Interstitial Fluid Adenosine and Sagittal Sinus Blood Flow during Bicuculline-Seizures in Newborn Piglets

Abstract

Changes of interstitial fluid adenosine concentrations and effects of O₂ supply on interstitial fluid adenosine were studied by the brain dialysis technique in the frontal cortex of newborn piglets subjected to bicuculline-induced seizures. The O₂ supply was changed globally by changing MABP and locally by varying PO₂ in the artificial CSF perfusing the dialysis cannula. Sagittal sinus blood flow (SSBF), cerebrovascular resistance (CVR), and CMRO₂ were also examined in the same animals. Seizures increased interstitial fluid adenosine 7.9-fold (p < 0.05) when ictal MABP was maintained at preictal level and perfusate PO₂ was 24 mm Hg (group 1, n = 6). Interstitial fluid adenosine increased 11.8-fold (p < 0.05) during seizures associated with moderate systemic hypotension and the low perfusate PO₂ (group 2, n = 6). By contrast, seizures increased interstitial fluid adenosine three-fold (p < 0. 05) when perfusate PO₂ was increased to 182 mm Hg and ictal MABP was maintained at preictal level (group 3, n = 8). When ictal MABP was elevated from the preictal level and the perfusate was rich in oxygen, seizures failed to increase interstitial fluid adenosine (group 4, n = 7). In groups 1 and 3, the increase in interstitial fluid adenosine during seizures was associated with significant increases in SSBF and CMRO₂, as well as significant decreases in CVR. These data suggest that the increase in O₂ supply during seizures in piglets did not match completely the increase in O₂ demand and resulted in enhanced release of adenosine into the interstitial space.