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Energy Metabolism of the Brain. Cerebrospinal Fluid František Duška.

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Presentation on theme: "Energy Metabolism of the Brain. Cerebrospinal Fluid František Duška."— Presentation transcript:

1 Energy Metabolism of the Brain. Cerebrospinal Fluid František Duška

2 Overview Brain metabolism ▫energy metabolism ▫ammonia handling Blood-brain barrier Cerebrospinal fluid

3 (except neurotransmiter metabolism – next lecture) 1.Energy metabolism of the brain 2.Ammonia handling

4 Energy metabolism of the brain 2% of body weight, 20% of energy expenditure GLUCOSE is the main fuel ▫daily consumption 120g ▫adopted starvation (3 weeks): oxidation of ketones in the brain covers up to 50% of energy

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6 What´s the first thing that happens when you think? Excitatory firing  Glu uptake by glia  Na+ influx  ATP consumption by Na-K-ATPase  activation of glycolysis  lactate transported to neurons Local increase in lactate increases blood flow Excitotoxity = excesive Glu release ▫epilepsy, traumatic brain injury ▫Na+ and Ca2+ IC accumulation  swelling

7 Functional imaging of ther brain PET = positron emission tomography ▫ 18 F-2-deoxy-2-fluoroglucose ▫taken up by glia, phosphorylated but not further metabolized ▫active areas of the brain accumulate tracer

8 Functional imaging: PET

9 Oxygen uptake Brain: 20% of whole-body O2 consumption The most vulnerable to hypoxia ▫5 min of VF/arrest may lead to irreversible brain damage ▫temperature dependent Clinical use: ▫jugular venous oxymetry ▫tissue pO2

10 Ammonia handling in the brain NH3 is a waste product of deamination reactions (Gln  Glu, Glu  2-OG etc.) Metabolism: ▫Glutamin synthetase: NH3 + Glu  Gln ▫Gln is metabolized in the liver/kidneys Ammonia toxicity: NH3 + 2OG + NADH  Glu + NAD+ ▫Krebs cycle impairment: 2-OG depletion ▫Glu excess, excitotoxicity

11 Ammonia handling Clinical consequences: liver disease impairs brain function ▫principle: insufficient urea synthesis  NH3 accumulation  neurotoxicity ▫Hepatic encephalopathy: gr.I-IV ▫Fulminant liver failure (i.e. paracetamol poisoning) threatens live also by  ICP

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13 Blood brain barrier History: ▫19th century, Ehrlich: aniline dye i.v. stains all organs except brain ▫1960: morphology by electron microscope Function: ▫BBB selectivity protects the brain

14 Blood brain barrier Morphology: endothelium, BM, astrocyte

15 Blood brain barrier selectivity Free permeability (passive diffusion): ▫small molecules: H2O, O2, CO2, NH3, ethanol ▫lipid soluble molecules: steroid hormones Carrier mediated transport: ▫glucose: GLUT-1 (insulin independent) ▫amino acids Pinocytosis

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17 Areas outside BBB Enables brain to sense and regulate blood composition Include: ▫Subfornical organ: osmoreceptors, regulate ADH ▫OVLT: dtto, thirst ▫Area postrema: chemoreceptors, vomining center

18 BBB – clinical significance CNS infection: ▫BBB protects against bacteria entry, but also antibodies and antibiotics Kernikterus: ▫hyperbilirubinemia damages the brain in neonates but not in adults Parkinsons disease: ▫=lack of dopamin in basal ganglia ▫cannot be treated with dopamin (does not cross BBB), but its precursor L-DOPA is useful

19 1.Function and circulation 2.Collection and laboratory assessment

20 Cerebrospinal fluid Volume = 150 ml, daily production = 500ml Function: ▫mechanical protection ▫distribution of neuroendocrine factors ▫„volume buffer“: helps to regulate ICP when tissue or intracranial blood volume rises (Monroe-Kelly doctrine: V-CSF+V-blood+V-brain tissue = const.)

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22 CSF normal composition MetaboliteCSFSerum Na+154 mM140 mM Cl-122 mM103 mM HCO3-22 mM24mM Glucose3,3 mM5 mM Lactate1.6 mM1 mM Protein0,35 g/l70 g/l IgG0,0018 g/l12g/l CSF does not contain cells (normal: up to 5 WBC/  l)

23 CSF collection for dg. purposes Lumbar puncture (rarely suboccipital puncture) 4 samples (2 ml): ▫biochemistry: ions, Glc, lac, proteins incl. ELFO ▫cytology: No of RBC and WBC/  l event. incl. differential count ▫bacteriology: standard culture and/or PCR ▫1 backup sample stored at 4°C

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25 CSF in diagnostics CNS infection ▫bacterial meningitis: voscous and opalescent CSF,  WBC,  Glucose,  Lac ▫viral meningitis: few cells,  protein Degenerative diseases ▫oligoclonal bands in multiple sclerosis ▫others Hematologic malignancy ▫leucemic cells infiltrate CNS


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