrier and cerebral blood flow in acute hypertension. Acta Med Scand Suppl 1983; 678:107–112PubMedGoogle Scholar
  32. 32.
    Johansson BB, Auer LM, Linder LE. Phenothiazine-mediated protection of the blood-brain barrier during acute hypertension. Stroke 1982 Mar–Apr; 13(2):220–225PubMedCrossRefGoogle Scholar
  33. 33.
    Johansson BB. Cerebral vascular bed in hypertension and consequences for the brain. Hypertension. 1984 Nov–Dec; 6(6 Pt 2):III81–III86Google Scholar
  34. 34.
    Johansson BB. Hypertension mechanisms causing stroke. Clin Exp Pharmacol Physiol 1999 Jul; 26(7):563–565. ReviewGoogle Scholar
  35. 35.
    Edvinsson L, Johansson BB, Larsson B, MacKenzie ET, Skärby T, Young AR. Calcium antagonists: effects on cerebral blood flow and blood-brain barrier permeability in the rat. Br J Pharmacol 1983 May; 79(1):141–148PubMedCrossRefGoogle Scholar
  36. 36.
    Larsson B, Skärby T, Edvinsson L, Hardebo JE, Owman C. Vincristine reduces damage of the blood-brain barrier induced by high intravascular pressure. Neurosci Lett 1980 Apr; 17(1–2):155–159PubMedCrossRefGoogle Scholar
  37. 37.
    Nag S, Harik SI. Cerebrovascular permeability to horseradish peroxidase in hypertensive rats: effects of unilateral locus ceruleus lesion. Acta Neuropathol 1987; 73(3):247–253PubMedCrossRefGoogle Scholar
  38. 38.
    Nag S. Cerebral endothelial plasma membrane alterations in acute hypertension. Acta Neuropathol 1986; 70(1):38–43PubMedCrossRefGoogle Scholar
  39. 39.
    Nag S. Cerebral changes in chronic hypertension: combined permeability and immunohistochemical studies. Acta Neuropathol 1984; 62(3):178–184PubMedCrossRefGoogle Scholar
  40. 40.
    Nag S. Cerebral endothelial surface charge in hypertension. Acta Neuropathol 1984; 63(4):276–281PubMedCrossRefGoogle Scholar
  41. 41.
    Nag S, Robertson DM, Dinsdale HB. Intracerebral arteriolar permeability to lanthanum. Am J Pathol 1982 Jun; 107(3):336–341PubMedGoogle Scholar
  42. 42.
    Nag S, Robertson DM, Dinsdale HB. Quantitative estimate of pinocytosis in experimental acute hypertension. Acta Neuropathol 1979 Apr 12; 46(1–2):107–116PubMedCrossRefGoogle Scholar
  43. 43.
    Sharma HS, Johanson CE. Blood-cerebrospinal fluid barrier in hyperthermia.Prog Brain Res 2007; 162:459–478. ReviewGoogle Scholar
  44. 44.
    Sharma HS, Johanson CE. Intracerebroventricularly administered neurotrophins attenuate blood cerebrospinal fluid barrier breakdown and brain pathology following whole-body hyperthermia: an experimental study in the rat using biochemical and morphological approaches. Ann NY Acad Sci. 2007 Dec; 1122:112–129PubMedCrossRefGoogle Scholar
  45. 45.
    Sharma HS, Duncan JA, Johanson CE. Whole-body hyperthermia in the rat disrupts the blood-cerebrospinal fluid barrier and induces brain edema. Acta Neurochir Suppl 2006; 96:426–431PubMedCrossRefGoogle Scholar
  46. 46.
    Selye H. A syndrome produced by diverse noccuous agents. Nature (Lond) 1936; 138:32CrossRefGoogle Scholar
  47. 47.
    Chrousos GP, Gold PW. The concept of stress and stress system disorders: Overview of physical and behavioral homeostasis. JAMA 1992; 267:1244–1252PubMedCrossRefGoogle Scholar
  48. 48.
    Friedman MJ, Charbey DS, Deutch AY. Neurobiological and Clinical Consequences of Stress, Lipincott-Raven, Philadelphia; 1995Google Scholar
  49. 49.
    Sharma HS, Westman J. Brain Functions in Hot Environment, Progress in Brain Research, 115, Elsevier, Amsterdam, 1998; pp. 1–516Google Scholar
  50. 50.
    Selye H. Stress in Health and Disease. Butterworths, London; 1976Google Scholar
  51. 51.
    Foa EB, Zinbarg R, Olasov-Rothbaum B. Uncontrollability and unpredictability in post-traumatic stress disorder: an animal model. Psychol Bull 1992; 112:218–238PubMedCrossRefGoogle Scholar
  52. 52.
    Gazzaniga MS. The Cognitive Neurosciences. MIT Press, Cambridge, MA; 1995Google Scholar
  53. 53.
    McEwen BS, Sapolsky RM. Stress and cognitive function. Curr Opin Neurobiol 1995; 5:205–217PubMedCrossRefGoogle Scholar
  54. 54.
    Sapolsky RM. Stress, the aging brain, and the mechanisms of neuronal death. MIT Press, Cambridge, MA; 1992Google Scholar
  55. 55.
    Sapolsky RM. Why stress is bad for your brain. Science 1996; 273:749–750PubMedCrossRefGoogle Scholar
  56. 56.
    Sharma HS, Westman J. Pathophysiology of hyperthermic brain injury. Current concepts, molecular mechanisms and pharmacological strategies. Research in Legal Medicine Vol. 21 Hyperthermia, Burning and Carbon Monoxide, Oehmichen M (ed) Lübeck Medical University Publications, Schmidt-Römhild Verlag, Lübeck, Germany, 2000; pp. 79–120Google Scholar
  57. 57.
    McEwen BS, Stellar E. Stress and the individual. Mechanisms leading to disease. Arch Intern Med 1993; 153:2093–2101PubMedCrossRefGoogle Scholar
  58. 58.
    Kathol RG, Jaeckle RS, Lopez JF, Meller WH. Consistent reduction of ACTH responses to stimulation with CRH, vasopressin and hypoglycaemia in patients with major depression. Br J Psychiatry 1989; 155:468–478PubMedCrossRefGoogle Scholar
  59. 59.
    Charney DS, Deutch AY, Krystal JH, Southwick SM, Davis M. Psychobiologic mechanisms of posttraumatic stress disorder. Arch Gen Psychiatry 1993; 50:295–305PubMedGoogle Scholar
  60. 60.
    Landfield PW, Eldridge JC. The glucocorticoid hypothesis of brain aging and neurodegeneration: recent modifications. Acta Endocrinol (Copenh) 1991; 125(Suppl 1):54–64Google Scholar
  61. 61.
    Herman JP, Cullinan WE. Neurocircuitry of stress: central control of the hypothalamo-pituitary-adrenocortical axis. Trends Neurosci 1997; 20:78–84PubMedCrossRefGoogle Scholar
  62. 62.
    Garthwaite J. Glutamate, nitric oxide and cell-cell signalling in the nervous system. Trends Neurosci 1991; 14:60–67PubMedCrossRefGoogle Scholar
  63. 63.
    Bronstein JM, Farber DB, Wasterlain CG. Regulation of type-II calmodulin kinase: functional implications. Brain Res Rev 1993; 18(1):135–147PubMedCrossRefGoogle Scholar
  64. 64.
    Hughes P, Dragunow M. Induction of immediate-early genes and the control of neurotransmitter-regulated gene expression within the nervous system. Pharmacol Rev 1995; 47(1):133–178PubMedGoogle Scholar
  65. 65.
    Sharma HS, Westman J. The heat shock proteins and hemeoxygenase response in central nervous system injuries. In: Sharma HS, Westman J (eds) The Blood-Spinal Cord and Brain Barriers in Health and Disease, Elsevier Academic Press, San Diego, 2004; pp. 329–360CrossRefGoogle Scholar
  66. 66.
    Abdul-Rahman A, Dahlgren N, Johansson BB, Siesjö BK. Increase in local cerebral blood flow induced by circulating adrenaline: involvement of blood-brain barrier dysfunction. Acta Physiol Scand 1979; 107:227–232PubMedCrossRefGoogle Scholar
  67. 67.
    Abercrombie ED, Jacobs BL. Single-unit response of noradrenergic neurons in the locus coeruleus of freely moving cats. II. Adaptation to chronically presented stressful stimuli. J Neurosci 1987; 7(9):2844–2848PubMedGoogle Scholar
  68. 68.
    Cullinan WE, Herman JP, Battaglia DF, Akil H, Watson SJ. Pattern and time course of immediate early gene expression in rat brain following acute stress. Neuroscience 1995; 64(2):477–505PubMedCrossRefGoogle Scholar
  69. 69.
    Smith MA, Brady LS, Glowa J, Gold PW, Herkenham M. Effects of stress and adrenalectomy on tyrosine hydroxylase mRNA levels in the locus coeruleus by in situ hybridization. Brain Res 1991; 544(1):26–32PubMedCrossRefGoogle Scholar
  70. 70.
    Uno H, Tarara R, Else JG, Suleman MA, Sapolsky RM. Hippocampal damage associated with prolonged and fatal stress in primates. J Neurosci 1989; 9:1705–1711PubMedGoogle Scholar
  71. 71.
    McEwen BS. Stress and hippocampal plasticity. Annu Rev Neurosci 1999; 22:105–122PubMedCrossRefGoogle Scholar
  72. 72.
    Magarinos AM, McEwen BS, Flugge G, Fuchs E. Chronic psychological stress causes apical dendritic atrophy of hippocampal CA3 pyramidal neurons in subordinate tree shrews. J Neurosci 1996; 16:3534–3540PubMedGoogle Scholar
  73. 73.
    Sharma HS, Westman J, Nyberg F, Cervós-Navarro J, Dey PK. Role of serotonin and prostaglandins in brain edema induced by heat stress. An experimental study in the rat. Acta Neurochirurgica (Suppl) 1994; 60:65–70Google Scholar
  74. 74.
    Sharma HS, Nyberg F, Olsson Y. Topical application of dynorphin antibodies reduces edema and cell changes in traumatised rat spinal cord. Regulatory Peptide (Supplement) 1994; 1:S91–S92CrossRefGoogle Scholar
  75. 75.
    Gazzaley AH, Weiland NG, McEwen BS, Morrison JH. Differential regulation of NMDAR1 mRNA and protein by estradiol in the rat hippocampus. J Neurosci 1996; 16:6830–6838PubMedGoogle Scholar
  76. 76.
    Popov VI, Bocharova LS, Bragin AG. Repeated changes of dendritic morphology in the hippocampus of ground squirrels in the course of hibernation. Neuroscience 1992; 48:45–51PubMedCrossRefGoogle Scholar
  77. 77.
    Wooley CS, Gould E, McEwen BS. Exposure to excess glucocorticoids alters dendritic morphology of adult hippocampal pyramidal neurons. Brain Res 1990; 531:225–231CrossRefGoogle Scholar
  78. 78.
    Watanabe Y, Gould E, McEwen BS. Stress induces atrophy of apical dendrites of hippocampal CA3 pyramidal neurons. Brain Res 1992; 588:341–345PubMedCrossRefGoogle Scholar
  79. 79.
    Lindvall O, Kokaia Z, Bengzon J, Elmer E, Kokaia M. Neurotrophins and brain insults. Trends Neurosci 1994; 17:490–496PubMedCrossRefGoogle Scholar
  80. 80.
    Zafra F, Lindholm D, Castren E, Hartikka J, Thoenen H. Regulation of brain-derived neurotrophic factor and nerve growth factor mRNA in primary cultures of hippocampal neurones and astrocytes. J Neurosci 1992; 12:4793–4799PubMedGoogle Scholar
  81. 81.
    Smith MA. The role of brain-derived neurotrophic factor in the central effects of stress. In: Levy A, Grauer E, Ben-Nathan D, de Kloet E R (eds) New frontiers in Stress Research. Modulation of Brain Function, Harwood Academic Publishers, The Netherlands, 1998; pp. 53–57Google Scholar
  82. 82.
    Smith MA, Makino S, Kvetnansky R, Post RM. Stress and glucocorticoid affect the expression of brain-derived neurotrophic factor and neurotrophin-3 mRNA levels in the hippocampus. J Neurosci 1995; 15:1768–1777PubMedGoogle Scholar
  83. 83.
    Sofroniew MV, Cooper JD, Svendsen CN, Crossman P, Ip NY, Lindsay RM, Zafra F, Lindholm D. Atrophy but not death of adult septal cholinergic neurones after ablation of target capacity to produce mRNAs for NGF, BDNF and NT3. J Neurosci 1993; 13:5263–5276PubMedGoogle Scholar
  84. 84.
    Nibuya M, Morinobu S, Duman RS. Regulation of BDNF and trkB in rat brain by chronic electroconvulsive seizures and antidepressant drug treatments. J Neurosci 1995; 15:7539–7547PubMedGoogle Scholar
  85. 85.
    Smith MA, Makino S, Kim S-Y, Kvetnansky R. Stress increases brain-derived neurotrophic factor mRNA in the hypothalamus and pituitary. Endocrinology 1995; 136:3743–3750PubMedCrossRefGoogle Scholar
  86. 86.
    Bremner JD, Scott TM, Delancy RC, Southwick SM, Mason JW, Johnson DR, Innis RB, McCarthy G, Charney DS. Deficits in short-term memory in posttraumatic stress disorder. Am J Psychiat 1993; 150:1015–1019PubMedGoogle Scholar
  87. 87.
    Diamond DM, Fleshner M, Ingersoll N, Rose GM. Psychological stress impairs spatial memory: relevance to electrophysiological studies of hippocampal function. Behav Neurosci 1996; 110:661–672PubMedCrossRefGoogle Scholar
  88. 88.
    Diamond DM, Ingersoll N, Branch BJ, Mesches MH, Coleman-Mesches K, Fleshner M. Stress impairs cognitive and electrophysiological measures of hippocampal function. In: Levy A, Grauer E, Ben-Nathan D, de Kloet ER (eds) New frontiers in Stress Research. Modulation of Brain Function, Harwood Academic Publishers, The Netherlands, 1998; pp. 117–126Google Scholar
  89. 89.
    Cahill L, Prins B, Weber M, McHaugh JL. b-adrenergic activation and memory for emotional events. Nature 1994; 371:702–704PubMedCrossRefGoogle Scholar
  90. 90.
    Kalimi M, Shafagoj Y, Loria R, Padgett D, Regelson W. Anti-glucocorticoid effects of dehydroepiandrosterone (DHEA). Mol Cell Biochem 1994; 131:99–104PubMedCrossRefGoogle Scholar
  91. 91.
    Diamond DM, Branch BJ, Coleman-Mesches K, Mesches HM, Fleshner M. DHEAS enhances spatial memory and hippocampal primed burst potentiation. Soc Neurosci Abstr 1996; 22:140Google Scholar
  92. 92.
    Diamond DM, Branch BJ, Fleshner M. The neurosteroid dehydroepiandrosterone sulfate (DHEAS) enhances hippocampal primed burst, but not long-term potentiation. Neurosci Lett 1996; 202:204–208PubMedCrossRefGoogle Scholar
  93. 93.
    Rasmussen AF, March JT, Brill NQ. Increased susceptibility to herpes simplex in mice subjected to avoidance-learning stress or restrain. Proc Soc Exp Biol Med 1957; 96:183–189PubMedGoogle Scholar
  94. 94.
    Feng N, Pagniano R, Tovar CA, Bonneaue RH, Glasser R, Sheridan JF. The effect of restraint stress on the kinetics, magnitude, and isotype of the humoral immune response to influenza virus infection. Brain Behav Immun 1991; 5:370–382PubMedCrossRefGoogle Scholar
  95. 95.
    Herman JP, Adams D, Prewitt C. Regulatory changes in neuroendocrine stress-integrative circuitry produced by a variable stress paradigm. Neuroendocrinology 1995; 61(2):180–190PubMedCrossRefGoogle Scholar
  96. 96.
    Ben-Nathan D, Lustig S, Daneberg H. Stress-induced neuroinvasiveness of a neurovirulent non invasive Sindbis virus in cold or isolation subjected mice. Life Sci 1991; 48:1493–1500PubMedCrossRefGoogle Scholar
  97. 97.
    Ben-Nathan D, Kobiler D, Loria RM, Lustig S. Stress-induced central nervous system penetration by non-invasive attenuated encephalitis viruses. In: Levy A, Grauer E, Ben-Nathan D, de Kloet ER (eds) New frontiers in Stress Research. Modulation of Brain Function, Harwood Academic Publishers, The Netherlands, 1998; pp. 277–2283Google Scholar
  98. 98.
    Friedman SB, Glasgow LA, Ader R. Differential susceptibility to viral agent in mice housed alone or in group. Psychosom Med 1970; 32:285–299PubMedGoogle Scholar
  99. 99.
    Sheridan JF, Dobbs C, Brown D, Swilling B. Psychoneuroimmunology: Stress effects on pathogenesis and immunity during infection. Clin Microbiol Rev 1994; 7:202–212Google Scholar
  100. 100.
    Sharp FR, Sagar SM, Hicks K, Lowenstein D, Hisanaga K. c-fos mRNA, Fos, and Fos-related antigen induction by hypertonic saline and stress. J Neurosci 1991; 11(8):2321–2331PubMedGoogle Scholar
  101. 101.
    Cohen S, Williamson GM. Stress and infectious disease in human. Psychol Bull 1991; 109:5–24PubMedCrossRefGoogle Scholar
  102. 102.
    Dantzer R, Kelley KW. Stress and immunity: An integrated view of the relationships between the brain and immune system. Life Sci 1989; 44:1995–2008PubMedCrossRefGoogle Scholar
  103. 103.
    Angel C. Starvation, stress and the blood-brain barrier. Dis Nerv Syst 1969; 30:94–97PubMedGoogle Scholar
  104. 104.
    Sharma HS, Westman J, Navarro JC, Dey PK, Nyberg F. Probable involvement of serotonin in the increased permeability of the blood-brain barrier by forced swimming. An experimental study using Evans blue and 131I-sodium tracers in the rat. Behav Brain Res 1995 Dec 14; 72(1–2):189–196PubMedCrossRefGoogle Scholar
  105. 105.
    Sharma HS. Methods to produce hyperthermia-induced brain dysfunction. Prog Brain Res 2007; 162:173–199. ReviewGoogle Scholar
  106. 106.
    Sharma HS. Interaction between amino acid neurotransmitters and opioid receptors in hyperthermia-induced brain pathology. Prog Brain Res 2007; 162:295–317. ReviewGoogle Scholar
  107. 107.
    Sharma HS, Sharma A. Nanoparticles aggravate heat stress induced cognitive deficits, blood-brain barrier disruption, edema formation and brain pathology. Prog Brain Res 2007; 162:245–273. ReviewGoogle Scholar
  108. 108.
    Sharma HS. Nanoneuroscience: emerging concepts on nanoneurotoxicity and nanoneuroprotection. Nanomedicine 2007 Dec; 2(6):753–758. ReviewGoogle Scholar
  109. 109.
    Sharma HS. Post-traumatic application of brain-derived neurotrophic factor and glia-derived neurotrophic factor on the rat spinal cord enhances neuroprotection and improves motor function. Acta Neurochir Suppl 2006; 96:329–334PubMedCrossRefGoogle Scholar
  110. 110.
    Sharma HS. Neurobiology of hyperthermia. Prog Brain Res 2007; 162:1–523, Elsevier, AmsterdamGoogle Scholar
  111. 111.
    Sharma HS, Sharma A. Antibodies As Promising Novel Neuroprotective Agents in the Central Nervous System Injuries. Central Nervous System Agents in Medicinal Chemistry (Formerly Current Medicinal, Vol. 8, No. 3, Sept 2008, pp. 143–169(27). DOI: 10.2174/187152408785699640Google Scholar
  112. 112.
    Sharma HS, Dey PK. Influence of heat and immobilization stressors on the permeability of blood-brain and blood-CSF barriers. Indian J Physiol Pharmacol 22, Supplement II, 1978; 59–60Google Scholar
  113. 113.
    Sapolsky RM, Zola-Morgan S, Squire LR. Inhibition of glucocorticoid secretion by the hippocampal formation in the primate. J Neurosci 1991; 11(12):3695–3704PubMedGoogle Scholar
  114. 114.
    Karst H, Wadman WJ, Joëls M. Corticosteroid receptor-dependent modulation of calcium currents in rat hippocampal CA1 neurons. Brain Res 1994; 649:234–242PubMedCrossRefGoogle Scholar
  115. 115.
    Chaouloff F. Physiopharmacological interactions between stress hormones and central serotonergic systems. Brain Res Rev 1993; 18(1):1–32PubMedCrossRefGoogle Scholar
  116. 116.
    Porsolt RD, Bertin A, Jalfre M. Behavioral despair in mice: a primary screening test for antidepressants. Arch Int Pharmacodyn Ther 1977; 229(2):327–336PubMedGoogle Scholar
  117. 117.
    Porsolt RD, Bertin A, Blavet N, Deniel M, Jalfre M. Immobility induced by forced swimming in rats: effects of agents which modify central catecholamine and serotonin activity. Eur J Pharmacol 1979; 57(2–3):201–210PubMedCrossRefGoogle Scholar
  118. 118.
    Kofman O, Levin U, Alpert C. Lithium attenuates hypokinesia induced by immobilization stress in rats. Prog Neuropsychopharmacol Biol Psychiatry 1995; 19(6):1081–1090PubMedCrossRefGoogle Scholar
  119. 119.
    Miyazato H, Skinner RD, Garcia-Rill E. Locus coeruleus involvement in the effects of immobilization stress on the p13 midlatency auditory evoked potential in the rat. Prog Neuropsychopharmacol Biol Psychiatry 2000; 24(7):1177–1201PubMedCrossRefGoogle Scholar
  120. 120.
    Belova TI, Jonsson G. Blood-brain barrier permeability and immobilization stress. Acta Physiol Scand 1982; 116:21–29PubMedCrossRefGoogle Scholar
  121. 121.
    Dvorská I, Brust P, Hrbas P, Rühle HJ, Barth T, Ermisch A. On the blood-brain barrier to peptides: effects of immobilization stress on regional blood supply and accumulation of labelled peptides in the rat brain. Endocr Regul 1992; 26(2):77–82PubMedGoogle Scholar
  122. 122.
    Esposito P, Gheorghe D, Kandere K, Pang X, Conally R, Jacobson S, Theoharides TC. Acute stress increase permeability of the blood-brain barrier through activation of mast cells. Brain Res 2001; 888:117–127PubMedCrossRefGoogle Scholar
  123. 123.
    Esposito P, Chandler N, Kandere K, Basu S, Jacobson S, Connolly R, Tutor D, Theoharides TC. Corticotropin-releasing hormone and brain mast cells regulate blood-brain barrier permeability by acute stress. J Pharmacol Exp Thera 2002; 303:1061–1066CrossRefGoogle Scholar
  124. 124.
    Ohata M, Fredericks WR, Sundaram U, Rapoport SI. Effects of immobilization stress on regional cerebral blood flow in the conscious rat. J Cereb Blood Flow Metab 1981; 1(2):187–194PubMedCrossRefGoogle Scholar
  125. 125.
    Ohata M, Takei H, Fredericks WR, Rapoport SI. Effects of immobilization stress on cerebral blood flow and cerebrovascular permeability in spontaneously hypertensive rats. J Cereb Blood Flow Metab 1982; 2(3):373–379PubMedCrossRefGoogle Scholar
  126. 126.
    Sharma HS, Dey PK. Increased permeability of blood-brain barrier (BBB) in stress: Blockade by p-CPA pretreatment. Indian J Physiol Pharmacol 1980; 24(Suppl I): 423–424Google Scholar
  127. 127.
    Lalonde R. Acquired immobility response in weaver mutant mice. Exp Neurol 1986; 94(3):808–811PubMedCrossRefGoogle Scholar
  128. 128.
    Sharma HS, Cervós-Navarro J, Dey PK. Increased blood-brain barrier permeability following acute short-term forced-swimming exercise in conscious normotensive young rats. Neurosci Res 1991; 10:211–221PubMedCrossRefGoogle Scholar
  129. 129.
    Miller WR, Seligman EP. Learned helplessness, depression and the perception of reinforcement. Behav Res Ther 1976; 14:7–17PubMedCrossRefGoogle Scholar
  130. 130.
    Maier SF, Watkins LR, Fleshner M. Psychoneuroimmunology: the interface between behaviour, brain and immunity. Amer Psych 1994; 49:1001–1018CrossRefGoogle Scholar
  131. 131.
    Van de Kar LD, Piechowski RA, Rittenhouse PA, Gray TS. Amygdaloid lesions: differential effect on conditioned stress and immobilization-induced increases in corticosterone and renin secretion. Neuroendocrinology 1991; 54(2):89–95PubMedCrossRefGoogle Scholar
  132. 132.
    Petty F, Kramer G, Wilson L, Jordan S. In vivo serotonin release and learned helplessness. Psychiatry Res 1994; 52:285–293PubMedCrossRefGoogle Scholar
  133. 133.
    Kupfer DJ. REM latency: a psychobiological marker for primary depressive disease. Biol Psychiatry 1976; 11: 159–174PubMedGoogle Scholar
  134. 134.
    Kupfer DJ, Spiker DG, Coble PA, Shaw DH. Electroencephalographic sleep recordings and depression in the elderly. J Am Geriatr Soc 1978 Feb; 26(2):53–57PubMedGoogle Scholar
  135. 135.
    Rotenberg VS, Boucsein W Adaptive versus maladaptive emotional tension. Genetic, Social and General Psychology Monographs 1993; 119:209–232Google Scholar
  136. 136.
    Maloney KJ, Mainville L, Jones BE. Differential c-Fos expression in cholinergic, monoaminergic, and GABAergic cell groups of the pontomesencephalic tegmentum after paradoxical sleep deprivation and recovery. J Neurosci 1999; 19(8):3057–3072PubMedGoogle Scholar
  137. 137.
    Maloney KJ, Mainville L, Jones BE. c-Fos expression in GABAergic, serotonergic, and other neurons of the pontomedullary reticular formation and raphe after paradoxical sleep deprivation and recovery. J Neurosci 2000; 20(12):4669–4679PubMedGoogle Scholar
  138. 138.
    Mendelson WB. The flower pot technique of rapid eye movement (REM) sleep deprivation. Pharmacol Biochem Behav 1974; 2:553–556PubMedCrossRefGoogle Scholar
  139. 139.
    Centers for Disease Control and Prevention (CDC). Heat-related deaths – United States, 1999–2003. MMWR Morb Mortal Wkly Rep. 2006 Jul 28; 55(29):796–798Google Scholar
  140. 140.
    Department of Health. Heatwave—plan for England—protecting health and reducing harm from extreme heat and heatwaves. London: DoH, 2004. (published 2004, superseded by 2005 edition; last accessed 10 Aug 2006)
  141. 141.
    Keatinge WR, Donaldson GC. The impact of global warming on health and mortality. South Med J 2004 Nov; 97(11):1093–1099. ReviewGoogle Scholar
  142. 142.
    Smoyer KE, Rainham DG, Hewko JN. Heat-stress-related mortality in five cities in Southern Ontario: 1980–1996. Int J Biometeorol 2000 Nov; 44(4):190–197PubMedCrossRefGoogle Scholar
  143. 143.
    Sharma HS. Heat-related deaths are largely due to brain damage. Indian J Med Res 2005 May; 121(5):621–623PubMedGoogle Scholar
  144. 144.
    Sharma HS. Hyperthermia influences excitatory and inhibitory amino acid neurotransmitters in the central nervous system. An experimental study in the rat using behavioural, biochemical, pharmacological, and morphological approaches. J Neural Transm 2006 Apr; 113(4):497–519PubMedCrossRefGoogle Scholar
  145. 145.
    Knochel JP. Environmental heat illness. An eclectic review. Arch Intern Med 1974 May; 133(5):841–864PubMedCrossRefGoogle Scholar
  146. 146.
    Centers for Disease Control and Prevention (CDC). Heat-related deaths – Los Angeles County, California, 1999–2000, and United States, 1979–1998. MMWR Morb Mortal Wkly Rep. 2001 Jul 27; 50(29):623–626Google Scholar
  147. 147.
    Garssen J, Harmsen C, de Beer J. The effect of the Summer 2003 heat wave on mortality in the Netherlands. Euro Surveill 2005 Jul; 10(7):165–168PubMedGoogle Scholar
  148. 148.
    Kunst AE, Looman CW, Mackenbach JP. Outdoor air temperature and mortality in The Netherlands: a time-series analysis. Am J Epidemiol 1993 Feb 1; 137(3):331–341PubMedGoogle Scholar
  149. 149.
    Bouchama A, Knochel JP. Heat stroke. N Engl J Med. 2002 Jun 20; 346(25):1978–1988. ReviewGoogle Scholar
  150. 150.
    Sharma HS, Hoopes PJ. Hyperthermia induced pathophysiology of the central nervous system. Int J Hypertherm 2003; 19:325–354CrossRefGoogle Scholar
  151. 151.
    Sharma HS, Cervos-Navarro J. Brain oedema and cellular changes induced by acute heat stress in young rats. Acta Neurochir Suppl (Wien) 1990; 51:383–386Google Scholar
  152. 152.
    Sharma HS. Nanoneuroscience: nanoneurotoxicity and nanoneuroprotection. J Nanosci Nanotechnol 2009; 9:4992–4995PubMedCrossRefGoogle Scholar
  153. 153.
    Sharma HS, Ali SF, Tian ZR, Hussain SM, Schlager JJ, Sjöquist P-O, Sharma A, Muresanu DF. Chronic treatment with nanoparticles exacerbate hyperthermia induced blood-brain barrier breakdown, cognitive dysfunction and brain pathology in the rat. Neuroprotective Effects of Nanowired-Antioxidant Compound H-290/51. J Nanosci Nanotechnol 2009; 9:5073–5090PubMedCrossRefGoogle Scholar
  154. 154.
    Sharma S, Ali SF, Hussain SM, Schlager JJ, Sharma A. Influence of engineered nanoparticles from metals on the blood-brain barrier permeability, cerebral blood flow, brain edema and neurotoxicity. An experimental study in the rat and mice using biochemical and morphological approaches. J Nanosci Nanotechnol 2009; 9:5055–5072PubMedCrossRefGoogle Scholar
  155. 155.
    Sharma HS, Ali S, Tian ZR, Patnaik R, Patnaik S, Lek P, Sharma A, Lundstedt T. Nano-drug delivery and neuroprotection in spinal cord injury. J Nanosci Nanotechnol 2009; 9:5014–5037. ReviewGoogle Scholar
  156. 156.
    Sharma HS, Patnaik R, Sharma A, Sjöquist P-O, Lafuente, LV. Silicon Dioxide Nanoparticles (SiO2, 40–50 nm) Exacerbate pathophysiology of traumatic spinal cord injury and deteriorate functional outcome in the rat. An experimental study using pharmacological and morphological approaches. J Nanosci Nanotechnol 2009; 9:4970–4980PubMedCrossRefGoogle Scholar
  157. 157.
    Brown DM, Stone V, Findlay P, MacNee W, Donaldson K. Increased inflammation and intracellular calcium caused by ultrafine carbon black is independent of transition metals or other soluble components. Occup Environ Med 2000; 57:685–691. [PubMed]Google Scholar
  158. 158.
    Brown DM, Wilson MR, MacNee W, Stone V, Donaldson K. Size-dependent proinflammatory effects of ultrafine polystyrene particles: a role for surface area and oxidative stress in the enhanced activity of ultrafines. Toxicol Appl Pharmacol 2001; 175:191–199PubMedCrossRefGoogle Scholar
  159. 159.
    Derfus AM, Chan WCW, Bhatia SN. Probing the cytotoxicity of semiconductor quantum dots. Nano Lett 2004; 4(1):11–18CrossRefGoogle Scholar
  160. 160.
    Joo SH, Feitz AJ, Waite TD. Oxidative degradation of the carbothioate herbicide, molinate, using nanoscale zerovalent iron. Environ Sci Technol 2004; 38:2242–2247PubMedCrossRefGoogle Scholar
  161. 161.
    Li N, Sioutas C, Cho A, Schmitz D, Misra C, Sempf J, et al. Ultrafine particulate pollutants induce oxidative stress and mitochondrial damage. Environ Health Perspect 2003; 111:455–460PubMedCrossRefGoogle Scholar
  162. 162.
    Oberdörster E. Manufactured nanomaterials (fullerenes, C60) induce oxidative stress in brain of juvenile largemouth bass. Environ Health Perspect 2004; 112:1058–1062PubMedCrossRefGoogle Scholar
  163. 163.
    Sayes C, Fortner J, Guo W, Lyon D, Boyd AM, Ausman KD, et al. The differential cytotoxicity of water-soluble fullerenes. Nano Lett 2004; 4:1881–1887CrossRefGoogle Scholar
  164. 164.
    Shvedova AA, Kisin ER, Murray A, Kommineni C, Vallyathan V, Castranova V. Pro/antioxidant status in murine skin following topical exposure to cumene hydroperoxide throughout the ontogeny of skin cancer. Biochemistry (Mosc) 2004 Jan; 69(1):23–31CrossRefGoogle Scholar
  165. 165.
    Shvedova AA, Kisin ER, Mercer R, Murray AR, Johnson VJ, Potapovich AI, Tyurina YY, Gorelik O, Arepalli S, Schwegler-Berry D, Hubbs AF, Antonini J, Evans DE, Ku BK, Ramsey D, Maynard A, Kagan VE, Castranova V, Baron P. Unusual inflammatory and fibrogenic pulmonary responses to single-walled carbon nanotubes in mice. Am J Physiol Lung Cell Mol Physiol 2005 Nov; 289(5):L698–L708PubMedCrossRefGoogle Scholar
  166. 166.
    Sharma HS, Sjöquist PO, Ali SF. Drugs of abuse-induced hyperthermia, blood-brain barrier dysfunction and neurotoxicity: neuroprotective effects of a new antioxidant compound H-290/51. Curr Pharm Des 2007; 13(18):1903–1923. ReviewGoogle Scholar
  167. 167.
    Sharma HS, Sjoquist PO, Alm P. A new antioxidant compound H-290151 attenuates spinal cord injury induced expression of constitutive and inducible isoforms of nitric oxide synthase and edema formation in the rat. Acta Neurochir Suppl 2003; 86:415–420PubMedCrossRefGoogle Scholar
  168. 168.
    Sharma HS, Gordh T, Wiklund L, Mohanty S, Sjoquist PO. Spinal cord injury induced heat shock protein expression is reduced by an antioxidant compound H-290/51. An experimental study using light and electron microscopy in the rat. J Neural Transm 2006 Apr; 113(4):521–536PubMedCrossRefGoogle Scholar
  169. 169.
    Jordan A, Scholz R, Maier-Hauff K, van Landeghem FK, Waldoefner N, Teichgraeber U, Pinkernelle J, Bruhn H, Neumann F, Thiesen B, von Deimling A, Felix R. The effect of thermotherapy using magnetic nanoparticles on rat malignant glioma. J Neurooncol 2006 May; 78(1):7–14PubMedCrossRefGoogle Scholar
  170. 170.
    Plotkin M, Gneveckow U, Meier-Hauff K, Amthauer H, Feussner A, Denecke T, Gutberlet M, Jordan A, Felix R, Wust P. 18F-FET PET for planning of thermotherapy using magnetic nanoparticles in recurrent glioblastoma. Int J Hyperthermia 2006 Jun; 22(4):319–325PubMedCrossRefGoogle Scholar
  171. 171.
    Inoue K, Takano H, Yanagisawa R, Hirano S, Sakurai M, Shimada A, Yoshikawa T. Effects of airway exposure to nanoparticles on lung inflammation induced by bacterial endotoxin in mice. Environ Health Perspect 2006 Sep; 114(9):1325–1330PubMedCrossRefGoogle Scholar
  172. 172.
    Sharma H S, Sjöquist P-O, Westman J. Pathophysiology of the blood-spinal cord barrier in spinal cord injury. Influence of a new antioxidant compound H-290/51. In: Kobiler D, Lustig S, Shapra S (eds) Blood-Brain Barrier. Drug Delivery and Brain Pathology, Kluwer Academic/Plenum Publishers, New York, 2001; pp. 401–416CrossRefGoogle Scholar
  173. 173.
    MacNee W, Donaldson K. How can ultrafine particles be responsible for increased mortality? Monaldi Arch Chest Dis 2000 Apr; 55(2):135–139. ReviewGoogle Scholar
  174. 174.
    Sharma HS, Olsson Y, Nyberg F. Influence of dynorphin A antibodies on the formation of edema and cell changes in spinal cord trauma. Prog Brain Res 1995; 104:401–416. ReviewPubMedCrossRefGoogle Scholar
  175. 175.
    Sharma HS, Westman J, Olsson Y, Alm P. Involvement of nitric oxide in acute spinal cord injury: an immunocytochemical study using light and electron microscopy in the rat. Neurosci Res 1996 Mar; 24(4):373–384PubMedCrossRefGoogle Scholar
  176. 176.
    Faden AI. Opioid and nonopioid mechanisms may contribute to dynorphin’s pathophysiological actions in spinal cord injury. Ann Neurol 1990 Jan; 27(1):67–74PubMedCrossRefGoogle Scholar
  177. 177.
    Sharma HS, Westman J, Nyberg F. Topical application of 5-HT antibodies reduces edema and cell changes following trauma of the rat spinal cord. Acta Neurochir Suppl 1997; 70:155–158PubMedGoogle Scholar
  178. 178.
    Sharma HS, Patnaik R, Patnaik S, Mohanty S, Sharma A, Vannemreddy P. Antibodies to serotonin attenuate closed head injury induced blood brain barrier disruption and brain pathology. Ann NY Acad Sci 2007 Dec; 1122:295–312PubMedCrossRefGoogle Scholar
  179. 179.
    Sharma HS, Winkler T, Stålberg E, Gordh T, Alm P, Westman J. Topical application of TNF-alpha antiserum attenuates spinal cord trauma induced edema formation, microvascular permeability disturbances and cell injury in the rat. Acta Neurochir Suppl 2003; 86:407–413PubMedCrossRefGoogle Scholar
  180. 180.
    Wahl M, Unterberg A, Baethmann A, Schilling L. Mediators of blood-brain barrier dysfunction and formation of vasogenic brain edema. J Cereb Blood Flow Metab 1988 Oct; 8(5):621–634. ReviewGoogle Scholar
  181. 181.
    Olsson Y, Sharma HS, Pettersson CA. Effects of p-chlorophenylalanine on microvascular permeability changes in spinal cord trauma. An experimental study in the rat using 131I-sodium and lanthanum tracers. Acta Neuropathol 1990; 79(6):595–603PubMedCrossRefGoogle Scholar
  182. 182.
    Sharma HS, Westman J, Olsson Y, Johansson O, Dey PK. Increased 5-hydroxytryptamine immunoreactivity in traumatized spinal cord. An experimental study in the rat. Acta Neuropathol 1990; 80(1):12–17PubMedCrossRefGoogle Scholar
  183. 183.
    Sharma HS, Olsson Y. Edema formation and cellular alterations following spinal cord injury in the rat and their modification with p-chlorophenylalanine. Acta Neuropathol 1990; 79(6):604–610PubMedCrossRefGoogle Scholar
  184. 184.
    Sharma HS, Olsson Y, Cervós-Navarro J. p-Chlorophenylalanine, a serotonin synthesis inhibitor, reduces the response of glial fibrillary acidic protein induced by trauma to the spinal cord. An immunohistochemical investigation in the rat. Acta Neuropathol 1993; 86(5):422–427PubMedCrossRefGoogle Scholar
  185. 185.
    Sharma HS Pathophysiology of the blood-spinal cord barrier in traumatic injury. In: Sharma HS, Westman J (eds) The Blood-Spinal Cord and Brain Barriers in Health and Disease, Elsevier Academic Press, San Diego, 2004; pp. 437–518Google Scholar
  186. 186.
    Sharma HS, Alm P, Westman J. Nitric oxide and carbon monoxide in the brain pathology of heat stress. Prog Brain Res 1998; 115:297–333. ReviewGoogle Scholar
  187. 187.
    Sharma HS, Nyberg F, Thörnwall M, Olsson Y. Met-enkephalin-Arg6-Phe7 in spinal cord and brain following traumatic injury to the spinal cord: influence of p-chlorophenylalanine. An experimental study in the rat using radioimmunoassay technique. Neuropharmacology 1993 Jul; 32(7):711–717PubMedCrossRefGoogle Scholar
  188. 188.
    Sharma HS, Olsson Y, Westman J. A serotonin synthesis inhibitor, p-chlorophenylalanine reduces the heat shock protein response following trauma to the spinal cord: an immunohistochemical and ultrastructural study in the rat. Neurosci Res 1995 Jan; 21(3):241–249PubMedCrossRefGoogle Scholar
  189. 189.
    Sharma HS, Olsson Y, Nyberg F, Dey PK. Prostaglandins modulate alterations of microvascular permeability, blood flow, edema and serotonin levels following spinal cord injury: an experimental study in the rat. Neuroscience 1993 Nov; 57(2):443–449PubMedCrossRefGoogle Scholar
  190. 190.
    Winkler T, Sharma HS, Stålberg E, Olsson Y. Indomethacin, an inhibitor of prostaglandin synthesis attenuates alteration in spinal cord evoked potentials and edema formation after trauma to the spinal cord: an experimental study in the rat. Neuroscience 1993 Feb; 52(4):1057–1067PubMedCrossRefGoogle Scholar
  191. 191.
    Sharma HS, Olsson Y, Cervós-Navarro J. Early perifocal cell changes and edema in traumatic injury of the spinal cord are reduced by indomethacin, an inhibitor of prostaglandin synthesis. Experimental study in the rat. Acta Neuropathol 1993; 85(2):145–153PubMedCrossRefGoogle Scholar
  192. 192.
    Sharma HS, Westman J. Prostaglandins modulate constitutive isoform of heat shock protein (72 kD) response following trauma to the rat spinal cord. Acta Neurochir Suppl 1997; 70:134–137PubMedGoogle Scholar
  193. 193.
    Ray SK, Banik NL. Calpain and its involvement in the pathophysiology of CNS injuries and diseases: therapeutic potential of calpain inhibitors for prevention of neurodegeneration. Curr Drug Targets CNS Neurol Disord 2003 Jun; 2(3):173–189. ReviewGoogle Scholar
  194. 194.
    Sharma HS, Drieu K, Alm P, Westman J. Role of nitric oxide in blood-brain barrier permeability, brain edema and cell damage following hyperthermic brain injury. An experimental study using EGB-761 and Gingkolide B pretreatment in the rat. Acta Neurochir Suppl 2000; 76:81–86PubMedGoogle Scholar
  195. 195.
    Sharma HS, Drieu K, Westman J. Antioxidant compounds EGB-761 and BN-52021 attenuate brain edema formation and hemeoxygenase expression following hyperthermic brain injury in the rat. Acta Neurochir Suppl 2003; 86:313–319PubMedCrossRefGoogle Scholar
  196. 196.
    Olesen SP. An electrophysiological study of microvascular permeability and its modulation by chemical mediators. Acta Physiol Scand Suppl 1989; 579:1–28PubMedGoogle Scholar
  197. 197.
    Kiyatkin EA, Sharma HS. Permeability of the blood-brain barrier depends on brain temperature. Neuroscience 2009 Jul 7; 161(3):926–939. Epub 2009 Apr 9Google Scholar
  198. 198.
    Sharma HS, Kiyatkin EA. Rapid morphological brain abnormalities during acute methamphetamine intoxication in the rat: an experimental study using light and electron microscopy. J Chem Neuroanat 2009 Jan; 37(1):18–32. Epub 2008 Aug 19Google Scholar
  199. 199.
    Kiyatkin EA, Brown PL, Sharma HS. Brain edema and breakdown of the blood-brain barrier during methamphetamine intoxication: critical role of brain hyperthermia. Eur J Neurosci 2007 Sep; 26(5):1242–1253PubMedCrossRefGoogle Scholar
  200. 200.
    Sharma HS, Ali SF. Alterations in blood-brain barrier function by morphine and methamphetamine. Ann NY Acad Sci 2006 Aug; 1074:198–224PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  1. 1.Laboratory of Cerebrovascular Research, Department of Surgical SciencesAnesthesiology & Intensive Care Medicine University Hospital, Uppsala UniversityUppsalaSweden
  2. 2.Anesthesiology & Intensive Care Medicine, Dept. of Surgical SciencesUniversity Hospital, Uppsala UniversityUppsalaSweden

Personalised recommendations