CNS metabolism Flashcards
Brain metabolism depends on
____% body weight
____% energy demand
____% of glucose
2% body weight
20% energy demand
25% of glucose
________ bodies are utilized during brain development and in the adult during prolonged __________ periods.
KETONES bodies are utilized during brain development and in the adult during prolonged FASTING periods.
Prolongated fasting consist on ___-___ weeks.
5-6 weeks
_______ body levels rise significantly and are able to contribute almost ____% of the brains energy requirement, thereby replacing ________ as the main fuel.
KETONE body levels rise significantly and are able to contribute almost 60 % of the brains energy requirement, thereby replacing GLUCOSE as the main fuel.
_________ utilization is _________ during ________ physical activity.
LACTATE utilization is INCREASED during INTENSE physical activity.
In brain _______ is present as a ___ distinct molecular forms with molecular weights of ___ and ___ kDa, which are encoded by the ______ gene and differ only in there extent of __________.
In brain GLUT-1 is present as a 2 distinct molecular forms with molecular weights of 55 and 45 kDa, which are encoded by the SAME gene and differ only in there extent of GLYCOSLATION.
The ____-kDa ______ of _______ is detected exclusively in brain __________ cells, while the 45-kDa ______ is expressed in __________ and ______ cells.
The 55-kDa ISOMORM of GLUT1 is detected exclusively in brain ENDOTHELIAL cells, while the 45-kDa ISOFORM is expressed in NEURONS and GLIAL cells.
A rare disease is __________________ (Glut1DS) is a rare genetic metabolic disorder characterized by deficiency of a protein that is required for ___________ to cross the BBB and other tissue barriers.
A rare disease is GLUCOSE TRANSPORTER TYPE 1 DEFICIENCY SYNDROME (Glut1DS) is a rare genetic metabolic disorder characterized by deficiency of a protein that is required for GLUCOSE to cross the BBB and other tissue barriers.
To compensate for varying in energy demand throughout the brain and to increase efficiency of metabolite supply, ______________ and _________ coupling mechanisms have evolved to enhance __________ and utilization of ___________ in areas of neural activity.
To compensate for varying in energy demand throughout the brain and to increase efficiency of metabolite supply, NEUROVASCULAR and NEUROMETABOLIC COUPLING mechanisms have evolved to enhance BLOOD FLOW and utilization of METABOLITES in areas of neural activity.
In _______________ coupling the ______________ (CBF), ________ volume, ___________ consumption and ________ metabolism are all _________ within localized regions of activity following _________ stimulation.
In NEUROVASCULAR coupling the CEREBRAL BLOOD FLOW (CBF), BLOOD volume, GLUCOSE consumption and OXYGEN metabolism are all INCREASE within localized regions of activity following NEURONAL stimulation.
BBB Dysfunction / Impairment: major neurological disorders associated with dysfunction.
1.
2
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
1.BRAIN TUMOR
2.LYSOSOMAL STORAGE DISEASE
3.CHRONIC TRAUMATIC ENCEPHALOPATHY
4.SEPTIC ENCEPHALOPATHY
5. ALS
6.MENINGITIS
7.SCHIZOPHRENIA
8.ALZHEIMER
9.MULTIPLE SCLEROSIS
10. PARKINGSON
11.STROKE
12.EPILEPSY
13.HIV ENCEPHALITIS
14.HUNTINGTONS DISEASE
___________ is the gatekeeper of neurological function.
CLAUDIN-5
_________ is insufficient oxygenation
HYPOXIC
__________ is insufficient blood flow
ISCHEMIC
_________ insufficient hemoglobin
ANEMIC
_____________ = electrical failure
LACK OF ENERGY
_______________ = arrest of cellular functions and cell death
LAST LONG ENOUGH
Hypoxia consist of 8 steps
1.
2.
3.
4.
5.
6. OR 7.
8.
Hypoxia consist of 8 steps
1. ENERGY FAILURE
2. DEPOLARIZATION (LOSS OF FUNCTION)
3. GLUTAMATE DISCHARGE IN SYNAPTIC CLEFT
4.OPENING OG NMDA, AMPA RECEPTOS
5.CALCIUM INFLUX
6. ACTIVATION OF CATABOLIC ENZYMES OR 7. ACTIVATION OF NO SYNTHASE NO PRODUCTION
8.CELULLAR INJURY
Main consequences of CNS Hypoxia / Ischemia
- Endothelial cells
Expression of
HIF-1a-2a
VEGF, VEGFR-1/-2
Epo
NO
angpt-1/-2
Tie -1,-2
Angiogenesis and vascular remodeling
Increased vascular permeabillity
Main consequences of CNS Hypoxia / Ischemia
- Basement membrane
Composed of laminin, collagen IV, fibronectin
Angiogenesis and vascular remodeling
Edema and hemorrhage formation
Main consequences of CNS Hypoxia / Ischemia
- ASTROCYTES
-Swollen and feet, expression of VEGF, Epo, angpt-1, AQ4
Edema and hemorrhage formation
Increase vascular permeability
Main consequences of CNS Hypoxia / Ischemia
- Tight junctions
Composed of Occluding, Claudins, JAMS, ZOs
Increase vascular permeability
Main consequences of CNS Hypoxia / Ischemia
- Pericytes
Migration away from vascular wall
Expression of VEGF, angpt-1
Increase vascular permeability
Decreased vascular stability
