Incongruence of regional cerebral blood flow increase and blood-brain barrier opening in rabbits at the onset of seizures induced by bicuculline, methoxypyridoxine, and kainic acid

Abstract

Cerebral blood flow (CBF) was estimated using [3H]nicotine as tracer in 18 discrete rabbit brain regions at the onset of generalized seizures induced by bicuculline (BC), methoxypyridoxine (MP), and kainic acid (KA) and compared with the previously described regional pattern of blood-brain barrier (BBB) opening. Regional CBF increased 3- to 5-fold in BC-seizures, 2- to 3-fold (except in inferior colliculus) in MP-seizures, and twofold (no change in inferior colliculus) and periaqueductal gray) in KA-seizures. In general, CBF elevation was greater in areas with a high original CBF, and below average in regions with a low control value. However, under each condition a few areas did not follow this rule, viz. the occipital cortex and the basal part of the cerebellar vermis with low flow values in BC-seizures, the inferior colliculus with no change and the pallidum with a relatively high flow during MP-seizures, and limbic system areas with an exceptionally high flow during KA-seizures. The usual rise in arterial blood pressure (BP) at the onset of the seizure, necessary for the development of a BBB lesion, was absent in a few animals with BC- and MP-seizures, yet, their CBF was elevated in most regions although to a lesser extent. No relationship appeared to exist between the rise in CBF and the regional pattern of BBB opening. It is concluded that a loss of cerebral autoregulation is a prerequisite for BBB leakage, but the location of the opening is determined by neuronally derived factors which differ from convulsant to convulsant and from brain region to brain region.