Continuous determination of the cerebrovascular changes induced by bicuculline and kainic acid in unanaesthetized spontaneously breathing rats.
Cerebral blood flow was sequentially determined (every 2-3 min) with helium clearance in two "vulnerable" structures: the hippocampus and the frontoparietal cortex during bicuculline (n = 11) and kainic acid (n = 9)-induced seizures in unanaesthetized, spontaneously breathing rats. Tissue partial pressures of oxygen and carbon dioxide were continuously and simultaneously evaluated in the same brain areas. All these variables were measured by mass spectrometry with a single gas sampling cannula previously implanted in each structure. The systemic variables, arterial blood pressure, arterial partial pressures of oxygen and carbon dioxide, pH, and bicarbonate concentration were also determined. Arterial and venous catheters were chronically implanted several days prior to the definitive experiments. Bicuculline induced short (about 15 min), recurrent, generalized seizures, with an abrupt rise in arterial blood pressure, an arterial metabolic acidosis and comparable blood flow increases (4-fold) in the hippocampus and the neocortex. A marked increase in tissue partial pressure of oxygen was always preceded by an increase in tissue partial pressure of carbon dioxide. After the seizures, in the 5 rats that survived, cerebral blood flow was significantly lowered; tissue partial pressure of oxygen and partial pressure of carbon dioxide also decreased, but to a lesser extent. Histological examination revealed two types of lesions: predominantly selective chromatolysis but also ischaemic cell change. Kainic acid first induced a decrease in arterial pressure and then hypertension during status epilepticus, with a return of arterial pressure towards basal levels during the recovery period (4 h after the injection). Respiratory alkalosis occurred throughout the experiment. Cerebral blood flow increased progressively to become maximal during status epilepticus. This vasodilatation was greater in the hippocampus (x 8) than in the neocortex (x 4). During recovery, cerebral blood flow tended to decrease but remained significantly elevated. In both structures, tissue partial pressure of oxygen was first lowered while tissue partial pressure of carbon dioxide was elevated; with the occurrence of the wet dog shakes, tissue partial pressure of O2 increased and tissue partial pressure of CO2 decreased. The changes in tissue gases were maximal during status epilepticus and tended to return to their basal levels thereafter, but no decrease in tissue partial pressure of O2 was observed, even 4 h after kainic acid administration. Histological analysis demonstrated ischaemic cell changes, particularly in the limbic system.(ABSTRACT TRUNCATED AT 400 WORDS)
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001640:Bicuculline; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D002245:Carbon Dioxide / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D005071:Evoked Potentials / Q000187:drug effects; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007608:Kainic Acid; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*
D002245:Carbon Dioxide; D007608:Kainic Acid; D001640:Bicuculline