Brain cell swelling during hypocapnia increases with hyperglycemia or ketosis.
BACKGROUND
Severe hypocapnia reduces cerebral blood flow (CBF) and is known to be a risk factor for diabetic ketoacidosis (DKA)-related cerebral edema and cerebral injury in children. Reductions in CBF resulting from hypocapnia alone, however, would not be expected to cause substantial cerebral injury. We hypothesized that either hyperglycemia or ketosis might alter the effects of hypocapnia on CBF and/or cerebral edema associated with CBF reduction.


METHODS
We induced hypocapnia (pCO₂ 20 ± 3 mmHg) via mechanical ventilation in three groups of juvenile rats: 25 controls, 22 hyperglycemic rats (serum glucose 451 ± 78 mg/dL), and 15 ketotic rats (β-hydroxy butyrate 3.0 ± 1.0 mmol/L). We used magnetic resonance imaging to measure CBF and apparent diffusion coefficient (ADC) values in these groups and in 17 ventilated rats with normal pCO₂ (40 ± 3 mmHg). In a subset (n = 35), after 2 h of hypocapnia, pCO₂ levels were normalized (40 ± 3 mmHg) and ADC and CBF measurements were repeated.


RESULTS
Declines in CBF with hypocapnia occurred in all groups. Normalization of pCO₂ after hypocapnia resulted in hyperemia in the striatum. These effects were not substantially altered by hyperglycemia or ketosis. Declines in ADC (suggesting brain cell swelling) during hypocapnia, however, were greater during both hyperglycemia and ketosis.


CONCLUSIONS
We conclude that brain cell swelling associated with hypocapnia is increased by both hyperglycemia and ketosis, suggesting that these metabolic conditions may make the brain more vulnerable to injury during hypocapnia.
Department of Pediatrics, University of California Davis, School of Medicine, Sacramento, CA, USA.
Nicole
N
Glaser
Angeliki
A
Bundros
Steve
S
Anderson
Daniel
D
Tancredi
Weei
W
Lo
Myra
M
Orgain
Martha
M
O'Donnell
D020155:3-Hydroxybutyric Acid / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001929:Brain Edema / Q000209:etiology*; D002245:Carbon Dioxide / Q000097:blood; D048429:Cell Size; D002540:Cerebral Cortex / Q000098:blood supply / Q000473:pathology*; D002560:Cerebrovascular Circulation; D003342:Corpus Striatum / Q000098:blood supply / Q000473:pathology*; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D016883:Diabetic Ketoacidosis / Q000503:physiopathology*; D004198:Disease Susceptibility; D006863:Hydrogen-Ion Concentration; D006943:Hyperglycemia / Q000503:physiopathology*; D016857:Hypocapnia / Q000209:etiology*; D008279:Magnetic Resonance Imaging; D009474:Neurons / Q000473:pathology; D017207:Rats, Sprague-Dawley; D014883:Water-Electrolyte Imbalance / Q000150:complications / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology
D001786:Blood Glucose; D002245:Carbon Dioxide; D020155:3-Hydroxybutyric Acid
CBF; DKA; brain injury; cerebral edema; hypocapnia