Oxygen & Physiological Function – Hypoxic Adaptation and Angioplasticity

Vocabulary flashcards summarizing key terms, molecules, physiological responses, and cellular mechanisms involved in brain adaptation to acute and chronic hypoxia (angioplasticity).

Hypoxia

A condition in which tissue oxygen tension (pO₂) falls below normal physiological levels.

Hypobaric Hypoxia

Reduced oxygen availability caused by lowered barometric pressure, often modeled at 0.5 ATM in rodents.

Angioplasticity

Dynamic remodeling of cerebral microvasculature in response to altered oxygen supply and demand.

HIF-1 (Hypoxia-Inducible Factor-1)

Transcription factor that accumulates under low O₂ and drives expression of genes such as VEGF, EPO, and GLUT-1.

HIF-2 (EPAS-1)

Hypoxia-inducible transcription factor isoform that complements HIF-1 in vascular and metabolic adaptation.

VHL (Von Hippel–Lindau Protein)

E3 ubiquitin-ligase component that targets hydroxylated HIF-α for proteasomal degradation under normoxia.

Prolyl Hydroxylase

O₂-, Fe²⁺- and α-ketoglutarate-dependent enzyme that hydroxylates HIF-α prolines, enabling VHL binding in normoxia.

VEGF (Vascular Endothelial Growth Factor)

Potent endothelial mitogen up-regulated by HIF-1 that initiates hypoxia-induced angiogenesis.

Angiopoietin-1 (Ang-1)

Vascular stabilizing ligand for Tie-2 receptor that promotes capillary maturation and quiescence.

Angiopoietin-2 (Ang-2)

Tie-2 ligand that destabilizes vessels; facilitates both angiogenesis and capillary regression depending on VEGF levels.

COX-2 (Cyclo-oxygenase-2)

Inducible enzyme producing PGE₂; implicated in hypoxia-triggered angiogenesis and in regression during re-oxygenation.

PGE₂ (Prostaglandin E₂)

Lipid mediator generated by COX-2 that modulates vascular remodeling in brain hypoxia.

GLUT-1

Glucose transporter at blood–brain barrier whose expression rises during chronic hypoxia to enhance glucose uptake.

CMRglu (Cerebral Metabolic Rate for Glucose)

Rate of glucose utilization by brain tissue; acutely increases during hypoxia.

Cytochrome Oxidase

Mitochondrial enzyme whose activity decreases after weeks of hypoxia, indicating hypometabolism.

Capillary Density

Number of microvessels per mm² of brain tissue; increases (~20–40 %) after 3 weeks of hypoxia.

Cerebral Blood Flow (CBF)

Volume of blood passing through brain tissue per unit time; rises acutely then renormalizes during chronic hypoxia.

Hematocrit (Hct)

Percentage of blood volume occupied by red cells; elevates during prolonged hypoxia to boost O₂ content.

Right Shift of Hb Dissociation Curve

Decrease in hemoglobin O₂ affinity (elevated P50) that facilitates O₂ unloading in tissues during hypoxia.

Bicarbonate Ion Secretion

Renal and choroid plexus response that compensates respiratory alkalosis from hyperventilation in hypoxia.

Ventilatory Response to Hypoxia

Increase in breathing frequency and tidal volume to augment alveolar O₂ uptake.

Blood–Brain Barrier (BBB)

Endothelial interface regulating brain entry of molecules; shows increased glucose transport but intact tight junctions in hypoxia.

Microvessel Density

Combined volume or surface area of capillaries plus small vessels; expands with chronic hypoxia and declines upon re-oxygenation.

Pericyte Coverage

Fraction of capillary circumference contacted by pericytes; modestly altered during hypoxic angiogenesis.

Endothelial Cell Apoptosis

Programmed cell death contributing to capillary pruning during re-adaptation to normoxia or hyperoxia.

Caspase-3

Executioner protease; its activation evidences endothelial apoptosis during capillary regression.

TUNEL Staining

Histological assay detecting DNA fragmentation indicative of apoptosis after hypoxia reversal.

EPO (Erythropoietin)

HIF-regulated hormone that stimulates erythropoiesis, elevating hematocrit in chronic hypoxia.

Tissue pO₂ Set Point

Narrow physiological oxygen tension (~25 mm Hg) actively maintained by angioplasticity despite ambient changes.

Hypometabolism

Lowered mitochondrial oxygen consumption observed after weeks of hypoxic adaptation.

Capillary Mean Transit Time

Average duration blood spends in capillaries; becomes faster during acute hypoxia owing to vasodilation.

Vascular Remodeling

Structural modifications of vessel caliber, length, and branching in response to persistent oxygen changes.

Re-oxygenation (De-adaptation)

Return to normoxia after hypoxic exposure, initiating capillary regression via Ang-2 and COX-2 signaling.

Physiological Apoptosis

Controlled cell death used to pare excess capillaries when oxygen supply exceeds metabolic demand.

Hypoxic Angiogenesis

Formation of new brain microvessels driven by HIF-1/VEGF during sustained low O₂.

Hyperoxia-Induced Vascular Pruning

Capillary loss resulting from excess oxygen, linked to reduced VEGF/COX-2 signaling.

Neurovascular Unit

Functional ensemble of neurons, astrocytes, endothelial cells, and pericytes coordinating blood flow with metabolism.

Tie-2 Receptor

Endothelial tyrosine kinase receptor for angiopoietins that regulates vessel stability or remodeling.

Hypoxic Ventilatory Drive

Chemoreceptor-mediated increase in ventilation rate upon sensing low arterial pO₂.

HIF-1α Hydroxylation Sites (Pro-402, Pro-564)

Proline residues whose oxygen-dependent hydroxylation targets HIF-α for degradation.

NADH Oxidation Signal

Fluorometric indicator of mitochondrial redox state; increases during acute hypoxia.

Brain Glucose Uptake (Tmax)

Maximal blood-to-brain glucose transport capacity; elevated (~50–80 %) after 3 weeks hypoxia.

Cytochrome a₃

Component of cytochrome oxidase; its redox changes track mitochondrial oxygen use in cortex.

Perivascular Astrocyte End-Feet

Astrocytic processes contacting vessels; secrete VEGF and COX-2–derived factors in hypoxia.

COX-2 Knockout

Genetic deletion reducing hypoxia-induced capillary proliferation, implicating COX-2 in angioplasticity.

Hypoxia-Triggered Body Weight Loss

Reduction in mass (~15–25 %) during acclimatization attributed to altered metabolism and appetite.

Core Temperature Fall

Initial drop in body temperature during hypoxia, later partially restored, aiding energy conservation.

Oxygen Delivery (CaO₂ × CBF)

Product of arterial O₂ content and blood flow; maintained near baseline through coordinated adaptations.

Hypoxic EEG Abnormalities

Electrical changes such as slowing or burst suppression during acute oxygen deprivation.

Capillary Regression Time Course

Weeks-long reduction in vessel density once normoxia or hyperoxia resumes, mediated by Ang-2 and apoptosis.