Effect of the calcium antagonist nimodipine on the delayed hypoperfusion following incomplete ischemia in the rat.

Regional cerebral blood flow (CBF) was measured autoradiographically in the recovery period following 15 min of forebrain ischemia in rats pretreated with either nimodipine (0.1 mg kg-1) or vehicle. The results showed that although nimodipine increased postischemic CBF, the flow enhancement was regionally heterogeneous, sometimes resulting in zones of gross hypoperfusion and overt hyperemia within the same structures.

Regional differences in vascular autoregulation in the rat brain in severe insulin-induced hypoglycemia.

The present experiments were undertaken to determine if loss of vascular autoregulation during severe hypoglycemia shows regional differences that could help to explain the localization of hypoglycemic cell damage. Artificially ventilated rats (70% N2O) were subjected to a 30-min insulin-induced hypoglycemic coma (with cessation of EEG activity), with mean arterial blood pressure being maintained at 140, 120, 100, and 80 mm Hg. After 30 min of hypoglycemia, local cerebral blood flow (CBF) in 25 brain structures was measured autoradiographically with a [14C]iodoantipyrine technique.

A venous outflow method for measurement of rapid changes of the cerebral blood flow and oxygen consumption in the rat.

A technique for continuous measurement of cerebral venous outflow in the rat is described. The method involves cannulation of one retroglenoid vein close to its exit from the skull, and diversion of cerebral venous blood through a closed extracorporal circuit with a drop recording device, the blood being returned to the central venous circulation via a catheter in the external jugular vein. Occlusion of the contralateral retroglenoid vein increases measured flow and minimizes extracerebral contamination of the diverted cerebral venous blood.

Local blood flow and glucose consumption in the rat brain during sustained bicuculline-induced seizures.

The present study addresses the problem of whether brain structures which have been shown to develop neuronal cell damage in recurrent or prolonged epileptic seizures have higher metabolic rates and/or less pronounced increases in blood flow rates than others during sustained seizures. To that end, local cerebral blood flow (CBF) and glucose utilization (CMRgl) were measured autoradiographically in ventilated rats, in which seizures of 20, 60, or 120 min duration were induced by i.v.

Cerebral circulatory responses to hypercapnia and hypoxia in the recovery period following complete and incomplete cerebral ischemia in the rat.

In this study we examined the reactions of cerebral vessels to hypercapnia and hypoxia during the recovery period following cerebral ischemia. We used ventilated, lightly anesthetized rats and induced complete ischemia by CSF compression, incomplete ischemia by bilateral carotid occlusion combined with hypotension. After 15 min of ischemia and 60 min of recirculation the animals were rendered hypercapnic or hypoxic for 2-3 min and local CBF was then measured autoradiographically with 14C-iodoantipyrine.

Cyclo-oxygenase inhibition by indomethacin and recirculation following cerebral ischemia.

In this study we examined the effect of pretreatment with the cyclo-oxygenase inhibitor indomethacin (10 mg . kg-1) on local cerebral blood flow (DBF) in the immediate recirculation period following complete and incomplete ischemia. Ischemia of 15 min duration was induced in lightly anaesthetized and artificially ventilated rats, and local CBF was measured with a 14C-iodoantipyrine autoradiographic technique after recirculation periods of 5 min.

Recirculation in the rat brain following incomplete ischemia.

The objective of this study was to characterize local cerebral blood flow (CBF) in the recirculation period following incomplete forebrain ischemia. Specifically, we wished to determine whether perfusion defects developed in the immediate recirculation period, to study how initial hyperemia and delayed hypoperfusion at the local level were related to the severity of the preceding ischemia, and to find out whether reflow was influenced by the nutritional state of the animals. To that end, forebrain ischemia of 15 min duration was induced in fed and fasted ventilated rats under 70% N2O.

Local cerebral blood flow in the recovery period following complete cerebral ischemia in the rat.

This study examines reflow patterns in the recirculation period following complete, global ischemia. Cerebrospinal fluid (CSF) compression ischemia was induced in ventilated rats for 5-30 min, and local cerebral blood flow (CBF) was measured autoradiographically after 5, 60, and 90 min of recirculation. Ischemia of 15 min duration was induced by four-vessel occlusion combined with arterial hypotension in two additional groups, with recovery periods of 5 or 60 min.

Influence of lesions of the noradrenergic locus coeruleus system on the cerebral metabolic response to bicuculline-induced seizures.

The objective of the present study was to explore if lesions of the ascending noradrenergic pathways, originating in the locus coeruleus, modulate the cerebral metabolic response to bicuculline-induced seizures in rats. Bilateral noradrenergic lesions were performed by 6-hydroxydopamine injections in the caudal mesencephalon, 12-22 days before seizures were induced in animals ventilated on N2O:O2 (75:25). After 5 min of seizures the brain was frozen in situ and cerebral cortex and hippocampus were sampled for analysis.

Intracellular pH in the brain following transient ischemia.

The objective of the present study was to discover whether or not intracellular alkalosis develops in the brain in the recovery period following transient ischemia. Forebrain ischemia of 15-min duration was induced by four-vessel occlusion in rats, with recovery periods of 15, 60, and 180 min. Intracellular pH was derived both by the HCO3- -H2CO3 method and from the creatine kinase equilibrium.

Influence of systemic factors on experimental epileptic brain injury. Structural changes accompanying bicuculline-induced seizures in rats following manipulations of tissue oxygenation or alpha-tocopherol levels.

A previous study from the laboratory showed that status epilepticus induced by bicuculline administration to ventilated rats produced astrocytic swelling and nerve cell changes ("type 1 and 2 injury") particularly in layers 3 and 5 of the neocortex (Söderfeldt et al. 1981). The type 1 injured neurons were characterized by condensation of cyto- and karyoplasm and the less common type 2 cells were characterized by swelling of endoplasmic reticulum including the nuclear envelope.

Bicuculline-induced epileptic brain injury. Transient and persistent cell changes in rat cerebral cortex in the early recovery period.

It was earlier shown that bicuculline-induced status epilepticus gives rise to profound acute changes in the rat cerebral cortex, i.e. edema and neuronal alterations.

Effect of nitrous oxide on local cerebral glucose utilization in rats.

The influence of 70-80% N2O on local local cerebral glucose utilization (CMRg1) in the rat brain was studied with the [14C]deoxyglucose method in minimally restrained, spontaneously breathing animals 75 min following discontinuation of halothane anaesthesia. Nitrous oxide was found to have only small effects on local CMRg1 in the majority of the 25 structures analyzed. When corrections were made for a small difference in body temperature between nitrous oxide--breathing animals and those breathing air nitrous oxide was found to significantly increase local CMRg1 in some subcortical structures by 15-25% (red nucleus, thalamus, geniculate bodies, and superior colliculus), and to decrease local CMRg1 in nucleus accumbens and sensorimotor cortex by comparable amounts.

Influence of blood glucose concentration on brain lactate accumulation during severe hypoxia and subsequent recovery of brain energy metabolism.

The effects of hypoxaemia on regional cerebral blood flow (CBF) and brain cortical metabolite concentrations were investigated at different blood glucose concentrations in rats under nitrous oxide anaesthesia. Tissue hypoxia of 15-min duration was induced by a combination of arterial hypoxaemia, hypotension, and clamping of the right carotid artery. Blood glucose concentrations were manipulated by varying the food intake in the 24 h before the experiment, and by glucose administration.

The influence of bicuculline-induced seizures on free fatty acid concentrations in cerebral cortex, hippocampus, and cerebellum.

Using ventilated rats maintained on N2O-O2 (70:30, vol/vol) we induced continuous seizures with i.v. bicuculline and analysed free fatty acids (FFA) in cerebral cortex, hippocampus, and cerebellum after seizures durations of 1-120 min.

Ischemic brain injury: the importance of calcium, lipolytic activities, and free fatty acids.

Ischemic brain insults are accompanied by several metabolic alterations. In the present review, the adverse reactions, which might be important for the outcome of these insults, are those related to phospholipid and polyunsaturated fatty acid metabolism triggered by the disturbed calcium ion homeostasis in combination with energy depletion following ischemia. The conditions lead to an activation of phospholipases and to a decreased rate of phospholipid resynthesis with a concomitant increase in the concentration of free fatty acids, in particular arachidonic acid.

Effect of diazepam on cerebral monoamine synthesis during hypoxia and hypercapnia in the rat.

In view of the fact that diazepam has been shown to prevent an increase in catecholamine synthesis and/or turnover rates in stressful situations, and to modify the cerebral metabolic (and circulatory) response to hypoxia and hypercapnia, the influence of the drug on synthesis rates of DOPA and 5-HTP in three regions of the rat brain were studied under normoxic-normocapnic conditions, as well as in hypoxia and hypercapnia. In order to exclude a modifying influence of variations in tissue pO2 during hypercapnia, cerebral venous pO2 was kept at control values by moderate arterial hypoxia. When compared to the control state (paralyzed animals maintained on 70% N2O) normoxic and normocapnic animals given diazepam (in the absence of N2O) showed a slightly enhanced DOPA synthesis in limbic structures and reduced 5-HTP synthesis in limbic structures and striatum.