The present study tested the hypothesis that adenosine is involved in mediating the hyperemic response of the newborn brain to hypoglycemia. By use of the cranial window and microdialysis-H2 clearance methodologies, changes in the diameter of pial arterioles (25-50 μm), extracellular adenosine concentrations ([ADO]), and local cerebral blood flow (CBF) were examined in isoflurane-anesthetized piglets subjected to insulin-induced hypoglycemia. Blood glucose concentrations ranged from 10 to 18 mg/dl after insulin administration (25 IU/kg/iv). Local CBF in the frontal cortex increased 36 ± 12% (P = 0.014) at 30 min of hypoglycemia (group 1, n = 12; control = 43 ± 3 ml · min-1 · 100 g-1). The mean increase in dialysate [ADO] sampled concurrently from the same cortical area was 59 ± 29% (P = 0.011; control = 0.11 ± 0.02 μM). At 30 min of hypoglycemia, pial diameters increased 55 ± 10% (P = 0.001; group 2, n = 9). The [ADO] in cranial window cerebrospinal fluid (CSF) increased 217 ± 71% (P = 0.04) in response to hypoglycemia (group 3, n = 8; control = 0.016 ± 0.006 μM). Local administration of an adenosine antagonist, 10 μM 8-sulfophenyltheophylline, to the cerebral cortex before hypoglycemia caused a 38% reduction (P = 0.011) in the pial arteriolar response at 30 min of hypoglycemia (group 4, n = 9). Similarly, local superfusion of CSF with 3.7 mM glucose attenuated the hypoglycemia- induced pial dilation 33% (P = 0.039; group 5, n = 9). Perfusion of microdialysis probes with 3.7 mM glucose in the CSF abolished the hypoglycemia-induced increase in dialysate [ADO] (group 1). Pial arteriolar diameters did not change when normoglycemic blood glucose levels were maintained by intravenous glucose after insulin administration (group 6, n = 6). These findings in newborn piglets indicate that hypoglycemia promotes increases in cerebral extracellular [ADO], which contribute to the observed pial dilation and parenchymal hyperemia.
|Journal||American Journal of Physiology - Heart and Circulatory Physiology|
|Issue number||5 34-5|
|State||Published - 1993|
- cerebral blood flow
- cranial window