On the physiological response of the cerebral cortex to acute stress (reversible asphyxia).
1. Rhesus monkey (Macaca mulatta) foetuses were delivered by Caesarean section 3-10 days before term. Aortic blood and cerebrospinal fluid (c.s.f.) samples were taken, the latter from the cortical subarachnoid space and the cisterna magna. The umbilical cord was clamped and foetal breathing prevented for 14-17 min. Blood and c.s.f. were sampled further during this total asphyxiation and for up to 24 hr thereafter.2. The [K(+)] in the cortical subarachnoid fluid started to rise within 2-3 min after the onset of asphyxia and increased up to 7 times the normal level. The [K(+)] of blood plasma and cisternal fluid also increased, but much more moderately. All these effects reversed rapidly upon resuscitation of the foetus.3. A pronounced rise in the cortical subarachnoid fluid [glucose] and a lesser effect on cisternal fluid [glucose] were noted in most cases by the end of, or immediately following, the period of asphyxia. The onset, magnitude and reversal of these effects on [glucose] were less predictable than the observed effects on [K(+)].4. There were no significant changes in the [Mg(2+)], [Ca(2+)] or [Na(+)] of any of these fluids. The calculated total osmolarity of the cortical subarachnoid fluid and, to a much lesser extent, of cisternal fluid and plasma, increased during asphyxia mainly as a result of increased [K(+)].5. The results are interpreted as indicative of a rapid release of K(+) from cortical cells during total asphyxia. The (immature) haematoencephalic K(+) transport system becomes saturated and thus K(+) accumulates in the extracellular fluid (e.c.f.) whence it diffuses into adjacent regions of the c.s.f. system.6. The intracellular fluid of apical dendrites must become even more hypertonic than the e.c.f., since these cellular processes are known to swell during asphyxia at the expense of the e.c.f. space. This apparent increase in intracellular osmolarity could be accounted for by the release of normally bound intracellular cations.7. On the basis of our results and review of the relevant literature, the following sequence of events is proposed: the cortex responds to acute physiological stress (asphyxia, overstimulation, chemical or physical irritation, etc.) by releasing intracellularly bound cations (K(+) and possibly Na(+)). The increased intracellular osmolarity results in the absorption of water from the e.c.f. space. Passage of water across the blood-brain barrier is restricted; thus the e.c.f. space of the cortex does not swell, but becomes hyperosmotic. Under these circumstances, swelling of the cortical cells is limited by the volume of e.c.f. available.8. It is proposed that the release of intracellularly bound cations is a result of their displacement from their binding sites by NH(4) (+) which is released to, and recovered from, these cation binding sites by a glutamate-glutamine interconversion.9. It is concluded that the apparent organized ;shutdown' of the cortical cells in response to acute stress may contribute to the relative insensitivity of this area of the brain to permanent histopathological damage.
D000818:Animals; D001237:Asphyxia / Q000503:physiopathology*; D001665:Binding Sites; D001812:Blood-Brain Barrier; D002118:Calcium / Q000134:cerebrospinal fluid; D002245:Carbon Dioxide / Q000097:blood; D002540:Cerebral Cortex / Q000378:metabolism / Q000503:physiopathology*; D005110:Extracellular Space; D005260:Female; D005333:Fetus; D005947:Glucose / Q000134:cerebrospinal fluid; D000882:Haplorhini; D006863:Hydrogen-Ion Concentration; D008251:Macaca; D008274:Magnesium / Q000134:cerebrospinal fluid; D009994:Osmolar Concentration; D010100:Oxygen / Q000097:blood; D011188:Potassium / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism; D011247:Pregnancy; D012964:Sodium / Q000134:cerebrospinal fluid; D013312:Stress, Physiological / Q000503:physiopathology*; D013346:Subarachnoid Space
D002245:Carbon Dioxide; D012964:Sodium; D008274:Magnesium; D005947:Glucose; D011188:Potassium; D010100:Oxygen; D002118:Calcium