The effects of kainic acid in rats with spontaneous recurrent seizures

1. Rats with spontaneous recurrent seizures (SRS) were obtained by injection of kainic acid (KA; 10 mg/kg SC) to drug-naive rats that regularly developed wet-dog shakes followed by complex partial seizures and status epilepticus. Three to five weeks later, the rats with manifest SRS were selected. 2. The SRS rats were challenged with KA (10 mg/kg SC). The seizures induced in SRS rats by KA were similar to SRS regarding their clinical stage and duration (mean duration of seizures: 44 sec and 43 sec, respectively). The frequency of seizures was, however, increased compared with the frequency of SRS in control, vehicle-treated SRS rats (mean frequency of seizures: 12.9 and 0.4 per 3 hr, respectively). The KA-induced seizures in SRS rats differ behaviorally from KA-induced seizures in naive rats-namely, neither wet-dog shakes nor the status epilepticus could be induced. 3. Repeated injection of an equal dose of KA, applied to the SRS rats 1 day after the previous KA challenge, did not induce seizures. The loss of seizure susceptibility to KA was only temporary, as shown after a 7-day drug-free period, when the repeated injection of KA regained its seizure-triggering capacity. 4. The results indicate that reactivity to the seizure-inducing agent kainic acid changes in rats with spontaneous recurrent seizures.     

The effect on cortical mirror foci produced by ouabain of gamma-aminobutyric acid, dopamine and haloperidol injected into the rabbit caudate nucleus

It is the experience of the urological author that radiculitis secondary to costovertebral joint derangement is the most common cause of lower abdominal pain. However, this pain is sometimes made worse when the patient is subjected to a flank incision for presumed renal disease, since the aftermath of a flank incision may be a downward pull on a rib owing to detachments of muscles attached to its superior surface. Emotional problems, too, befall many patients with radiculitis--despondency over delayed diagnoses or sensitivity at having been told their complaints are psychosomatic. Most often these difficulties disappear spontaneously once the pain is relieved. Definitive diagnosis requires orthopedic techniques. Unfortunately, few orthopedists are well versed or interested in the syndrome of renal pain. When they are, erroneous diagnosis can be corrected and a course of conservative or surgical treatment prescribed, with excellent results.     

Effects of substantia nigra and caudate nucleus lesions on avoidance learning in rats.

Compared to 21 operated and 14 nonoperated controls, 36 male Sprague-Dawley albino rats with small bilateral lesions in the anteroventral caudate nucleus or the rostral substantia nigra were significantly impaired in the acquisition of 1-way active avoidance, passive avoidance requiring the inhibition of the previously acquired 1-way response, and shuttle-box avoidance. Ss with nigral lesions took significantly more trials to criterion than Ss with caudate lesions on 1-way avoidance. Results are considered in terms of the intimate anatomical and neurochemical relationships between these structures, and a circuit of structures involved in avoidance learning is suggested. (34 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The developing caudate nucleus in the euthyroid and hypothyroid rat

The basal ganglia are presently implicated in learning, and thyroid deficiency induced neonatally is known to affect mentation. The effects of such a deficiency on the developing causate nucleus might be used to provide insight into structure and function of the normal subcortical brain, as well as possible influences of these extrapyramidal structures on mental retardation. Propylthiouracil was added to the diet of lactating rat dams and observations of the developing caudate nuclei of normal hypothyroid rats were made at 8, 14, 20, 30 and 42 days by using various tissue stains and Golgi-Cox preparations. Seven different types of neurons were distinguished in the caudate nucleus. Differences in the size of cell somata and the varying morphology of axons and dendrites were criteria used to make distinctions. Normally, the nucleus acquires cytoarchitectural complexity during the first three postnatal weeks. Within this period, neuron incidence increases in the caudate neuropil with age while the germinal matrix density decreases. Neuron accumulation reaches a plateau after the third week and cell migration is essentially complete at the end of the first postnatal month as shown by computer analysis of Nissl stained cell counts. Branching of cellular processes, attainment of receptor spines and complexity of the fiber network also appeared during this period. Retardation of structural development with thyroid hormone deficiency was shown by decreased numbers of neurons, inhibition of dendritic arborization, decreased numbers of dendritic spines and a reduced complexity of axonal plexuses. Thyroid deficiency delays cell migration during the first three weeks when compared to age-matched normal controls. The lack of thyroid hormone does not appear to influence the size of neuron somata, and the extent of related dendritic fields, nor does hypothyroidism affect a specific cell type population. Generalized disturbances of caudate nuclear morphological maturation are caused by the deficiency. An apparent compensatory process, including a spurt of neural growth and differentiation, takes place in the period between days 14 and 30 in the deficient animals and a seemingly "normal" caudate cytoarchitecture is seen after the third postnatal week. Quantitative data, however, show that this rapid "catch up" process is inadequate. The developmental imperfection of the caudate nucleus which persists might be a part of the underlying substrate for the mental retardation, disturbed motor performance and perceptual handicaps which are found in the human patient.     

Kynurenic acid protects against the neurochemical and behavioral effects of unilateral quinolinic acid injections into the nucleus basalis of rats.

Investigated whether unilateral coinjections of kynurenic acid (KYN) and quinolinic acid (QUIN) into the rat nucleus basalis magnocellularis (nbm) antagonized the effects of QUIN alone. Food-deprived rats were pretrained on an 8-arm radial maze, with four arms baited, until choice accuracy stabilized to ≥87% correct. Postoperatively, rats were tested on the radial maze for 32 consecutive days. Feeding behavior and locomotor activity were also measured to determine if nonassociative factors accounted for any observed behavioral deficits. QUIN lesions resulted in significantly more working and reference memory errors compared with sham-operated and coinjected animals, which did not differ significantly from each other. There were no reliable group differences in amount of food eaten or locomotor activity. The QUIN group had a reliable decrease in cortical choline acetyltransferase, with no significant changes for the sham and coinjected groups. Results confirm that KYN antagonizes the neurotoxic and mnemonic effects of QUIN alone and suggest that the memory deficits induced by nbm lesions cannot be solely attributed to changes in feeding or locomotor activity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential effects of unilateral and bilateral caudate lesions on side preferences and timing behavior in rats.

Trained 24 female Sprague-Dawley rats to barpress on a DRL-16 sec schedule for water reinforcement. Ss were allowed to barpress on either of 2 levers (left and right). All Ss showed consistent side preferences. For the nonsignaled condition, normal rates were related to the strength of side preferences; lower rates and better timing performance were significantly correlated with greater preferences. Unilateral lesions in the caudate nucleus ipsilateral to side preferences facilitated performance during nonsignaled test sessions and increased side preferences during both. Unilateral lesions contralateral to side preferences impaired performance during nonsignaled test sessions and decreased side preferences during all sessions. Bilateral lesions transiently depressed response rates without significantly affecting timing performance or side preferences. It is suggested that side preferences are intimately involved in the control of behavior by internal stimuli and that an inherent asymmetry in nigrostriatal function underlies side preferences; the effect of a unilateral striatal lesion will depend on whether the lesion is placed in the more or less active striatum. (22 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Unilateral striatal grafts induce behavioral and electrophysiological asymmetry in rats with bilateral kainate lesions of the caudate nucleus.

Rats (n?=?11) with bilateral kainate lesions of the caudate nucleus and subsequent unilateral transplantation of embryonic striatal tissue into the damaged area preferred 4 months later to reach for food with the forepaw contralateral to the graft. No such asymmetry was observed in lesioned, nontransplanted (n?=?8) or unoperated (n?=?5) control rats. Good integration of the graft with the host brain was indicated by the finding that cortical spreading depression did not enter the lesioned caudate nucleus but did penetrate into the lesioned caudate with the graft almost as regularly as in intact rats. Behavioral asymmetry produced by unilateral grafts in bilaterally lesioned animals reveals the effects of transplantation with more sensitivity than the graft-induced compensation of the asymmetries caused by unilateral lesions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

In vivo electrophysiological characterization of 5-HT receptors in the guinea pig head of caudate nucleus and orbitofrontal cortex

The aim of the present study was to characterize in vivo the 5-HT receptor subtypes which mediate the effect of microiontophoretic applied 5-HT in the guinea pig head of caudate nucleus and orbitofrontal cortex. 5-HT and the preferential 5-HT2A receptor agonist DOI and the preferential 5-HT2C receptor agonist mCPP, suppressed the quisqualate (QUIS)-induced activation of neurons in both structures. The inhibitory effect of DOI and mCPP was not prevented by acute intravenous administration of the 5-HT1/2 receptor antagonist metergoline (2 mg/kg) and the 5-HT2A/2C receptor antagonist ritanserin (2 mg/kg) in the two regions nor by the selective 5-HT2A receptor antagonist MDL100907 (1 mg/kg) in the head of caudate nucleus. However, the inhibitory effect of DOI, but not that of mCPP, was antagonized by a 4-day treatment with metergoline and ritanserin (2 mg/kg/day; using minipumps implanted subcutaneously) in head of caudate nucleus, but not in orbitofrontal cortex. Microiontophoretic ejection of the 5-HT1A/7 receptor agonist 8-OH-DPAT and of the 5-HT1A receptor antagonist WAY100635 both suppressed the spontaneous and QUIS-activated firing activity of orbitofrontal cortex neurons. At current which did not affect the basal discharge activity of the neuron recorded, microiontophoretic application of WAY100635 and BMY7378 failed to prevent the inhibitory effect of 8-OH-DPAT. The inhibitory effect of gepirone, which is a 5-HT1A receptor agonist but devoid of affinity for 5-HT7 receptors, was also not antagonized by WAY100635. Altogether, these results suggest the presence of atypical 5-HT1A receptors in the orbitofrontal cortex. The present results also indicate that the suppressant effect of DOI may be mediated by 5-HT2A receptors in head of caudate nucleus and atypical 5-HT2 receptors in orbitofrontal cortex.     

Electrocortical desynchronization after microinfusion of kainic acid into the locus coeruleus in rats

CD-1, a genetically-engineered CHO cell line, was cultivated with a Biosilon microcarrier culture system. We successfully cultivated CD-1 cells to a very high density (over 1 x 10(7) cells/ml). Prourokinase was stably secreted at about 180 IU/10(6) cells/24 h. Experiments showed that CD-1 cells growing on Biosilon microcarriers were able to spontaneously release from the microcarriers, then reattach and proliferate on fresh microcarriers. This makes it very easy to scale up production. The microcarriers could be reused several times without affecting adhesion, proliferation and prourokinase secretion. With CM-PECC membrane radial flow chromatography and MPG chromatography, the prourokinase in conditioned medium could be purified to a specific activity of 1 x 10(5) IU/mg of protein. The purification factor was about 600 fold, and approximately 90% of the biological activity was recovered.     

Influence of ZnCl2 pretreatment on behavioral and histological responses to kainic acid in rats

Kainic acid evokes behavioral convulsions and causes lesions in hippocampal pyramidal cell layers in rats. The effects of ZnCl2 pretreatments on these events were examined. Rats were given ZnCl2 (35 mg/kg, subcutaneously (s.c.)) 15 min prior to kainic acid administration (12 mg/kg, intraperitoneally (i.p.)). Another group of animals was given an additional dose of ZnCl2 (35 mg/kg, i.p.) 24 h prior to the s.c. ZnCl2 and i.p. kainic acid. All rats that received kainic acid, whether saline controls or ZnCl2 pretreated, experienced wet dog shakes (WDS) and convulsions. No significant differences were seen between groups in number or latency of WDS or convulsions. Two days after behavioral data were collected, the brains were perfused and the extent of lesioning among hippocampal CA1 and CA3 pyramidal cells was quantified. A single dose of ZnCl2 had either no effect or a slight protective effect on cell lesioning induced by kainic acid. However, lesioning was more pronounced in animals treated twice with zinc. It is concluded that zinc, co-administered with kainic acid, augments kainate cytotoxicity when the dose and timing of zinc exposure are within a critical period.     

The effect of cycloheximide on the regulation of proenkephalin and prodynorphin gene expressions induced by kainic acid in rat hippocampus

The effect of cycloheximide (CHX), a protein synthesis inhibitor, on the regulation of proenkephalin (proENK) and prodynorphin (proDYN) mRNA levels, proto-oncogenes, such as c-fos, 35-kDa fra and c-jun mRNA, and the levels of their products induced by kainic acid (KA) in rat hippocampus was studied. The proENK and proDYN mRNA levels were markedly increased 4 and 8 h after KA (10 mg/kg i.p.) administration. However, the intracellular proENK protein level was not affected by KA. The elevations of both proENK and proDYN mRNA levels induced by KA were inhibited by pre-administration of CHX (15 mg/kg i.p.). The increases of proENK and proDYN mRNA levels induced by KA were well-correlated with the increases of c-Fos, 35-kDa Fra and c-Jun protein levels. KA administration increased the hippocampal levels of c-Fos, 35-kDa Fra and c-Jun proteins with the time. The increases of c-Fos, 35-kDa Fra and c-Jun protein levels induced by KA administration were also inhibited by CHX pre-administration. KA administration markedly increased both c-fos and c-jun mRNA levels during 1 and 4 h and the increased levels of these proto-oncogene mRNA were further prolonged by the treatment with CHX. In addition, CHX alone increased both c-fos and c-jun mRNA levels although the onset times of induction were different. In electrophoretic mobility shift-assay, both AP-1 and ENKCRE-2 DNA-binding activities were increased by KA. KA-induced increases of AP-1 and ENKCRE-2 DNA-binding activities were also attenuated by CHX. In addition, KA-induced AP-1 and ENKCRE-2 DNA-binding activities were diminished by the antibodies against Fos and Jun family proteins. Furthermore, the cross-competition studies revealed that AP-1 proteins actively participated in ENKCRE-2 DNA domain. The results suggest that KA-induced proENK and proDYN mRNA expressions may require on-going synthesis of proteins, such as c-Fos, c-Jun and 35-kDa Fra, which may have a possible role in the up-regulation of proENK and proDYN gene expression through the binding with AP-1 and ENKCRE-2 DNA-binding motifs.     

The effect of neocortical lesions on the number of cells in neonatal or adult feline caudate nucleus: comparison to fetal lesions

After a unilateral resection of the frontal cortex in fetal cats the volume of the caudate nucleus increases while the packing density of neuronal and glial cells does not change. In the present report we address the questions of whether a similar lesion sustained neonatally or a more extensive neodecortication sustained neonatally or in adulthood may have the same unusual effect. Stereological methods were used to determine bilaterally the volume of the caudate nucleus as well as to estimate the total number and packing density of neurons and glial cells in the caudate nucleus ipsilateral to the lesion. Comparisons between each of three experimental groups and intact animals were made at a time when all animals were young adults. In cats with a unilateral frontal cortical lesion performed between postnatal days 8 and 14, none of the measured parameters changed significantly compared to intact controls. In cats with removal of the entire left neocortex in adulthood, the ipsilateral caudate nucleus volume decreased by 18.1% and by 21.5% relative to intact and to neonatal hemidecorticated cats respectively (P < 0.05), with no change in the contralateral caudate. In the ipsilateral caudate the total number of neurons decreased by 21.8% (P < 0.05) compared to controls while the number of glial cells did not change significantly. In the same caudate the packing density of neurons did not change significantly (except for a 17.1% decrease, P < 0.05, relative to frontal-lesioned cats) while that of glial cells increased by 19.9% and by 24.7% compared to intact and neonatal neodecorticated cats respectively (P < 0.05). In adult cats in which a similar hemineodecortication was performed between postnatal days 8 and 13, the only significant changes were a 25.8% (P < 0.05) and a 30.6% (P < 0.05) decrease in neuron packing density compared to intact and frontal-lesioned cats, respectively. In summary, a restricted unilateral neocortical resection in neonatal cats did not induce any morphological changes in the caudate nucleus that we could detect with the methods employed. In contrast, an extensive neodecortication sustained in adulthood produced ipsilateral caudate shrinkage with substantial neuron loss and increase in packing density of glial cells, while a similar lesion but sustained neonatally only altered substantially the packing density of glial cells (decreased). Therefore, we concluded that (i) the caudate nucleus hypertrophy which we reported after a unilateral discrete cortical removal during the prenatal period is a unique phenomenon which is peculiar to the cat brain during the last third of gestation; (ii) the caudate nucleus changes seen in the cats with hemineodecortication in adulthood are degenerative in nature and closely resemble those which we reported for other subcortical nuclei following a similar lesion; and (iii) the animals with neonatal hemidecortication are relatively spared from these degenerative effects. Overall, these results indicate that, as for other structures, the morphological changes of the caudate nucleus following neocortical damage depend on the maturational state of the brain at the time of the injury and on the size of the lesion, and support the notion that the consequences of cerebral cortex lesions upon subcortical brain nuclei are of a different nature when sustained in prenatal as compared to postnatal cats.     

Sound localizations after kainic acid lesions of the dorsal nucleus of the lateral lemniscus in the albino rat.

The ability of rats to localize sounds in space was determined before and after kainic acid lesions of the dorsal nucleus of the lateral lemniscus (DNLL). The rats were trained to approach a 45-msec noise burst delivered from loudspeakers on the right or left of midline. Lesions were made by local injection of kainic acid into the DNLL. Rats with unilateral lesions of DNLL were impaired in their postoperative ability to localize a single noise burst. Rats with bilateral lesions also had deficits in postoperative performance, but the severity of the impairment was not substantially greater than that expected from a unilateral lesion. The mean pre- and postoperative minimum audible angles were 14.8° and 40.4° for rats with complete unilateral lesions and 13.5° and 36.0° for rats with bilateral lesions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of entopeduncular nucleus and reticular part of substantia nigra on the antiepileptic activity of the caudate nucleus in the neocortex

Experiments carried out on rats show that inhibiting influences from striatal electrostimulation on the cortical epileptic activity are removed under conditions of destruction of entopeduncular nucleus (EPN). They decrease under conditions of lesion of substantia nigra pars retieulata (SNR). It is found that both EPN and SNR destruction resulted in antiepileptic effect on the development of the neocortex epileptic activity complexes. Possible mechanisms realizing inhibition of the caudate nucleus effects on the neocortex epileptic activity are discussed.     

Selective speech motor, syntax and cognitive deficits associated with bilateral damage to the putamen and the head of the caudate nucleus: a case study

This article describes emotional distress in 44 women with Human Immunodeficiency Virus (HIV) symptomatic disease. Measures of self-reported symptoms of anxiety and depression revealed that emotional distress was prevalent in this group and may be sufficiently robust to warrant clinical diagnoses. Limits to functioning and disruptions in physical well-being were found to be associated with both anxiety and depression. Additionally, level of optimism was inversely related to anxiety and depression, and social support was inversely related to anxiety. These findings indicate that emotional distress in women with HIV disease is associated with, and could be ameliorated by, interventions targeted at functional status, social support, and level of optimism.