Effects of etoposide-induced blood-brain barrier disruption on brain water, intracranial pressure, and cerebral vasomotor tone.
This study investigated the effects of hypertension and water loading on etoposide-induced, reversible blood-brain barrier disruption in a rat model. Twenty-nine animals were divided into four groups: group 1--intracarotid (i.c.) injection of saline followed in 1 h by 5 ml i.c. water; group 2--i.c. etoposide followed by i.c. water; group 3--i.c. saline followed by i.v. metaraminol to increase systemic blood pressure; group 4--i.c. etoposide followed by i.v. metaraminol. Systemic blood pressure and intracranial pressure were monitored continuously. Evans blue staining of the brain was used as a monitor of blood-brain barrier disruption. Animals were killed 1 h after either aramine or water infusion, and the brains removed and inspected for the degree of disruption. After dehydration, brain water was calculated for each hemisphere. Two-thirds of the animals infused with etoposide had evidence of barrier disruption, whereas none of the control animals infused with saline were disrupted. Neither control groups 1 or 3 showed significant change in intracranial pressure after water loading or augmentation of systemic blood pressure, respectively. Group 4 animals failed to demonstrate any significant change in intracranial pressure despite marked barrier disruption and acute hypertension (within the limits of normal autoregulation). A small but statistically significant increase in intracranial pressure was noted in group 2 animals with the greatest degree of barrier disruption. A significant increase in brain water was observed ipsilateral to etoposide infusion in only those animals with the most marked barrier disruption. These results indicate that etoposide-induced blood-brain barrier disruption caused significant increases in brain water without significant alteration of cerebral vasomotor tone or increases in intracranial pressure after water loading except in the most severe disruption. The classic untoward consequences of vasogenic edema were not encountered in the present model.
Hollis
P H
PH
Department of Neurosurgery, Mount Sinai Medical School, New York, New York 10029.
Zappulla
R A
RA
Spigelman
M K
MK
Feuer
E J
EJ
Holland
J F
JF
Malis
L I
LI
D000818:Animals; D001794:Blood Pressure; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001834:Body Water / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002560:Cerebrovascular Circulation; D005047:Etoposide / Q000494:pharmacology*; D005260:Female; D007427:Intracranial Pressure; D051381:Rats; D011919:Rats, Inbred Strains; D014666:Vasomotor System / Q000502:physiology
D005047:Etoposide