Influence of hypoglycemic coma on brain water and osmolality.
To study the effects of pronounced hypoglycemia on brain osmolality and brain edema formation, fasted rats were rendered hypoglycemic by injection of insulin, and subjected to 30 min of hypoglycemic coma. Recovery was accomplished by glucose administration. The change in water content in different brain regions was measured as a change in specific gravity after 30 min of hypoglycemic coma, or 30, 60, and 180 min after glucose administration. Plasma and brain tissue osmolality were measured in separate animals. The results show a significant decrease in specific gravity (increase in water content) in all structures measured (caudoputamen, neocortex, hippocampus, and cerebellum) at the end of the period of coma, as well as after 30 min and 60 min of recovery. At 180 min of recovery, brain water was normalized. The edema affected all structures to the same degree regardless of their vulnerability to hypoglycemic damage. Brain tissue osmolality showed a tendency to decrease with decreasing tissue glucose content. The decrease was significant (P<0.01) at 30 min of isoelectric coma. In the recovery phase, normal brain osmolality was restored within 30 min. Measurements of blood-brain barrier (BBB) permeability after 30 min of hypoglycemic coma showed no extravasation of Evan's blue, though a small but significant increase in the permeability for aminoisobutyric acid (AIB) in caudoputamen and in cerebellum was found. To analyze the importance of tissue acidosis for formation of edema, hypoglycemic animals were made acidotic by increasing the CO2 concentration in inspired air to produce an arterial plasma pH of 6.8-6.9. In these animals the edema was of a similar degree to the normocapnic animals, and the permeability for AIB was normal. We conclude that osmolytic mechanisms are not the primary cause of the selective neuronal vulnerability in hypoglycemic coma. Furthermore, the BBB is largely intact during a hypoglycemic insult.
Gisselsson
L
L
Laboratory for Experimental Brain Research, Wallenberg Neuroscience Center, University Hospital, Lund, Sweden.
Smith
M L
ML
Siesjö
B K
BK
D000138:Acidosis / Q000139:chemically induced / Q000378:metabolism; D000621:Aminoisobutyric Acids / Q000493:pharmacokinetics*; D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology*; D001921:Brain / Q000098:blood supply / Q000378:metabolism; D001923:Brain Chemistry / Q000502:physiology; D001929:Brain Edema / Q000139:chemically induced / Q000378:metabolism*; D002545:Brain Ischemia / Q000139:chemically induced / Q000378:metabolism; D002245:Carbon Dioxide / Q000097:blood; D003128:Coma / Q000139:chemically induced / Q000378:metabolism*; D005070:Evans Blue / Q000493:pharmacokinetics; D007003:Hypoglycemia / Q000139:chemically induced / Q000378:metabolism*; D007004:Hypoglycemic Agents; D007328:Insulin; D008297:Male; D009994:Osmolar Concentration; D010949:Plasma / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D013046:Specific Gravity; D014867:Water / Q000378:metabolism; D014882:Water-Electrolyte Balance / Q000502:physiology
D000621:Aminoisobutyric Acids; D007004:Hypoglycemic Agents; D007328:Insulin; D014867:Water; D002245:Carbon Dioxide; D005070:Evans Blue