Methods and apparatus for modifying properties of the bbb and cerebral circulation by using the neuroexcitatory and/or neuroinhibitory effects of odorants on nerves in the head

• US 20050266099A1
• Filed: 04/25/2003
• Published: 12/01/2005
• Est. Priority Date: 04/25/2002
• Status: Abandoned Application

• Current Assignee: BrainsGate Ltd.
• Original Assignee: BrainsGate Ltd.
• Inventors: Shalev, Alon
• Application Number:
  US10/512,780
• Publication Number:
  US 20050266099A1
• Time in Patent Office: Days
• US Class Current: 424/725
• CPC Class Codes: A61K 38/47 acting on glycosyl compounds (3.2), e.g. cellulases, lactases
• CPC Class Codes: A61K 41/0004 Homeopathy; Vitalisation; Resonance; Dynamisation, e.g. esoteric applications; Oxygenation of blood
• CPC Class Codes: A61K 49/00 Preparations for testing in vivo
• CPC Class Codes: A61K 9/0043 Nose
• CPC Class Codes: A61K 9/007 Pulmonary tract; Aromatherapy
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/08 Vasodilators for multiple indications

Abstract

A method for modifying a property of a brain of a patient includes presenting an odorant to an air passage of the patient, the odorant having been selected for presentation to the air passage because it is such as to increase conductance of molecules from a systemic blood circulation of the patient through a blood brain barrier (BBB) of the brain into brain tissue of the patient. The molecules are selected from the group consisting of: a pharmacological agent, a therapeutic agent, an endogenous agent, and an agent for facilitating a diagnostic procedure.

Claims

1. A method for modifying a property of a brain of a patient, comprising presenting an odorant to an air passage of the patient, the odorant having been selected for presentation to the air passage because it is such as to increase conductance of molecules between a systemic blood circulation of the patient and brain tissue of the patient, by way of a blood brain barrier (BBB) of the brain.

2. A method according to claim 1, comprising sensing a parameter of the patient and presenting the odorant responsive thereto.

3. A method according to claim 2, wherein the parameter includes an indication of a behavior of the patient, and wherein sensing the parameter comprises sensing the indication of the behavior of the patient.

4. A method according to claim 2, wherein the parameter is selected from the list consisting of:

a biochemical value of the patient and a physiological value of the patient, and wherein sensing the parameter comprises sensing the parameter selected from the list.

5. A method according to claim 4, wherein sensing the parameter selected from the list comprises sensing the parameter using a modality selected from the list consisting of:

CT, MRI, PET, SPECT, angiography, ophthalmoscopy, fluoroscopy, light microscopy, and oximetry.

6. A method according to claim 4, wherein sensing the parameter selected from the list comprises measuring a level of the molecules in the patient.

7. A method according to claim 6, wherein measuring the level of the molecules comprises sampling a body fluid of the patient selected from the list consisting of:

blood, plasma, serum, ascites fluid, and urine.

8. A method according to claim 1, wherein presenting the odorant to the air passage of the patient comprises presenting the odorant, the odorant having been selected for presentation to the air passage because it is such as to increase conductance of the molecules from the systemic blood circulation of the patient through the blood brain barrier (BBB) into brain tissue of the patient, the molecules being selected from the group consisting of:

an endogenous agent, a pharmacological agent, a therapeutic agent, and an agent for facilitating a diagnostic procedure.

9. A method according to claim 8, wherein presenting the odorant comprises presenting the odorant in a dosage determined to increase the conductance of the molecules.

10. A method according to claim 8, comprising administering the molecules for inhalation by the patient.

11. A method according to claim 8, comprising administering the molecules to the patient in a bolus.

12. A method according to claim 8, comprising administering the molecules to the patient in a generally continuous manner.

13. A method according to claim 8, comprising administering an agent capable of blocking a P-glycoprotein transporter from transporting the molecules from a target site in the brain tissue.

14. A method according to claim 8, comprising administering the molecules to the systemic blood circulation.

15. A method according to claim 14, wherein administering the molecules comprises administering the molecules mixed with the odorant.

16. A method according to claim 14, wherein administering the molecules comprises administering the molecules to the systemic blood circulation using a technique selected from the list consisting of:

per-oral administration intravenous administration, intra-arterial administration, intraperitoneal administration, subcutaneous administration, and intramuscular administration.

17. A method according to claim 8, wherein the molecules include the agent for facilitating a diagnostic procedure, and wherein presenting the odorant comprises presenting the odorant, the odorant being such as to increase the conductance of the agent for facilitating the diagnostic procedure.

18. A method according to claim 17, wherein the agent for facilitating a diagnostic procedure includes an imaging contrast agent, and wherein presenting the odorant comprises presenting the odorant, the odorant being such as to increase the conductance of the imaging contrast agent

19. A method according to claim 17, wherein the agent for facilitating a diagnostic procedure includes a radio-opaque material, and wherein presenting the odorant comprises presenting the odorant, the odorant being such as to increase the conductance of the radio-opaque material.

20. A method according to claim 17, wherein the agent for facilitating a diagnostic procedure includes an antibody, and wherein presenting the odorant comprises presenting the odorant, the odorant being such as to increase the conductance of the antibody.

21. A method according to claim 8, wherein presenting the odorant comprises selecting the molecules, the molecules being appropriate for treating a disorder of the central nervous system (CNS) of the patient.

22. A method according to claim 21, wherein the CNS disorder is selected from the list consisting of:

a brain tumor, epilepsy, Parkinson'"'"'s disease, Alzheimer'"'"'s disease, multiple sclerosis, schizophrenia, depression, stress, obesity, pain, and anxiety, and wherein selecting the molecules comprises selecting the molecules, the molecules being appropriate for treating the selected CNS disorder.

23. A method according to claim 8, comprising regulating a parameter of the odorant presentation.

24. A method according to claim 23, wherein regulating the parameter comprises regulating a parameter selected from the list consisting of:

relative concentrations of two or more ingredients of the odorant, a quantity of the odorant presented, a rate of presentation of the odorant, a pressure of the odorant at presentation, and a temperature of at least a portion of the odorant.

25. A method according to claim 23, comprising administering the molecules to the patient during a treatment session that is subsequent to regulating the parameter of the odorant presentation.

26. A method according to claim 23, comprising administering the molecules to the patient during a treatment session, and regulating the parameter of the odorant presentation during the same treatment session.

27. A method according to claim 23, wherein regulating the parameter of the odorant presentation comprises selecting the parameter from a predefined set of parameters for the odorant presentation.

28. A method according to claim 23, comprising sensing a parameter of the patient and regulating the parameter of the odorant presentation responsive thereto.

29. A method according to claim 28, wherein the parameter of the patient includes an indication of a behavior of the patient, and wherein sensing the parameter of the patient comprises sensing the indication of the behavior of the patient.

30. A method according to claim 28, wherein the parameter of the patient is selected from the list consisting of:

a biochemical value of the patient and a physiological value of the patient, and wherein sensing the parameter of the patient comprises sensing the parameter of the patient selected from the list.

31. A method according to claim 8, wherein the molecules include the therapeutic agent, and wherein presenting the odorant comprises presenting the odorant, the odorant being such as to increase the conductance of the therapeutic agent.

32. A method according to claim 31, wherein the therapeutic agent includes a neurological drug, and wherein presenting the odorant comprises presenting the odorant, the odorant being such as to increase the conductance of the neurological drug.

33. A method according to claim 31, wherein the therapeutic agent includes a protein, and wherein presenting the odorant comprises presenting the odorant, the odorant being such as to increase the conductance of the protein.

34. A method according to claim 31, wherein the therapeutic agent includes a polymer, and wherein presenting the odorant comprises presenting the odorant, the odorant being such as to increase the conductance of the polymer.

35. A method according to claim 31, wherein the therapeutic agent includes a viral vector, and wherein presenting the odorant comprises presenting the odorant, the odorant being such as to increase the conductance of the viral vector.

36. A method according to claim 31, wherein the therapeutic agent includes an anti-cancer drug, and wherein presenting the odorant comprises presenting the odorant, the odorant being such as to increase the conductance of the anti-cancer drug.

37. A method according to claim 31, wherein the therapeutic agent includes an agent from the list consisting of:

glatiramer acetate and interferon beta-1b, and wherein presenting the odorant comprises presenting the odorant, the odorant being such as to increase the conductance of the agent selected from the list.

38. A method according to claim 31, wherein the therapeutic agent includes an agent from the list consisting of:

an agent for DNA therapy and an agent for RNA therapy, and wherein presenting the odorant comprises presenting the odorant, the odorant being such as to increase the conductance of the agent selected from the list.

39. A method according to claim 38, wherein the therapeutic agent includes an agent from the list consisting of:

(a) an antisense molecule against type-1 insulin-like growth factor receptor, and (b) ADV-HSV-tk, and wherein presenting the odorant comprises presenting the odorant, the odorant being such as to increase the conductance of the agent selected from the list consisting of the antisense molecule and the ADV-HSV-tk.

40. A method according to claim 8, comprising administering the molecules in conjunction with presenting the odorant.

41. A method according to claim 40, wherein administering the molecules in conjunction with presenting the odorant comprises administering the molecules at a time determined with respect to a time of presenting the odorant.

42. A method according to claim 41, wherein administering the molecules comprises administering the molecules at least a predetermined time prior to presenting the odorant.

43. A method according to claim 41, wherein administering the molecules comprises administering the molecules at generally the same time as presenting the odorant.

44. A method according to claim 41, wherein administering the molecules comprises administering the molecules at least a predetermined time subsequent to presenting the odorant.

45. A method according to claim 8, wherein the molecules include the pharmacological agent, and wherein presenting the odorant comprises presenting the odorant, the odorant being such as to increase the conductance of the pharmacological agent.

46. A method according to claim 45, wherein the pharmacological agent includes a viral vector, and wherein presenting the odorant comprises presenting the odorant, the odorant being such as to increase the conductance of the viral vector.

47. A method according to claim 45, wherein the pharmacological agent includes an antibody, and wherein presenting the odorant comprises presenting the odorant, the odorant being such as to increase the conductance of the antibody.

48. A method according to claim 47, wherein the antibody is selected from the list consisting of:

a toxin-antibody complex, a radiolabeled antibody, and anti-HER2 mAb, and wherein presenting the odorant comprises presenting the odorant, the odorant being such as to increase the conductance of the selected antibody.

49. A method according to claim 47, wherein the antibody is selected from the list consisting of:

anti-b-amyloid antibody and anti-amyloid-precursor-protein antibody, and wherein presenting the odorant comprises presenting the odorant, the odorant being such as to increase the conductance of the selected antibody.

50. A method according to claim 8, wherein the molecules include the endogenous agent, and wherein presenting the odorant comprises presenting the odorant, the odorant being such as to increase the conductance of the endogenous agent.

51. A method according to claim 50, wherein the endogenous agent includes an endogenous agent substantially unmodified by artificial means, and wherein presenting the odorant comprises presenting the odorant, the odorant being such as to increase the conductance of the endogenous agent that is substantially unmodified by artificial means.

52. A method according to claim 50, wherein the endogenous agent includes an endogenous agent an aspect of which is modified by artificial means, and wherein presenting the odorant comprises presenting the odorant, the odorant being such as to increase the conductance of the endogenous agent the aspect of which is modified by artificial means.

53. A method according to claim 50, wherein the endogenous agent includes an enzyme, and wherein presenting the odorant comprises presenting the odorant, the odorant being such as to increase the conductance of the enzyme.

54. A method according to claim 53, wherein the enzyme includes hexosamimidase, and wherein presenting the odorant comprises presenting the odorant, the odorant being such as to increase the conductance of the hexosamimidase.

55. A method according to claim 8, comprising administering the molecules to a mucous membrane of the patient.

56. A method according to claim 55, wherein administering the molecules comprises administering the molecules to oral mucosa of the patient.

57. A method according to claim 55, wherein administering the molecules comprises administering the molecules to nasal mucosa of the patient.

58. A method according to claim 55, wherein administering the molecules comprises administering the molecules in combination with the odorant.

59. A method according to claim 55, wherein administering the molecules comprises administering the molecules separately from the odorant.

60. A method according to claim 1, wherein presenting the odorant to the air passage of the patient comprises presenting the odorant, the odorant having been selected for presentation to the air passage because it is such as to increase conductance of molecules from the brain tissue of the patient through the blood brain barrier (BBB) into the systemic blood circulation.

61. A method according to claim 60, comprising sensing a quantity of the molecules from a site outside of the brain of the patient, following initiation of presentation of the odorant.

62. A method according to claim 61, wherein sensing the quantity of the molecules comprises sensing using a modality selected from the list consisting of:

CT, MRI, PET, SPECT, angiography, ophthalmoscopy, fluoroscopy, light microscopy, and oximetry.

63. A method according to claim 61, wherein sensing the quantity of the molecules comprises sampling a fluid of the patient selected from the list consisting of:

blood, plasma, serum, ascites fluid, and urine.

64. A method according to claim 61, comprising determining a diagnostically-relevant parameter responsive to sensing the quantity of the molecules.

65. A method according to claim 60, comprising selecting a dosage of the odorant responsive to a disorder of the patient.

66. A method according to claim 65, wherein selecting the dosage of the odorant comprises determining a dosage of the odorant that increases conductance of the molecules, responsive to presentation of the odorant, to an extent sufficient to treat the disorder at least in part.

67. A method according to claim 65, wherein selecting the dosage comprises selecting the dosage responsive to the disorder of the patient, the disorder being selected from the list consisting of:

a brain tumor, epilepsy, Parkinson'"'"'s disease, Alzheimer'"'"'s disease, multiple sclerosis, schizophrenia, depression, stress, obesity, pain, and anxiety.

68. A method according to any one of claims 1, 8, or 60, comprising administering a hyperosmolarity-inducing agent to the patient at a dosage sufficient to augment an increase in conductance of the molecules caused by presentation of the odorant.

69. A method according to any one of claims 1, 8, or 60, comprising inducing a state of dehydration of the patient, of an extent sufficient to augment an increase in conductance of the molecules caused by presentation of the odorant.

70. A method according to any one of claims 1, 8, or 60, comprising administering an agent to the patient that modulates synthesis or metabolism of nitric-oxide (NO) in blood vessels of the brain, at a dosage sufficient to augment an increase in conductance of the molecules caused by presentation of the odorant.

86. A method according to any one of claims 1, 8, 60, 71, 73, 78, or 84, and comprising presenting in association with the odorant an analgesic in a dosage configured to reduce a sensation associated with the presenting of the odorant.

87. A method according to claim 86, wherein presenting the analgesic comprises topically presenting the analgesic at a site selected from the list consisting of:

a vicinity of one or more nerves in a nasal cavity of the patient, a vicinity of one or more nerves in an oral cavity of the patient, and a vicinity of one or more nerves innervating a face of the patient.

88. A method according to claim 86, wherein presenting the analgesic comprises topically presenting the analgesic in a vicinity of a sphenopalatine ganglion (SPG) of the patient.

89. A method according to claim 86, wherein presenting the analgesic comprises administering the analgesic for inhalation at generally the same time as the presenting of the odorant.

90. A method according to any one of claims 1, 8, 60, 71, 73, 78, or 84, wherein the air passage includes a nasal cavity of the patient, and wherein presenting the odorant comprises presenting the odorant to the nasal cavity.

91. A method according to any one of claims 1, 8, 60, 71, 73, 78, or 84, wherein the air passage includes a throat of the patient, and wherein presenting the odorant comprises presenting the odorant to the throat.

92. A method according to any one of claims 1, 8, 60, 71, 73, 78, or 84, wherein the odorant is selected from the list consisting of:

propionic acid, cyclohexanone, and amyl acetate, and wherein presenting the odorant comprises presenting the selected odorant.

93. A method according to any one of claims 1, 8, 60, 71, 73, 78, or 84, wherein the odorant is selected from the list consisting of:

acetic acid, citric acid, carbon dioxide, sodium chloride, and ammonia, and wherein presenting the odorant comprises presenting the selected odorant.

94. A method according to any one of claims 1, 8, 60, 71, 73, 78, or 84, wherein the odorant is selected from the list consisting of:

menthol, alcohol, nicotine, piperine, gingerol, zingerone, allyl isothiocyanate, cinnamaldehyde, cuminaldehyde, 2-propenyl/2-phenylethyl isothiocyanate, thymol, and eucalyptol, and wherein presenting the odorant comprises presenting the selected odorant.

95. A method according to any one of claims 1, 8, 60, 71, 73, 78, or 84, wherein presenting the odorant comprises presenting a capsule for placement within a mouth of the patient, the capsule being configured to dissolve upon contact with salivary liquids of the patient, whereupon the odorant is presented to the air passage.

96. A method according to any one of claims 1, 60, 71, 73, 78, or 84, comprising regulating a parameter of the odorant presentation.

97. A method according to claim 96, wherein regulating the parameter comprises regulating a parameter selected from the list consisting of:

relative concentrations of two or more ingredients of the odorant, a quantity of the odorant presented, a rate of presentation of the odorant, a pressure of the odorant at presentation, and a temperature of at least a portion of the odorant.

98. A method according to claim 96, wherein regulating the parameter of the odorant presentation comprises selecting the parameter from a predefined set of parameters for the odorant presentation.

99. A method according to claim 96, comprising sensing a parameter of the patient and regulating the parameter of the odorant presentation responsive thereto.

100. A method according to claim 99, wherein the parameter of the patient includes an indication of a behavior of the patient, and wherein sensing the parameter of the patient comprises sensing the indication of the behavior of the patient.

101. A method according to claim 99, wherein the parameter of the patient is selected from the list consisting of:

a biochemical value of the patient and a physiological value of the patient, and wherein sensing the parameter of the patient comprises sensing the parameter of the patient selected from the list.

71. A method for modifying a property of a brain of a patient during or following a stroke event, comprising presenting an odorant to an air passage of the patient, the odorant having been selected for presentation to the air passage because it is capable of inducing an increase in cerebral blood flow of the patient, so as to reduce a pathology associated with the stroke event.

72. A method according to claim 71, wherein presenting the odorant comprises presenting the odorant in a dosage determined to increase the cerebral blood flow.

102. A method according to any one of claims 71, 73, 78, or 84, comprising sensing a parameter of the patient and presenting the odorant responsive thereto.

103. A method according to claim 102, wherein the parameter includes an indication of a behavior of the patient, and wherein sensing the parameter comprises sensing the indication of the behavior of the patient.

104. A method according to claim 102, wherein the parameter is selected from the list consisting of:

a biochemical value of the patient and a physiological value of the patient, and wherein sensing the parameter comprises sensing the parameter selected from the list.

105. A method according to claim 104, wherein sensing the parameter selected from the list comprises sensing the parameter using a modality selected from the list consisting of:

CT, MRI, PET, SPECT, angiography, ophthalmoscopy, fluoroscopy, light microscopy, and oximetry.

106. A method according to claim 104, wherein sensing the parameter selected from the list comprises sampling a body fluid of the patient selected from the list consisting of:

blood, plasma, serum, ascites fluid, and urine.

73. A method for modifying a property of a brain of a patient who suffers from headache attacks, comprising presenting an odorant to an air passage of the patient, the odorant having been selected for presentation to the air passage because it is capable of modifying cerebral blood flow of the patient, so as to reduce a severity of a headache attack of the patient.

74. A method according to claim 73, wherein presenting the odorant comprises presenting the odorant in a dosage determined to modify the cerebral blood flow.

75. A method according to claim 73, wherein presenting the odorant comprises selecting the odorant, the odorant being capable of decreasing the cerebral blood flow, so as to reduce the severity of the headache attack.

76. A method according to claim 73, wherein the headache attack includes a migraine headache attack of the patient, and wherein presenting the odorant comprises presenting to the air passage an odorant that is capable of reducing the cerebral blood flow, so as to reduce the severity of the migraine headache attack.

77. A method according to claim 73, wherein the headache attack includes a cluster headache attack of the patient, and wherein presenting the odorant comprises presenting to the air passage an odorant that is capable of reducing the cerebral blood flow, so as to reduce the severity of the cluster headache attack.

78. A method for modifying a property of a brain of a patient who suffers from a disorder of the central nervous system (CNS), comprising presenting an odorant to an air passage of the patient, the odorant having been selected for presentation to the air passage because it is capable of modifying cerebral blood flow of the patient, so as to treat the CNS disorder.

79. A method according to claim 78, wherein presenting the odorant comprises presenting the odorant in a dosage determined to modify the cerebral blood flow.

80. A method according to claim 78, wherein the CNS disorder is selected from the list consisting of:

a brain tumor, epilepsy, Parkinson'"'"'s disease, Alzheimer'"'"'s disease, multiple sclerosis, schizophrenia, depression, stress, obesity, pain, and anxiety, and wherein presenting the odorant comprises presenting the odorant that is capable of modifying the cerebral blood flow, so as to treat the selected CNS disorder.

81. A method according to claim 78, wherein presenting the odorant comprises selecting the odorant, the odorant being capable of decreasing the cerebral blood flow.

82. A method according to claim 78, wherein presenting the odorant comprises selecting the odorant, the odorant being capable of increasing cerebral blood flow of the patient.

83. A method according to claim 82, wherein presenting the odorant comprises selecting the odorant, the odorant being capable of increasing cortical blood flow of the patient.

84. A method for modifying a property of a brain of a patient, comprising presenting an odorant to an air passage of the patient, the odorant having been selected for presentation to the air passage because it is such as to decrease conductance of molecules from a systemic blood circulation of the patient through a blood brain barrier (BBB) of the brain into brain tissue of the patient.

85. A method according to claim 84, wherein presenting the odorant comprises presenting the odorant in a dosage determined to decrease the conductance of the molecules.

107. Apparatus for modifying a property of a brain of a patient, comprising:

an odorant-storage vessel;

an odorant for storage within the odorant-storage vessel, the odorant being capable of increasing conductance of molecules from a systemic blood circulation of the patient through a blood brain barrier (BBB) of the brain into brain tissue of the patient, the molecules being selected from the group consisting of;

a pharmacological agent, a therapeutic agent, and an agent for facilitating a diagnostic procedure; and

an odorant-delivery element, adapted to present the odorant to an air passage of the patient.

108. Apparatus according to claim 107, wherein the odorant-storage vessel is adapted to store the odorant mixed with the molecules.

109. Apparatus according to claim 107, wherein the molecules include the therapeutic agent, and wherein the odorant is such as to increase the conductance of the therapeutic agent.

110. Apparatus according to claim 109, wherein the therapeutic agent includes a neurological drug, and wherein the odorant is such as to increase the conductance of the neurological drug.

111. Apparatus according to claim 107, wherein the molecules include the agent for facilitating a diagnostic procedure, and wherein the odorant is such as to increase the conductance of the agent for facilitating the diagnostic procedure.

112. Apparatus according to claim 111, wherein the agent for facilitating a diagnostic procedure includes a radio-opaque material, and wherein the odorant is such as to increase the conductance of the radio-opaque material.

113. Apparatus according to claim 107, wherein the odorant comprises an agent for facilitating treatment of a disorder of the central nervous system (CNS) of the patient.

114. Apparatus according to claim 113, wherein the CNS disorder is selected from the list consisting of:

a brain tumor, epilepsy, Parkinson'"'"'s disease, Alzheimer'"'"'s disease, multiple sclerosis, schizophrenia, depression, stress, obesity, pain, and anxiety, and wherein the odorant comprises an agent for facilitating treatment of the selected CNS disorder.

126. Apparatus according to any one of claims 107, 115, 116, 120, or 125, comprising an analgesic for storage within the odorant-storage vessel in a dosage configured to reduce a sensation associated with the presenting of the odorant, and wherein the odorant-delivery element is adapted to present the analgesic to the air passage in association with the odorant.

127. Apparatus according to any one of claims 107, 115, 116, 120, or 125, wherein the odorant-storage vessel in combination with the odorant-delivery element comprises an aqueous spray nasal inhaler.

128. Apparatus according to any one of claims 107, 115, 116, 120, or 125, wherein the odorant-storage vessel in combination with the odorant-delivery element comprises a metered dose nasal inhaler.

129. Apparatus according to any one of claims 107, 115, 116, 120, or 125, wherein the odorant-storage vessel in combination with the odorant-delivery element comprises an air-dilution olfactometer.

130. Apparatus according to any one of claims 107, 115, 116, 120, or 125, wherein the air passage includes a nasal cavity of the patient, and wherein the odorant-delivery element is adapted to present the odorant to the nasal cavity.

131. Apparatus according to any one of claims 107, 115, 116, 120, or 125, wherein the air passage includes a throat of the patient, and wherein the odorant-delivery element is adapted to present the odorant to the throat.

132. Apparatus according to any one of claims 107, 115, 116, 120, or 125, wherein the odorant comprises an agent selected from the list consisting of propionic acid, cyclohexanone, and amyl acetate.

133. Apparatus according to any one of claims 107, 115, 116, 120, or 125, wherein the odorant comprises an agent selected from the list consisting of:

acetic acid, citric acid, carbon dioxide, sodium chloride, and ammonia.

134. Apparatus according to any one of claims 107, 115, 116, 120, or 125, wherein the odorant comprises an agent selected from the list consisting of:

menthol, alcohol, nicotine, piperine, gingerol, zingerone, allyl isothiocyanate, cinnamaldehyde, cuminaldehyde, 2-propenyl/2-phenylethyl isothiocyanate, thymol, and eucalyptol.

135. Apparatus according to any one of claims 107, 115, 116, 120, or 125, wherein the odorant-storage vessel comprises a capsule for placement in a mouth of the patient, and wherein the odorant-delivery element comprises a portion of the capsule adapted to dissolve upon contact with salivary liquids of the patient, whereupon the odorant is presented to the air passage of the patient.

115. Apparatus for modifying a property of a brain of a patient during or following a stroke event, comprising:

an odorant-storage vessel;

an odorant, for storage within the odorant-storage vessel, the odorant being capable of inducing an increase in cerebral blood flow of the patient; and

an odorant-delivery element, adapted to present the odorant to an air passage of the patient, so as to reduce a pathology associated with the stroke event.

116. Apparatus for modifying a property of a brain of a patient who suffers from headache attacks, comprising:

an odorant-storage vessel;

an odorant, for storage within the odorant-storage vessel, the odorant being capable of modifying cerebral blood flow of the patient; and

an odorant-delivery element, configured to present the odorant to an air passage of the patient, so as to reduce a severity of a headache attack of the patient.

117. Apparatus according to claim 116, wherein the odorant is capable of decreasing the cerebral blood flow.

118. Apparatus according to claim 116, wherein the headache attack includes a migraine headache attack of the patient, and wherein the odorant is capable of reducing the severity of the migraine headache attack.

119. Apparatus according to claim 116, wherein the headache attack includes a cluster headache attack of the patient, and wherein the odorant is capable of reducing the severity of the cluster headache attack.

120. Apparatus for modifying a property of a brain of a patient who suffers from a disorder of the central nervous system (CNS), comprising:

an odorant-storage vessel;

an odorant for storage within the odorant-storage vessel, the odorant being capable of modifying cerebral blood flow of the patient; and

an odorant-delivery element, configured to present the odorant to an air passage of the patient, so as to treat the CNS disorder.

121. Apparatus according to claim 120, wherein the CNS disorder is selected from the list consisting of:

a brain tumor, epilepsy, Parkinson'"'"'s disease, Alzheimer'"'"'s disease, multiple sclerosis, schizophrenia, depression, stress, obesity, pain, and anxiety, and wherein the odorant comprises an agent for facilitating treatment of the selected CNS disorder.

122. Apparatus according to claim 120, wherein the odorant is capable of decreasing the cerebral blood flow.

123. Apparatus according to claim 120, wherein the odorant is capable of increasing the cerebral blood flow.

124. Apparatus according to claim 123, wherein the odorant is capable of increasing cortical blood flow of the patient.

125. Apparatus for modifying a property of a brain of a patient, comprising:

an odorant-storage vessel;

an odorant, for storage within the odorant-storage vessel, the odorant being capable of decreasing conductance of molecules from a systemic blood circulation of the patient through a blood brain barrier (BBB) of the brain into brain tissue of the patient; and

an odorant-delivery element, adapted to present the odorant to an air passage of the patient.