Effect of beta-hydroxybutyrate, a cerebral function improving agent, on cerebral hypoxia, anoxia and ischemia in mice and rats. 2001

M Suzuki, and M Suzuki, and K Sato, and S Dohi, and T Sato, and A Matsuura, and A Hiraide
Shimizu Research Center, Research and Development Division, Shimizu Pharmaceutical Co., Ltd., Shizuoka, Japan. motohisa-s@shimizu-pharm.co.jp

Although improving energy metabolism in ischemic brain has been accepted for the treatment of cerebrovascular diseases, administration of glucose, as an energy substrate, would aggravate ischemic brain damage via activating anaerobic glycolysis, which leads to lactate accumulation. Beta-hydroxybutyrate (BHB) is one of the ketone bodies that can be utilized as an energy source during starvation. The purpose of our study was to define the protective effects of BHB on brain damage induced by hypoxia, anoxia and ischemia. The isotonic solution of BHB administered 30 min before the induction of ischemia at doses over 50 mg x kg(-1) x h(-1) showed remarkable protective effects against hypoxia and anoxia. BHB administered immediately after a bilateral carotid artery ligation at a dose of 30 mg x kg(-1) x h(-1) significantly suppressed the elevation of cerebral water and sodium contents as well as maintaining high ATP and low lactate levels. In contrast, glycerin, a hypertonic agent, substantially reduced the water content but did not show any significant effect on other parameters. We demonstrated that BHB, unlike glycerin, when used as an energy substrate in ischemic brain, has protective effects on cerebral hypoxia, anoxia and ischemia-induced metabolic change.

UI MeSH Term Description Entries
D008297 Male Males
D009584 Nitrogen An element with the atomic symbol N, atomic number 7, and atomic weight [14.00643; 14.00728]. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells.
D011190 Potassium Cyanide A highly poisonous compound that is an inhibitor of many metabolic processes, but has been shown to be an especially potent inhibitor of heme enzymes and hemeproteins. It is used in many industrial processes. Potassium Cyanide (K(14)CN),Potassium Cyanide (K(C(15)N)),Cyanide, Potassium
D001794 Blood Pressure PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS. Systolic Pressure,Diastolic Pressure,Pulse Pressure,Pressure, Blood,Pressure, Diastolic,Pressure, Pulse,Pressure, Systolic,Pressures, Systolic
D001834 Body Water Fluids composed mainly of water found within the body. Water, Body
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D001929 Brain Edema Increased intracellular or extracellular fluid in brain tissue. Cytotoxic brain edema (swelling due to increased intracellular fluid) is indicative of a disturbance in cell metabolism, and is commonly associated with hypoxic or ischemic injuries (see HYPOXIA, BRAIN). An increase in extracellular fluid may be caused by increased brain capillary permeability (vasogenic edema), an osmotic gradient, local blockages in interstitial fluid pathways, or by obstruction of CSF flow (e.g., obstructive HYDROCEPHALUS). (From Childs Nerv Syst 1992 Sep; 8(6):301-6) Brain Swelling,Cerebral Edema,Cytotoxic Brain Edema,Intracranial Edema,Vasogenic Cerebral Edema,Cerebral Edema, Cytotoxic,Cerebral Edema, Vasogenic,Cytotoxic Cerebral Edema,Vasogenic Brain Edema,Brain Edema, Cytotoxic,Brain Edema, Vasogenic,Brain Swellings,Cerebral Edemas, Vasogenic,Edema, Brain,Edema, Cerebral,Edema, Cytotoxic Brain,Edema, Cytotoxic Cerebral,Edema, Intracranial,Edema, Vasogenic Brain,Edema, Vasogenic Cerebral,Swelling, Brain
D002534 Hypoxia, Brain A reduction in brain oxygen supply due to ANOXEMIA (a reduced amount of oxygen being carried in the blood by HEMOGLOBIN), or to a restriction of the blood supply to the brain, or both. Severe hypoxia is referred to as anoxia and is a relatively common cause of injury to the central nervous system. Prolonged brain anoxia may lead to BRAIN DEATH or a PERSISTENT VEGETATIVE STATE. Histologically, this condition is characterized by neuronal loss which is most prominent in the HIPPOCAMPUS; GLOBUS PALLIDUS; CEREBELLUM; and inferior olives. Anoxia, Brain,Anoxic Encephalopathy,Brain Hypoxia,Cerebral Anoxia,Encephalopathy, Hypoxic,Hypoxic Encephalopathy,Anoxia, Cerebral,Anoxic Brain Damage,Brain Anoxia,Cerebral Hypoxia,Hypoxia, Cerebral,Hypoxic Brain Damage,Anoxic Encephalopathies,Brain Damage, Anoxic,Brain Damage, Hypoxic,Damage, Anoxic Brain,Damage, Hypoxic Brain,Encephalopathies, Anoxic,Encephalopathies, Hypoxic,Encephalopathy, Anoxic,Hypoxic Encephalopathies
D002545 Brain Ischemia Localized reduction of blood flow to brain tissue due to arterial obstruction or systemic hypoperfusion. This frequently occurs in conjunction with brain hypoxia (HYPOXIA, BRAIN). Prolonged ischemia is associated with BRAIN INFARCTION. Cerebral Ischemia,Ischemic Encephalopathy,Encephalopathy, Ischemic,Ischemia, Cerebral,Brain Ischemias,Cerebral Ischemias,Ischemia, Brain,Ischemias, Cerebral,Ischemic Encephalopathies
D002560 Cerebrovascular Circulation The circulation of blood through the BLOOD VESSELS of the BRAIN. Brain Blood Flow,Regional Cerebral Blood Flow,Cerebral Blood Flow,Cerebral Circulation,Cerebral Perfusion Pressure,Circulation, Cerebrovascular,Blood Flow, Brain,Blood Flow, Cerebral,Brain Blood Flows,Cerebral Blood Flows,Cerebral Circulations,Cerebral Perfusion Pressures,Circulation, Cerebral,Flow, Brain Blood,Flow, Cerebral Blood,Perfusion Pressure, Cerebral,Pressure, Cerebral Perfusion

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