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T L Pazdernik

Publications and source records attributed to T L Pazdernik.

At least 37 records · Page 2Linked to original sources
PubMed1990

Effects of microdialysis on brain metabolism in normal and seizure states.

The effect of intracranial microdialysis on brain glucose metabolism in control and kainic acid-treated rats was assessed by semi-quantitative [14C]2-deoxyglucose autoradiography. A dialysis fiber loop was implanted into the piriform cortex or a horizontal Vita fiber into the hippocampus, and 24 h later, fibers were perfused with Krebs-Ringer bicarbonate solution before and after injection of kainic acid (16 mg/kg, i.p.) [14C]2-Deoxyglucose was injected i.p. 3 h after the injection of kainic acid. Rats injected with kainic acid were initially lethargic and then proceeded through behavioral phases of staring, "wet-dog shakes", Straub tail, rearing, forepaw clonus, and, in some cases, tonic-clonic convulsions. Three hours after kainic acid, the fiber presence in the piriform cortex enhanced kainic acid-induced metabolic activity in areas adjacent to the fiber assembly, whereas the fiber in hippocampus attenuated kainic acid-induced metabolic activity in areas adjacent to the fiber assembly. The results indicate that intracranial microdialysis alters the already abnormal brain metabolism in a kainic acid-induced seizure state, but has no significant effect in the non-seizure control state.

Animals↗
PubMed1990

Soman- or kainic acid-induced convulsions decrease muscarinic receptors but not benzodiazepine receptors.

[3H]Quinuclidinyl benzilate (QNB) binding to muscarinic receptors decreased in the rat forebrain after convulsions induced by a single dose of either soman, a potent inhibitor of acetylcholinesterase, or kainic acid, an excitotoxin. A Rosenthal plot revealed that the receptors decreased in number rather than affinity. When the soman-induced convulsions were blocked, the decrease in muscarinic receptors at 3 days was less extensive than when convulsions occurred and at 10 days they approached control levels in most of the brain areas. The most prominent decrements in QNB binding were in the piriform cortex where the decline in QNB binding is probably related to the extensive convulsion-associated neuropathology. The decrements in QNB binding after convulsions suggest that the convulsive state leads to a down-regulation of muscarinic receptors in some brain areas. In contrast to the decrease in QNB binding after convulsions, [3H]flunitrazepam binding to benzodiazepine receptors did not change even in the piriform cortex where the loss in muscarinic receptors was most prominent. Thus, it appears that those neuronal processes that bear muscarinic receptors are more vulnerable to convulsion-induced change than those with benzodiazepine receptors.

Animals↗
PubMed1989

Kainic acid-induced seizures: changes in brain extracellular ions as assessed by intracranial microdialysis.

The effect of kainic acid on extracellular [K+], [Ca2+], and [Na+] in the rat piriform cortex and hippocampus was studied by means of intracranial microdialysis. Either a dialysis fiber loop or horizontal Vita fiber were stereotaxically implanted within the piriform cortex or hippocampus, respectively. About 24 h later, fibers were perfused (1 ml/min) with Krebs-Ringer bicarbonate solution. Effluent samples were collected before (four at 30 min intervals), and after (six at 30 min intervals) administration of kainic acid (16 mg/kg, i.p.) or kainic acid vehicle. Kainic acid induced sequential signs of lethargy, staring, "wet-dog shakes," forepaw clonus, and tonic-clonic convulsions. In these awake free-moving rats, kainic acid induced a rapid and prolonged increase in extracellular [K+] and an apparent, but not statistically significant, decrease in extracellular [Ca2+] within the hippocampus. In the piriform cortex, kainic acid induced increases in extracellular [K+] and [Na+], which were associated with early pre-convulsive signs. In contrast to the pronounced ion changes commonly seen when the brain is activated by factors such as local application of excitatory substances or when the brain is made ischemic or hypoxic, extracellular ion concentrations are relatively well maintained during parenteral kainic acid-induced seizures.

Animals↗
PubMed1988

Soman-induced convulsions affect the inositol lipid signaling system: potentiation by lithium; attenuation by atropine and diazepam.

Effects of atropine or diazepam pretreatment on soman-induced convulsions and brain phosphoinositide (PI) metabolism, as assessed by brain regional inositol-1-phosphate (IP1) levels, were studied in saline and LiCl-pretreated rats. IP1, an intermediate in PI turnover, was measured in cortex, caudate, thalamus, hippocampus, and cerebellum. Soman (100 micrograms/kg; sc) produced convulsions in 63% of the saline-pretreated rats, whereas with LiCl pretreatment all rats exposed to 100 micrograms/kg of soman had tonic-clonic convulsions. Thus, LiCl pretreatment potentiated soman-induced convulsions. Tissue IP1 increased severalfold in soman-exposed convulsing rats with the highest increases being in frontal cortex and caudate. In contrast, no marked increases of IP1 occurred in similarly treated nonconvulsing rats. LiCl treatment itself increased IP1 levels without causing convulsions. In LiCl-pretreated rats, soman again markedly elevated IP1 levels above LiCl alone in convulsing rats, whereas no such effect occurred in nonconvulsing rats. In LiCl-pretreated rats, the increased IP1 levels associated with soman-induced convulsions were greatest in hippocampus and piriform cortex. Thus, LiCl appears to lower the threshold for the spread of seizure activity through limbic structures, thereby potentiating cholinergic-induced convulsions. Diazepam and atropine both blocked soman-induced convulsions, and brain regional IP1 elevations were concomitantly abolished as well. These results indicate that soman-induced convulsions involve the inositol lipid signaling system. This involvement is potentiated by lithium but attenuated by atropine and diazepam.

Animals↗
PubMed1988

A possible role for taurine in osmoregulation within the brain.

Intracranial microdialysis was used to measure changes in extracellular amino acids within the rat brain during local osmotic alteration of the extracellular microenvironment or during systemic water intoxication. Increased cellular hydration produced by either of these methods was accompanied by a marked increase in extracellular taurine levels without affecting the other amino acids measured. With local osmotic alteration, this increase was osmolarity dependent and reversible. The specificity, sensitivity, and reversibility of the increase in extracellular taurine strongly suggest a functional role in osmoregulation in the brain under normal as well as pathological conditions.

Animals↗
PubMed1988

Convulsions and cerebral inositol-1-phosphate levels in rats treated with diisopropyl fluorophosphate.

In order to examine the relationship of organophosphate-induced cholinergic stimulation to phosphoinositide (PI) hydrolysis in the brain, diisopropyl fluorophosphate (DFP; 1.3 or 1.5 mg/kg subcutaneously) was given to rats pretreated with saline or LiCl (5 meq/kg subcutaneously). Behaviour was monitored 60 min. after the administration of DFP, and inositol-1-phosphate (IP1), an intermediate in PI metabolism, was measured in the brain DFP alone caused tremors, whereas with LiCl pretreatment, DFP caused tremors and tonic-clonic convulsions. DFP alone did not increase IP1 above control levels. LiCl alone elevated IP1 2-5 fold but did not alter rat behavior. With LiCl pretreatment, DFP caused IP1 to increase 2-4 fold above LiCl control values in convulsing rats. LiCl increased the potential of DFP to induce convulsions and greatly amplified IP1 elevations induced by DFP.

Animals↗
PubMed1987

Attenuation of cerebral glucose use in kainic acid-treated rats by diazepam.

Diazepam's impact on kainic acid seizure-induced local cerebral glucose utilization (LCGU) was assessed by a quantitative [14C]2-deoxyglucose method. Male rats were injected i.p. with either kainic acid (12 mg/kg) or its vehicle, 3 or 48 h before LCGU determination. Diazepam (3.2 mg/kg) or its vehicle were injected i.m. 15 min before, 1 and 2.5 h after kainic acid. Diazepam blocked kainic acid-induced overt convulsions, attenuated LCGU increases at 3 h and prevented 48 h LCGU decreases in piriform cortex and amygdala. LCGU in (% of vehicle): CA3 (438%), CA4 (537%) and CA1-ventral (340%) of hippocampus, interpeduncular nucleus (200%) and lateral lemniscus (213%) were still significantly above vehicle levels in the 3 h diazepam-kainic acid group. These results suggest that diazepam suppresses the spread of kainic acid-induced seizure activity from the proposed CA3 epileptogenic focus. In addition, diazepam reduces, but does not abolish, hypermetabolic activity at the foci itself.

Animals↗
PubMed1987

Cholinergic systems influence local cerebral glucose use in specific anatomical areas: diisopropyl phosphorofluoridate versus soman.

The organophosphates, diisopropyl phosphorofluoridate and soman have a common mechanism of action (inhibition of acetylcholinesterase), but result in very different behavioral responses in the rat. Soman rapidly produced persistent tonic convulsions whereas diisopropyl phosphorofluoridate only infrequently produced transient convulsive-like activity. Soman increased local cerebral glucose use in most of the cortex, striato-pallido-nigral pathway, limbic system and in specific thalamic nuclei whereas diisopropyl phosphorofluoridate increased glucose use in a limited fashion, primarily in the dorsal striato-pallido-nigral pathway. When diazepam blocked soman-induced convulsions, the pattern of glucose use was strikingly similar to that caused by diisopropyl phosphorofluoridate. Soman or diisopropyl phosphorofluoridate depressed local cerebral glucose use in rats pretreated with the antidotal mixture of trimedoxime, atropine and benactyzine (muscarinic antagonists). Also, this antidotal mixture blocked the increased glucose use in the dorsal striato-pallido-nigral system produced by either acetylcholinesterase inhibitor, indicating that muscarinic receptors mediate the excitation of this pathway. Both diisopropyl phosphorofluoridate and soman activate the striato-pallido-nigral pathway but soman also causes spread of activity producing overt motor convulsions. Possible explanations for this difference in response to the organophosphates are differential responses in cholinergic actions within specific brain regions or some non-cholinergic action of soman.

Animals↗
PubMed1987

Changes in extracellular amino acids during soman- and kainic acid-induced seizures.

Extracellular amino acid levels in the rat piriform cortex, an area highly susceptible to seizure-induced neuropathology, were determined by means of intracranial microdialysis. Seizures were induced by systemic administration of either soman (O-1,2,2-trimethylpropyl methylphosphonofluoridate), a potent inhibitor of acetylcholinesterase, or the excitotoxin kainic acid. Extracellular glutamate levels increased in animals with seizures shortly after administration of either convulsant, but this change was statistically significant only in the case of soman-treated animals. Extracellular taurine levels increased markedly, reaching two- and fourfold baseline levels during the second hour of soman- and kainic acid-induced seizures, respectively. Taurine levels did not increase in the subpopulation of soman-treated animals without seizures, a finding indicating that elevation of extracellular taurine level is seizure related. Thus, we propose that taurine efflux may be a physiological cellular response to neuronal changes produced by excitotoxic chemicals, either directly or as a consequence of seizures.

Amino Acids↗
PubMed1986

Effects of antidotes on soman-induced brain changes.

Rats were pretreated with either diazepam, atropine or benactyzine 10 min prior to soman injection. Local cerebral glucose use (LCGU) was determined during the seizure phase (15 min post soman) or pathology phase (72 h post soman). Diazepam and benactyzine pretreatment prevented convulsive activity, whereas atropine pretreatment only reduced the duration of convulsive activity after soman exposure. Each pretreatment agent had a unique impact on LCGU pattern during the seizure phase. During the pathology phase, the marked reduction in LCGU and the conspicuous brain damage associated with soman-induced seizures was minimized by all three pretreatments.

Animals↗
PubMed1985

Effect of thyroidectomy and thyroxine on 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced immunotoxicity.

Radiothyroidectomy protected against 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced immunotoxicity in rats as assessed by the spleen anti-SRBC plaque-forming cell assay. Thyroxine (T4) replacement therapy partially reversed the effects of thyroidectomy on T4 and triiodothyronine (T3) serum levels, body weight and immune function as well as restored TCDD-induced immunotoxicity. Thus, hypothyroidism induced by TCDD exposure can be viewed as a protective response of the organism to reduce the insult caused by TCDD.

Animals↗
PubMed1985

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-induced immunotoxicity.

The selective toxicity of TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) for the thymus, consisting primarily of immature T-cells, led us to search for an analogous selective toxicity for the immature B-lymphocytes in the bone marrow. In the dose-response study C57B1/6 male mice were injected with either vehicle alone (corn oil), 30, 60, or 120 micrograms/kg of TCDD i.p. The mice were killed by cervical dislocation 7 days later. In the time-response study, mice were injected with either saline or 120 micrograms/kg i.p. TCDD, 3, 7, 14, or 21 days before killing. In both studies, the following were analyzed: change in body weight, thymus weight, spleen and bone marrow cellularity, and spleen and marrow B-lymphocyte function, measured using the in vitro B-lymphocyte colony forming unit in culture assay, with the mitogen lipopolysaccharide (LPS) from Salmonella typhosa, and the in vitro plaque forming cell assay, with the thymus independent antigen, TNP-LPS. In the dose-response study there was a reduction in thymic weight, spleen B-cell functional response (per spleen), and bone marrow B-cell functional response to 14%, 35-54%, and 20-32% of control, respectively, at a dosage of 120 micrograms/kg. In the time-response study, thymic weight and bone marrow B-cell functional response (per femur) were reduced to 6% and 18% of control, respectively, at day 21. The results indicate that TCDD was selectively more toxic to the immature B-cells in the bone marrow than the more mature B-cells in the spleen. This immunotoxicity was dose-dependent.

Animals↗
PubMed1985

Changes in local cerebral glucose utilization induced by convulsants.

With the six convulsants studied (Soman, intrahippocampal penicillin, bicuculline, pentylenetetrazol, picrotoxin and strychnine), the anatomical distribution of changes in local cerebral glucose utilization was related to the type of seizure observed. Strychnine induced a few very intense motor convulsions during the 2-deoxyglucose experimental period without having a major effect on brain local cerebral glucose utilization, in support of the view that its actions are predominantly in the spinal cord. Pentylenetetrazol and picrotoxin induced intermittent intense seizures and marked increases in local cerebral glucose utilization in the globus pallidus and substantia nigra. Soman, intrahippocampal penicillin and bicuculline all induced persistent status epilepticus associated with increases in local cerebral glucose utilization in many brain areas; those with striking increases in glucose use include: cortical areas, the limbic system, basal ganglia and substantia nigra. The glucose use changes produced by Soman, penicillin and bicuculline greatly exceeded those induced by pentylenetetrazol and picrotoxin. Activation of the substantia nigra and basal ganglia occurred with all centrally mediated convulsions and with status epilepticus there was also marked activation of cortical and limbic structures.

Animals↗
PubMed1985

Blood platelet uptake of serotonin in men alcoholics.

Blood platelet uptake of 3H-serotonin (5HT uptake) was determined in a group of inpatient alcoholics who had just undergone detoxication (N = 19) and an age-matched group of nonalcoholic controls (N = 19). Mean 5HT uptake was 18% lower in the alcoholics (p less than .01). A 3-min 5HT uptake of less than 6 pmoles/10(7) platelets identified 58% of the alcoholics, but only 15% of the controls had a 5HT uptake lower than this value. These results support the hypothesis that serotonergic dysfunction may exist in alcoholics.

Adult↗
PubMed1985

Soman-induced brain lesions demonstrated by muscarinic receptor autoradiography.

Repeated exposure of rats to sublethal doses of soman resulted in moderate to severe symptoms of anticholinesterase intoxication and a pronounced weight loss within a small subgroup of these animals. A consistent pattern of cell loss and extensive neuronal necrosis appeared in specific brain areas within this subgroup. This neuropathology was not noted in rats unless they showed marked symptoms of poisoning including a precipitous weight loss. Neuropathology was most notable in the piriform cortex and thalamus. Quantitative receptor autoradiography indicated that these subjects had a significant decrease in muscarinic receptors in the piriform cortex and thalamus. The ratio of the muscarinic receptor densities in soman-treated rats with lesions to soman-treated rats without lesions was 57%, piriform cortex; 64%, ventrolateral thalamus; and 50%, mediodorsal thalamus. These decrements are distinguished from adaptive down-regulation because they are larger, there is no indication of recovery and there is a correspondence between histological lesions and the areas with decreases in muscarinic receptors. Thus, quantitative receptor autoradiography provides, in addition to kinetic information and topographical distribution, radiohistochemical evidence of neuronal damage.

Animals↗
PubMed1985

Delayed effects of Soman: brain glucose use and pathology.

The [14C]-2-deoxyglucose (2-DG) technique was used to determine the delayed effects of Soman, a potent anticholinesterase inhibitor, on local cerebral glucose utilization (LCGU). Rats were given 100 micrograms/kg of Soman (0.9 LD50; i.m.) or saline and LCGU was assessed 24, 48 or 72 hours later. All Soman injected rats had strong, continuous seizures which persisted for at least one hour. At 24 hours post-Soman there was greater than a 2-fold reduction in LCGU in the frontal cortex, cingulate gyrus, anterior and ventral thalamic nuclei, lateral habenula, parietal cortex, lateral geniculate and medial geniculate. On the other hand, the hippocampal structures did not show a significant decrease in LCGU until 48 hours post-Soman exposure. Conspicuous neuropathology was obvious in a number of structures upon inspection of the frozen brain sections, hematoxylin and eosin stained sections or the 2-DG autoradiograms, 24 to 72 hours post soman-exposure. Damage was most severe in the piriform cortex and amygdala. The lateral and ventral thalamic nuclei, many cortical regions and variable segments of the hippocampus were also consistently damaged. We suggest that energy deprivation, inadequate perfusion and/or inadequate calcium sequestration may contribute to the delayed effects following Soman-induced seizures. The 2-deoxyglucose method provides information about the dynamic process of cerebral glucose utilization and serves as a "window" for identifying neuroanatomical structures affected by neurotoxins.

Animals↗